Distinct and complementary functions of rho kinase isoforms ROCK1 and ROCK2 in prefrontal cortex structural plasticity
Abstract Rho-associated protein kinases (ROCK) 1 and 2 are attractive drug targets for a range of neurologic disorders; however, a critical barrier to ROCK-based therapeutics is ambiguity over whether there are isoform-specific roles for ROCKs in neuronal structural plasticity. Here, we used a genet...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Greathouse, Kelsey M. [verfasserIn] Boros, Benjamin D. [verfasserIn] Deslauriers, Josue F. [verfasserIn] Henderson, Benjamin W. [verfasserIn] Curtis, Kendall A. [verfasserIn] Gentry, Erik G. [verfasserIn] Herskowitz, Jeremy H. [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2018 |
|---|
| Schlagwörter: |
|---|
| Übergeordnetes Werk: |
Enthalten in: Anatomy and embryology - Berlin : Springer, 1891, 223(2018), 9 vom: 08. Sept., Seite 4227-4241 |
|---|---|
| Übergeordnetes Werk: |
volume:223 ; year:2018 ; number:9 ; day:08 ; month:09 ; pages:4227-4241 |
| Links: |
|---|
| DOI / URN: |
10.1007/s00429-018-1748-4 |
|---|
| Katalog-ID: |
SPR005734193 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | SPR005734193 | ||
| 003 | DE-627 | ||
| 005 | 20230519211805.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 201002s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s00429-018-1748-4 |2 doi | |
| 035 | |a (DE-627)SPR005734193 | ||
| 035 | |a (SPR)s00429-018-1748-4-e | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 610 |q ASE |
| 084 | |a 44.34 |2 bkl | ||
| 100 | 1 | |a Greathouse, Kelsey M. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Distinct and complementary functions of rho kinase isoforms ROCK1 and ROCK2 in prefrontal cortex structural plasticity |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Rho-associated protein kinases (ROCK) 1 and 2 are attractive drug targets for a range of neurologic disorders; however, a critical barrier to ROCK-based therapeutics is ambiguity over whether there are isoform-specific roles for ROCKs in neuronal structural plasticity. Here, we used a genetics approach to address this long-standing question by analyzing both male and female adult $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice compared to littermate controls. Individual pyramidal neurons in the medial prefrontal cortex (mPFC) were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. Increased apical and basal dendritic length and intersections were observed in $ ROCK1^{+/−} $ but not $ ROCK2^{+/−} $ mice. Although dendritic spine densities were comparable among genotypes, apical spine length was decreased in $ ROCK1^{+/−} $ but increased in $ ROCK2^{+/−} $ mice. Spine head and neck diameter were reduced similarly in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice; however, certain spine morphologic subclasses were more affected than others in a genotype-dependent manner. Biochemical analyses of ROCK substrates in synaptic fractions revealed that phosphorylation of LIM kinase and cofilin were reduced in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice, while phosphorylation of myosin light chain was decreased exclusively in $ ROCK1^{+/−} $ mice. Collectively, these observations implicate ROCK1 as a novel regulatory factor of neuronal dendritic structure and detail distinct and complementary roles of ROCKs in mPFC dendritic spine structure. | ||
| 650 | 4 | |a Rho kinase |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a LIM kinase |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Dendritic spines |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Prefrontal cortex |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Dendritic arbor |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Morphometry |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Synaptosomes |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Boros, Benjamin D. |e verfasserin |4 aut | |
| 700 | 1 | |a Deslauriers, Josue F. |e verfasserin |4 aut | |
| 700 | 1 | |a Henderson, Benjamin W. |e verfasserin |4 aut | |
| 700 | 1 | |a Curtis, Kendall A. |e verfasserin |4 aut | |
| 700 | 1 | |a Gentry, Erik G. |e verfasserin |4 aut | |
| 700 | 1 | |a Herskowitz, Jeremy H. |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Anatomy and embryology |d Berlin : Springer, 1891 |g 223(2018), 9 vom: 08. Sept., Seite 4227-4241 |w (DE-627)253389798 |w (DE-600)1458423-2 |x 1432-0568 |7 nnns |
| 773 | 1 | 8 | |g volume:223 |g year:2018 |g number:9 |g day:08 |g month:09 |g pages:4227-4241 |
| 856 | 4 | 0 | |u https://dx.doi.org/10.1007/s00429-018-1748-4 |z lizenzpflichtig |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_SPRINGER | ||
| 912 | |a SSG-OLC-PHA | ||
| 912 | |a GBV_ILN_20 | ||
| 912 | |a GBV_ILN_22 | ||
| 912 | |a GBV_ILN_23 | ||
| 912 | |a GBV_ILN_24 | ||
| 912 | |a GBV_ILN_31 | ||
| 912 | |a GBV_ILN_32 | ||
| 912 | |a GBV_ILN_39 | ||
| 912 | |a GBV_ILN_40 | ||
| 912 | |a GBV_ILN_60 | ||
| 912 | |a GBV_ILN_62 | ||
| 912 | |a GBV_ILN_69 | ||
| 912 | |a GBV_ILN_70 | ||
| 912 | |a GBV_ILN_73 | ||
| 912 | |a GBV_ILN_74 | ||
| 912 | |a GBV_ILN_90 | ||
| 912 | |a GBV_ILN_95 | ||
| 912 | |a GBV_ILN_100 | ||
| 912 | |a GBV_ILN_105 | ||
| 912 | |a GBV_ILN_110 | ||
| 912 | |a GBV_ILN_120 | ||
| 912 | |a GBV_ILN_138 | ||
| 912 | |a GBV_ILN_152 | ||
| 912 | |a GBV_ILN_161 | ||
| 912 | |a GBV_ILN_171 | ||
| 912 | |a GBV_ILN_187 | ||
| 912 | |a GBV_ILN_224 | ||
| 912 | |a GBV_ILN_250 | ||
| 912 | |a GBV_ILN_267 | ||
| 912 | |a GBV_ILN_281 | ||
| 912 | |a GBV_ILN_285 | ||
| 912 | |a GBV_ILN_293 | ||
| 912 | |a GBV_ILN_370 | ||
| 912 | |a GBV_ILN_602 | ||
| 912 | |a GBV_ILN_702 | ||
| 912 | |a GBV_ILN_711 | ||
| 936 | b | k | |a 44.34 |q ASE |
| 951 | |a AR | ||
| 952 | |d 223 |j 2018 |e 9 |b 08 |c 09 |h 4227-4241 | ||
| author_variant |
k m g km kmg b d b bd bdb j f d jf jfd b w h bw bwh k a c ka kac e g g eg egg j h h jh jhh |
|---|---|
| matchkey_str |
article:14320568:2018----::itntncmlmnayucinoroiaesfrsokadokipern |
| hierarchy_sort_str |
2018 |
| bklnumber |
44.34 |
| publishDate |
2018 |
| allfields |
10.1007/s00429-018-1748-4 doi (DE-627)SPR005734193 (SPR)s00429-018-1748-4-e DE-627 ger DE-627 rakwb eng 610 ASE 44.34 bkl Greathouse, Kelsey M. verfasserin aut Distinct and complementary functions of rho kinase isoforms ROCK1 and ROCK2 in prefrontal cortex structural plasticity 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Rho-associated protein kinases (ROCK) 1 and 2 are attractive drug targets for a range of neurologic disorders; however, a critical barrier to ROCK-based therapeutics is ambiguity over whether there are isoform-specific roles for ROCKs in neuronal structural plasticity. Here, we used a genetics approach to address this long-standing question by analyzing both male and female adult $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice compared to littermate controls. Individual pyramidal neurons in the medial prefrontal cortex (mPFC) were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. Increased apical and basal dendritic length and intersections were observed in $ ROCK1^{+/−} $ but not $ ROCK2^{+/−} $ mice. Although dendritic spine densities were comparable among genotypes, apical spine length was decreased in $ ROCK1^{+/−} $ but increased in $ ROCK2^{+/−} $ mice. Spine head and neck diameter were reduced similarly in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice; however, certain spine morphologic subclasses were more affected than others in a genotype-dependent manner. Biochemical analyses of ROCK substrates in synaptic fractions revealed that phosphorylation of LIM kinase and cofilin were reduced in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice, while phosphorylation of myosin light chain was decreased exclusively in $ ROCK1^{+/−} $ mice. Collectively, these observations implicate ROCK1 as a novel regulatory factor of neuronal dendritic structure and detail distinct and complementary roles of ROCKs in mPFC dendritic spine structure. Rho kinase (dpeaa)DE-He213 LIM kinase (dpeaa)DE-He213 Dendritic spines (dpeaa)DE-He213 Prefrontal cortex (dpeaa)DE-He213 Dendritic arbor (dpeaa)DE-He213 Morphometry (dpeaa)DE-He213 Synaptosomes (dpeaa)DE-He213 Boros, Benjamin D. verfasserin aut Deslauriers, Josue F. verfasserin aut Henderson, Benjamin W. verfasserin aut Curtis, Kendall A. verfasserin aut Gentry, Erik G. verfasserin aut Herskowitz, Jeremy H. verfasserin aut Enthalten in Anatomy and embryology Berlin : Springer, 1891 223(2018), 9 vom: 08. Sept., Seite 4227-4241 (DE-627)253389798 (DE-600)1458423-2 1432-0568 nnns volume:223 year:2018 number:9 day:08 month:09 pages:4227-4241 https://dx.doi.org/10.1007/s00429-018-1748-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_711 44.34 ASE AR 223 2018 9 08 09 4227-4241 |
| spelling |
10.1007/s00429-018-1748-4 doi (DE-627)SPR005734193 (SPR)s00429-018-1748-4-e DE-627 ger DE-627 rakwb eng 610 ASE 44.34 bkl Greathouse, Kelsey M. verfasserin aut Distinct and complementary functions of rho kinase isoforms ROCK1 and ROCK2 in prefrontal cortex structural plasticity 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Rho-associated protein kinases (ROCK) 1 and 2 are attractive drug targets for a range of neurologic disorders; however, a critical barrier to ROCK-based therapeutics is ambiguity over whether there are isoform-specific roles for ROCKs in neuronal structural plasticity. Here, we used a genetics approach to address this long-standing question by analyzing both male and female adult $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice compared to littermate controls. Individual pyramidal neurons in the medial prefrontal cortex (mPFC) were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. Increased apical and basal dendritic length and intersections were observed in $ ROCK1^{+/−} $ but not $ ROCK2^{+/−} $ mice. Although dendritic spine densities were comparable among genotypes, apical spine length was decreased in $ ROCK1^{+/−} $ but increased in $ ROCK2^{+/−} $ mice. Spine head and neck diameter were reduced similarly in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice; however, certain spine morphologic subclasses were more affected than others in a genotype-dependent manner. Biochemical analyses of ROCK substrates in synaptic fractions revealed that phosphorylation of LIM kinase and cofilin were reduced in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice, while phosphorylation of myosin light chain was decreased exclusively in $ ROCK1^{+/−} $ mice. Collectively, these observations implicate ROCK1 as a novel regulatory factor of neuronal dendritic structure and detail distinct and complementary roles of ROCKs in mPFC dendritic spine structure. Rho kinase (dpeaa)DE-He213 LIM kinase (dpeaa)DE-He213 Dendritic spines (dpeaa)DE-He213 Prefrontal cortex (dpeaa)DE-He213 Dendritic arbor (dpeaa)DE-He213 Morphometry (dpeaa)DE-He213 Synaptosomes (dpeaa)DE-He213 Boros, Benjamin D. verfasserin aut Deslauriers, Josue F. verfasserin aut Henderson, Benjamin W. verfasserin aut Curtis, Kendall A. verfasserin aut Gentry, Erik G. verfasserin aut Herskowitz, Jeremy H. verfasserin aut Enthalten in Anatomy and embryology Berlin : Springer, 1891 223(2018), 9 vom: 08. Sept., Seite 4227-4241 (DE-627)253389798 (DE-600)1458423-2 1432-0568 nnns volume:223 year:2018 number:9 day:08 month:09 pages:4227-4241 https://dx.doi.org/10.1007/s00429-018-1748-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_711 44.34 ASE AR 223 2018 9 08 09 4227-4241 |
| allfields_unstemmed |
10.1007/s00429-018-1748-4 doi (DE-627)SPR005734193 (SPR)s00429-018-1748-4-e DE-627 ger DE-627 rakwb eng 610 ASE 44.34 bkl Greathouse, Kelsey M. verfasserin aut Distinct and complementary functions of rho kinase isoforms ROCK1 and ROCK2 in prefrontal cortex structural plasticity 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Rho-associated protein kinases (ROCK) 1 and 2 are attractive drug targets for a range of neurologic disorders; however, a critical barrier to ROCK-based therapeutics is ambiguity over whether there are isoform-specific roles for ROCKs in neuronal structural plasticity. Here, we used a genetics approach to address this long-standing question by analyzing both male and female adult $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice compared to littermate controls. Individual pyramidal neurons in the medial prefrontal cortex (mPFC) were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. Increased apical and basal dendritic length and intersections were observed in $ ROCK1^{+/−} $ but not $ ROCK2^{+/−} $ mice. Although dendritic spine densities were comparable among genotypes, apical spine length was decreased in $ ROCK1^{+/−} $ but increased in $ ROCK2^{+/−} $ mice. Spine head and neck diameter were reduced similarly in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice; however, certain spine morphologic subclasses were more affected than others in a genotype-dependent manner. Biochemical analyses of ROCK substrates in synaptic fractions revealed that phosphorylation of LIM kinase and cofilin were reduced in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice, while phosphorylation of myosin light chain was decreased exclusively in $ ROCK1^{+/−} $ mice. Collectively, these observations implicate ROCK1 as a novel regulatory factor of neuronal dendritic structure and detail distinct and complementary roles of ROCKs in mPFC dendritic spine structure. Rho kinase (dpeaa)DE-He213 LIM kinase (dpeaa)DE-He213 Dendritic spines (dpeaa)DE-He213 Prefrontal cortex (dpeaa)DE-He213 Dendritic arbor (dpeaa)DE-He213 Morphometry (dpeaa)DE-He213 Synaptosomes (dpeaa)DE-He213 Boros, Benjamin D. verfasserin aut Deslauriers, Josue F. verfasserin aut Henderson, Benjamin W. verfasserin aut Curtis, Kendall A. verfasserin aut Gentry, Erik G. verfasserin aut Herskowitz, Jeremy H. verfasserin aut Enthalten in Anatomy and embryology Berlin : Springer, 1891 223(2018), 9 vom: 08. Sept., Seite 4227-4241 (DE-627)253389798 (DE-600)1458423-2 1432-0568 nnns volume:223 year:2018 number:9 day:08 month:09 pages:4227-4241 https://dx.doi.org/10.1007/s00429-018-1748-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_711 44.34 ASE AR 223 2018 9 08 09 4227-4241 |
| allfieldsGer |
10.1007/s00429-018-1748-4 doi (DE-627)SPR005734193 (SPR)s00429-018-1748-4-e DE-627 ger DE-627 rakwb eng 610 ASE 44.34 bkl Greathouse, Kelsey M. verfasserin aut Distinct and complementary functions of rho kinase isoforms ROCK1 and ROCK2 in prefrontal cortex structural plasticity 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Rho-associated protein kinases (ROCK) 1 and 2 are attractive drug targets for a range of neurologic disorders; however, a critical barrier to ROCK-based therapeutics is ambiguity over whether there are isoform-specific roles for ROCKs in neuronal structural plasticity. Here, we used a genetics approach to address this long-standing question by analyzing both male and female adult $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice compared to littermate controls. Individual pyramidal neurons in the medial prefrontal cortex (mPFC) were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. Increased apical and basal dendritic length and intersections were observed in $ ROCK1^{+/−} $ but not $ ROCK2^{+/−} $ mice. Although dendritic spine densities were comparable among genotypes, apical spine length was decreased in $ ROCK1^{+/−} $ but increased in $ ROCK2^{+/−} $ mice. Spine head and neck diameter were reduced similarly in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice; however, certain spine morphologic subclasses were more affected than others in a genotype-dependent manner. Biochemical analyses of ROCK substrates in synaptic fractions revealed that phosphorylation of LIM kinase and cofilin were reduced in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice, while phosphorylation of myosin light chain was decreased exclusively in $ ROCK1^{+/−} $ mice. Collectively, these observations implicate ROCK1 as a novel regulatory factor of neuronal dendritic structure and detail distinct and complementary roles of ROCKs in mPFC dendritic spine structure. Rho kinase (dpeaa)DE-He213 LIM kinase (dpeaa)DE-He213 Dendritic spines (dpeaa)DE-He213 Prefrontal cortex (dpeaa)DE-He213 Dendritic arbor (dpeaa)DE-He213 Morphometry (dpeaa)DE-He213 Synaptosomes (dpeaa)DE-He213 Boros, Benjamin D. verfasserin aut Deslauriers, Josue F. verfasserin aut Henderson, Benjamin W. verfasserin aut Curtis, Kendall A. verfasserin aut Gentry, Erik G. verfasserin aut Herskowitz, Jeremy H. verfasserin aut Enthalten in Anatomy and embryology Berlin : Springer, 1891 223(2018), 9 vom: 08. Sept., Seite 4227-4241 (DE-627)253389798 (DE-600)1458423-2 1432-0568 nnns volume:223 year:2018 number:9 day:08 month:09 pages:4227-4241 https://dx.doi.org/10.1007/s00429-018-1748-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_711 44.34 ASE AR 223 2018 9 08 09 4227-4241 |
| allfieldsSound |
10.1007/s00429-018-1748-4 doi (DE-627)SPR005734193 (SPR)s00429-018-1748-4-e DE-627 ger DE-627 rakwb eng 610 ASE 44.34 bkl Greathouse, Kelsey M. verfasserin aut Distinct and complementary functions of rho kinase isoforms ROCK1 and ROCK2 in prefrontal cortex structural plasticity 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Rho-associated protein kinases (ROCK) 1 and 2 are attractive drug targets for a range of neurologic disorders; however, a critical barrier to ROCK-based therapeutics is ambiguity over whether there are isoform-specific roles for ROCKs in neuronal structural plasticity. Here, we used a genetics approach to address this long-standing question by analyzing both male and female adult $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice compared to littermate controls. Individual pyramidal neurons in the medial prefrontal cortex (mPFC) were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. Increased apical and basal dendritic length and intersections were observed in $ ROCK1^{+/−} $ but not $ ROCK2^{+/−} $ mice. Although dendritic spine densities were comparable among genotypes, apical spine length was decreased in $ ROCK1^{+/−} $ but increased in $ ROCK2^{+/−} $ mice. Spine head and neck diameter were reduced similarly in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice; however, certain spine morphologic subclasses were more affected than others in a genotype-dependent manner. Biochemical analyses of ROCK substrates in synaptic fractions revealed that phosphorylation of LIM kinase and cofilin were reduced in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice, while phosphorylation of myosin light chain was decreased exclusively in $ ROCK1^{+/−} $ mice. Collectively, these observations implicate ROCK1 as a novel regulatory factor of neuronal dendritic structure and detail distinct and complementary roles of ROCKs in mPFC dendritic spine structure. Rho kinase (dpeaa)DE-He213 LIM kinase (dpeaa)DE-He213 Dendritic spines (dpeaa)DE-He213 Prefrontal cortex (dpeaa)DE-He213 Dendritic arbor (dpeaa)DE-He213 Morphometry (dpeaa)DE-He213 Synaptosomes (dpeaa)DE-He213 Boros, Benjamin D. verfasserin aut Deslauriers, Josue F. verfasserin aut Henderson, Benjamin W. verfasserin aut Curtis, Kendall A. verfasserin aut Gentry, Erik G. verfasserin aut Herskowitz, Jeremy H. verfasserin aut Enthalten in Anatomy and embryology Berlin : Springer, 1891 223(2018), 9 vom: 08. Sept., Seite 4227-4241 (DE-627)253389798 (DE-600)1458423-2 1432-0568 nnns volume:223 year:2018 number:9 day:08 month:09 pages:4227-4241 https://dx.doi.org/10.1007/s00429-018-1748-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_711 44.34 ASE AR 223 2018 9 08 09 4227-4241 |
| language |
English |
| source |
Enthalten in Anatomy and embryology 223(2018), 9 vom: 08. Sept., Seite 4227-4241 volume:223 year:2018 number:9 day:08 month:09 pages:4227-4241 |
| sourceStr |
Enthalten in Anatomy and embryology 223(2018), 9 vom: 08. Sept., Seite 4227-4241 volume:223 year:2018 number:9 day:08 month:09 pages:4227-4241 |
| format_phy_str_mv |
Article |
| institution |
findex.gbv.de |
| topic_facet |
Rho kinase LIM kinase Dendritic spines Prefrontal cortex Dendritic arbor Morphometry Synaptosomes |
| dewey-raw |
610 |
| isfreeaccess_bool |
false |
| container_title |
Anatomy and embryology |
| authorswithroles_txt_mv |
Greathouse, Kelsey M. @@aut@@ Boros, Benjamin D. @@aut@@ Deslauriers, Josue F. @@aut@@ Henderson, Benjamin W. @@aut@@ Curtis, Kendall A. @@aut@@ Gentry, Erik G. @@aut@@ Herskowitz, Jeremy H. @@aut@@ |
| publishDateDaySort_date |
2018-09-08T00:00:00Z |
| hierarchy_top_id |
253389798 |
| dewey-sort |
3610 |
| id |
SPR005734193 |
| language_de |
englisch |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR005734193</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519211805.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201002s2018 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s00429-018-1748-4</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR005734193</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s00429-018-1748-4-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.34</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Greathouse, Kelsey M.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Distinct and complementary functions of rho kinase isoforms ROCK1 and ROCK2 in prefrontal cortex structural plasticity</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2018</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Rho-associated protein kinases (ROCK) 1 and 2 are attractive drug targets for a range of neurologic disorders; however, a critical barrier to ROCK-based therapeutics is ambiguity over whether there are isoform-specific roles for ROCKs in neuronal structural plasticity. Here, we used a genetics approach to address this long-standing question by analyzing both male and female adult $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice compared to littermate controls. Individual pyramidal neurons in the medial prefrontal cortex (mPFC) were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. Increased apical and basal dendritic length and intersections were observed in $ ROCK1^{+/−} $ but not $ ROCK2^{+/−} $ mice. Although dendritic spine densities were comparable among genotypes, apical spine length was decreased in $ ROCK1^{+/−} $ but increased in $ ROCK2^{+/−} $ mice. Spine head and neck diameter were reduced similarly in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice; however, certain spine morphologic subclasses were more affected than others in a genotype-dependent manner. Biochemical analyses of ROCK substrates in synaptic fractions revealed that phosphorylation of LIM kinase and cofilin were reduced in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice, while phosphorylation of myosin light chain was decreased exclusively in $ ROCK1^{+/−} $ mice. Collectively, these observations implicate ROCK1 as a novel regulatory factor of neuronal dendritic structure and detail distinct and complementary roles of ROCKs in mPFC dendritic spine structure.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Rho kinase</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">LIM kinase</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Dendritic spines</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Prefrontal cortex</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Dendritic arbor</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Morphometry</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Synaptosomes</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Boros, Benjamin D.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Deslauriers, Josue F.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Henderson, Benjamin W.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Curtis, Kendall A.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Gentry, Erik G.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Herskowitz, Jeremy H.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Anatomy and embryology</subfield><subfield code="d">Berlin : Springer, 1891</subfield><subfield code="g">223(2018), 9 vom: 08. Sept., Seite 4227-4241</subfield><subfield code="w">(DE-627)253389798</subfield><subfield code="w">(DE-600)1458423-2</subfield><subfield code="x">1432-0568</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:223</subfield><subfield code="g">year:2018</subfield><subfield code="g">number:9</subfield><subfield code="g">day:08</subfield><subfield code="g">month:09</subfield><subfield code="g">pages:4227-4241</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://dx.doi.org/10.1007/s00429-018-1748-4</subfield><subfield code="z">lizenzpflichtig</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_SPRINGER</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_32</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_90</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_100</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_120</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_138</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_152</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_171</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_187</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_224</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_250</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_267</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_281</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_370</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_702</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_711</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">44.34</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">223</subfield><subfield code="j">2018</subfield><subfield code="e">9</subfield><subfield code="b">08</subfield><subfield code="c">09</subfield><subfield code="h">4227-4241</subfield></datafield></record></collection>
|
| author |
Greathouse, Kelsey M. |
| spellingShingle |
Greathouse, Kelsey M. ddc 610 bkl 44.34 misc Rho kinase misc LIM kinase misc Dendritic spines misc Prefrontal cortex misc Dendritic arbor misc Morphometry misc Synaptosomes Distinct and complementary functions of rho kinase isoforms ROCK1 and ROCK2 in prefrontal cortex structural plasticity |
| authorStr |
Greathouse, Kelsey M. |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)253389798 |
| format |
electronic Article |
| dewey-ones |
610 - Medicine & health |
| delete_txt_mv |
keep |
| author_role |
aut aut aut aut aut aut aut |
| collection |
springer |
| remote_str |
true |
| illustrated |
Not Illustrated |
| issn |
1432-0568 |
| topic_title |
610 ASE 44.34 bkl Distinct and complementary functions of rho kinase isoforms ROCK1 and ROCK2 in prefrontal cortex structural plasticity Rho kinase (dpeaa)DE-He213 LIM kinase (dpeaa)DE-He213 Dendritic spines (dpeaa)DE-He213 Prefrontal cortex (dpeaa)DE-He213 Dendritic arbor (dpeaa)DE-He213 Morphometry (dpeaa)DE-He213 Synaptosomes (dpeaa)DE-He213 |
| topic |
ddc 610 bkl 44.34 misc Rho kinase misc LIM kinase misc Dendritic spines misc Prefrontal cortex misc Dendritic arbor misc Morphometry misc Synaptosomes |
| topic_unstemmed |
ddc 610 bkl 44.34 misc Rho kinase misc LIM kinase misc Dendritic spines misc Prefrontal cortex misc Dendritic arbor misc Morphometry misc Synaptosomes |
| topic_browse |
ddc 610 bkl 44.34 misc Rho kinase misc LIM kinase misc Dendritic spines misc Prefrontal cortex misc Dendritic arbor misc Morphometry misc Synaptosomes |
| format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
cr |
| hierarchy_parent_title |
Anatomy and embryology |
| hierarchy_parent_id |
253389798 |
| dewey-tens |
610 - Medicine & health |
| hierarchy_top_title |
Anatomy and embryology |
| isfreeaccess_txt |
false |
| familylinks_str_mv |
(DE-627)253389798 (DE-600)1458423-2 |
| title |
Distinct and complementary functions of rho kinase isoforms ROCK1 and ROCK2 in prefrontal cortex structural plasticity |
| ctrlnum |
(DE-627)SPR005734193 (SPR)s00429-018-1748-4-e |
| title_full |
Distinct and complementary functions of rho kinase isoforms ROCK1 and ROCK2 in prefrontal cortex structural plasticity |
| author_sort |
Greathouse, Kelsey M. |
| journal |
Anatomy and embryology |
| journalStr |
Anatomy and embryology |
| lang_code |
eng |
| isOA_bool |
false |
| dewey-hundreds |
600 - Technology |
| recordtype |
marc |
| publishDateSort |
2018 |
| contenttype_str_mv |
txt |
| container_start_page |
4227 |
| author_browse |
Greathouse, Kelsey M. Boros, Benjamin D. Deslauriers, Josue F. Henderson, Benjamin W. Curtis, Kendall A. Gentry, Erik G. Herskowitz, Jeremy H. |
| container_volume |
223 |
| class |
610 ASE 44.34 bkl |
| format_se |
Elektronische Aufsätze |
| author-letter |
Greathouse, Kelsey M. |
| doi_str_mv |
10.1007/s00429-018-1748-4 |
| dewey-full |
610 |
| author2-role |
verfasserin |
| title_sort |
distinct and complementary functions of rho kinase isoforms rock1 and rock2 in prefrontal cortex structural plasticity |
| title_auth |
Distinct and complementary functions of rho kinase isoforms ROCK1 and ROCK2 in prefrontal cortex structural plasticity |
| abstract |
Abstract Rho-associated protein kinases (ROCK) 1 and 2 are attractive drug targets for a range of neurologic disorders; however, a critical barrier to ROCK-based therapeutics is ambiguity over whether there are isoform-specific roles for ROCKs in neuronal structural plasticity. Here, we used a genetics approach to address this long-standing question by analyzing both male and female adult $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice compared to littermate controls. Individual pyramidal neurons in the medial prefrontal cortex (mPFC) were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. Increased apical and basal dendritic length and intersections were observed in $ ROCK1^{+/−} $ but not $ ROCK2^{+/−} $ mice. Although dendritic spine densities were comparable among genotypes, apical spine length was decreased in $ ROCK1^{+/−} $ but increased in $ ROCK2^{+/−} $ mice. Spine head and neck diameter were reduced similarly in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice; however, certain spine morphologic subclasses were more affected than others in a genotype-dependent manner. Biochemical analyses of ROCK substrates in synaptic fractions revealed that phosphorylation of LIM kinase and cofilin were reduced in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice, while phosphorylation of myosin light chain was decreased exclusively in $ ROCK1^{+/−} $ mice. Collectively, these observations implicate ROCK1 as a novel regulatory factor of neuronal dendritic structure and detail distinct and complementary roles of ROCKs in mPFC dendritic spine structure. |
| abstractGer |
Abstract Rho-associated protein kinases (ROCK) 1 and 2 are attractive drug targets for a range of neurologic disorders; however, a critical barrier to ROCK-based therapeutics is ambiguity over whether there are isoform-specific roles for ROCKs in neuronal structural plasticity. Here, we used a genetics approach to address this long-standing question by analyzing both male and female adult $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice compared to littermate controls. Individual pyramidal neurons in the medial prefrontal cortex (mPFC) were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. Increased apical and basal dendritic length and intersections were observed in $ ROCK1^{+/−} $ but not $ ROCK2^{+/−} $ mice. Although dendritic spine densities were comparable among genotypes, apical spine length was decreased in $ ROCK1^{+/−} $ but increased in $ ROCK2^{+/−} $ mice. Spine head and neck diameter were reduced similarly in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice; however, certain spine morphologic subclasses were more affected than others in a genotype-dependent manner. Biochemical analyses of ROCK substrates in synaptic fractions revealed that phosphorylation of LIM kinase and cofilin were reduced in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice, while phosphorylation of myosin light chain was decreased exclusively in $ ROCK1^{+/−} $ mice. Collectively, these observations implicate ROCK1 as a novel regulatory factor of neuronal dendritic structure and detail distinct and complementary roles of ROCKs in mPFC dendritic spine structure. |
| abstract_unstemmed |
Abstract Rho-associated protein kinases (ROCK) 1 and 2 are attractive drug targets for a range of neurologic disorders; however, a critical barrier to ROCK-based therapeutics is ambiguity over whether there are isoform-specific roles for ROCKs in neuronal structural plasticity. Here, we used a genetics approach to address this long-standing question by analyzing both male and female adult $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice compared to littermate controls. Individual pyramidal neurons in the medial prefrontal cortex (mPFC) were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. Increased apical and basal dendritic length and intersections were observed in $ ROCK1^{+/−} $ but not $ ROCK2^{+/−} $ mice. Although dendritic spine densities were comparable among genotypes, apical spine length was decreased in $ ROCK1^{+/−} $ but increased in $ ROCK2^{+/−} $ mice. Spine head and neck diameter were reduced similarly in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice; however, certain spine morphologic subclasses were more affected than others in a genotype-dependent manner. Biochemical analyses of ROCK substrates in synaptic fractions revealed that phosphorylation of LIM kinase and cofilin were reduced in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice, while phosphorylation of myosin light chain was decreased exclusively in $ ROCK1^{+/−} $ mice. Collectively, these observations implicate ROCK1 as a novel regulatory factor of neuronal dendritic structure and detail distinct and complementary roles of ROCKs in mPFC dendritic spine structure. |
| collection_details |
GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_711 |
| container_issue |
9 |
| title_short |
Distinct and complementary functions of rho kinase isoforms ROCK1 and ROCK2 in prefrontal cortex structural plasticity |
| url |
https://dx.doi.org/10.1007/s00429-018-1748-4 |
| remote_bool |
true |
| author2 |
Boros, Benjamin D. Deslauriers, Josue F. Henderson, Benjamin W. Curtis, Kendall A. Gentry, Erik G. Herskowitz, Jeremy H. |
| author2Str |
Boros, Benjamin D. Deslauriers, Josue F. Henderson, Benjamin W. Curtis, Kendall A. Gentry, Erik G. Herskowitz, Jeremy H. |
| ppnlink |
253389798 |
| mediatype_str_mv |
c |
| isOA_txt |
false |
| hochschulschrift_bool |
false |
| doi_str |
10.1007/s00429-018-1748-4 |
| up_date |
2024-07-03T18:19:59.712Z |
| _version_ |
1803583015840907264 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR005734193</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519211805.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201002s2018 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s00429-018-1748-4</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR005734193</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s00429-018-1748-4-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.34</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Greathouse, Kelsey M.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Distinct and complementary functions of rho kinase isoforms ROCK1 and ROCK2 in prefrontal cortex structural plasticity</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2018</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Rho-associated protein kinases (ROCK) 1 and 2 are attractive drug targets for a range of neurologic disorders; however, a critical barrier to ROCK-based therapeutics is ambiguity over whether there are isoform-specific roles for ROCKs in neuronal structural plasticity. Here, we used a genetics approach to address this long-standing question by analyzing both male and female adult $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice compared to littermate controls. Individual pyramidal neurons in the medial prefrontal cortex (mPFC) were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and neuronal 3D reconstructions for morphometry analysis. Increased apical and basal dendritic length and intersections were observed in $ ROCK1^{+/−} $ but not $ ROCK2^{+/−} $ mice. Although dendritic spine densities were comparable among genotypes, apical spine length was decreased in $ ROCK1^{+/−} $ but increased in $ ROCK2^{+/−} $ mice. Spine head and neck diameter were reduced similarly in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice; however, certain spine morphologic subclasses were more affected than others in a genotype-dependent manner. Biochemical analyses of ROCK substrates in synaptic fractions revealed that phosphorylation of LIM kinase and cofilin were reduced in $ ROCK1^{+/−} $ and $ ROCK2^{+/−} $ mice, while phosphorylation of myosin light chain was decreased exclusively in $ ROCK1^{+/−} $ mice. Collectively, these observations implicate ROCK1 as a novel regulatory factor of neuronal dendritic structure and detail distinct and complementary roles of ROCKs in mPFC dendritic spine structure.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Rho kinase</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">LIM kinase</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Dendritic spines</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Prefrontal cortex</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Dendritic arbor</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Morphometry</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Synaptosomes</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Boros, Benjamin D.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Deslauriers, Josue F.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Henderson, Benjamin W.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Curtis, Kendall A.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Gentry, Erik G.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Herskowitz, Jeremy H.</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Anatomy and embryology</subfield><subfield code="d">Berlin : Springer, 1891</subfield><subfield code="g">223(2018), 9 vom: 08. Sept., Seite 4227-4241</subfield><subfield code="w">(DE-627)253389798</subfield><subfield code="w">(DE-600)1458423-2</subfield><subfield code="x">1432-0568</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:223</subfield><subfield code="g">year:2018</subfield><subfield code="g">number:9</subfield><subfield code="g">day:08</subfield><subfield code="g">month:09</subfield><subfield code="g">pages:4227-4241</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://dx.doi.org/10.1007/s00429-018-1748-4</subfield><subfield code="z">lizenzpflichtig</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_SPRINGER</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_32</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_90</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_100</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_120</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_138</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_152</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_171</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_187</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_224</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_250</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_267</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_281</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_370</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_702</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_711</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">44.34</subfield><subfield code="q">ASE</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">223</subfield><subfield code="j">2018</subfield><subfield code="e">9</subfield><subfield code="b">08</subfield><subfield code="c">09</subfield><subfield code="h">4227-4241</subfield></datafield></record></collection>
|
| score |
7.397897 |