60404 HIV Tat Induced Neuroinflammation

ABSTRACT IMPACT: Demonstrate the role of astrocyte released MMPs in response to pathogenic HIV protein Tat. OBJECTIVES/GOALS: In the presence of the pathogenic HIV protein Tat, astrocytes have been demonstrated to adopt an inflammatory phenotype as well as release extracellular matrix degrading enzymes, MMPs. Our work aims to identify whether MMPs alter perineuronal net integrity and working memory in a mouse model of Tat-induced neuroinflammation. METHODS/STUDY POPULATION: Stereotaxic Injection: C57BL6/J mice were injected bilaterally with HIV-1 IIIB Tat 5ug in 5uL or Vehicle (0.2M KCl, 5mM DTT, 50mM Tris, pH 8.0), into the hippocampus (CA1; -1.9mm AP, ±1.6mm ML, -1.5mm DV from pial surface). All outcome measurements were performed 14-days post injection. Behavior: T-maze was used to assess working memory following Tat exposure. qRT-PCR: TaqMan probes were used according to manufacturer on extracted whole hippocampus mRNA. IF: GFAP and CD68 immunofluorescence was used to determine inflammation post injection. Inhibitory interneurons (parvalbumin positive) and peri-neuronal nets (WFA positive) were quantified. WB: Synaptosomes from whole hippocampi (Syn-PER) were isolated and synaptic excitatory markers were quantified (PSD-95, synaptophysin, GluR2a). RESULTS/ANTICIPATED RESULTS: Tat exposure resulted in impairments in working memory as measured by T-maze alternations and an increase in hippocampal mRNA expression of MMP-13 and IL-1β, indicative of neuroinflammation. We also noted an increase in GFAP+ injection site width 14 days post-Tat injection, suggesting robust gliosis. While there were no changes in the excitatory pre and post synaptic markers we found a significant decrease in the percent of PV+ interneurons with peri-neuronal nets (PNNs) following Tat exposure. Taken together, this preliminary data supports a role for inflammation and PNN integrity in Tat-induced alterations in working memory. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings suggest that Tat contributes to cognitive impairment and that astrogliosis with elevated MMP-13 facilitates the degradation of peri-neuronal nets (PNNs) within the hippocampus. Since PNN degradation can alter neuronal circuitry future studies will focus on Tat-induced changes in hippocampal signaling. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Sean Carey [verfasserIn] Kathleen Maguire-Zeiss [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Übergeordnetes Werk:	In: Journal of Clinical and Translational Science - Cambridge University Press, 2019, 5(2021), Seite 3-3
Übergeordnetes Werk:	volume:5 ; year:2021 ; pages:3-3

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1017/cts.2021.410

Katalog-ID:	DOAJ088062120

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520			\|a ABSTRACT IMPACT: Demonstrate the role of astrocyte released MMPs in response to pathogenic HIV protein Tat. OBJECTIVES/GOALS: In the presence of the pathogenic HIV protein Tat, astrocytes have been demonstrated to adopt an inflammatory phenotype as well as release extracellular matrix degrading enzymes, MMPs. Our work aims to identify whether MMPs alter perineuronal net integrity and working memory in a mouse model of Tat-induced neuroinflammation. METHODS/STUDY POPULATION: Stereotaxic Injection: C57BL6/J mice were injected bilaterally with HIV-1 IIIB Tat 5ug in 5uL or Vehicle (0.2M KCl, 5mM DTT, 50mM Tris, pH 8.0), into the hippocampus (CA1; -1.9mm AP, ±1.6mm ML, -1.5mm DV from pial surface). All outcome measurements were performed 14-days post injection. Behavior: T-maze was used to assess working memory following Tat exposure. qRT-PCR: TaqMan probes were used according to manufacturer on extracted whole hippocampus mRNA. IF: GFAP and CD68 immunofluorescence was used to determine inflammation post injection. Inhibitory interneurons (parvalbumin positive) and peri-neuronal nets (WFA positive) were quantified. WB: Synaptosomes from whole hippocampi (Syn-PER) were isolated and synaptic excitatory markers were quantified (PSD-95, synaptophysin, GluR2a). RESULTS/ANTICIPATED RESULTS: Tat exposure resulted in impairments in working memory as measured by T-maze alternations and an increase in hippocampal mRNA expression of MMP-13 and IL-1β, indicative of neuroinflammation. We also noted an increase in GFAP+ injection site width 14 days post-Tat injection, suggesting robust gliosis. While there were no changes in the excitatory pre and post synaptic markers we found a significant decrease in the percent of PV+ interneurons with peri-neuronal nets (PNNs) following Tat exposure. Taken together, this preliminary data supports a role for inflammation and PNN integrity in Tat-induced alterations in working memory. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings suggest that Tat contributes to cognitive impairment and that astrogliosis with elevated MMP-13 facilitates the degradation of peri-neuronal nets (PNNs) within the hippocampus. Since PNN degradation can alter neuronal circuitry future studies will focus on Tat-induced changes in hippocampal signaling.
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allfields	10.1017/cts.2021.410 doi (DE-627)DOAJ088062120 (DE-599)DOAJ4d2d4b29a4964e1bab10bb0134ee8ae3 DE-627 ger DE-627 rakwb eng Sean Carey verfasserin aut 60404 HIV Tat Induced Neuroinflammation 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACT IMPACT: Demonstrate the role of astrocyte released MMPs in response to pathogenic HIV protein Tat. OBJECTIVES/GOALS: In the presence of the pathogenic HIV protein Tat, astrocytes have been demonstrated to adopt an inflammatory phenotype as well as release extracellular matrix degrading enzymes, MMPs. Our work aims to identify whether MMPs alter perineuronal net integrity and working memory in a mouse model of Tat-induced neuroinflammation. METHODS/STUDY POPULATION: Stereotaxic Injection: C57BL6/J mice were injected bilaterally with HIV-1 IIIB Tat 5ug in 5uL or Vehicle (0.2M KCl, 5mM DTT, 50mM Tris, pH 8.0), into the hippocampus (CA1; -1.9mm AP, ±1.6mm ML, -1.5mm DV from pial surface). All outcome measurements were performed 14-days post injection. Behavior: T-maze was used to assess working memory following Tat exposure. qRT-PCR: TaqMan probes were used according to manufacturer on extracted whole hippocampus mRNA. IF: GFAP and CD68 immunofluorescence was used to determine inflammation post injection. Inhibitory interneurons (parvalbumin positive) and peri-neuronal nets (WFA positive) were quantified. WB: Synaptosomes from whole hippocampi (Syn-PER) were isolated and synaptic excitatory markers were quantified (PSD-95, synaptophysin, GluR2a). RESULTS/ANTICIPATED RESULTS: Tat exposure resulted in impairments in working memory as measured by T-maze alternations and an increase in hippocampal mRNA expression of MMP-13 and IL-1β, indicative of neuroinflammation. We also noted an increase in GFAP+ injection site width 14 days post-Tat injection, suggesting robust gliosis. While there were no changes in the excitatory pre and post synaptic markers we found a significant decrease in the percent of PV+ interneurons with peri-neuronal nets (PNNs) following Tat exposure. Taken together, this preliminary data supports a role for inflammation and PNN integrity in Tat-induced alterations in working memory. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings suggest that Tat contributes to cognitive impairment and that astrogliosis with elevated MMP-13 facilitates the degradation of peri-neuronal nets (PNNs) within the hippocampus. Since PNN degradation can alter neuronal circuitry future studies will focus on Tat-induced changes in hippocampal signaling. Medicine R Kathleen Maguire-Zeiss verfasserin aut In Journal of Clinical and Translational Science Cambridge University Press, 2019 5(2021), Seite 3-3 (DE-627)891016082 (DE-600)2898186-8 20598661 nnns volume:5 year:2021 pages:3-3 https://doi.org/10.1017/cts.2021.410 kostenfrei https://doaj.org/article/4d2d4b29a4964e1bab10bb0134ee8ae3 kostenfrei https://www.cambridge.org/core/product/identifier/S2059866121004106/type/journal_article kostenfrei https://doaj.org/toc/2059-8661 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2110 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2924 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2021 3-3
spelling	10.1017/cts.2021.410 doi (DE-627)DOAJ088062120 (DE-599)DOAJ4d2d4b29a4964e1bab10bb0134ee8ae3 DE-627 ger DE-627 rakwb eng Sean Carey verfasserin aut 60404 HIV Tat Induced Neuroinflammation 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACT IMPACT: Demonstrate the role of astrocyte released MMPs in response to pathogenic HIV protein Tat. OBJECTIVES/GOALS: In the presence of the pathogenic HIV protein Tat, astrocytes have been demonstrated to adopt an inflammatory phenotype as well as release extracellular matrix degrading enzymes, MMPs. Our work aims to identify whether MMPs alter perineuronal net integrity and working memory in a mouse model of Tat-induced neuroinflammation. METHODS/STUDY POPULATION: Stereotaxic Injection: C57BL6/J mice were injected bilaterally with HIV-1 IIIB Tat 5ug in 5uL or Vehicle (0.2M KCl, 5mM DTT, 50mM Tris, pH 8.0), into the hippocampus (CA1; -1.9mm AP, ±1.6mm ML, -1.5mm DV from pial surface). All outcome measurements were performed 14-days post injection. Behavior: T-maze was used to assess working memory following Tat exposure. qRT-PCR: TaqMan probes were used according to manufacturer on extracted whole hippocampus mRNA. IF: GFAP and CD68 immunofluorescence was used to determine inflammation post injection. Inhibitory interneurons (parvalbumin positive) and peri-neuronal nets (WFA positive) were quantified. WB: Synaptosomes from whole hippocampi (Syn-PER) were isolated and synaptic excitatory markers were quantified (PSD-95, synaptophysin, GluR2a). RESULTS/ANTICIPATED RESULTS: Tat exposure resulted in impairments in working memory as measured by T-maze alternations and an increase in hippocampal mRNA expression of MMP-13 and IL-1β, indicative of neuroinflammation. We also noted an increase in GFAP+ injection site width 14 days post-Tat injection, suggesting robust gliosis. While there were no changes in the excitatory pre and post synaptic markers we found a significant decrease in the percent of PV+ interneurons with peri-neuronal nets (PNNs) following Tat exposure. Taken together, this preliminary data supports a role for inflammation and PNN integrity in Tat-induced alterations in working memory. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings suggest that Tat contributes to cognitive impairment and that astrogliosis with elevated MMP-13 facilitates the degradation of peri-neuronal nets (PNNs) within the hippocampus. Since PNN degradation can alter neuronal circuitry future studies will focus on Tat-induced changes in hippocampal signaling. Medicine R Kathleen Maguire-Zeiss verfasserin aut In Journal of Clinical and Translational Science Cambridge University Press, 2019 5(2021), Seite 3-3 (DE-627)891016082 (DE-600)2898186-8 20598661 nnns volume:5 year:2021 pages:3-3 https://doi.org/10.1017/cts.2021.410 kostenfrei https://doaj.org/article/4d2d4b29a4964e1bab10bb0134ee8ae3 kostenfrei https://www.cambridge.org/core/product/identifier/S2059866121004106/type/journal_article kostenfrei https://doaj.org/toc/2059-8661 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2110 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2924 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2021 3-3
allfields_unstemmed	10.1017/cts.2021.410 doi (DE-627)DOAJ088062120 (DE-599)DOAJ4d2d4b29a4964e1bab10bb0134ee8ae3 DE-627 ger DE-627 rakwb eng Sean Carey verfasserin aut 60404 HIV Tat Induced Neuroinflammation 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACT IMPACT: Demonstrate the role of astrocyte released MMPs in response to pathogenic HIV protein Tat. OBJECTIVES/GOALS: In the presence of the pathogenic HIV protein Tat, astrocytes have been demonstrated to adopt an inflammatory phenotype as well as release extracellular matrix degrading enzymes, MMPs. Our work aims to identify whether MMPs alter perineuronal net integrity and working memory in a mouse model of Tat-induced neuroinflammation. METHODS/STUDY POPULATION: Stereotaxic Injection: C57BL6/J mice were injected bilaterally with HIV-1 IIIB Tat 5ug in 5uL or Vehicle (0.2M KCl, 5mM DTT, 50mM Tris, pH 8.0), into the hippocampus (CA1; -1.9mm AP, ±1.6mm ML, -1.5mm DV from pial surface). All outcome measurements were performed 14-days post injection. Behavior: T-maze was used to assess working memory following Tat exposure. qRT-PCR: TaqMan probes were used according to manufacturer on extracted whole hippocampus mRNA. IF: GFAP and CD68 immunofluorescence was used to determine inflammation post injection. Inhibitory interneurons (parvalbumin positive) and peri-neuronal nets (WFA positive) were quantified. WB: Synaptosomes from whole hippocampi (Syn-PER) were isolated and synaptic excitatory markers were quantified (PSD-95, synaptophysin, GluR2a). RESULTS/ANTICIPATED RESULTS: Tat exposure resulted in impairments in working memory as measured by T-maze alternations and an increase in hippocampal mRNA expression of MMP-13 and IL-1β, indicative of neuroinflammation. We also noted an increase in GFAP+ injection site width 14 days post-Tat injection, suggesting robust gliosis. While there were no changes in the excitatory pre and post synaptic markers we found a significant decrease in the percent of PV+ interneurons with peri-neuronal nets (PNNs) following Tat exposure. Taken together, this preliminary data supports a role for inflammation and PNN integrity in Tat-induced alterations in working memory. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings suggest that Tat contributes to cognitive impairment and that astrogliosis with elevated MMP-13 facilitates the degradation of peri-neuronal nets (PNNs) within the hippocampus. Since PNN degradation can alter neuronal circuitry future studies will focus on Tat-induced changes in hippocampal signaling. Medicine R Kathleen Maguire-Zeiss verfasserin aut In Journal of Clinical and Translational Science Cambridge University Press, 2019 5(2021), Seite 3-3 (DE-627)891016082 (DE-600)2898186-8 20598661 nnns volume:5 year:2021 pages:3-3 https://doi.org/10.1017/cts.2021.410 kostenfrei https://doaj.org/article/4d2d4b29a4964e1bab10bb0134ee8ae3 kostenfrei https://www.cambridge.org/core/product/identifier/S2059866121004106/type/journal_article kostenfrei https://doaj.org/toc/2059-8661 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2110 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2924 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2021 3-3
allfieldsGer	10.1017/cts.2021.410 doi (DE-627)DOAJ088062120 (DE-599)DOAJ4d2d4b29a4964e1bab10bb0134ee8ae3 DE-627 ger DE-627 rakwb eng Sean Carey verfasserin aut 60404 HIV Tat Induced Neuroinflammation 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACT IMPACT: Demonstrate the role of astrocyte released MMPs in response to pathogenic HIV protein Tat. OBJECTIVES/GOALS: In the presence of the pathogenic HIV protein Tat, astrocytes have been demonstrated to adopt an inflammatory phenotype as well as release extracellular matrix degrading enzymes, MMPs. Our work aims to identify whether MMPs alter perineuronal net integrity and working memory in a mouse model of Tat-induced neuroinflammation. METHODS/STUDY POPULATION: Stereotaxic Injection: C57BL6/J mice were injected bilaterally with HIV-1 IIIB Tat 5ug in 5uL or Vehicle (0.2M KCl, 5mM DTT, 50mM Tris, pH 8.0), into the hippocampus (CA1; -1.9mm AP, ±1.6mm ML, -1.5mm DV from pial surface). All outcome measurements were performed 14-days post injection. Behavior: T-maze was used to assess working memory following Tat exposure. qRT-PCR: TaqMan probes were used according to manufacturer on extracted whole hippocampus mRNA. IF: GFAP and CD68 immunofluorescence was used to determine inflammation post injection. Inhibitory interneurons (parvalbumin positive) and peri-neuronal nets (WFA positive) were quantified. WB: Synaptosomes from whole hippocampi (Syn-PER) were isolated and synaptic excitatory markers were quantified (PSD-95, synaptophysin, GluR2a). RESULTS/ANTICIPATED RESULTS: Tat exposure resulted in impairments in working memory as measured by T-maze alternations and an increase in hippocampal mRNA expression of MMP-13 and IL-1β, indicative of neuroinflammation. We also noted an increase in GFAP+ injection site width 14 days post-Tat injection, suggesting robust gliosis. While there were no changes in the excitatory pre and post synaptic markers we found a significant decrease in the percent of PV+ interneurons with peri-neuronal nets (PNNs) following Tat exposure. Taken together, this preliminary data supports a role for inflammation and PNN integrity in Tat-induced alterations in working memory. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings suggest that Tat contributes to cognitive impairment and that astrogliosis with elevated MMP-13 facilitates the degradation of peri-neuronal nets (PNNs) within the hippocampus. Since PNN degradation can alter neuronal circuitry future studies will focus on Tat-induced changes in hippocampal signaling. Medicine R Kathleen Maguire-Zeiss verfasserin aut In Journal of Clinical and Translational Science Cambridge University Press, 2019 5(2021), Seite 3-3 (DE-627)891016082 (DE-600)2898186-8 20598661 nnns volume:5 year:2021 pages:3-3 https://doi.org/10.1017/cts.2021.410 kostenfrei https://doaj.org/article/4d2d4b29a4964e1bab10bb0134ee8ae3 kostenfrei https://www.cambridge.org/core/product/identifier/S2059866121004106/type/journal_article kostenfrei https://doaj.org/toc/2059-8661 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2110 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2924 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2021 3-3
allfieldsSound	10.1017/cts.2021.410 doi (DE-627)DOAJ088062120 (DE-599)DOAJ4d2d4b29a4964e1bab10bb0134ee8ae3 DE-627 ger DE-627 rakwb eng Sean Carey verfasserin aut 60404 HIV Tat Induced Neuroinflammation 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier ABSTRACT IMPACT: Demonstrate the role of astrocyte released MMPs in response to pathogenic HIV protein Tat. OBJECTIVES/GOALS: In the presence of the pathogenic HIV protein Tat, astrocytes have been demonstrated to adopt an inflammatory phenotype as well as release extracellular matrix degrading enzymes, MMPs. Our work aims to identify whether MMPs alter perineuronal net integrity and working memory in a mouse model of Tat-induced neuroinflammation. METHODS/STUDY POPULATION: Stereotaxic Injection: C57BL6/J mice were injected bilaterally with HIV-1 IIIB Tat 5ug in 5uL or Vehicle (0.2M KCl, 5mM DTT, 50mM Tris, pH 8.0), into the hippocampus (CA1; -1.9mm AP, ±1.6mm ML, -1.5mm DV from pial surface). All outcome measurements were performed 14-days post injection. Behavior: T-maze was used to assess working memory following Tat exposure. qRT-PCR: TaqMan probes were used according to manufacturer on extracted whole hippocampus mRNA. IF: GFAP and CD68 immunofluorescence was used to determine inflammation post injection. Inhibitory interneurons (parvalbumin positive) and peri-neuronal nets (WFA positive) were quantified. WB: Synaptosomes from whole hippocampi (Syn-PER) were isolated and synaptic excitatory markers were quantified (PSD-95, synaptophysin, GluR2a). RESULTS/ANTICIPATED RESULTS: Tat exposure resulted in impairments in working memory as measured by T-maze alternations and an increase in hippocampal mRNA expression of MMP-13 and IL-1β, indicative of neuroinflammation. We also noted an increase in GFAP+ injection site width 14 days post-Tat injection, suggesting robust gliosis. While there were no changes in the excitatory pre and post synaptic markers we found a significant decrease in the percent of PV+ interneurons with peri-neuronal nets (PNNs) following Tat exposure. Taken together, this preliminary data supports a role for inflammation and PNN integrity in Tat-induced alterations in working memory. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings suggest that Tat contributes to cognitive impairment and that astrogliosis with elevated MMP-13 facilitates the degradation of peri-neuronal nets (PNNs) within the hippocampus. Since PNN degradation can alter neuronal circuitry future studies will focus on Tat-induced changes in hippocampal signaling. Medicine R Kathleen Maguire-Zeiss verfasserin aut In Journal of Clinical and Translational Science Cambridge University Press, 2019 5(2021), Seite 3-3 (DE-627)891016082 (DE-600)2898186-8 20598661 nnns volume:5 year:2021 pages:3-3 https://doi.org/10.1017/cts.2021.410 kostenfrei https://doaj.org/article/4d2d4b29a4964e1bab10bb0134ee8ae3 kostenfrei https://www.cambridge.org/core/product/identifier/S2059866121004106/type/journal_article kostenfrei https://doaj.org/toc/2059-8661 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_374 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2110 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2924 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2021 3-3
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OBJECTIVES/GOALS: In the presence of the pathogenic HIV protein Tat, astrocytes have been demonstrated to adopt an inflammatory phenotype as well as release extracellular matrix degrading enzymes, MMPs. Our work aims to identify whether MMPs alter perineuronal net integrity and working memory in a mouse model of Tat-induced neuroinflammation. METHODS/STUDY POPULATION: Stereotaxic Injection: C57BL6/J mice were injected bilaterally with HIV-1 IIIB Tat 5ug in 5uL or Vehicle (0.2M KCl, 5mM DTT, 50mM Tris, pH 8.0), into the hippocampus (CA1; -1.9mm AP, ±1.6mm ML, -1.5mm DV from pial surface). All outcome measurements were performed 14-days post injection. Behavior: T-maze was used to assess working memory following Tat exposure. qRT-PCR: TaqMan probes were used according to manufacturer on extracted whole hippocampus mRNA. IF: GFAP and CD68 immunofluorescence was used to determine inflammation post injection. Inhibitory interneurons (parvalbumin positive) and peri-neuronal nets (WFA positive) were quantified. WB: Synaptosomes from whole hippocampi (Syn-PER) were isolated and synaptic excitatory markers were quantified (PSD-95, synaptophysin, GluR2a). RESULTS/ANTICIPATED RESULTS: Tat exposure resulted in impairments in working memory as measured by T-maze alternations and an increase in hippocampal mRNA expression of MMP-13 and IL-1β, indicative of neuroinflammation. We also noted an increase in GFAP+ injection site width 14 days post-Tat injection, suggesting robust gliosis. While there were no changes in the excitatory pre and post synaptic markers we found a significant decrease in the percent of PV+ interneurons with peri-neuronal nets (PNNs) following Tat exposure. Taken together, this preliminary data supports a role for inflammation and PNN integrity in Tat-induced alterations in working memory. 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author_browse	Sean Carey Kathleen Maguire-Zeiss
container_volume	5
format_se	Elektronische Aufsätze
author-letter	Sean Carey
doi_str_mv	10.1017/cts.2021.410
author2-role	verfasserin
title_sort	60404 hiv tat induced neuroinflammation
title_auth	60404 HIV Tat Induced Neuroinflammation
abstract	ABSTRACT IMPACT: Demonstrate the role of astrocyte released MMPs in response to pathogenic HIV protein Tat. OBJECTIVES/GOALS: In the presence of the pathogenic HIV protein Tat, astrocytes have been demonstrated to adopt an inflammatory phenotype as well as release extracellular matrix degrading enzymes, MMPs. Our work aims to identify whether MMPs alter perineuronal net integrity and working memory in a mouse model of Tat-induced neuroinflammation. METHODS/STUDY POPULATION: Stereotaxic Injection: C57BL6/J mice were injected bilaterally with HIV-1 IIIB Tat 5ug in 5uL or Vehicle (0.2M KCl, 5mM DTT, 50mM Tris, pH 8.0), into the hippocampus (CA1; -1.9mm AP, ±1.6mm ML, -1.5mm DV from pial surface). All outcome measurements were performed 14-days post injection. Behavior: T-maze was used to assess working memory following Tat exposure. qRT-PCR: TaqMan probes were used according to manufacturer on extracted whole hippocampus mRNA. IF: GFAP and CD68 immunofluorescence was used to determine inflammation post injection. Inhibitory interneurons (parvalbumin positive) and peri-neuronal nets (WFA positive) were quantified. WB: Synaptosomes from whole hippocampi (Syn-PER) were isolated and synaptic excitatory markers were quantified (PSD-95, synaptophysin, GluR2a). RESULTS/ANTICIPATED RESULTS: Tat exposure resulted in impairments in working memory as measured by T-maze alternations and an increase in hippocampal mRNA expression of MMP-13 and IL-1β, indicative of neuroinflammation. We also noted an increase in GFAP+ injection site width 14 days post-Tat injection, suggesting robust gliosis. While there were no changes in the excitatory pre and post synaptic markers we found a significant decrease in the percent of PV+ interneurons with peri-neuronal nets (PNNs) following Tat exposure. Taken together, this preliminary data supports a role for inflammation and PNN integrity in Tat-induced alterations in working memory. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings suggest that Tat contributes to cognitive impairment and that astrogliosis with elevated MMP-13 facilitates the degradation of peri-neuronal nets (PNNs) within the hippocampus. Since PNN degradation can alter neuronal circuitry future studies will focus on Tat-induced changes in hippocampal signaling.
abstractGer	ABSTRACT IMPACT: Demonstrate the role of astrocyte released MMPs in response to pathogenic HIV protein Tat. OBJECTIVES/GOALS: In the presence of the pathogenic HIV protein Tat, astrocytes have been demonstrated to adopt an inflammatory phenotype as well as release extracellular matrix degrading enzymes, MMPs. Our work aims to identify whether MMPs alter perineuronal net integrity and working memory in a mouse model of Tat-induced neuroinflammation. METHODS/STUDY POPULATION: Stereotaxic Injection: C57BL6/J mice were injected bilaterally with HIV-1 IIIB Tat 5ug in 5uL or Vehicle (0.2M KCl, 5mM DTT, 50mM Tris, pH 8.0), into the hippocampus (CA1; -1.9mm AP, ±1.6mm ML, -1.5mm DV from pial surface). All outcome measurements were performed 14-days post injection. Behavior: T-maze was used to assess working memory following Tat exposure. qRT-PCR: TaqMan probes were used according to manufacturer on extracted whole hippocampus mRNA. IF: GFAP and CD68 immunofluorescence was used to determine inflammation post injection. Inhibitory interneurons (parvalbumin positive) and peri-neuronal nets (WFA positive) were quantified. WB: Synaptosomes from whole hippocampi (Syn-PER) were isolated and synaptic excitatory markers were quantified (PSD-95, synaptophysin, GluR2a). RESULTS/ANTICIPATED RESULTS: Tat exposure resulted in impairments in working memory as measured by T-maze alternations and an increase in hippocampal mRNA expression of MMP-13 and IL-1β, indicative of neuroinflammation. We also noted an increase in GFAP+ injection site width 14 days post-Tat injection, suggesting robust gliosis. While there were no changes in the excitatory pre and post synaptic markers we found a significant decrease in the percent of PV+ interneurons with peri-neuronal nets (PNNs) following Tat exposure. Taken together, this preliminary data supports a role for inflammation and PNN integrity in Tat-induced alterations in working memory. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings suggest that Tat contributes to cognitive impairment and that astrogliosis with elevated MMP-13 facilitates the degradation of peri-neuronal nets (PNNs) within the hippocampus. Since PNN degradation can alter neuronal circuitry future studies will focus on Tat-induced changes in hippocampal signaling.
abstract_unstemmed	ABSTRACT IMPACT: Demonstrate the role of astrocyte released MMPs in response to pathogenic HIV protein Tat. OBJECTIVES/GOALS: In the presence of the pathogenic HIV protein Tat, astrocytes have been demonstrated to adopt an inflammatory phenotype as well as release extracellular matrix degrading enzymes, MMPs. Our work aims to identify whether MMPs alter perineuronal net integrity and working memory in a mouse model of Tat-induced neuroinflammation. METHODS/STUDY POPULATION: Stereotaxic Injection: C57BL6/J mice were injected bilaterally with HIV-1 IIIB Tat 5ug in 5uL or Vehicle (0.2M KCl, 5mM DTT, 50mM Tris, pH 8.0), into the hippocampus (CA1; -1.9mm AP, ±1.6mm ML, -1.5mm DV from pial surface). All outcome measurements were performed 14-days post injection. Behavior: T-maze was used to assess working memory following Tat exposure. qRT-PCR: TaqMan probes were used according to manufacturer on extracted whole hippocampus mRNA. IF: GFAP and CD68 immunofluorescence was used to determine inflammation post injection. Inhibitory interneurons (parvalbumin positive) and peri-neuronal nets (WFA positive) were quantified. WB: Synaptosomes from whole hippocampi (Syn-PER) were isolated and synaptic excitatory markers were quantified (PSD-95, synaptophysin, GluR2a). RESULTS/ANTICIPATED RESULTS: Tat exposure resulted in impairments in working memory as measured by T-maze alternations and an increase in hippocampal mRNA expression of MMP-13 and IL-1β, indicative of neuroinflammation. We also noted an increase in GFAP+ injection site width 14 days post-Tat injection, suggesting robust gliosis. While there were no changes in the excitatory pre and post synaptic markers we found a significant decrease in the percent of PV+ interneurons with peri-neuronal nets (PNNs) following Tat exposure. Taken together, this preliminary data supports a role for inflammation and PNN integrity in Tat-induced alterations in working memory. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings suggest that Tat contributes to cognitive impairment and that astrogliosis with elevated MMP-13 facilitates the degradation of peri-neuronal nets (PNNs) within the hippocampus. Since PNN degradation can alter neuronal circuitry future studies will focus on Tat-induced changes in hippocampal signaling.
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title_short	60404 HIV Tat Induced Neuroinflammation
url	https://doi.org/10.1017/cts.2021.410 https://doaj.org/article/4d2d4b29a4964e1bab10bb0134ee8ae3 https://www.cambridge.org/core/product/identifier/S2059866121004106/type/journal_article https://doaj.org/toc/2059-8661
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author2	Kathleen Maguire-Zeiss
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doi_str	10.1017/cts.2021.410
up_date	2024-07-03T15:35:35.065Z
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