Alteration of Selected Neurotrophic Factors and their Receptor Expression in Mouse Brain Response to Whole-Brain Irradiation

Ionizing radiation can significantly affect brain function in children and young adults, particularly in the hippocampus where neurogenic niches are located. Injury to normal tissue is a major concern when whole-brain irradiation (WBI) is used to treat central nervous system (CNS) tumors, and the pa...
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Autor*in:	Ewa Pius-Sadowska [verfasserIn] Milosz Piotr Kawa Patrycja Klos Dorota Roginska Michal Rudnicki Marek Boehlke Piotr Waloszczyk Boguslaw Machalinski

Format:	Artikel
Sprache:	Englisch

Erschienen:	2016

Systematik:	WA 15000

Übergeordnetes Werk:	Enthalten in: Radiation research - Lawrence, Kan. : Soc., 1954, 186(2016), 5, Seite 489-507
Übergeordnetes Werk:	volume:186 ; year:2016 ; number:5 ; pages:489-507

Links:	Volltext Link aufrufen

DOI / URN:	10.1667/RR14457.1

Katalog-ID:	OLC1984081497

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520			\|a Ionizing radiation can significantly affect brain function in children and young adults, particularly in the hippocampus where neurogenic niches are located. Injury to normal tissue is a major concern when whole-brain irradiation (WBI) is used to treat central nervous system (CNS) tumors, and the pathogenesis of this injury remains poorly understood. We assessed the expression of selected neurotrophins (NTs) and NT receptors (NTRs) in brains of young mice after a single 10 Gy gamma-ray exposure using morphological and molecular analyses [qRT-PCR, Western blot, immunohistochemistry (IHC)] to evaluate WBI-induced injury in its acute phase. Activity of the NT-NTR axes was examined by analysis of ERK and Akt phosphorylation. Using Nissl staining of hippocampus slices to visualize morphological changes, and TUNEL assay and active caspase-3 detection to assess apoptotic cell death, we found evidence of apoptosis and degenerative changes in hippocampal tissue after WBI. Shortly after WBI, we also observed significant overexpression of several NTs (BDNF, NT-3, NGF and GDNF) and NTRs (TrkA, TrkB, TrkC, GFRa-1, and p75NTR) compared to control animals. The upregulated NT and NTR proteins, in part, originated from two analyzed neurogenic areas: the subgranular zone of the hippocampal dentate gyrus and the subventricular zone, as confirmed by IHC. Finally, components of intracellular signaling pathways, including Akt and MAPK, were activated in acute phase after WBI. Given the role of NTs in diverse biological mechanisms, including maintenance and growth of neurons in the adult brain, our findings of altered expression of neurotrophins and their receptors in brain tissue shortly after irradiation suggest that these molecules play a vital role in the pathophysiology of the acute phase of WBI-induced injury.
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700	0		\|a Marek Boehlke \|4 oth
700	0		\|a Piotr Waloszczyk \|4 oth
700	0		\|a Boguslaw Machalinski \|4 oth
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allfields	10.1667/RR14457.1 doi PQ20161201 (DE-627)OLC1984081497 (DE-599)GBVOLC1984081497 (PRQ)c915-bd462b803d99add12d42f9503590a3b5bca93e330d0415f056ad85709c323ecb0 (KEY)0012922420160000186000500489alterationofselectedneurotrophicfactorsandtheirrec DE-627 ger DE-627 rakwb eng 610 530 DNB WA 15000 AVZ rvk 44.64 bkl 44.40 bkl 33.30 bkl Ewa Pius-Sadowska verfasserin aut Alteration of Selected Neurotrophic Factors and their Receptor Expression in Mouse Brain Response to Whole-Brain Irradiation 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Ionizing radiation can significantly affect brain function in children and young adults, particularly in the hippocampus where neurogenic niches are located. Injury to normal tissue is a major concern when whole-brain irradiation (WBI) is used to treat central nervous system (CNS) tumors, and the pathogenesis of this injury remains poorly understood. We assessed the expression of selected neurotrophins (NTs) and NT receptors (NTRs) in brains of young mice after a single 10 Gy gamma-ray exposure using morphological and molecular analyses [qRT-PCR, Western blot, immunohistochemistry (IHC)] to evaluate WBI-induced injury in its acute phase. Activity of the NT-NTR axes was examined by analysis of ERK and Akt phosphorylation. Using Nissl staining of hippocampus slices to visualize morphological changes, and TUNEL assay and active caspase-3 detection to assess apoptotic cell death, we found evidence of apoptosis and degenerative changes in hippocampal tissue after WBI. Shortly after WBI, we also observed significant overexpression of several NTs (BDNF, NT-3, NGF and GDNF) and NTRs (TrkA, TrkB, TrkC, GFRa-1, and p75NTR) compared to control animals. The upregulated NT and NTR proteins, in part, originated from two analyzed neurogenic areas: the subgranular zone of the hippocampal dentate gyrus and the subventricular zone, as confirmed by IHC. Finally, components of intracellular signaling pathways, including Akt and MAPK, were activated in acute phase after WBI. Given the role of NTs in diverse biological mechanisms, including maintenance and growth of neurons in the adult brain, our findings of altered expression of neurotrophins and their receptors in brain tissue shortly after irradiation suggest that these molecules play a vital role in the pathophysiology of the acute phase of WBI-induced injury. Milosz Piotr Kawa oth Patrycja Klos oth Dorota Roginska oth Michal Rudnicki oth Marek Boehlke oth Piotr Waloszczyk oth Boguslaw Machalinski oth Enthalten in Radiation research Lawrence, Kan. : Soc., 1954 186(2016), 5, Seite 489-507 (DE-627)129270644 (DE-600)80322-4 (DE-576)01446120X 0033-7587 nnns volume:186 year:2016 number:5 pages:489-507 http://dx.doi.org/10.1667/RR14457.1 Volltext http://search.proquest.com/docview/1841983345 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-PHA GBV_ILN_170 GBV_ILN_2006 GBV_ILN_4112 GBV_ILN_4219 GBV_ILN_4256 GBV_ILN_4305 GBV_ILN_4306 WA 15000 44.64 AVZ 44.40 AVZ 33.30 AVZ AR 186 2016 5 489-507
spelling	10.1667/RR14457.1 doi PQ20161201 (DE-627)OLC1984081497 (DE-599)GBVOLC1984081497 (PRQ)c915-bd462b803d99add12d42f9503590a3b5bca93e330d0415f056ad85709c323ecb0 (KEY)0012922420160000186000500489alterationofselectedneurotrophicfactorsandtheirrec DE-627 ger DE-627 rakwb eng 610 530 DNB WA 15000 AVZ rvk 44.64 bkl 44.40 bkl 33.30 bkl Ewa Pius-Sadowska verfasserin aut Alteration of Selected Neurotrophic Factors and their Receptor Expression in Mouse Brain Response to Whole-Brain Irradiation 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Ionizing radiation can significantly affect brain function in children and young adults, particularly in the hippocampus where neurogenic niches are located. Injury to normal tissue is a major concern when whole-brain irradiation (WBI) is used to treat central nervous system (CNS) tumors, and the pathogenesis of this injury remains poorly understood. We assessed the expression of selected neurotrophins (NTs) and NT receptors (NTRs) in brains of young mice after a single 10 Gy gamma-ray exposure using morphological and molecular analyses [qRT-PCR, Western blot, immunohistochemistry (IHC)] to evaluate WBI-induced injury in its acute phase. Activity of the NT-NTR axes was examined by analysis of ERK and Akt phosphorylation. Using Nissl staining of hippocampus slices to visualize morphological changes, and TUNEL assay and active caspase-3 detection to assess apoptotic cell death, we found evidence of apoptosis and degenerative changes in hippocampal tissue after WBI. Shortly after WBI, we also observed significant overexpression of several NTs (BDNF, NT-3, NGF and GDNF) and NTRs (TrkA, TrkB, TrkC, GFRa-1, and p75NTR) compared to control animals. The upregulated NT and NTR proteins, in part, originated from two analyzed neurogenic areas: the subgranular zone of the hippocampal dentate gyrus and the subventricular zone, as confirmed by IHC. Finally, components of intracellular signaling pathways, including Akt and MAPK, were activated in acute phase after WBI. Given the role of NTs in diverse biological mechanisms, including maintenance and growth of neurons in the adult brain, our findings of altered expression of neurotrophins and their receptors in brain tissue shortly after irradiation suggest that these molecules play a vital role in the pathophysiology of the acute phase of WBI-induced injury. Milosz Piotr Kawa oth Patrycja Klos oth Dorota Roginska oth Michal Rudnicki oth Marek Boehlke oth Piotr Waloszczyk oth Boguslaw Machalinski oth Enthalten in Radiation research Lawrence, Kan. : Soc., 1954 186(2016), 5, Seite 489-507 (DE-627)129270644 (DE-600)80322-4 (DE-576)01446120X 0033-7587 nnns volume:186 year:2016 number:5 pages:489-507 http://dx.doi.org/10.1667/RR14457.1 Volltext http://search.proquest.com/docview/1841983345 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-PHA GBV_ILN_170 GBV_ILN_2006 GBV_ILN_4112 GBV_ILN_4219 GBV_ILN_4256 GBV_ILN_4305 GBV_ILN_4306 WA 15000 44.64 AVZ 44.40 AVZ 33.30 AVZ AR 186 2016 5 489-507
allfields_unstemmed	10.1667/RR14457.1 doi PQ20161201 (DE-627)OLC1984081497 (DE-599)GBVOLC1984081497 (PRQ)c915-bd462b803d99add12d42f9503590a3b5bca93e330d0415f056ad85709c323ecb0 (KEY)0012922420160000186000500489alterationofselectedneurotrophicfactorsandtheirrec DE-627 ger DE-627 rakwb eng 610 530 DNB WA 15000 AVZ rvk 44.64 bkl 44.40 bkl 33.30 bkl Ewa Pius-Sadowska verfasserin aut Alteration of Selected Neurotrophic Factors and their Receptor Expression in Mouse Brain Response to Whole-Brain Irradiation 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Ionizing radiation can significantly affect brain function in children and young adults, particularly in the hippocampus where neurogenic niches are located. Injury to normal tissue is a major concern when whole-brain irradiation (WBI) is used to treat central nervous system (CNS) tumors, and the pathogenesis of this injury remains poorly understood. We assessed the expression of selected neurotrophins (NTs) and NT receptors (NTRs) in brains of young mice after a single 10 Gy gamma-ray exposure using morphological and molecular analyses [qRT-PCR, Western blot, immunohistochemistry (IHC)] to evaluate WBI-induced injury in its acute phase. Activity of the NT-NTR axes was examined by analysis of ERK and Akt phosphorylation. Using Nissl staining of hippocampus slices to visualize morphological changes, and TUNEL assay and active caspase-3 detection to assess apoptotic cell death, we found evidence of apoptosis and degenerative changes in hippocampal tissue after WBI. Shortly after WBI, we also observed significant overexpression of several NTs (BDNF, NT-3, NGF and GDNF) and NTRs (TrkA, TrkB, TrkC, GFRa-1, and p75NTR) compared to control animals. The upregulated NT and NTR proteins, in part, originated from two analyzed neurogenic areas: the subgranular zone of the hippocampal dentate gyrus and the subventricular zone, as confirmed by IHC. Finally, components of intracellular signaling pathways, including Akt and MAPK, were activated in acute phase after WBI. Given the role of NTs in diverse biological mechanisms, including maintenance and growth of neurons in the adult brain, our findings of altered expression of neurotrophins and their receptors in brain tissue shortly after irradiation suggest that these molecules play a vital role in the pathophysiology of the acute phase of WBI-induced injury. Milosz Piotr Kawa oth Patrycja Klos oth Dorota Roginska oth Michal Rudnicki oth Marek Boehlke oth Piotr Waloszczyk oth Boguslaw Machalinski oth Enthalten in Radiation research Lawrence, Kan. : Soc., 1954 186(2016), 5, Seite 489-507 (DE-627)129270644 (DE-600)80322-4 (DE-576)01446120X 0033-7587 nnns volume:186 year:2016 number:5 pages:489-507 http://dx.doi.org/10.1667/RR14457.1 Volltext http://search.proquest.com/docview/1841983345 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-PHA GBV_ILN_170 GBV_ILN_2006 GBV_ILN_4112 GBV_ILN_4219 GBV_ILN_4256 GBV_ILN_4305 GBV_ILN_4306 WA 15000 44.64 AVZ 44.40 AVZ 33.30 AVZ AR 186 2016 5 489-507
allfieldsGer	10.1667/RR14457.1 doi PQ20161201 (DE-627)OLC1984081497 (DE-599)GBVOLC1984081497 (PRQ)c915-bd462b803d99add12d42f9503590a3b5bca93e330d0415f056ad85709c323ecb0 (KEY)0012922420160000186000500489alterationofselectedneurotrophicfactorsandtheirrec DE-627 ger DE-627 rakwb eng 610 530 DNB WA 15000 AVZ rvk 44.64 bkl 44.40 bkl 33.30 bkl Ewa Pius-Sadowska verfasserin aut Alteration of Selected Neurotrophic Factors and their Receptor Expression in Mouse Brain Response to Whole-Brain Irradiation 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Ionizing radiation can significantly affect brain function in children and young adults, particularly in the hippocampus where neurogenic niches are located. Injury to normal tissue is a major concern when whole-brain irradiation (WBI) is used to treat central nervous system (CNS) tumors, and the pathogenesis of this injury remains poorly understood. We assessed the expression of selected neurotrophins (NTs) and NT receptors (NTRs) in brains of young mice after a single 10 Gy gamma-ray exposure using morphological and molecular analyses [qRT-PCR, Western blot, immunohistochemistry (IHC)] to evaluate WBI-induced injury in its acute phase. Activity of the NT-NTR axes was examined by analysis of ERK and Akt phosphorylation. Using Nissl staining of hippocampus slices to visualize morphological changes, and TUNEL assay and active caspase-3 detection to assess apoptotic cell death, we found evidence of apoptosis and degenerative changes in hippocampal tissue after WBI. Shortly after WBI, we also observed significant overexpression of several NTs (BDNF, NT-3, NGF and GDNF) and NTRs (TrkA, TrkB, TrkC, GFRa-1, and p75NTR) compared to control animals. The upregulated NT and NTR proteins, in part, originated from two analyzed neurogenic areas: the subgranular zone of the hippocampal dentate gyrus and the subventricular zone, as confirmed by IHC. Finally, components of intracellular signaling pathways, including Akt and MAPK, were activated in acute phase after WBI. Given the role of NTs in diverse biological mechanisms, including maintenance and growth of neurons in the adult brain, our findings of altered expression of neurotrophins and their receptors in brain tissue shortly after irradiation suggest that these molecules play a vital role in the pathophysiology of the acute phase of WBI-induced injury. Milosz Piotr Kawa oth Patrycja Klos oth Dorota Roginska oth Michal Rudnicki oth Marek Boehlke oth Piotr Waloszczyk oth Boguslaw Machalinski oth Enthalten in Radiation research Lawrence, Kan. : Soc., 1954 186(2016), 5, Seite 489-507 (DE-627)129270644 (DE-600)80322-4 (DE-576)01446120X 0033-7587 nnns volume:186 year:2016 number:5 pages:489-507 http://dx.doi.org/10.1667/RR14457.1 Volltext http://search.proquest.com/docview/1841983345 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-PHA GBV_ILN_170 GBV_ILN_2006 GBV_ILN_4112 GBV_ILN_4219 GBV_ILN_4256 GBV_ILN_4305 GBV_ILN_4306 WA 15000 44.64 AVZ 44.40 AVZ 33.30 AVZ AR 186 2016 5 489-507
allfieldsSound	10.1667/RR14457.1 doi PQ20161201 (DE-627)OLC1984081497 (DE-599)GBVOLC1984081497 (PRQ)c915-bd462b803d99add12d42f9503590a3b5bca93e330d0415f056ad85709c323ecb0 (KEY)0012922420160000186000500489alterationofselectedneurotrophicfactorsandtheirrec DE-627 ger DE-627 rakwb eng 610 530 DNB WA 15000 AVZ rvk 44.64 bkl 44.40 bkl 33.30 bkl Ewa Pius-Sadowska verfasserin aut Alteration of Selected Neurotrophic Factors and their Receptor Expression in Mouse Brain Response to Whole-Brain Irradiation 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Ionizing radiation can significantly affect brain function in children and young adults, particularly in the hippocampus where neurogenic niches are located. Injury to normal tissue is a major concern when whole-brain irradiation (WBI) is used to treat central nervous system (CNS) tumors, and the pathogenesis of this injury remains poorly understood. We assessed the expression of selected neurotrophins (NTs) and NT receptors (NTRs) in brains of young mice after a single 10 Gy gamma-ray exposure using morphological and molecular analyses [qRT-PCR, Western blot, immunohistochemistry (IHC)] to evaluate WBI-induced injury in its acute phase. Activity of the NT-NTR axes was examined by analysis of ERK and Akt phosphorylation. Using Nissl staining of hippocampus slices to visualize morphological changes, and TUNEL assay and active caspase-3 detection to assess apoptotic cell death, we found evidence of apoptosis and degenerative changes in hippocampal tissue after WBI. Shortly after WBI, we also observed significant overexpression of several NTs (BDNF, NT-3, NGF and GDNF) and NTRs (TrkA, TrkB, TrkC, GFRa-1, and p75NTR) compared to control animals. The upregulated NT and NTR proteins, in part, originated from two analyzed neurogenic areas: the subgranular zone of the hippocampal dentate gyrus and the subventricular zone, as confirmed by IHC. Finally, components of intracellular signaling pathways, including Akt and MAPK, were activated in acute phase after WBI. Given the role of NTs in diverse biological mechanisms, including maintenance and growth of neurons in the adult brain, our findings of altered expression of neurotrophins and their receptors in brain tissue shortly after irradiation suggest that these molecules play a vital role in the pathophysiology of the acute phase of WBI-induced injury. Milosz Piotr Kawa oth Patrycja Klos oth Dorota Roginska oth Michal Rudnicki oth Marek Boehlke oth Piotr Waloszczyk oth Boguslaw Machalinski oth Enthalten in Radiation research Lawrence, Kan. : Soc., 1954 186(2016), 5, Seite 489-507 (DE-627)129270644 (DE-600)80322-4 (DE-576)01446120X 0033-7587 nnns volume:186 year:2016 number:5 pages:489-507 http://dx.doi.org/10.1667/RR14457.1 Volltext http://search.proquest.com/docview/1841983345 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-PHA GBV_ILN_170 GBV_ILN_2006 GBV_ILN_4112 GBV_ILN_4219 GBV_ILN_4256 GBV_ILN_4305 GBV_ILN_4306 WA 15000 44.64 AVZ 44.40 AVZ 33.30 AVZ AR 186 2016 5 489-507
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source	Enthalten in Radiation research 186(2016), 5, Seite 489-507 volume:186 year:2016 number:5 pages:489-507
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author	Ewa Pius-Sadowska
spellingShingle	Ewa Pius-Sadowska ddc 610 rvk WA 15000 bkl 44.64 bkl 44.40 bkl 33.30 Alteration of Selected Neurotrophic Factors and their Receptor Expression in Mouse Brain Response to Whole-Brain Irradiation
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topic_title	610 530 DNB WA 15000 AVZ rvk 44.64 bkl 44.40 bkl 33.30 bkl Alteration of Selected Neurotrophic Factors and their Receptor Expression in Mouse Brain Response to Whole-Brain Irradiation
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title	Alteration of Selected Neurotrophic Factors and their Receptor Expression in Mouse Brain Response to Whole-Brain Irradiation
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title_full	Alteration of Selected Neurotrophic Factors and their Receptor Expression in Mouse Brain Response to Whole-Brain Irradiation
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title_sort	alteration of selected neurotrophic factors and their receptor expression in mouse brain response to whole-brain irradiation
title_auth	Alteration of Selected Neurotrophic Factors and their Receptor Expression in Mouse Brain Response to Whole-Brain Irradiation
abstract	Ionizing radiation can significantly affect brain function in children and young adults, particularly in the hippocampus where neurogenic niches are located. Injury to normal tissue is a major concern when whole-brain irradiation (WBI) is used to treat central nervous system (CNS) tumors, and the pathogenesis of this injury remains poorly understood. We assessed the expression of selected neurotrophins (NTs) and NT receptors (NTRs) in brains of young mice after a single 10 Gy gamma-ray exposure using morphological and molecular analyses [qRT-PCR, Western blot, immunohistochemistry (IHC)] to evaluate WBI-induced injury in its acute phase. Activity of the NT-NTR axes was examined by analysis of ERK and Akt phosphorylation. Using Nissl staining of hippocampus slices to visualize morphological changes, and TUNEL assay and active caspase-3 detection to assess apoptotic cell death, we found evidence of apoptosis and degenerative changes in hippocampal tissue after WBI. Shortly after WBI, we also observed significant overexpression of several NTs (BDNF, NT-3, NGF and GDNF) and NTRs (TrkA, TrkB, TrkC, GFRa-1, and p75NTR) compared to control animals. The upregulated NT and NTR proteins, in part, originated from two analyzed neurogenic areas: the subgranular zone of the hippocampal dentate gyrus and the subventricular zone, as confirmed by IHC. Finally, components of intracellular signaling pathways, including Akt and MAPK, were activated in acute phase after WBI. Given the role of NTs in diverse biological mechanisms, including maintenance and growth of neurons in the adult brain, our findings of altered expression of neurotrophins and their receptors in brain tissue shortly after irradiation suggest that these molecules play a vital role in the pathophysiology of the acute phase of WBI-induced injury.
abstractGer	Ionizing radiation can significantly affect brain function in children and young adults, particularly in the hippocampus where neurogenic niches are located. Injury to normal tissue is a major concern when whole-brain irradiation (WBI) is used to treat central nervous system (CNS) tumors, and the pathogenesis of this injury remains poorly understood. We assessed the expression of selected neurotrophins (NTs) and NT receptors (NTRs) in brains of young mice after a single 10 Gy gamma-ray exposure using morphological and molecular analyses [qRT-PCR, Western blot, immunohistochemistry (IHC)] to evaluate WBI-induced injury in its acute phase. Activity of the NT-NTR axes was examined by analysis of ERK and Akt phosphorylation. Using Nissl staining of hippocampus slices to visualize morphological changes, and TUNEL assay and active caspase-3 detection to assess apoptotic cell death, we found evidence of apoptosis and degenerative changes in hippocampal tissue after WBI. Shortly after WBI, we also observed significant overexpression of several NTs (BDNF, NT-3, NGF and GDNF) and NTRs (TrkA, TrkB, TrkC, GFRa-1, and p75NTR) compared to control animals. The upregulated NT and NTR proteins, in part, originated from two analyzed neurogenic areas: the subgranular zone of the hippocampal dentate gyrus and the subventricular zone, as confirmed by IHC. Finally, components of intracellular signaling pathways, including Akt and MAPK, were activated in acute phase after WBI. Given the role of NTs in diverse biological mechanisms, including maintenance and growth of neurons in the adult brain, our findings of altered expression of neurotrophins and their receptors in brain tissue shortly after irradiation suggest that these molecules play a vital role in the pathophysiology of the acute phase of WBI-induced injury.
abstract_unstemmed	Ionizing radiation can significantly affect brain function in children and young adults, particularly in the hippocampus where neurogenic niches are located. Injury to normal tissue is a major concern when whole-brain irradiation (WBI) is used to treat central nervous system (CNS) tumors, and the pathogenesis of this injury remains poorly understood. We assessed the expression of selected neurotrophins (NTs) and NT receptors (NTRs) in brains of young mice after a single 10 Gy gamma-ray exposure using morphological and molecular analyses [qRT-PCR, Western blot, immunohistochemistry (IHC)] to evaluate WBI-induced injury in its acute phase. Activity of the NT-NTR axes was examined by analysis of ERK and Akt phosphorylation. Using Nissl staining of hippocampus slices to visualize morphological changes, and TUNEL assay and active caspase-3 detection to assess apoptotic cell death, we found evidence of apoptosis and degenerative changes in hippocampal tissue after WBI. Shortly after WBI, we also observed significant overexpression of several NTs (BDNF, NT-3, NGF and GDNF) and NTRs (TrkA, TrkB, TrkC, GFRa-1, and p75NTR) compared to control animals. The upregulated NT and NTR proteins, in part, originated from two analyzed neurogenic areas: the subgranular zone of the hippocampal dentate gyrus and the subventricular zone, as confirmed by IHC. Finally, components of intracellular signaling pathways, including Akt and MAPK, were activated in acute phase after WBI. Given the role of NTs in diverse biological mechanisms, including maintenance and growth of neurons in the adult brain, our findings of altered expression of neurotrophins and their receptors in brain tissue shortly after irradiation suggest that these molecules play a vital role in the pathophysiology of the acute phase of WBI-induced injury.
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container_issue	5
title_short	Alteration of Selected Neurotrophic Factors and their Receptor Expression in Mouse Brain Response to Whole-Brain Irradiation
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