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The p75 neurotrophin receptor regulates cranial irradiation-induced hippocampus-dependent cognitive dysfunction

Cognitive deficits, characterized by progressive problems with hippocampus-dependent learning, memory and spatial processing, are the most serious complication of cranial irradiation. However, the underlying mechanisms remain obscure. The p75 neurotrophin receptor (p75(NTR)) is involved in a diverse...

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Autores principales: Ding, Xin, Wu, Hao-Hao, Ji, Sheng-Jun, Cai, Shang, Dai, Pei-Wen, Xu, Mei-Ling, Zhang, Jun-Jun, Zhang, Qi-Xian, Tian, Ye, Ma, Quan-Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522261/
https://www.ncbi.nlm.nih.gov/pubmed/28380447
http://dx.doi.org/10.18632/oncotarget.16492
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author Ding, Xin
Wu, Hao-Hao
Ji, Sheng-Jun
Cai, Shang
Dai, Pei-Wen
Xu, Mei-Ling
Zhang, Jun-Jun
Zhang, Qi-Xian
Tian, Ye
Ma, Quan-Hong
author_facet Ding, Xin
Wu, Hao-Hao
Ji, Sheng-Jun
Cai, Shang
Dai, Pei-Wen
Xu, Mei-Ling
Zhang, Jun-Jun
Zhang, Qi-Xian
Tian, Ye
Ma, Quan-Hong
author_sort Ding, Xin
collection PubMed
description Cognitive deficits, characterized by progressive problems with hippocampus-dependent learning, memory and spatial processing, are the most serious complication of cranial irradiation. However, the underlying mechanisms remain obscure. The p75 neurotrophin receptor (p75(NTR)) is involved in a diverse arrays of cellular responses, including neurite outgrowth, neurogenesis, and negative regulation of spine density, which are associated with various neurological disorders. In this study, male Sprague-Dawley (SD) rats received 10 Gy cranial irradiation. Then, we evaluated the expression of p75(NTR) in the hippocampus after cranial irradiation and explored its potential role in radiation-induced synaptic dysfunction and memory deficits. We found that the expression of p75(NTR) was significantly increased in the irradiated rat hippocampus. Knockdown of p75(NTR) by intrahippocampal infusion of AAV8-shp75 ameliorated dendritic spine abnormalities, and restored synapse-related protein levels, thus preventing memory deficits, likely through normalization the phosphor-AKT activity. Moreover, viral-mediated overexpression of p75(NTR) in the normal hippocampus reproduced learning and memory deficits. Overall, this study demonstrates that p75(NTR) is an important mediator of irradiation-induced cognitive deficits by regulating dendritic development and synapse structure.
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spelling pubmed-55222612017-08-21 The p75 neurotrophin receptor regulates cranial irradiation-induced hippocampus-dependent cognitive dysfunction Ding, Xin Wu, Hao-Hao Ji, Sheng-Jun Cai, Shang Dai, Pei-Wen Xu, Mei-Ling Zhang, Jun-Jun Zhang, Qi-Xian Tian, Ye Ma, Quan-Hong Oncotarget Research Paper Cognitive deficits, characterized by progressive problems with hippocampus-dependent learning, memory and spatial processing, are the most serious complication of cranial irradiation. However, the underlying mechanisms remain obscure. The p75 neurotrophin receptor (p75(NTR)) is involved in a diverse arrays of cellular responses, including neurite outgrowth, neurogenesis, and negative regulation of spine density, which are associated with various neurological disorders. In this study, male Sprague-Dawley (SD) rats received 10 Gy cranial irradiation. Then, we evaluated the expression of p75(NTR) in the hippocampus after cranial irradiation and explored its potential role in radiation-induced synaptic dysfunction and memory deficits. We found that the expression of p75(NTR) was significantly increased in the irradiated rat hippocampus. Knockdown of p75(NTR) by intrahippocampal infusion of AAV8-shp75 ameliorated dendritic spine abnormalities, and restored synapse-related protein levels, thus preventing memory deficits, likely through normalization the phosphor-AKT activity. Moreover, viral-mediated overexpression of p75(NTR) in the normal hippocampus reproduced learning and memory deficits. Overall, this study demonstrates that p75(NTR) is an important mediator of irradiation-induced cognitive deficits by regulating dendritic development and synapse structure. Impact Journals LLC 2017-03-23 /pmc/articles/PMC5522261/ /pubmed/28380447 http://dx.doi.org/10.18632/oncotarget.16492 Text en Copyright: © 2017 Ding et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Ding, Xin
Wu, Hao-Hao
Ji, Sheng-Jun
Cai, Shang
Dai, Pei-Wen
Xu, Mei-Ling
Zhang, Jun-Jun
Zhang, Qi-Xian
Tian, Ye
Ma, Quan-Hong
The p75 neurotrophin receptor regulates cranial irradiation-induced hippocampus-dependent cognitive dysfunction
title The p75 neurotrophin receptor regulates cranial irradiation-induced hippocampus-dependent cognitive dysfunction
title_full The p75 neurotrophin receptor regulates cranial irradiation-induced hippocampus-dependent cognitive dysfunction
title_fullStr The p75 neurotrophin receptor regulates cranial irradiation-induced hippocampus-dependent cognitive dysfunction
title_full_unstemmed The p75 neurotrophin receptor regulates cranial irradiation-induced hippocampus-dependent cognitive dysfunction
title_short The p75 neurotrophin receptor regulates cranial irradiation-induced hippocampus-dependent cognitive dysfunction
title_sort p75 neurotrophin receptor regulates cranial irradiation-induced hippocampus-dependent cognitive dysfunction
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522261/
https://www.ncbi.nlm.nih.gov/pubmed/28380447
http://dx.doi.org/10.18632/oncotarget.16492
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