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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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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 |
Sumario: | 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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