[PMID]: | 27576527 |
[Au] Autor: | Feng X; Jopson TD; Paladini MS; Liu S; West BL; Gupta N; Rosi S |
[Ad] Endereço: | Brain and Spinal Injury Center, University of California, 1001 Potrero Ave, Bldg. 1, Room 101, San Francisco, CA, 94110, USA. |
[Ti] Título: | Colony-stimulating factor 1 receptor blockade prevents fractionated whole-brain irradiation-induced memory deficits. |
[So] Source: | J Neuroinflammation;13(1):215, 2016 Aug 30. |
[Is] ISSN: | 1742-2094 |
[Cp] País de publicação: | England |
[La] Idioma: | eng |
[Ab] Resumo: | BACKGROUND: Primary central nervous system (CNS) neoplasms and brain metastases are routinely treated with whole-brain radiation. Long-term survival occurs in many patients, but their quality of life is severely affected by the development of cognitive deficits, and there is no treatment to prevent these adverse effects. Neuroinflammation, associated with activation of brain-resident microglia and infiltrating monocytes, plays a pivotal role in loss of neurological function and has been shown to be associated with acute and long-term effects of brain irradiation. Colony-stimulating factor 1 receptor (CSF-1R) signaling is essential for the survival and differentiation of microglia and monocytes. Here, we tested the effects of CSF-1R blockade by PLX5622 on cognitive function in mice treated with three fractions of 3.3 Gy whole-brain irradiation. METHODS: Young adult C57BL/6J mice were given three fractions of 3.3 Gy whole-brain irradiation while they were on diet supplemented with PLX5622, and the effects on periphery monocyte accumulation, microglia numbers, and neuronal functions were assessed. RESULTS: The mice developed hippocampal-dependent cognitive deficits at 1 and 3 months after they received fractionated whole-brain irradiation. The impaired cognitive function correlated with increased number of periphery monocyte accumulation in the CNS and decreased dendritic spine density in hippocampal granule neurons. PLX5622 treatment caused temporary reduction of microglia numbers, inhibited monocyte accumulation in the brain, and prevented radiation-induced cognitive deficits. CONCLUSIONS: Blockade of CSF-1R by PLX5622 prevents fractionated whole-brain irradiation-induced memory deficits. Therapeutic targeting of CSF-1R may provide a new avenue for protection from radiation-induced memory deficits. |
[Mh] Termos MeSH primário: |
Encéfalo/efeitos dos fármacos Encéfalo/efeitos da radiação Transtornos da Memória/metabolismo Transtornos da Memória/prevenção & controle Receptor de Fator Estimulador de Colônias de Macrófagos/antagonistas & inibidores Receptor de Fator Estimulador de Colônias de Macrófagos/metabolismo
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[Mh] Termos MeSH secundário: |
Aminopiridinas/farmacologia Aminopiridinas/uso terapêutico Animais Masculino Camundongos Camundongos Endogâmicos C57BL Camundongos Transgênicos Pirróis/farmacologia Pirróis/uso terapêutico Efeitos da Radiação
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (5-((5-chloro-1H-pyrrolo(2,3-b)pyridin-3-yl)methyl)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)pyridin-2-amine); 0 (Aminopyridines); 0 (Pyrroles); EC 2.7.10.1 (Receptor, Macrophage Colony-Stimulating Factor) |
[Em] Mês de entrada: | 1710 |
[Cu] Atualização por classe: | 171009 |
[Lr] Data última revisão:
| 171009 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 160901 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1186/s12974-016-0671-y |
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