慢性应激与去睾丸减少成年小鼠脑中NT-3和BDNF的蛋白表达(英文)

Chronic stress and gonadectomy decrease the levels of neurotrophin-3 and brain-derived neurotrophic factor in adult mouse brain

研究了慢性应激对小鼠脑中神经营养因子蛋白表达的影响 ,并探讨了性激素降低是否参与此过程 .性成熟完整雄性小鼠和去睾丸小鼠接受慢性应激 6 0d ,完整动物海马和大脑皮层中神经营养因子3(NT 3)和脑源性神经营养因子 (BDNF)蛋白水平显著降低 ,而且NT 3在海马齿状回的降低呈现某种程度的特异性 ,此外 ,齿状回颗粒细胞的形态退化在整个脑中也最为明显 ;去睾丸应激动物海马和大脑皮层中BDNF和NT 3蛋白水平较完整动物进一步降低 ,尤其是海马齿状回NT 3蛋白水平的降低与其他脑区相比表现出明显的特异性 ,同样 ,慢性应激引起的大脑皮层和海马特别是齿状回的神经元退化进一步被去睾丸恶化 .结果表明 ,慢性应激可抑制脑中NT 3和BDNF蛋白表达 ,去睾丸可使这种变化进一步加剧 ,海马齿状回对应激神经毒性较为敏感 ,提示 :脑中BDNF和NT 3蛋白水平降低与慢性应激过程中大脑形态退化密切相关 ;

The present study was to determine the impact of exposure to chronic stress on the levels of neurotrophic factors in the mouse brain, and investigate whether the stress induced decline in reproductive hormone may implicate this process. Intact adult male mice and gonadectomized ones were exposed to the scheduled stress episode for 60 consecutive days. The protein levels of brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT 3) were significantly decreased in the dentate gyrus, CA1, CA2 and CA3 subfields of the hippocampus and in the cerebral cortex, consistently, these brain regions showed significantly neurodegeneration in intact stressed mice. Interestingly, the stress induced diminution of BDNF and NT 3 protein levels in these brain regions were significantly intensified by gonadectomy. Particularly, NT 3 level in the dentate gyrus of stressed mice was preferentially decreased by gonadectomy. Likewise, the stress induced neurodegeneration in these brain regions, especially the dentate gyrus was also aggravated by gonadectomy. The results demonstrate that chronic stress decreases NT 3 and BDNF protein levels and produces neurodegeneration in the hippocampus and the cerebral cortex, and gonadectomy exacerbates these deleterious effects of chronic stress on the brain, indicating that gonadectomy increases the vulnerability of neurons to neuropathology of stress, and suggesting that stress induced testosterone deficit play a contributive role in neurodegeneration. This study also suggests that the diminishments of BDNF and NT 3 protein levels contribute to the neurodegeneration in the brain during chronic stress.