奶油
慢性应激
NMDA受体
神经营养因子
脑源性神经营养因子
神经科学
原肌球蛋白受体激酶B
下调和上调
谷氨酸受体
神经传递
谷氨酸的
海马结构
抗抑郁药
心理学
海马体
医学
内科学
内分泌学
受体
生物
转录因子
生物化学
基因
作者
Carol E. Vásquez,Romina Riener,Elaine R. Reynolds,Gabrielle B. Britton
标识
DOI:10.1016/j.neuint.2014.09.007
摘要
Several lines of evidence indicate that chronic stress and downregulation of brain-derived neurotrophic factor (BNDF) are the key components of depression pathology. Evidence from animal models of depression demonstrates that chronic stress impairs hippocampal BDNF expression and that antidepressant drug effects correlate with increased BDNF synthesis and activity in the hippocampus. Studies with human carriers of BDNF Met-allele polymorphism link stress vulnerability and risk for depression. The mechanism by which chronic stress downregulates BDNF and promotes depressive-like responses is not established yet. It has been reported that chronic stress mediates alterations in several calcium-related components involved in BDNF synthesis, including CAMKII, CAMKIV and cAMP-response element-binding protein (CREB), and glutamatergic neurotransmission through N-Methyl-D-Aspartate receptors (NMDAR). Treatments with NMDAR antagonists like ketamine modulate glutamate signals, upregulate CREB and BDNF expression, and correct stress-induced cognitive and behavioral alterations. With the increasing interest to develop NMDAR modulators, it is crucial to understand the conditions that lead to depression pathology in order to develop rational therapies aimed at reestablishing proper neuronal function. We present here the current knowledge regarding the relation between chronic stress, BDNF and NMDARs and its implications in depression. We discuss a plausible mechanism where chronic stress induced NMDAR stimulation could lead to dysregulated calcium signaling and decreased BDNF activity. In these circumstances, neurons become vulnerable to the effects of stress, leading to dysfunctional neurotransmission and behavioral alterations. We propose that treatment with NMDAR antagonists may help to return the balance of calcium signaling, promote proper BDNF signaling and correct depressive symptoms.
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