Abstract

Chronic stress can predispose vulnerable individuals to mood disorders, including depression. Glutamate, one of the key participants in this process, may exert both pathological and therapeutic psycho-emotional effects. However, the role of expression of genes encoding proteins that provide glutamatergic signal is still unclear. In this study, we attempted to distinguish changes in expression of glutamatergic genes associated with stress-induced anhedonia, a core symptom of depression, from those related to other stress-related effects. For this, expression of genes was compared between rats after a short-term stress, which did not yet cause depressive-like symptoms, and animals exposed chronically to different stressors that produce anhedonia-like responses. The changes in gene expression induced by chronic restraint or forced swimming concomitantly with anhedonia development demonstrated similar for both stressors patterns. Main features of the expression patterns include the decrease in mRNA levels for AMPA and NMDA subunits in the midbrain and hippocampus that is consistent with the hypothesis that “monoamine (serotonin)-Glutamate/GABA long neural circuit” involved in mood regulation. The decrease in expression of these subunits in the midbrain may attenuate glutamatergic drive on the serotonergic neurons promoting a shift of excitation/inhibition balance between glutamate and GABA in the forebrain regions resulting in anhedonia. In general, changes in expression of multiple genes involved in glutamatergic neurotransmission in the forebrain and brainstem regions suggest that stress-induced anhedonia may result from the network dysfunction of this neurotransmitter system.

摘要

慢性压力会使脆弱的人容易患上情绪低落，包括抑郁。谷氨酸是该过程的关键参与者之一，可能同时发挥病理和治疗上的心理情感作用。但是，尚不清楚编码提供谷氨酸能信号的蛋白质的基因表达的作用。在这项研究中，我们试图将与压力引起的快感低下有关的谷氨酸能基因表达的变化与抑郁症的其他症状区分开来。为此，在尚未引起抑郁样症状的短期应激后的大鼠与长期暴露于不同应激源的动物之间进行了基因表达的比较，这些应激源会产生类似于麻醉品的反应。慢性束缚或强迫游泳伴随着快感不足的发展而诱导的基因表达变化，在两种应激模式中均显示出相似的结果。表达模式的主要特征包括中脑和海马中AMPA和NMDA亚基的mRNA水平下降，这与“单胺（5-羟色胺）-谷氨酸/ GABA长神经回路”参与情绪调节这一假设相一致。这些亚基在中脑中的表达减少可能会削弱血清素能神经元上的谷氨酸能驱动，从而促进前脑区谷氨酸和GABA之间的兴奋/抑制平衡转移，从而导致快感缺失。一般来说，