GABA能系统在应激诱发的抑郁症中的作用

The role of stress-induced GABAergic system alteration in depression

γ-氨基丁酸(γ-aminobutyric acid,GABA)是中枢神经系统中最重要的抑制性神经递质,在维持大脑的兴奋-抑制平衡中起到重要作用。越来越多的临床和基础研究显示抑郁症与各种GABA能神经元活动不足相关,抗抑郁药物可以缓解或恢复上述变化。GABA能系统延迟发育至成年早期基本成熟。应激,尤其是早期应激是抑郁症发病的重要风险因素,可以通过扰动GABA能系统的发育轨迹从而造成对该系统结构和功能的持续后果,并与后期抑郁症易感密切相关。未来的研究需要进一步鉴别二者之间的关系,进而提出以GABA能系统为靶标的抑郁症治疗新策略。

γ-aminobutyric acid（GABA） is the most important inhibitory amino acid neurotransmitter in the central nervous system to maintain the excitatory-inhibitory balance of the brain. Increasing clinical and pre-clinical evidence shows a central and causal role of GABAergic deficits in depressive disorders. Depressive patients commonly indicate reduced GABAergic transmission in emotional and cognitive brain areas, especially prefrontal cortex and limbic areas like hippocampus and amygdala, and antidepressants can alleviate or reverse depressive symptoms by augmenting GABAergic activity in these areas. Furthermore, deficits in GABAergic transmission are sufficient to cause most of the neural and behavioral alterations expected in an animal model of depression. GABAergic system undergoes a prolonged development to structural and functional maturation until into early adulthood in both human and rodents. Stress, especially early stress, may disturb the mature trajectory of the GABAergic system, and result in continuing negative consequences of neural development and late functioning, which can contribute to the increased susceptibility for the onset of depression across late life. It would be important to further elucidate GABAergic mechanisms underlying depressive disorders and action of antidepressant in order to improve strategy for early recognition and intervention of depression.