McNally Leah, Bhagwagar Zubin, Hannestad Jonas
Yale University School of Medicine, New Haven, CT 06519, USA.
CNS Spectr. 2008 Jun;13(6):501-10. doi: 10.1017/s1092852900016734.
Multiple lines of evidence suggest that inflammation and glutamate dysfunction contribute to the pathophysiology of depression. In this review we provide an overview of how these two systems may interact. Excess levels of inflammatory mediators occur in a subgroup of depressed patients. Studies of acute experimental activation of the immune system with endotoxin and of chronic activation during interferon-alpha treatment show that inflammation can cause depression. Peripheral inflammation leads to microglial activation which could interfere with excitatory amino acid metabolism leading to inappropriate glutamate receptor activation. Loss of astroglia, a feature of depression, upsets the balance of anti- and pro-inflammatory mediators and further impairs the removal of excitatory amino acids. Microglia activated by excess inflammation, astroglial loss, and inappropriate glutamate receptor activation ultimately disrupt the delicate balance of neuroprotective versus neurotoxic effects in the brain, potentially leading to depression.
多条证据表明，炎症和谷氨酸功能障碍在抑郁症的病理生理学中起作用。在本综述中，我们概述了这两个系统可能如何相互作用。炎症介质水平过高出现在一部分抑郁症患者中。对内毒素急性激活免疫系统以及在α-干扰素治疗期间慢性激活免疫系统的研究表明，炎症可导致抑郁症。外周炎症会导致小胶质细胞激活，这可能会干扰兴奋性氨基酸代谢，导致谷氨酸受体异常激活。星形胶质细胞缺失是抑郁症的一个特征，它会破坏抗炎和促炎介质的平衡，并进一步损害兴奋性氨基酸的清除。过度炎症激活的小胶质细胞、星形胶质细胞缺失和谷氨酸受体异常激活最终会破坏大脑中神经保护与神经毒性作用之间的微妙平衡，可能导致抑郁症。
