Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, P.O. Box 122120, 68072 Mannheim, Germany.
J Neural Transm (Vienna). 2011 Jun;118(6):849-55. doi: 10.1007/s00702-010-0536-y. Epub 2010 Dec 16.
Synaptic pathology and disturbed glutamatergic neurotransmission contribute to the neurobiology of depression. Reduced expression of glutamate transporters, most importantly excitatory amino acid transporter (EAAT2), was reported in human studies and animal models. We therefore assessed the effects of antidepressant treatment upon EAAT2 expression. Male Sprague-Dawley rats received daily intraperitoneal injections of the antidepressants desipramine (DES, N = 7), fluoxetine (FLU, N = 7), tranylcypromine (TRAN, N = 5) or a saline control (CON, N = 5) for a period of 14 days. The expression of the major glial glutamate transporter EAAT2 was evaluated by semi-quantitative in situ hybridizations using a (35)S-labeled cRNA probe. Treatment with FLU significantly induced EAAT2 expression in hippocampal and cortical regions in comparison with saline injections, while DES and TRAN-applications did not exert significant effects. It can be postulated that increased expression of EAAT2 may counterbalance the tonus of glutamatergic neurotransmission. Our findings are in concert with human post-mortem findings, valid animal models of depression, antidepressive effects of NMDA-antagonists, and the glutamatergic theory of depression. Further studies should examine the effects of antidepressant treatments upon EAAT2 expression in rodent models of depression to further elucidate the underlying molecular mechanisms.
突触病理学和谷氨酸能神经传递的紊乱导致了抑郁症的神经生物学基础。在人类研究和动物模型中都报道了谷氨酸转运体（特别是兴奋性氨基酸转运体 2，EAAT2）的表达减少。因此，我们评估了抗抑郁治疗对 EAAT2 表达的影响。雄性 Sprague-Dawley 大鼠接受了为期 14 天的每日腹腔注射抗抑郁药去甲丙咪嗪（DES，N = 7）、氟西汀（FLU，N = 7）、曲马普汀（TRAN，N = 5）或生理盐水对照（CON，N = 5）。使用（35）S 标记的 cRNA 探针通过半定量原位杂交评估主要的胶质谷氨酸转运体 EAAT2 的表达。与生理盐水注射相比，FLU 治疗显著诱导了海马和皮质区域的 EAAT2 表达，而 DES 和 TRAN 应用没有产生显著的效果。可以假设，EAAT2 的表达增加可能会抵消谷氨酸能神经传递的紧张。我们的发现与人类死后发现、抑郁症的有效动物模型、NMDA 拮抗剂的抗抑郁作用以及抑郁症的谷氨酸能理论一致。进一步的研究应该在抑郁症的啮齿动物模型中检查抗抑郁治疗对 EAAT2 表达的影响，以进一步阐明潜在的分子机制。
