Department of Pathology and Pathophysiology, Shantou University Medical College, Shantou, 515041, Guangdong, China; Department of Pathology and Pathophysiology, Medical School, Jianghan University, Wuhan, 430056, Hubei, China.
Department of Pathology and Pathophysiology, Medical School, Jianghan University, Wuhan, 430056, Hubei, China.
Psychiatry Res. 2011 Dec 30;194(3):385-392. doi: 10.1016/j.pscychresns.2011.02.007. Epub 2011 Nov 1.
Stress-induced hippocampal volume loss and decrease in N-acetylaspartate (NAA) level have been reported to be associated with impaired neural plasticity and neuronal damage in adults. Accordingly, reversing structural and metabolite damage in the hippocampus may be a desirable goal for antidepressant therapy. The present study investigated the effects of tianeptine on chronic stress-induced hippocampal volume loss and metabolite alterations in vivo in 24 Sprague-Dawley rats. Rats were subjected to a consecutive 28-day forced swimming test stress. Tianeptine (50mg/kg) or saline was administered intragastrically 4h after swimming each day. Spontaneous behaviors, serum corticosterone concentration, hippocampal volume and NAA level were evaluated after stress. Chronic tianeptine treatment counteracted the chronic stress-induced suppression of spontaneous behaviors, elevated serum corticosterone concentration, reduced hippocampal volume and decreased NAA level. Moreover, we found asymmetrical right-left hippocampal volume loss in stressed rats, with the left hippocampus more sensitive to chronic stress than the right hippocampus. In addition, stressed rats showed a decreased level of hippocampal metabolites, without significant loss of hippocampal volume. These findings provide experimental evidence for impaired structural plasticity of the brain being an important feature of depressive illness and suggest that prophylactic tianeptine treatments could reverse structural changes in brain. The structural and neurochemical alterations in the hippocampus may be valuable indexes for evaluating the prophylactic and curative effect of antidepressant treatments in depressive and stress-related disorders.
压力诱导的海马体体积缩小和 N-乙酰天冬氨酸（NAA）水平下降与成年人的神经可塑性受损和神经元损伤有关。因此，逆转海马体的结构和代谢损伤可能是抗抑郁治疗的理想目标。本研究在 24 只 Sprague-Dawley 大鼠体内研究了噻奈普汀对慢性应激诱导的海马体体积缩小和代谢物改变的影响。大鼠连续接受 28 天的强迫游泳试验应激。游泳后每天 4 小时通过胃内给予噻奈普汀（50mg/kg）或生理盐水。应激后评估自发行为、血清皮质酮浓度、海马体体积和 NAA 水平。慢性噻奈普汀治疗可拮抗慢性应激引起的自发行为抑制、血清皮质酮浓度升高、海马体体积缩小和 NAA 水平降低。此外，我们发现应激大鼠存在左右海马体不对称的体积缩小，左海马体比右海马体对慢性应激更敏感。此外，应激大鼠表现出海马代谢物水平降低，而海马体体积无明显损失。这些发现为大脑结构可塑性受损是抑郁障碍的一个重要特征提供了实验证据，并表明预防性噻奈普汀治疗可能逆转大脑的结构变化。海马体的结构和神经化学改变可能是评估抗抑郁治疗在抑郁和应激相关障碍中的预防和治疗效果的有价值指标。
