Chinese Academy of Science Key Laboratory of Brain Function and Diseases, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, Anhui, China.
J Affect Disord. 2020 Sep 1;274:678-689. doi: 10.1016/j.jad.2020.05.114. Epub 2020 May 23.
More and more people are suffering from depression in modern society. It is believed that the development of depression results from alterations in synaptic transmission, especially in the hippocampus. Animal experiments and clinical studies have demonstrated that retinoids are essential components in hippocampal synaptic plasticity, and they have a close relationship with depression. However, it is still unclear how excessive retinoic acid (RA) causes depression and what synaptic and molecular mechanisms underlie it.
Behavioral, electrophysiological, and molecular approaches were employed to characterize the effects of RA on depression and synaptic plasticity. RA was continuously administered intracerebroventricularly through an osmotic pump.
RA treatment induced depression-like behaviors, as evidenced by decreased sucrose preference and increased immobile duration in both the forced swim test and the tail suspension test. RA administration also induced anxiety-like behaviors, indicated by decreased duration in the open arms of the elevated plus maze and the central of the open field. RA treatment decreased the neuronal excitability of the hippocampus either by changing the excitatory/inhibitory receptor balance or by promoting the synthesis of inhibitory neurotransmitters. Moreover, long-term potentiation was decreased in both the excitatory postsynaptic potential and the population spike in RA-treated rats, presumably a consequence of the reduced glur1 transcript level.
The mechanism of how excess RA affects the hippocampal gene expression and synaptic plasticity requires further study.
RA treatment can induce depression-like behavior in rats and impair hippocampal plasticity. Thus, improving synaptic plasticity in the hippocampus may ameliorate the affective disorders caused by excessive RA.
在现代社会，越来越多的人患有抑郁症。据信，抑郁症的发展是由于突触传递的改变，尤其是海马体。动物实验和临床研究表明，类视黄醇是海马体突触可塑性的重要组成部分，它们与抑郁症密切相关。然而，目前尚不清楚过量的视黄酸（RA）如何导致抑郁症，以及其背后的突触和分子机制是什么。
采用行为学、电生理学和分子学方法来描述 RA 对抑郁症和突触可塑性的影响。通过渗透泵持续向脑室内给药 RA。
RA 处理诱导出类似于抑郁症的行为，表现在强迫游泳试验和悬尾试验中蔗糖偏好降低和不动时间增加。RA 给药还诱导出类似于焦虑的行为，表现在高架十字迷宫的开放臂和旷场的中央区域停留时间减少。RA 处理通过改变兴奋性/抑制性受体平衡或促进抑制性神经递质的合成来降低海马神经元的兴奋性。此外，在 RA 处理的大鼠中，无论是在兴奋性突触后电位还是在群体锋电位中，长时程增强都减少了，这可能是由于 glur1 转录物水平降低所致。
过量 RA 如何影响海马体基因表达和突触可塑性的机制需要进一步研究。
RA 处理可诱导大鼠出现类似抑郁症的行为，并损害海马体的可塑性。因此，改善海马体的突触可塑性可能改善由过量 RA 引起的情感障碍。
