Trichostatin A, a histone deacetylase inhibitor, alleviates the emotional abnormality induced by maladaptation to stress in mice
Trichostatin A, a histone deacetylase inhibitor, alleviates the emotional abnormality induced by maladaptation to stress in mice
复制标题
组蛋白脱乙酰酶抑制剂曲古抑菌素 A 可减轻小鼠压力适应不良引起的情绪异常
DOI：
10.1016/j.neulet.2021.136340
复制
发表时间：
2022
影响因子：
2.5
通讯作者：
Tsuji Minoru
中科院分区：
文献类型：
--
作者：
Kimijima Hidenao;Miyagawa Kazuya;Kurokawa Kazuhiro;Mochida-Saito Atsumi;Takahashi Kohei;Takeda Hiroshi;Tsuji Minoru
最近的报告表明，异常的生化过程在大脑中经常伴随着微妙的变化，在细胞表观遗传的档案，可能是精神疾病的致病进展。本研究旨在探讨组蛋白去乙酰化酶（HDAC）抑制剂--将小鼠暴露于重复束缚应激240分钟/天，持续14天。我们采用了给药方案。在一个方案中，从应激暴露的第3天开始，用TSA（1650 μM/4 μL，i. c. v.）在每天暴露于束缚应激后立即进行。在另一个时间表中，从应激暴露的第1天开始，在暴露于束缚应激之前2小时用TSA处理小鼠。在最终暴露于束缚应激后，使用孔板测试来评估小鼠的情绪性。将小鼠暴露于束缚应激240分钟/天，持续14天，显示头部浸入行为减少。这种减少的情绪在应激适应不良的小鼠中观察到的显着恢复与TSA的长期治疗2小时前，每天暴露于约束压力，这证实了发展的压力适应。另一方面，没有这样的压力适应下观察到的TSA慢性治疗后立即每日应激暴露。一项生化研究表明，色氨酸羟化酶，5-羟色胺（5-HT）合成的限速酶，增加中脑中缝核获得的压力适应小鼠，长期治疗TSA 2小时前每天的压力暴露。这些发现表明，HDAC抑制剂可能通过影响大脑中的5-HT神经功能对应激适应产生有益影响，并减轻过度应激条件下的情绪异常。
Recent reports have implied that aberrant biochemical processes in the brain are frequently accompanied by subtle shifts in the cellular epigenetic profile that might underlie the pathogenic progression of psychiatric disorders. The aim of the present study was to examine the effect of trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, on the emotional abnormality induced by maladaptation to stress in mice. Mice were exposed to repeated restraint stress for 240 min/day for 14 days. We applied dosing schedules. In one schedule, from the 3rd day of stress exposure, mice were treated with TSA (1650 μM/4 μL, i.c.v.) immediately after the daily exposure to restraint stress. In the other schedule, from the 1st day of stress exposure, mice were treated with TSA 2 h before exposure to restraint stress. After the final exposure to restraint stress, the emotionality of mice was evaluated using the hole-board test. Mice that were exposed to restraint stress for 240 min/day for 14 days showed a decrease in head-dipping behavior. This decreased emotionality observed in stress-maladaptive mice was significantly recovered by chronic treatment with TSA 2 h before daily exposure to restraint stress, which confirmed the development of stress adaptation. On the other hand, no such stress adaptation was observed under chronic treatment with TSA immediately after daily stress exposure. A biochemical study showed that tryptophan hydroxylase, the rate-limiting enzyme in serotonin (5-HT) synthesis, was increased in midbrain containing raphe nuclei obtained from stress-adapted mice that were chronically treated with TSA 2 h before daily stress exposure. These findings suggest that an HDAC inhibitor may have a beneficial effect on stress adaptation by affecting 5-HT neural function in the brain and alleviate the emotional abnormality under conditions of excessive stress.
登录
查看更多内容
影响因子：
7.9
作者：
Tsuji, Minoru;Takeuchi, Tomoko;Takeda, Hiroshi
通讯作者：
Takeda, Hiroshi
人色氨酸羟化酶 2 基因表达中神经元限制性沉默元件的功能特征
影响因子：
4.7
作者：
Yukino Nawa;H. Kaneko;M. Oda;Masaaki Tsubonoya;T. Hiroi;M. Gentile;L. Colucci;R. Takahashi;Hiroaki Matsui
通讯作者：
Hiroaki Matsui
影响因子：
--
作者：
Guidotti, A;Auta, J;Costa, E
通讯作者：
Costa, E
影响因子：
1.7
作者：
D. Haleem;T. Parveen
通讯作者：
T. Parveen