First Affiliated Hospital Xi'an Jiaotong University Xi'an China.
College of Medicine & Forensics Key Laboratory of the Health Ministry for Forensic Medicine Key Laboratory of Environment and Genes Related to Diseases of the Education Ministry Xi'an Jiaotong University Health Science Center Xi'an China.
Brain Behav. 2017 Sep 23;7(10):e00831. doi: 10.1002/brb3.831. eCollection 2017 Oct.
Histidine triad nucleotide-binding protein 1 (HINT1) is regarded as a haplo-insufficient tumor suppressor and is closely associated with diverse neuropsychiatric diseases. Moreover, HINT1 is related to gender-specific acute behavior changes in schizophrenia and in response to nicotine. Stress has a range of molecular effects in emotional disorders, which can cause a reduction in brain-derived neurotrophic factor (BDNF) expression in the hippocampus, resulting in hippocampal atrophy and neuronal cell loss.
This study examined the role of HINT1 deficiency in anxiety-related and depression-like behaviors and BDNF expression in the hippocampus under chronic immobilization stress, and investigated whether the sex-specific and haplo-insufficient effects exist in emotional-like behaviors under the same condition.
In a battery of behavior tests, the results of the control group, not exposed to stress, showed that knockout (KO) and heterozygosity (HT) of had anxiolytic-like and antidepression-like effects on the male and female mice. However, both male and female -KO mice showed elevated anxiety-related and antidepression-like behavior under chronic immobilization stress; moreover, both male and female -HT mice displayed elevated anxiety-related behavior and increased depression-like behavior under chronic immobilization stress. There were no significant differences in general locomotor activity between -KO and -HT mice and their wild-type (WT) littermates. -KO mice under basal and chronic immobilization stress conditions expressed more BDNF in the hippocampus than did -HT and WT mice; overall, there were no significant sex differences in emotional-like behaviors of -KO and -HT mice. Additionally, Hint1-HT mice showed haplo-insufficient effects on emotional-like behaviors under basic conditions, rather than under chronic immobilization stress.
Both male and female HINT 1 KO and HT mice had a trend of anxiolytic-like behavior and antidepression-like behavior at control group. However, both male and female HINT1 KO mice showed elevated anxiety-related and antidepression-like behavior under chronic immobilization stress; moreover, both male and female HINT1 HT mice displayed elevated anxiety-related behavior and increased depression-like behavior under chronic immobilization stress.
组氨酸三核苷酸结合蛋白 1（HINT1）被认为是单倍不足的肿瘤抑制因子，与多种神经精神疾病密切相关。此外，HINT1 与精神分裂症和尼古丁反应中的性别特异性急性行为改变有关。应激在情感障碍中有一系列的分子效应，会导致海马脑源性神经营养因子（BDNF）表达减少，导致海马萎缩和神经元细胞丢失。
本研究探讨了慢性束缚应激下 HINT1 缺乏对焦虑相关和抑郁样行为以及海马脑源性神经营养因子（BDNF）表达的影响，并研究了在相同条件下，情绪样行为是否存在性别特异性和单倍不足效应。
在一系列行为测试中，对照组（未暴露于应激）的结果表明，敲除（KO）和杂合（HT）对雄性和雌性小鼠有抗焦虑和抗抑郁作用。然而，慢性束缚应激下，雄性和雌性 -KO 小鼠均表现出焦虑相关和抑郁样行为增加；此外，慢性束缚应激下，雄性和雌性 -HT 小鼠均表现出焦虑相关行为增加和抑郁样行为增加。-KO 和 -HT 小鼠及其野生型（WT）同窝仔鼠之间的一般运动活性无显著差异。慢性束缚应激条件下，-KO 小鼠的海马中 BDNF 表达高于 -HT 和 WT 小鼠；总的来说，-KO 和 -HT 小鼠的情绪样行为在性别上无显著差异。此外，在基础条件下，Hint1-HT 小鼠表现出情绪样行为的单倍不足效应，而在慢性束缚应激下则没有。
在对照组中，雄性和雌性 HINT1 KO 和 HT 小鼠均有抗焦虑样行为和抗抑郁样行为的趋势。然而，慢性束缚应激下，雄性和雌性 HINT1 KO 小鼠均表现出焦虑相关和抑郁样行为增加；此外，慢性束缚应激下，雄性和雌性 HINT1 HT 小鼠均表现出焦虑相关行为增加和抑郁样行为增加。
