PMID- 29075577 OWN - NLM STAT- MEDLINE DCOM- 20180709 LR - 20210109 IS - 2162-3279 (Electronic) VI - 7 IP - 10 DP - 2017 Oct TI - Effects of Hint1 deficiency on emotional-like behaviors in mice under chronic immobilization stress. PG - e00831 LID - 10.1002/brb3.831 [doi] LID - e00831 AB - BACKGROUND: 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. METHODS: 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. RESULTS: In a battery of behavior tests, the results of the control group, not exposed to stress, showed that knockout (KO) and heterozygosity (HT) of Hint1 had anxiolytic-like and antidepression-like effects on the male and female mice. 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. There were no significant differences in general locomotor activity between Hint1-KO and -HT mice and their wild-type (WT) littermates. Hint1-KO mice under basal and chronic immobilization stress conditions expressed more BDNF in the hippocampus than did Hint1-HT and WT mice; overall, there were no significant sex differences in emotional-like behaviors of Hint1-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. CONCLUSIONS: 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. FAU - Sun, Liankang AU - Sun L AD - First Affiliated Hospital Xi'an Jiaotong University Xi'an China. FAU - Liu, Peng AU - Liu P AD - 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. FAU - Liu, Fei AU - Liu F AD - 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. AD - Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases College of Stomatology Xi'an Jiaotong University Xi'an China. FAU - Zhou, Yuan AU - Zhou Y AD - Qi De College Xi'an Jiaotong University Xi'an China. FAU - Chu, Zheng AU - Chu Z AD - 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. FAU - Li, Yuqi AU - Li Y AD - Qi De College Xi'an Jiaotong University Xi'an China. FAU - Chu, Guang AU - Chu G AD - Zong Lian College Xi'an Jiaotong University Xi'an China. FAU - Zhang, Ying AU - Zhang Y AD - Qi De College Xi'an Jiaotong University Xi'an China. FAU - Wang, Jiabei AU - Wang J AD - Department of Pharmaceutical Sciences School of Pharmacy University of Maryland Baltimore MD USA. FAU - Dang, Yong-Hui AU - Dang YH AUID- ORCID: 0000-0001-9399-9615 AD - 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. LA - eng PT - Journal Article DEP - 20170923 PL - United States TA - Brain Behav JT - Brain and behavior JID - 101570837 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Hint1 protein, mouse) RN - 0 (Nerve Tissue Proteins) RN - 7171WSG8A2 (BDNF protein, human) SB - IM MH - Animals MH - Anxiety/*metabolism MH - Behavior, Animal/physiology MH - Brain-Derived Neurotrophic Factor/metabolism MH - Depression/*metabolism MH - Female MH - Hippocampus/*metabolism MH - *Immobilization/physiology/psychology MH - Male MH - Mice MH - Mice, Knockout MH - Nerve Tissue Proteins/*deficiency/metabolism MH - Statistics as Topic PMC - PMC5651401 OTO - NOTNLM OT - brain-derived neurotrophic factor OT - chronic immobilization stress OT - haplo-insufficient effect OT - hippocampus OT - histidine triad nucleotide-binding protein 1 OT - sex specific EDAT- 2017/10/28 06:00 MHDA- 2018/07/10 06:00 PMCR- 2017/09/23 CRDT- 2017/10/28 06:00 PHST- 2016/09/23 00:00 [received] PHST- 2017/07/08 00:00 [revised] PHST- 2017/08/15 00:00 [accepted] PHST- 2017/10/28 06:00 [entrez] PHST- 2017/10/28 06:00 [pubmed] PHST- 2018/07/10 06:00 [medline] PHST- 2017/09/23 00:00 [pmc-release] AID - BRB3831 [pii] AID - 10.1002/brb3.831 [doi] PST - epublish SO - Brain Behav. 2017 Sep 23;7(10):e00831. doi: 10.1002/brb3.831. eCollection 2017 Oct.