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Brain Behav. 2017 Sep 23;7(10):e00831. doi: 10.1002/brb3.831. eCollection 2017 Oct.

Effects of Hint1 deficiency on emotional-like behaviors in mice under chronic immobilization stress.

Author information

1
First Affiliated Hospital Xi'an Jiaotong University Xi'an China.
2
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.
3
Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases College of Stomatology Xi'an Jiaotong University Xi'an China.
4
Qi De College Xi'an Jiaotong University Xi'an China.
5
Zong Lian College Xi'an Jiaotong University Xi'an China.
6
Department of Pharmaceutical Sciences School of Pharmacy University of Maryland Baltimore MD USA.

Abstract

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.

KEYWORDS:

brain‐derived neurotrophic factor; chronic immobilization stress; haplo‐insufficient effect; hippocampus; histidine triad nucleotide‐binding protein 1; sex specific

PMID:
29075577
PMCID:
PMC5651401
DOI:
10.1002/brb3.831
[Indexed for MEDLINE]
Free PMC Article

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