Abstract
BackgroundHistidine 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.MethodsThis 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.ResultsIn 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.ConclusionsBoth 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.
Highlights
Mood and anxiety disorders are among the most common mental health conditions, resulting in functional disability, and major depressive disorder (MDD), with a lifetime risk of 20%–25% in women and 7%–12% in men has already created an enormous financial burden for modern human societies
This study investigated whether Hint1 gene deficiency has effects on emotional-like behaviors in mice and the expression of brain-d erived neurotrophic factor (BDNF) in their hippocampus under chronic immobilization stress (CIS) conditions, to determine whether the effects of Hint1 deficiency has sex-specific and haplo-insufficient effects on emotional-like behaviors of mice under CIS
In the Open-field test (OFT), there were no significant differences in the general locomotor activity of Hint1-KO, -HT, and WT littermates, which were in line with the previous findings of Varadarajulua and colleagues, and Barbier and colleagues (Barbier et al, 2007; Varadarajulu et al, 2011)
Summary
Mood and anxiety disorders are among the most common mental health conditions, resulting in functional disability, and major depressive disorder (MDD), with a lifetime risk of 20%–25% in women and 7%–12% in men has already created an enormous financial burden for modern human societies. The correlations between schizophrenia and HINT1 are sex specific (Chen et al, 2008; Jackson et al, 2012; Vawter et al, 2004), and nicotine-mediated acute behavior changes show different effects in males and females (Jackson et al, 2012) It remains unknown whether HINT1 involved in the regulation of anxious and depressed behaviors under chronic immobilization stress is sex specific or haplo insufficient. We considered whether Hint deficiency would have effects on the emotional-like behaviors of mice, as well as on the expression of BDNF in the hippocampus under chronic immobilization stress (CIS), and whether such effects would be influenced by gender and gene dosage (haplo-insufficient effects). We used a battery of behavioral tests to examine changes in emotional-like behavior, and explored BDNF protein expression in the hippocampus of these mice
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