title: Increased anxiety-related behaviour in Hint1 knockout mice.
abstract: Several reports have implicated a role for the histidine triad nucleotide-binding protein-1 (Hint1) in psychiatric disorders. We have studied the emotional behaviour of male Hint1 knockout (Hint1 KO) mice in a battery of tests and performed biochemical analyses on brain tissue. The behavioural analysis revealed that Hint1 KO mice exhibit an increased emotionality phenotype compared to wildtype (WT) mice, while no significant differences in locomotion or general exploratory activity were noted. In the elevated plus-maze (EPM) test, the Hint1 KO animals entered the open arms of the apparatus less often than WT littermates. Similarly, in the dark-light box test, Hint1 KO mice spent less time in the lit compartment and the number of entries were reduced, which further confirmed an increased anxiety-related behaviour. Moreover, the Hint1 KO animals showed significantly more struggling and less floating behaviour in the forced swim test (FST), indicating an increased emotional arousal in aversive situations. Hint1 is known as a protein kinase C (PKC) interacting protein. Western blot analysis showed that PKCγ expression was elevated in Hint1 KO compared to WT mice. Interestingly, PKCγ mRNA levels of the two groups did not show a significant difference, implying a post-transcriptional PKCγ regulation. In addition, PKC enzymatic activity was increased in Hint1 KO compared to WT mice. In summary, our results indicate a role for Hint1 and PKCγ in modulating anxiety-related and stress-coping behaviour in mice.
authors.affiliation: Research Group of Proteomics & Biomarkers and Research Group of Psychoneuroendocrinology, Max Planck Institute of Psychiatry, Kraepelinstrasse 2, Munich, Germany.
authors.forename: Jeeva
authors.initials: J
authors.lastname: Varadarajulu
authors.forename: Maria
authors.initials: M
authors.lastname: Lebar
authors.forename: Gurumoorthy
authors.initials: G
authors.lastname: Krishnamoorthy
authors.forename: Sonja
authors.initials: S
authors.lastname: Habelt
authors.forename: Jia
authors.initials: J
authors.lastname: Lu
authors.forename: I
authors.initials: I
authors.lastname: Bernard Weinstein
authors.forename: Haiyang
authors.initials: H
authors.lastname: Li
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Turck
authors.forename: Chadi
authors.initials: C
authors.lastname: Touma
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D003623:Dark Adaptation / Q000235:genetics; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018709:Statistics, Nonparametric; D013550:Swimming / Q000523:psychology
chemical_list: C489275:Hint1 protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011493:Protein Kinase C; D003345:Corticosterone