title: Glutamic acid decarboxylase 67 haplodeficiency impairs social behavior in mice.
abstract: Reduced glutamic acid decarboxylase (GAD)67 expression may be causally involved in the development of social withdrawal in neuropsychiatric states such as autism, schizophrenia and bipolar disorder. In this study, we report disturbance of social behavior in male GAD67 haplodeficient mice. GAD67(+/-) mice, compared to GAD67(+/+) littermates, show reduced sociability and decreased intermale aggression, but normal nest building and urine marking behavior, as well as unchanged locomotor activity and anxiety-like behavior. Moreover, the mutants display a reduced sensitivity to both social and non-social odors, indicating a disturbance in the detection and/or processing of socially relevant olfactory stimuli. Indeed, we observed reduced activation of the lateral septum, medial preoptic area, bed nucleus of the stria terminalis, medial and cortical amygdala upon exposure of GAD67(+/-) mice to social interaction paradigm, as indicated by c-Fos immunohistochemistry. These data suggest a disturbance of stimulus processing in the brain circuitry controlling social behavior in GAD67(+/-) mice, which may provide a useful model for studying the impact of a reduced GAD67 expression on alterations of social behavior related to neuropsychiatric disorders.
authors.affiliation: Department of Genetics & Molecular Neurobiology, Institute of Biology, Magdeburg, Germany.
authors.forename: K V
authors.initials: KV
authors.lastname: Sandhu
authors.forename: D
authors.initials: D
authors.lastname: Lang
authors.forename: B
authors.initials: B
authors.lastname: Müller
authors.forename: S
authors.initials: S
authors.lastname: Nullmeier
authors.forename: Y
authors.initials: Y
authors.lastname: Yanagawa
authors.forename: H
authors.initials: H
authors.lastname: Schwegler
authors.forename: O
authors.initials: O
authors.lastname: Stork
mesh_terms: D000374:Aggression; D000818:Animals; D001007:Anxiety; D001921:Brain / Q000378:metabolism; D005106:Exploratory Behavior; D005968:Glutamate Decarboxylase / Q000235:genetics* / Q000378:metabolism; D006239:Haplotypes; D008124:Locomotion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009425:Nesting Behavior; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012903:Smell
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
keywords: Aggressive behavior; GABA; GAD67; amygdala; animal model; c-Fos immunohistochemistry; olfactory bulb; social interaction; social odor