title: Gene-environment interaction of reelin and stress in cognitive behaviours in mice: Implications for schizophrenia.
abstract: Cognitive deficits are a particularly debilitating symptom group in schizophrenia. We investigated the effect of a 'two hit' combination of two factors implicated in schizophrenia development, reelin deficiency and stress, on cognitive behaviours in mice. Male and female heterozygous reelin mice (HRM) and wild-type (WT) controls received the stress hormone, corticosterone (CORT), during early adulthood to simulate chronic stress. The Y-maze, novel object recognition task (NORT), social interaction task and prepulse inhibition (PPI) were used to assess short-term spatial memory, visual non-spatial memory, social recognition memory and sensory gating, respectively. Reelin protein expression was measured in the prefrontal cortex (PFC) and hippocampus. CORT induced spatial memory deficits in male and female HRM but not in WT controls suggesting increased vulnerability of HRM to the effects of stress on cognition. By contrast, CORT disrupted PPI only in male WT mice, but not in male HRM, suggesting a protective role of reelin deficiency against effects of stress on PPI. Male HRM performed worse in the social recognition memory task compared to wild-type controls, irrespective of CORT treatment. No differences were detected in the NORT. Reelin protein expression was increased in the PFC of female CORT-treated HRM but there were no group differences in the hippocampus. Overall, these findings extend our understanding of the role of reelin-stress interactions in schizophrenia.
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: Schroeder
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia; School of Psychology and Public Health, La Trobe University, Melbourne, Australia.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Buret
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Hill
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia; School of Psychology and Public Health, La Trobe University, Melbourne, Australia. Electronic address: m.vandenbuuse@latrobe.edu.au.
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Buuse
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001835:Body Weight; D001921:Brain / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D003071:Cognition; D003345:Corticosterone / Q000032:analysis / Q000633:toxicity; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics*; D000091042:Reelin Protein; D012559:Schizophrenia / Q000209:etiology; D055139:Sensory Gating / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics*; D012737:Sex Factors; D012938:Social Perception; D065852:Spatial Memory / Q000502:physiology; D013315:Stress, Psychological / Q000139:chemically induced / Q000378:metabolism / Q000523:psychology*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D003345:Corticosterone
keywords: Corticosterone; Prepulse inhibition; Reelin; Schizophrenia; Social interaction; Y-maze