Poster Presentation The International Congress of Neuroendocrinology 2014

Sex specific sensitivity to early intervention strategies in a mouse model of schizophrenia (#142)

Udani Ratnayake 1 , Maarten van den Buuse 1
  1. University of Melbourne, Melbourne, VIC, Australia

Extensive evidence from human and animal studies have demonstrated that the neurotrophin, brain derived neurotrophic factor (BDNF), plays a role in schizophrenia. The present study aimed to assess mice heterozygous for a mutation in the brain derived neurotrophic factor gene (BDNF HET) in behavioural and cognitive paradigms of the schizophrenia. We also sought to determine if environmental enrichment (EE) during adolescence, which is known to lower stress-responsive hormones, can prevent the development of symptoms in adult BDNF HET mice. Male and female, BDNF HET and wild-type (WT) mice were housed in normal or environmentally enriched cages for 3 weeks (weeks 7,8 and 9 of age). We assessed amphetamine-induced locomotor hyperactivity and prepulse inhibition (PPI) between 14-15 weeks. Male and female BDNF HET mice, that are normally housed, travelled a greater distance after amphetamine treatment compared to WT littermates. In female mice, EE was able to cause a reduction in amphetamine-induced hyperlocomotor activity, irrespective of genotype in female mice. While there was no difference between groups in PPI, BNDF Het mice had increased acoustic startle response compared to WT littermates, irrespective of sex or housing. BDNF Het mice display a schizophrenia-like phenotype, including dopaminergic hyperactivity, which can be prevented by early intervention in a sex specific manner. It is currently being investigating if EE can also prevent the cognitive deficits known to occur in BDNF Het mice that are exposed to an adolescent stressor. This study reveals that by providing a stimulating environment during a critical time in adolescent development it is possible to prevent the severity of schizophrenia symptoms.