Psycho-social phenotype and brain n-sulfated heparan sulfates in MeCP2 mutant mice

Abstract

A variety of inbred and mutant strains of mice exhibit impairments in social behaviors and restricted, repetitive behaviors; these constitute face validity for autism models. However, researchers rarely evaluate the psychological state eliciting the impaired social investigation and there remain no reliable biomarkers for autism. A series of studies was conducted to assess social behavior in methyl CpG binding protein 2 (MeCP2308/Y) mutant mice, which were subsequently shown to be hypersocial. Analyses of psychostimulant-based behavioral responses were assessed in the hypersocial MeCP2 mutant mice and in hypo-social BTBR T+tf/J mice relative to their respective controls. This body of work suggests that dysregulated reward processing in candidate mutant mice, and specifically, MeCP2 hypomorphs, may underlie inflexible and abnormal social behaviors. N-sulfated heparan sulfate alterations in the brain may underlie brain developmental and behavioral abnormalities in autism. To ascertain whether MeCP2 mutation influences heparan sulfate proteoglycan systems, fluorescence immunohistochemistry was performed on wild-type and mutant mouse brains throughout the neurogenic lateral ventricle subventricular zone and it was shown that, counter to the prediction, MeCP2308/Y mutants display normal levels of heparan sulfate and laminin extracellular matrix markers in the neurogenic subventricular zone. Perhaps other brain regions or alternative markers should be included in future analyses; yet, the overall influence of adult neurogenesis and other brain plasticity processes in autism-relevant behavior deficits has not been fully characterized. This body of work utilizes multiple levels of analyses in an attempt to elucidate neurobiological and psychological contributions to abnormal and autism-relevant behavioral disturbances.