Brain Wide Alterations in levels of FOXP2 in an Idiopathic Model of ASD

Abstract

The gene encoding the fork-head box p2 (FOXP2) transcription factor is commonly understood to be a potential Autism Spectrum Disorder (ASD) candidate gene, reportedly expressed in multiple cortical and subcortical areas such as the globus pallidus external (GPe) and the basolateral amygdala (BLA). Morphological and functional alterations within these regions may be associated with the repetitive motor behaviours and social communication deficits observed in ASD, respectively. Though the potential role of altered FOXP2 expression in relation to alterations in these regions have not yet been fully elucidated. The aim of the current study is to explore population number of FOXP2 expressing neurons and investigate the relative concentration of FOXP2 within these neurons in the GPe and BLA of an idiopathic model of ASD (BTBR T+tf/j). To explore this, tissue from adult C57BL/6J mice (n=4) and BTBR T+tf/j mice (n=4) was processed using immunohistochemical techniques and fluorescent microscopy. The number of FOXP2 expressing neurons, and their relative levels of expression, were compared between animal model and brain region. Significant main effects were seen in relative expression levels of FOXP2 between brain regions and animal models (F(1,14)=15.30, p=.002, Eta2=.552(52.2%);F(1,14)=5.62, p=.003, Eta2=.287(28.7%)). BTBR animals displayed significantly lower levels of FOXP2 expression in all regions, compared to controls. Whereas no significant differences in the number of FOXP2 expressing neurons were noted between animal models in both regions. This may suggest that alterations in FOXP2 observed in ASD may relate to altered neuronal functioning on a molecular level, rather than a circuit level with alterations localised to specific brain regions/components of circuits, with downstream effects potentially contributing to the observed behavioural phenotype of ASD.