Parvalbumin and Perineuronal net expression in the medial and lateral regions of the Dorsal Striatum in an Idiopathic model of ASD, through development.

Abstract

Parvalbumin-expressing fast-spiking interneurons (PV+FSIs) within the dorsal striatum, associated with the generation of habitual behaviour and motor stereotypy, are a commonly reported node of alteration in various forms of autism spectrum disorder (ASD). Previous investigations of altered striatal PV+FSIs and their associated perineuronal nets (PNNs) in ASD lack consideration of the potential differences between dorsal striatum subregions (dorsomedial and dorsolateral striatum), sex, and developmental stage. This study utilised immunohistochemical and qPCR methods on tissue from an idiopathic murine model of ASD (BTBR T+ Itpr3tf/J mice; n = 20) and C57 L/J control mice (n = 20). The density of PV+FSIs, PNNs, their colocalisation, and the relative intensity of fluorescent staining within the dorsal striatum was compared between mouse strain, subregion, sex, and developmental stage. The relative expression of pvalb, hapln1, tnr, and acan mRNA was compared between mouse strain, sex, and developmental stage. A significantly lower density of PV+FSIs and colocalised PNN+PV+FSIs was observed within the dorsomedial striatum of BTBR T+ Itpr3tf/J relative to C57 L/J mice (F(1,58) = 21.6, p = 0.0134; F(1,58) = 8.56, p = 0.007). Whilst a significant reduction in the density of PV+FSIs was identified through development in C57 L/J mice, this was not significantly different between 3-4 and 6-8wk BTBR T+ Itpr3tf/J mice (F(1,58)=18.9, p = 0.000138; p = 0.400). Further, a greater basal density of PV+FSIs within the dorsomedial striatum was observed in male relative to female mice whereas a greater basal density in the dorsolateral striatum was observed in female mice (F(1,58) = 25.91, p = 0.0002; p = 18 0.0427). A greater basal density of colocalised PNN+PV+FSIs within the dorsolateral striatum was also observed in female mice (F(1,58) = 9.99, p > 0.0001). Altered expression of PV+FSIs and colocalised PNN+PV+FSIs in the dorsal striatum may be a common biological phenotype for idiopathic and other models of ASD, largely explained by downregulation within the dorsomedial striatum. These subregion specific alterations may contribute to different elements of the ASD behavioural phenotype. Further, the identification of basal sex differences in the expression of colocalised PNN+PV+FSIs within dorsal striatum subregions highlights the importance of considering sex within investigations of ASD aetiology.