Sex and age impact the developmental trajectory of perineuronal net number in the rat dorsal hippocampus

Abstract Background As there has been increased focus on sex differences in neuroscience research, perineuronal nets have come forward as a possible piece in the sex difference puzzle. There are sex differences in neurodevelopmental disorders such as autism spectrum disorder (ASD) as well as sex differences in perineuronal net development. Day to day changes in perineuronal net density in the developing hippocampus may be relevant to further understanding a relationship between neurodevelopmental disorders and perineuronal nets. Methods In this study we aimed to determine a timeline of perineuronal net onset in juvenile Sprague Dawley rats aged postnatal day (p) p14, p16, p18, and p22 in the subiculum and regions cornu-ammonis − 1 (CA1), CA2, CA3 and the dentate gyrus (DG) of the hippocampus, and whether that timeline differed between males and females. Animals were perfused at the given ages and the tissue was processed for immunofluorescence staining of perineuronal nets and parvalbumin interneurons. Results We found males to generally have fewer perineuronal nets than did females across subregions of the hippocampus; but importantly, we also found that males and females demonstrated different patterns of perineuronal net development over the time course investigated, with females showing a decrease in PNN count at p16 before rebounding, and males showing a steep decrease in perineuronal net count two days later at p18 before rebounding. Conclusions These data suggest that perineuronal net development is not a steady linear increase over time, but rather a process that fluctuates according to sex and developmental stage. This may translate to the development of developmental disorders that also show a sex difference such as ASD, and suggest windows of both increased and decreased vulnerability to neurons and neuronal circuitry during early neurodevelopment specific to sex.