Age-dependent sexual dimorphism in hippocampal cornu ammonis-1 perineuronal net expression in rats

Abstract

Introduction: Perineuronal nets (PNNs) are extracellular matrices that encompass parvalbumin-expressing parvalbumin positive (PVALB+) fast-spiking inhibitory interneurons where they protect and stabilize afferent synapses. Recent observations that gonadal hormones influence PVALB+ neuron development suggest that PNN regulation may be sexually dimorphic. Sex differences in PNN abundance and complexity have been reported in sexually dimorphic nuclei in zebra finch brains; however, corresponding differences in mammalian brains have not been investigated. Methods: In this study we assessed the number of cortical and hippocampal PNNs in juvenile and young adult male and female rats using fluorescent immunohistochemistry for PVALB and the PNN marker Wisteria Floribunda Lectin. Results: We report here that PNNs are numerous and well developed in hippocampal cornu ammonis-1 of adult males but are lower in juvenile and possibly adult females. No significant differences were observed between sexes in cornu ammonis-3 or adjacent neocortex. There was an observed developmental difference in the neocortex as juveniles had more PVALB+ cells, but fewer PNN+ cells, than adults. Conclusions: Because PNNs are integral for several hippocampal-mediated learning and memory tasks, these observations have potential sex-dependent translational implications for clinical strategies targeting cognitive dysfunction.