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

Brian B Griffiths,Amanda M K Madden,Creed M Stary,Susan L Zup,Kimbra A Edwards

doi:10.1002/brb3.1265

Brian B Griffiths, Amanda M K Madden + Show 3 more

Open Access

https://doi.org/10.1002/brb3.1265

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Abstract

IntroductionPerineuronal 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.MethodsIn 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.ResultsWe 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.ConclusionsBecause 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.

Highlights

Perineuronal nets (PNNs) are extracellular matrices that encompass parvalbumin‐expressing parvalbumin positive (PVALB+) fast‐spiking inhibitory in‐ terneurons where they protect and stabilize afferent synapses
Exposure to gonadal hormones during perinatal development helps sculpt many sex differences in the mammalian brain, so a sexual dimorphism may exist in mammalian hippo‐ campal PNN expression
In addition to the differ‐ ences between sexes, we report that male rats show greater differences in PNN expression and PVALB co‐expression between developmental time points than do female rats

Summary

| INTRODUCTION

Hippocampal perineuronal nets (PNNs) have been demon‐ strated to play a central role in neural plasticity, fear conditioning (Hylin, Orsi, Moore, & Dash, 2013; Thompson et al, 2018), and long‐term potentiation (Yamada & Jinno, 2013). PNNs regulate learning and memory via stabilization of inhibitory parvalbumin positive (PVALB+) interneurons (Yamada, Ohgomori, & Jinno, 2015), providing protection against physical forces and reactive oxygen species (Cabungcal et al, 2013). Several sexually dimorphic brain structures within the song learning and song production circuit exhibit sex‐specific expression of PNNs, notably the HVC (cor‐ tex) and the robust nucleus of the arcopallium (amygdala homolog; Meyer, Boroda, & Nick, 2014). Exposure to gonadal hormones during perinatal development helps sculpt many sex differences in the mammalian brain (reviewed in Zup & Forger, 2017; McCarthy, 2016), so a sexual dimorphism may exist in mammalian hippo‐ campal PNN expression. In this study we assessed corti‐ cal and hippocampal PNNs expression in male and female juvenile and young adult rats

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Findings

CONFLICT OF INTEREST