RT Journal Article
SR Electronic
T1 A two-hit adversity model in developing rats reveals sex-specific impacts on prefrontal cortex structure and behavior
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.23.352161
DO 10.1101/2020.10.23.352161
A1 Kelsea R. Gildawie
A1 Lilly M. Ryll
A1 Jessica C. Hexter
A1 Shayna Peterzell
A1 Alissa A. Valentine
A1 Heather C. Brenhouse
YR 2020
UL http://biorxiv.org/content/early/2020/10/25/2020.10.23.352161.abstract
AB Adversity early in life substantially impacts prefrontal cortex (PFC) development and vulnerability to later-life psychopathology. Importantly, repeated adverse experiences throughout childhood increase the risk for PFC-mediated behavioral deficits more commonly in women. Evidence from animal models points to effects of adversity on later-life neural and behavioral dysfunction; however, few studies have investigated the neurobiological underpinnings of sex-specific, long term consequences of multiple developmental stressors. We modeled early life adversity in rats via maternal separation (postnatal day (P)2-20) and juvenile social isolation (P21-35). Adult (P85) male and female rats were assessed for differences in the presence and structural integrity of PFC perineuronal nets (PNNs) enwrapping parvalbumin (PV)-expressing interneurons. PNNs are extracellular matrix structures formed during critical periods in postnatal development that play a key role in the plasticity of PV cells. Females – but not males – exposed to multiple hits of adversity demonstrated a reduction in PFC PV cells in adulthood. We also observed a sex-specific, potentiated reduction in PV+ PNN structural integrity. Moreover, correlations between neural disruption and hyperactivity/risk-assessment behavior were altered by adversity differently in males and females. These findings suggest a sex-specific impact of repeated adversity on neurostructural development and implicate PNNs as a contributor to associated behavioral dysfunction.Competing Interest StatementThe authors have declared no competing interest.PFCprefrontal cortexPLprelimbicILinfralimbicPNNperineuronal netWFAWisteria floribunda agglutininMSmaternal separationConcontrolSIsocial isolationPHpair-housedPpostnatal dayPBSphosphate buffered salinePFAparaformaldehydeEZMelevated zero maze