A two-hit adversity model in developing rats reveals sex-specific impacts on prefrontal cortex structure and behavior

Developmental Cognitive Neuroscience

Heather C. Brenhouse¹  Lilly M. Ryll²  Shayna Peterzell²  Alissa A. Valentine²  Kelsea R. Gildawie²  Jessica C. Hexter² 

[1] Corresponding author at: 325 Nightingale Hall, Northeastern University, 360 Huntington Ave, Boston, MA, 02115, USA.;Department of Psychology, Northeastern University, Boston, MA, USA;

关键词: Maternal separation;    Prefrontal cortex;    Perineuronal nets;    Parvalbumin;    Sex differences;    Anxiety;   

DOI  :  

来源: DOAJ

【 摘 要 】

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). In adulthood, anxiety-like behavior was assessed in the elevated zero maze and the presence and structural integrity of PFC perineuronal nets (PNNs) enwrapping parvalbumin (PV)-expressing interneurons was quantified. PNNs are extracellular matrix structures formed during critical periods in postnatal development that play a key role in the plasticity of PV cells. We observed a female-specific effect of adversity on hyperactivity and risk-assessment behavior. Moreover, 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. These findings suggest a sex-specific impact of repeated adversity on neurostructural development and implicate PNNs as a contributor to associated behavioral dysfunction.

【 授权许可】

Unknown