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Valentine, A. A.

Publications and source records attributed to Valentine, A. A..

2 recordsLinked to original sources

{triangleup}FOSB in the nucleus accumbens core is required for increased anxiety, but not decreased social motivation, following estrogen withdrawal in female mice

During pregnancy, estrogen levels rise dramatically, but quickly drop to prepartum levels following birth, and remain suppressed until ovulation resumes. This "postpartum estrogen withdrawal" state has been linked to changes in the brain and behavior in humans and rodents. Previous research has demonstrated that following a hormone-simulated pseudopregnancy (HSP), an experimental model of postpartum estrogen withdrawal, female mice show increased anxiety-like behaviors and decreased social motivation. Further, these behavioral changes occur concurrently with an increase in {Delta}FOSB, a transcription factor associated with stable long-term plasticity, in the nucleus accumbens core. To test whether this increase in {Delta}FOSB is required for these behavioral changes, we used a viral-mediated gene transfer approach to prevent {Delta}FOSB-mediated transcription in the NAcC during HSP and found that it reduced the high-anxiety behavioral phenotype in estrogen-withdrawn females. However, preventing {Delta}FOSB-mediated transcription had little effect on social motivation. Together, these results suggest that postpartum estrogen withdrawal increases {Delta}FOSB in the NAc core to impact anxiety-like behaviors, but not social motivation, following estrogen withdrawal.

neuroscience↗

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

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.

neuroscience↗