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bioRxiv · 10.1101/2024.03.11.584421

Prelimbic cortex perineuronal net expression and social behavior: Impact of adolescent intermittent ethanol exposure

Towner, T.·Coleman, H. J.·Goyden, M. A.·Vore, A. S.·Papastrat, K. M.·Varlinskaya, E. I.·Werner, D. F.
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Abstract

Adolescent intermittent ethanol (AIE) exposure in rats leads to social deficits. Parvalbumin (PV) expressing interneurons in the prelimbic cortex (PrL) contribute to social behavior, and perineuronal nets (PNNs) within the PrL preferentially encompass PV interneurons, acting as significant regulators of these cells. AIE exposure increases PNNs, however, it is unknown if this upregulation contributes to AIE-induced social impairments. The current study was designed to determine the effect of AIE exposure on PNN expression in the PrL and to assess whether PNN dysregulation contributes to social deficits elicited by AIE. cFos-LacZ male and female rats were exposed every other day to tap water or ethanol (4g/kg, 25% w/v) via intragastric gavage between postnatal day (P) 25-45. We evaluated neuronal activation by {beta}-galactosidase expression and PNN levels either at the end of the exposure regimen on P45 and/or in adulthood on P70. In addition, we used Chondroitinase ABC (ChABC) to deplete PNNs following adolescent exposure (P48) and allowed for PNN restoration before social testing in adulthhod. AIE exposure increased PNN expressionin the PrL of adult males, whereas a decrease in PNNs was evident immediately following AIE. Vesicular glutamate transporter 2 (vGlut2) and vesicular GABA transporter (vGat) near PNNs were moderately downregulated only in AIE-exposed females. Gene expression of PNN components were largely unaffected by AIE exposure. Removal and reestablishment of PNNs in the PrL led to upregulation of PNNs and social impairments in males, regardless of adolescent exposure. These data suggest that AIE exposure in males produces an upregulation of PrL PNNs that likely contribute to social impairments induced by AIE.

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Towner, T., Coleman, H. J., Goyden, M. A., Vore, A. S., Papastrat, K. M., Varlinskaya, E. I., Werner, D. F.. 2024-03-13. Prelimbic cortex perineuronal net expression and social behavior: Impact of adolescent intermittent ethanol exposure. https://doi.org/10.1101/2024.03.11.584421

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