Abstract

Adolescent development of prefrontal cortex (PFC) parallels maturation of executive functions as well as increasing white matter and myelination. Studies using MRI and other methods find that PFC white matter increases across adolescence into adulthood in both humans and rodents. Adolescent binge drinking is common and has been found to alter adult behaviors and PFC functions. This study examines development of oligoprogenitor (OPC) and oligodendrocytes (OLs) in Wistar rats from adolescence to adulthood within PFC white matter, corpus callosum forceps minor (fmi), PFC gray matter, and the neurogenic subventricular zone (SVZ) using immunohistochemistry for marker proteins. In addition, the effects of adolescent intermittent ethanol exposure [AIE; 5.0 g/kg/day, intragastric, 2 days on/2 days off on postnatal day (P)25–54], which is a weekend binge drinking model, were determined. OPC markers NG2+, PDGFRα+ and Olig2+IHC were differentially impacted by both age and PFC region. In both fmi and SVZ, NG2+IHC cells declined from adolescence to adulthood with AIE increasing adult NG2+IHC cells and their association with microglial marker Iba1. PFC gray matter decline in NG2+IHC in adulthood was not altered by AIE. Both adult maturation and AIE impacted OL expression of PLP+, MBP+, MAG+, MOG+, CNPase+, Olig1+, and Olig2+IHC in all three PFC regions, but in region- and marker-specific patterns. These findings are consistent with PFC region-specific changes in OPC and OL markers from adolescence to adulthood as well as following AIE that could contribute to lasting changes in PFC function.

Highlights

  • Adolescent maturation of cognitive abilities and emotional responses parallels brain development of prefrontal cortical (PFC) networks across species (Spear, 2000; Dahl, 2004; Crews and Vetreno, 2016)

  • We investigated the expression of oligodendrocyte progenitor cells (OPCs) markers NG2, PDGF receptor α (PDGFRα), and transcription factors Olig1 and Olig2 as well as several OL proteins, including myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG), myelin oligodendrocyte glycoprotein (MOG), and Cyclic-nucleotide 3′-phosphodiesterase (CNPase) in post-pubertal adolescent (P57) and adult (P95) rat frontal white matter, frontal gray matter (PrL, infralimbic cortex (IL)) and frontal neuro-oligogenesis subventricular zone (SVZ)

  • We found the OPC markers NG2+, PDGFRα+ and Olig2+IHC, across frontal white matter, gray matter and SZV neurogenic zones

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Summary

Introduction

Adolescent maturation of cognitive abilities and emotional responses parallels brain development of prefrontal cortical (PFC) networks across species (Spear, 2000; Dahl, 2004; Crews and Vetreno, 2016). White matter integrity investigated using diffusion tensor magnetic resonance imaging (DTI) is altered during adolescence in rats (Oguz et al, 2013; Vetreno et al, 2016) as well as humans, where it parallels maturation of cognitive ability (Lenroot and Giedd, 2006; Bava and Tapert, 2010; Fan et al, 2019).

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