Hippocampal neurogenesis in the C57BL/6J mice at early adulthood following prenatal alcohol exposure

Abstract

We examined the effect of chronic prenatal alcohol exposure (PAE) on the process of adult neurogenesis in C57BL/6J mice at early adulthood (PND 56). Pregnant mice, and their in utero litters, were exposed to alcohol, through oral gavage, on gestational days 7-16, with recorded blood alcohol concentrations averaging 184 mg/dL (CA group). Two control groups, sucrose (CAc) and non-treated (NTc) control groups were also examined. The brains of pups at PND 56 from each experimental group were sectioned in a sagittal plane, and stained for Nissl substance with cresyl violet, and immunostained for Ki-67 which labels proliferative cells and doublecortin (DCX) for immature neurons. Morphologically, the neurogenic pattern was identical in all three groups studied. Populations of Ki-67 immunopositive cells in the dentate gyrus were not statistically significantly different between the experimental groups and there were no differences between the sexes. Thus, the PAE in this study does not appear to have a strong effect on the proliferative process in the adult hippocampus. In contrast, the numbers of immature neurons, labeled with DCX, was statistically significantly lower in the prenatal alcohol exposed mice compared with the two control groups. Alcohol significantly lowered the number of DCX hippocampal cells in the male mice, but not in the female mice. This indicates that the PAE appears to lower the rate of conversion of proliferative cells to immature neurons and this effect of alcohol is sexually dimorphic. This lowered number of immature neurons in the hippocampus appears to mirror hippocampal dysfunctions observed in FASD children.

Effect of Alcohol on Hippocampal-Dependent Plasticity and Behavior: Role of Glutamatergic Synaptic Transmission

“…All of these findings indicate that a single dose of perinatal ethanol diminishes the progenitor cells and thus reduces adult neurogenesis (Ieraci and Herrera, 2007). Pregnant mice administrated with alcohol for 10 days, starting from gestational day 7, produced a reduction in DCX-positive cells but not Ki-67-positive cells in offspring prenatally exposed to alcohol when analyzed at postnatal day 56, suggesting that prenatal alcohol exposure maintains the damage throughout the adolescent and adult lifespan (Olateju et al, 2018). This observation is also perceived in other species, as macaques prenatally exposed to alcohol showed decreased neurogenesis in the young adult stage (Fedorchak and Miller, 2019).…”

Murine Models for the Study of Fetal Alcohol Spectrum Disorders: An Overview

“…Quantification of immature neurons labeled with DCX in mouse was lower in the group of individuals exposed to alcohol in the prenatal period compared to controls. Moreover, DCX levels were lower in males than in females ( 108 ). Broadwater et al obtained similar results after PAE by oral gavage on PND28–48, with decreased DCX levels in the DG of adolescent mice.…”

A Systematic Review of the Effects of Perinatal Alcohol Exposure and Perinatal Marijuana Exposure on Adult Neurogenesis in the Dentate Gyrus

“…Thus, DCX‐positive cells represent a set cells across a broad developmental spectrum, ranging from immature neural progenitor (INP) cells (also known as type 2B cells) to immature granule neurons (IGN) (Kronenberg et al, 2003). Four papers assessed DCX immunoreactivity in the dentate gyrus (Table 2) following perinatal EtOH exposure (Elibol‐Can et al, 2014; Gil‐Mohapel et al, 2011, 2014; Olateju et al, 2018). Two papers showed no change in DCX immunoreactivity (Elibol‐Can et al, 2014; Gil‐Mohapel et al, 2014), one showed a significant decrease in DCX‐positive cells that was restricted to females (Gil‐Mohapel et al, 2011), and one paper found a decrease in DCX cells in both males and females (Olateju et al, 2018) (see Fig.…”