Effects of neonatal ethanol on cerebral cortex development through adolescence
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Neonatal brain lesions cause deficits in structure and function of the cerebral cortex that sometimes are not fully expressed until adolescence. To better understand the onset and persistence of changes caused by postnatal day 7 (P7) ethanol treatment, we examined neocortical cell numbers, volume, surface area and thickness from neonatal to post-adolescent ages. In control mice, total neuron number decreased from P8 to reach approximately stable levels at about P30, as expected from normal programmed cell death. Cortical thickness reached adult levels by P14, but cortical volume and surface area continued to increase from juvenile (P20–30) to post-adolescent (P54–93) ages. P7 ethanol caused a reduction of total neurons by P14, but this deficit was transient, with later ages having only small and non-significant reductions. Previous studies also reported transient neuron loss after neonatal lesions that might be partially explained by an acute acceleration of normally occurring programmed cell death. GABAergic neurons expressing parvalbumin, calretinin, or somatostatin were reduced by P14, but unlike total neurons the reductions persisted or increased in later ages. Cortical volume, surface area and thickness were also reduced by P7 ethanol. Cortical volume showed evidence of a transient reduction at P14, and then was reduced again in post-adolescent ages. The results show a developmental sequence of neonatal ethanol effects. By juvenile ages the cortex overcomes the P14 deficit of total neurons, whereas P14 GABA cell deficits persist. Cortical volume reductions were present at P14, and again in post-adolescent ages.
KeywordsAdolescence Neonatal Stereology GABA Fetal alcohol Programmed cell death
This work was supported by a grant from National Institute on Alcohol Abuse and Alcoholism (R01- AA023181) to M.S. and D.A.W.
Compliance with ethical standards
Conflict of interest
The authors declare that they do not have financial conflicts of interest that would influence this research.
All procedures were approved by the Nathan Kline Institute IACUC and were in accordance with NIH guidelines for the proper treatment of animals.
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