Voluntary exercise partially reverses neonatal alcohol-induced deficits in mPFC layer II/III dendritic morphology of male adolescent rats.

Developmental alcohol exposure in humans can produce a wide range of deficits collectively referred to as fetal alcohol spectrum disorders (FASD). FASD-related impairments in executive functioning later in life suggest long-term damage to the prefrontal cortex (PFC). In rodent neonates, moderate to high levels of alcohol exposure decreased frontal lobe brain size and altered medial PFC pyramidal neuron dendritic morphology. Previous research in our lab demonstrated that neonatal alcohol exposure decreased basilar dendritic complexity but did not affect spine density in Layer II/III pyramidal neurons in 26- to 30-day-old rats. The current study adds to the literature by evaluating the effect of neonatal alcohol exposure on mPFC Layer II/III basilar dendritic morphology in adolescent male rats. Additionally, it examines the potential for voluntary exercise to mitigate alcohol-induced deficits on mPFC dendritic complexity. An animal model of binge drinking during the third trimester of pregnancy was used. Rats were intubated with alcohol (alcohol-exposed, AE; 5.25 g kg(-1) day(-1)) on postnatal days (PD) 4-9; two control groups were included (suckle control and sham-intubated). Rats were anesthetized and perfused with heparinized saline solution on PD 42, and brains were processed for Golgi-Cox staining. Developmental alcohol exposure decreased spine density and dendritic complexity of basilar dendrites of Layer II/III neurons in the medial PFC (mPFC) compared to dendrites of control animals. Voluntary exercise increased spine density and dendritic length in AE animals resulting in elimination of the differences between AE and SH rats. Thus, voluntary exercise during early adolescence selectively rescued alcohol-induced morphological deficits in the mPFC.

Effects of developmental alcohol exposure vs. intubation stress on BDNF and TrkB expression in the hippocampus and frontal cortex of neonatal rats.

Third trimester-equivalent alcohol exposure causes significant deficits in hippocampal and cortical neuroplasticity, resulting in alterations to dendritic arborization, hippocampal adult neurogenesis, and performance on learning tasks. The current study investigated the impact of neonatal alcohol exposure (postnatal days 4-9, 5.25 g/kg/day) on expression of brain-derived neurotrophic factor (BDNF) and the tropomyosin-related kinase B (TrkB) receptor in the hippocampal and frontal cortex of infant Long-Evans rats. Levels of BDNF protein were increased in the hippocampus, but not frontal cortex, of alcohol-exposed rats 24h after the last dose, when compared with undisturbed (but not sham-intubated) control animals. BDNF protein levels showed a trend toward increase in hippocampus of sham-intubated animals as well, suggesting an effect of the intubation procedure. TrkB protein was increased in the hippocampus of alcohol-exposed animals compared to sham-intubated pups, indicating an alcohol-specific effect on receptor expression. In addition, expression of bdnf total mRNA in alcohol-exposed and sham-intubated pups was enhanced in the hippocampus; however, there was a differential effect of alcohol and intubation stress on exon I- and IV-specific mRNA transcripts. Further, plasma corticosterone was found to be increased in both alcohol-exposed and sham-intubated pups compared to undisturbed animals. Upregulation of BDNF could potentially represent a neuroprotective mechanism activated following alcohol exposure or stress. The results suggest that alcohol exposure and stress have both overlapping and unique effects on BDNF, and highlight the need for the stress of intubation to be taken into consideration in studies that implement this route of drug delivery.