Environmental enrichment alters neurotrophin levels after fetal alcohol exposure in rats.

BACKGROUND: Prenatal alcohol exposure causes abnormal brain development, leading to behavioral deficits, some of which can be ameliorated by environmental enrichment. As both environmental enrichment and prenatal alcohol exposure can individually alter neurotrophin expression, we studied the interaction of prenatal alcohol and postweaning environmental enrichment on brain neurotrophin levels in rats. METHODS: Pregnant rats received alcohol by gavage, 0, 4, or 6 g/kg/d (Zero, Low, or High groups), or no treatment (Naïve group), on gestational days 8 to 20. After weaning on postnatal day 21, offspring were housed for 6 weeks in Isolated, Social, or Enriched conditions. Levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were then measured in frontal cortex, occipital cortex, hippocampus, and cerebellar vermis. RESULTS: Prenatal alcohol exposure increased NGF levels in frontal cortex (High-dose group) and cerebellar vermis (High- and Low-dose groups); increased BDNF in frontal cortex, occipital cortex and hippocampus (Low-dose groups), and increased NT-3 in hippocampus and cerebellar vermis (High-dose). Environmental enrichment resulted in lower NGF, BDNF, and NT-3 levels in occipital cortex and lower NGF in frontal cortex. The only significant interaction between prenatal alcohol treatment and environment was in cerebellar vermis where NT-3 levels were higher for enriched animals after prenatal alcohol exposure, but not for animals housed under Isolated or Social conditions. CONCLUSIONS: Both prenatal alcohol exposure and postweaning housing conditions alter brain neurotrophin levels, but the effects appear to be largely independent. Although environmental enrichment can improve functional outcomes, these results do not provide strong support for the hypothesis that rearing in a complex environment ameliorates prenatal alcohol effects on brain neurotrophin levels in rats.

Neonatal alcohol-induced region-dependent changes in rat brain neurochemistry measured by high-resolution magnetic resonance spectroscopy.

BACKGROUND: Maternal drinking during pregnancy can lead to a range of deleterious outcomes in the developing offspring that have been collectively termed fetal alcohol spectrum disorders (FASDs). There is interest and recognized value in using non-invasive neuroimaging techniques such as magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to characterize, respectively, structural and biochemical alterations in individuals with FASDs. To date, however, results with MRS have been inconsistent regarding the degree and/or nature of abnormalities. METHODS: High-resolution magic angle spinning (HR-MAS) proton ((1)H) MRS is an ex vivo neuroimaging technique that can acquire spectra in small punches of intact tissue, providing clinically relevant neurochemical information about discrete brain regions. In this study, HR-MAS (1)H MRS was used to examine regional neurochemistry in frontal cortex, striatum, hippocampus, and cerebellum of young rats previously exposed to ethanol as neonates. Key neurochemicals of interest included N-acetyl-aspartate (NAA), glutamate, GABA, glutamine, creatine, choline and myo-inositol. RESULTS: Daily neonatal alcohol exposure from postnatal day 4 (PN4) through PN9 significantly reduced levels of NAA and taurine in the cerebellum and striatum, and induced sex-dependent reductions in cerebellar glutamate when measured on PN16. In addition, myo-inositol was significantly increased in cerebellum. The frontal cortex and hippocampus were virtually unaffected by this neonatal alcohol exposure. CONCLUSION: Results of this research may have implications for understanding the underlying neurobiology associated with FASDs and aid in testing treatments in the future. Ongoing studies are assessing the developmental persistence of and/or maturational recovery from these changes.

Reversal learning after prenatal or early postnatal alcohol exposure in juvenile and adult rats.

Learning tasks that require the reversal of a previously learned contingency are disrupted in animals and humans exposed to alcohol during the perinatal period. The current experiments examined how varying the time of alcohol exposure and the age at which subjects were tested would affect the expression of reversal deficits in a T-maze task. Groups of rats were exposed to alcohol from gestational day (GD) 8 to GD20 or from postnatal day (PN) 4 to PN9, and then tested in a spatial reversal task at either PN28 or PN63. Results indicate that exposure to alcohol during the prenatal period did not lead to substantial dose-dependent reversal learning deficits in males or females at either age tested. However, exposure to alcohol during the early postnatal period, a period that corresponds to the third trimester in human neural development, selectively disrupted reversal learning performance in male rats at PN28 but not PN63. Statistically significant sex differences were seen when subjects were tested at PN63. These results demonstrate how the timing of alcohol exposure leads to variability in the age-dependent expression of learning deficits associated with fetal alcohol effects.

Neurochemical changes after acute binge toluene inhalation in adolescent and adult rats: a high-resolution magnetic resonance spectroscopy study.

Inhalant abuse in young people is a growing public health concern. We reported previously that acute toluene intoxication in young rats, using a pattern of exposures that approximate abuse patterns of inhalant use in humans, significantly altered neurochemical measures in select brain regions. In this study, adolescent and young adult rats were exposed similarly to an acute (2 x 15 min), high dose (8000-12,000 ppm) of toluene and high-resolution magic angle spinning proton magnetic resonance spectroscopy (HR-MAS 1H-MRS) was used to assess neurochemical profiles of tissue samples from a number of brain regions collected immediately following solvent exposure. The current investigation focused on N-acetyl-aspartate (NAA), choline-containing compounds, creatine, glutamate, GABA, and glutamine. Contrary to our predictions, no significant alterations were found in the levels of NAA, choline, creatine, glutamate, or glutamine in adolescent animals. In contrast to these minimal effects in adolescents, binge toluene exposure altered several neurochemical parameters in young adult rats, including decreased levels of choline and GABA in the frontal cortex and striatum and lowered glutamine and NAA levels in the frontal cortex. One of the more robust findings was a wide-ranging increase in lactate after toluene exposure in adult animals, an effect not observed in adolescents. These age-dependent effects of toluene are distinct from those reported previously in juvenile rats and suggest a developmental difference in vulnerability to the effects of inhalants. Specifically, the results suggest that the neurochemical response to toluene in adolescents is attenuated compared to adults, and imply an association between these neurochemical differences and age-influenced differences in solvent abuse in humans.

Effects of prenatal alcohol exposure on forepaw digit length and digit ratios in rats.

Prenatal exposure to alcohol can cause limb and digit defects. Variations in digit ratios in humans are associated with prenatal testosterone exposure. Since prenatal alcohol can reduce testosterone in rats, the effects of prenatal alcohol were measured on rat digit length. Pregnant Sprague-Dawley rats were intubated with 0 g/kg, 4 g/kg, or 6 g/kg of ethanol from Gestational Day 8 (GD8) to GD20. The 0-g/kg group and a nonintubated group served as controls. At postnatal day 31, forepaw digit lengths were measured and digit ratios calculated. Females had smaller digits on both forepaws and higher digit ratios on the right forepaw than males. Rats exposed to 6 g/kg of ethanol had smaller digits than controls on both forepaws and higher digit ratios than controls on the left forepaw. Rat digit ratios differ between the sexes, and prenatal alcohol exposure affects digit ratios. The results are consistent with a perinatal disruption of testosterone levels by alcohol and/or of testosterone's effects on digit length and ratios. An alternate interpretation is consistent with a retinoic acid-mediated effect of alcohol on digit length and ratios.