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Prenatal ethanol exposure produces severe changes in brain, liver, and kidney through mechanisms involving growth factors. These molecules regulate survival, differentiation, maintenance, and connectivity of brain, liver, and kidney cells. Despite the abundant available data on the short and mid-lasting effects of ethanol intoxication, only few data show the long-lasting damage induced by early ethanol administration. The aim of this study was to investigate changes in nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) in brain areas, liver, and kidney of 18-mo-old male mice exposed perinatally to ethanol at 11% vol or to red wine at the same ethanol concentration. The authors found that ethanol per se elevated NGF, BDNF, HGF, and VEGF measured by ELISA in brain limbic system areas. In the liver, early exposure to ethanol solution and red wine depleted BDNF and VEGF concentrations. In the kidney, red wine exposure only decreased VEGF. In conclusion, the present study shows that, in aged mice, early administration of ethanol solution induced long-lasting damage at growth factor levels in frontal cortex, hippocampus, and liver but not in kidney. Otherwise, in mice exposed to red wine, significant changes were observed in the liver and kidney but not in the hippocampus and frontal cortex. The brain differences in ethanol-induced toxicity when ethanol is administered alone or in red wine may be related to compounds with antioxidant properties present in the red wine.

Early experiences have profound influences on individual developmental trajectories. For example alcohol exposure during central nervous system development relates to a number of pathological consequences in adulthood. An increased risk of developing psychiatric disorders, like major depression and impulse-control-related pathologies is associated with alcohol exposure during fetal life and/or during adolescence. Additionally, adverse life experiences occurring early in development may exacerbate these consequences, while impinging on the same neural systems affected by precocious alcohol exposure. Conversely, a protective and/or stimulating environment may mitigate these alcohol-related negative outcomes. Experimental research in animal models constitutes a primary source of information in understanding both functional and dysfunctional human adaptations to these events. In this review, a selection of rodent and primate studies shows that developmental ethanol exposure on the one hand, and environmental treatments aimed at modifying the mother-offspring interaction on the other hand, independently modulate similar neuro-endocrine systems. In particular, we discuss the effects that the above-mentioned independent variables exert on the hypothalamic-pituitary-adrenal (HPA)-axis and on brain serotonergic pathways. Experimental evidence indicates that pathological adaptations of these systems are valuable predictors of human neuro-behavioral abnormalities like depression, impaired impulse control and alcohol abuse. Finally, a working hypothesis is proposed, which combines primate and rodent studies aimed: (i) at studying functional and pathological individual development following early ethanol consumption, and (ii) at heading towards a better definition of potential intervention strategies.

Ethanol exposure during pregnancy is one of the major causes of mental retardation in western countries by inducing fetal-alcohol-like-syndromes. Red wine is known to contain ethanol but also compounds with putative antioxidant properties. It has also been shown that nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are severely affected by ethanol during prenatal and postnatal life. The aim of the current study was to investigate in male CD1 mice brain alterations in NGF and BDNF due to chronic early exposure to ethanol solution (11 vol%) or to red wine at the same alcohol concentration starting from 60 days before pregnancy up to pups weaning. Data revealed no differences between groups of dams in pregnancy duration, neither in pups delivery, pups mortality and sex ratio. Data also showed that adult animals exposed to only ethanol had disrupted levels of both NGF and BDNF in the hippocampus and other brain areas. This profile was associated with impaired ChAT immunopositivity in the septum and Nuclei Basalis and with altered cognition and emotional behavior. Quite interestingly mice exposed to red wine had no change in the behavior or in ChAT immunopositivity but a decrease in hippocampal BDNF and a mild NGF decrease in the cortex. Also NGF-induced neuritic outgrowth in PC-12 cells was still present when exposed to red wine but not when exposed to ethanol solution only. Data suggest differences in ethanol-induced neurotoxicity between red wine and ethanol solution only.