Hippocampal cell proliferation is reduced following prenatal ethanol exposure but can be rescued with voluntary exercise

Abstract

The ingestion of ethanol during pregnancy has a number of deleterious consequences for the unborn offspring, producing structural and functional deficits that affect the brain and many other organs into adulthood. The hippocampus is a brain area that is particularly sensitive to ethanol's adverse effects. In a previous study we showed that voluntary exercise can ameliorate deficits in long-term potentiation and behavior that occur following prenatal ethanol exposure (Eur J Neurosci, 2005, 21, 1719-1726). In the present study, we investigated the effects of prenatal ethanol exposure on neurogenesis in adulthood, and tested the hypothesis that voluntary exercise would ameliorate any deficits observed. Sprague-Dawley females were administered one of three diets throughout gestation: (i) ethanol (E), a liquid diet containing 36.5% ethanol-derived calories; (ii) pair-fed (PF), a liquid control diet, with maltose-dextrin isocalorically substituted for ethanol, in the amount consumed by an E partner (g/kg body wt/day of gestation); and (iii) ad-libitum-fed control (C), normal laboratory chow and water, ad libitum. The offspring were housed individually at postnatal day (PND) 35, and at PND 50 were randomly assigned to cages either with or without an exercise wheel. BrdU (200 mg/kg, I.P.) was injected on PND 57, and animals terminated either 24 h (proliferation) or 4 weeks (neurogenesis) later. Our results demonstrate that prenatal ethanol exposure significantly decreases both cell proliferation and neurogenesis in the adult dentate gyrus. Animals in the PF condition also showed reduced neurogenesis. In contrast, all animals that engaged in voluntary exercise showed a significant increase in cell proliferation and neurogenesis. These results indicate that prenatal ethanol exposure can suppress both cell proliferation and neurogenesis, and that these effects may be, at least in part, nutritionally mediated. Importantly, voluntary exercise appears to have beneficial effects for these long-lasting deficits in hippocampal volume and cell number that have been observed in animals exposed to ethanol in utero.

Prenatal Exposure to Alcohol and 3,4-Methylenedioxymethamphetamine (Ecstasy) Alters Adult Hippocampal Neurogenesis and Causes Enduring Memory Deficits

“…The direction and magnitude of changes in neurogenesis in models of foetal alcohol spectrum disorders depend on several factors, including blood alcohol concentration attained, frequency of exposure and phase of gestation during which alcohol is administered [40]. In agreement with our findings, some studies have reported no significant changes on proliferation and survival of neuronal precursors following exposure to alcohol throughout the pregnancy [41,42], but others have after similarly long exposure [17]. Further, a study in females revealed no effects of prenatal alcohol exposure on hippocampal cytogenesis and survival [43].…”

“…Similarly, recent research has shown that exposure to either of these drugs during prolonged periods of embryonic development can have long-term effects on adult neurogenesis [16,17], raising the possibility that such alterations may underlie long-lasting deficits in learning and memory function. However, the effects of embryonic exposure to MDMA and alcohol combined have not been previously investigated.…”

Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain

“…Moreover, exercise during pregnancy can up-regulate postnatal neurogenesis in the offspring at P9 (41). Voluntary exercise is also able to compensate for decreased levels of proliferation induced by prenatal ethanol exposure (42). In addition, an enriched environment is effective in boosting neuronal numbers and enhancing cognitive function after status epilepticus in P20 mice (43).…”

Involvement of the Cytoplasmic C-Terminal Domain of Connexin43 in Neuronal Migration

“…(Redila et al, 2006). Pregnant female mice were injected with BrdU once, and animals were allowed to survive for either 2 or 96 h. Embryonic brains obtained from either E14 or E18 mice were sectioned and mounted on coverslips, and DNA was denatured by incubating the slides in HCl for 30 min at 37°C.…”