Neocortical neurodegeneration in young adult Wistar rats prenatally exposed to ethanol

Fakoya, Francis Adelade; Caxton-Martins, Ezekiel A.

doi:10.1016/j.ntt.2005.11.001

Cited by 18 publications

(23 citation statements)

References 66 publications

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“…As revealed by a significant increase in the number of single-labeled BrdU + cells and of BrdU + cells that double-label NeuN, this effect that was evident at both doses (1 and 3 g/kg) and both ages (P0 and P15) tested. In contrast, prenatal ethanol had no effect on the number of GFAP + cells in these areas, indicating no change in gliogenesis, consistent with some studies in other brain areas (Ramos et al, 2002; Uban et al, 2010), or on TUNEL + cells, indicating no effect on apoptosis as previously found in hippocampus and cortex (Fakoya and Caxton-Martins, 2006; Rubert et al, 2006). These newly generated neurons stimulated by in utero ethanol exposure expressed the peptides, as demonstrated by an increased density of BrdU + cells that co-labeled ENK in the PVN and NAcC, GAL in the PVN, and OX in the PFLH, and they were evident in precisely the same areas where peptide expression is stimulated by ethanol intake in adults (Barson et al, 2011; Morganstern et al, 2011).…”

Section: Discussionsupporting

confidence: 91%

Prenatal ethanol exposure stimulates neurogenesis in hypothalamic and limbic peptide systems: Possible mechanism for offspring ethanol overconsumption

et al. 2012

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Exposure to ethanol during the prenatal period contributes to increased alcohol consumption and preference in rodents and increased risk for alcoholism in humans. With studies in adult animals showing the orexigenic peptides, enkephalin (ENK), galanin (GAL) and orexin (OX), to stimulate ethanol consumption, the question addressed here is whether prenatal ethanol alters the development in utero of specific neurons that express these peptides. With reports describing suppressive effects of high doses of ethanol, we examined the offspring of dams gavaged from embryonic day 9 to parturition with a control solution or lower ethanol doses, 1 and 3 g/kg/day, known to promote ethanol consumption in the offspring. To understand underlying mechanisms, measurements were taken in postnatal offspring of the expression of ENK in the hypothalamic paraventricular nucleus (PVN) and nucleus accumbens (NAc), GAL in the PVN, and OX in the perifornical lateral hypothalamus (PFLH) using real-time qPCR and in situ hybridization, and also of the cell proliferation marker, 5-bromo-2-deoxyuridine (BrdU), and its double-labeling with either neuronal nuclei (NeuN), a marker of mature neurons, or the peptides. On postnatal day 15 (P15), after two weeks without ethanol, the offspring showed increased expression of ENK in the PVN and NAc core but not shell, GAL in the PVN, and OX in the PFLH. In these same areas, prenatal ethanol compared to control increased the density at birth (P0) of neurons expressing these peptides and at P0 and P15 of neurons double-labeling BrdU and NeuN, indicating increased neurogenesis. These BrdU-positive neurons were found to express ENK, GAL and OX, indicating that prenatal ethanol promotes neurogenesis in these specific peptide systems. There were no changes in gliogenesis or apoptosis. This increase in neurogenesis and density of peptide-expressing neurons suggests the involvement of these hypothalamic and accumbal peptide systems in mediating the increased alcohol consumption observed in prenatal ethanol-exposed offspring.

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Section: Discussionsupporting

confidence: 91%

Prenatal ethanol exposure stimulates neurogenesis in hypothalamic and limbic peptide systems: Possible mechanism for offspring ethanol overconsumption

et al. 2012

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“…Necrosis is the major cell death phenotype in the brain following acute neonatal HI injury in rat pup forms of neurodegeneration in the developing brain similar to Bcontinuum^cell death has been previously described and termed Bpathological apoptosis^and excitotoxic neurodegeneration [37]. Similar to earlier studies [38], our study was histologically observed that ethanol caused significant damage on brain cortex tissue. Especially on neurons, the damage was evident in terms of necrosis.…”

Section: Discussionsupporting

confidence: 88%

The investigation of the prenatal and postnatal alcohol exposure-induced neurodegeneration in rat brain: protection by betaine and/or omega-3

Kanbak

İlhan

et al. 2016

Childs Nerv Syst

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“…Moreover, a previous study showed that pregnant guinea pigs can be successfully exposed to moderate ethanol concentrations using a 24-hour voluntary drinking paradigm, which is expected to be less stressful (Shea et al, 2012). It is also important to determine whether ethanol exposure during the equivalent to the first and second trimesters of human pregnancy (i.e., pregnancy in rodents; Clancy et al, 2007) also causes fetal brain micro-hemorrhages and whether these contribute to the morphological and functional alterations that have been detected in different brain regions, including the cerebral cortex (Kuhn and Miller, 1998, Climent et al, 2002, Fakoya and Caxton-Martins, 2006, El Shawa et al, 2013, Abbott et al, 2016). …”

Section: Discussionmentioning

confidence: 99%

Third trimester-equivalent ethanol exposure causes micro-hemorrhages in the rat brain

et al. 2016

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Exposure to ethanol during fetal development produces long-lasting neurobehavioral deficits caused by functional alterations in neuronal circuits across multiple brain regions. Therapeutic interventions currently used to treat these deficits are only partially efficacious, which is a consequence of limited understanding of the mechanism of action of ethanol. Here, we describe a novel effect of ethanol in the developing brain. Specifically, we show that exposure of rats to ethanol in vapor chambers during the equivalent to the third trimester of human pregnancy causes brain micro-hemorrhages. This effect was observed both at low and high doses of ethanol vapor exposure, and was not specific to this exposure paradigm as it was also observed when ethanol was administered via intra-esophageal gavage. The vast majority of the micro-hemorrhages were located in the cerebral cortex but were also observed in the hypothalamus, midbrain, olfactory tubercle, and striatum. The auditory, cingulate, insular, motor, orbital, retrosplenial, somatosensory, and visual cortices were primarily affected. Immunohistochemical experiments showed that the micro-hemorrhages caused neuronal loss, as well as reactive astrogliosis and microglial activation. Analysis with the Catwalk test revealed subtle deficits in motor function during adolescence/young adulthood. In conclusion, our study provides additional evidence linking developmental ethanol exposure with alterations in the fetal cerebral vasculature. Given that this effect was observed at moderate levels of ethanol exposure, our findings lend additional support to the recommendation that women abstain from consuming alcoholic beverages during pregnancy.

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Neocortical neurodegeneration in young adult Wistar rats prenatally exposed to ethanol

Cited by 18 publications

References 66 publications

Prenatal ethanol exposure stimulates neurogenesis in hypothalamic and limbic peptide systems: Possible mechanism for offspring ethanol overconsumption

Prenatal ethanol exposure stimulates neurogenesis in hypothalamic and limbic peptide systems: Possible mechanism for offspring ethanol overconsumption

The investigation of the prenatal and postnatal alcohol exposure-induced neurodegeneration in rat brain: protection by betaine and/or omega-3

Third trimester-equivalent ethanol exposure causes micro-hemorrhages in the rat brain

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