Abstract
We examined the effect of chronic prenatal alcohol exposure on certain neuronal systems involved with the sleep-wake cycle of C57BL/6J mice exposed to prenatal alcohol once they had reached 56 days post-natal. Pregnant mice were exposed to alcohol, through oral gavage, on gestational days 7–16, with recorded blood alcohol concentration (BAC)s averaging 1.84 mg/ml (chronic alcohol group, CA). Two control groups, an oral gavage sucrose control group (chronic alcohol control group, CAc) and a non-treated control group (NTc), were also examined. At 56 days post-natal, the pups from each group were sacrificed and the whole brain sectioned in a coronal plane and immunolabeled for cholineacetyltransferase (ChAT), tyrosine hydroxylase (TH), serotonin (5HT) and orexin-A (OxA) which labels cholinergic, catecholaminergic, serotonergic and orexinergic structures respectively. The overall nuclear organization and neuronal morphology were identical in all three groups studied, and resemble that previously reported for laboratory rodents. Quantification of the estimated numbers of ChAT immunopositive (+) neurons of the pons, the TH+ neurons of the pons and the OxA+ neurons of the hypothalamus showed no statistically significant difference between the three experimental groups. The stereologically estimated areas and volumes of OxA+ neurons in the CA group were statistically significantly larger than the groups not exposed to prenatal alcohol, but the ChAT+ neurons in the CA group were statistically significantly smaller. The density of orexinergic boutons in the anterior cingulate cortex was lower in the CA group than the other groups. No statistically significant difference was found in the area and volume of TH+ neurons between the three experimental groups. These differences are discussed in relation to the sleep disorders recorded in children with fetal alcohol spectrum disorder (FASD).
Highlights
Adequate quality sleep, especially in children, is important for the development of the brain (Chen et al, 2012; Ipsiroglu et al, 2013)
In laboratory rodents exposed to intrauterine alcohol, polysomnographic recording of the sleep-wake cycle demonstrated that total sleep duration was significantly reduced, with a concomitant increase in total wake time, and increases in the numbers of both sleep and wake episodes (Hilakivi, 1986; Stone et al, 1996)
In addition to qualitative examination of these neurons involved in sleep, stereological analysis of neuronal numbers and neuronal size was undertaken for the cholinergic laterodorsal tegmental (LDT) and pedunculopontine tegmental nucleus (PPT), the noradrenergic LC, the orexinergic neurons of the hypothalamus, and orexinergic bouton density in the anterior cingulate cortex
Summary
Especially in children, is important for the development of the brain (Chen et al, 2012; Ipsiroglu et al, 2013). The neural systems that control and regulate sleep are comprised of neurons in specific nuclear clusters in the basal forebrain, hypothalamus and pons, which produce a variety of neurotransmitters and project throughout the brain. These neurons depolarize in specific patterns during wake, slow wave sleep (SWS) and rapid eye movement sleep (REM; Datta and MacLean, 2007; Lyamin et al, 2008; Takahashi et al, 2010; Dell et al, 2012; Bhagwandin et al, 2013; Petrovic et al, 2013). In addition to qualitative examination of these neurons involved in sleep, stereological analysis of neuronal numbers and neuronal size was undertaken for the cholinergic LDT and pedunculopontine tegmental nucleus (PPT), the noradrenergic LC, the orexinergic neurons of the hypothalamus, and orexinergic bouton density in the anterior cingulate cortex
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