Altered Purkinje cell maturation in rats exposed prenatally to ethanol

Mohamed, Seham M.; Nathaniel, E.J.H.; Nathaniel, Doris R.; Snell, Linda

doi:10.1016/0014-4886(87)90281-0

Cited by 17 publications

(6 citation statements)

References 23 publications

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“…Rats were monitored daily to ensure equivalent caloric consumption and maintenance of body weight. Since the cerebellum represents a major target of ethanol neurotoxicity [3, 25,26], cerebella were used to study the effects of chronic gestational exposure to ethanol on insulin and IGF signaling in the developing CNS. Fresh tissue harvested immediately after birth was snap frozen in a dry ice-methanol bath and then stored at -80 °C for mRNA and protein studies.…”

Section: Methodsmentioning

confidence: 99%

Chronic gestational exposure to ethanol causes insulin and IGF resistance and impairs acetylcholine homeostasis in the brain

Soscia

Tong

et al. 2006

Cell. Mol. Life Sci.

131

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In fetal alcohol syndrome (FAS), cerebellar hypoplasia is associated with impaired insulin-stimulated survival signaling. This study characterizes ethanol dose-effects on cerebellar development, expression of genes required for insulin and insulin-like growth factor (IGF) signaling, and the upstream mechanisms and downstream consequences of impaired signaling in relation to acetylcholine (ACh) homeostasis. Pregnant Long Evans rats were fed isocaloric liquid diets containing 0%, 2%, 4.5%, 6.5%, or 9.25% ethanol from gestation day 6. Ethanol caused dose-dependent increases in severity of cerebellar hypoplasia, neuronal loss, proliferation of astrocytes and microglia, and DNA damage. Ethanol also reduced insulin, IGF-I, and IGF-II receptor binding, insulin and IGF-I receptor tyrosine kinase activities, ATP, membrane cholesterol, and choline acetyltransferase (ChAT) expression. In vitro studies linked membrane cholesterol depletion to impaired insulin receptor binding and insulin-stimulated ChAT. In conclusion, cerebellar hypoplasia in FAS is mediated by insulin/IGF resistance with attendant impairments in energy production and ACh homeostasis.

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Section: Methodsmentioning

confidence: 99%

Chronic gestational exposure to ethanol causes insulin and IGF resistance and impairs acetylcholine homeostasis in the brain

Soscia

Tong

et al. 2006

Cell. Mol. Life Sci.

131

View full text Add to dashboard Cite

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“…Studies were conducted with cerebella harvested at birth to evaluate the effects of ethanol in the early postnatal period and prior to the occurrence of any major compensatory developmental responses. Cerebellar tissue was studied because it represents a major in vivo target of ethanol neurotoxicity [2,42]. Fresh cerebellar tissue was snap frozen in a dry ice-methanol bath and then stored at -80°C for use in mRNA and protein studies, and assays of kinase or phosphatase activity.…”

Section: Methodsmentioning

confidence: 99%

Ethanol inhibits insulin expression and actions in the developing brain

Monte

Wands

2005

CMLS, Cell. Mol. Life Sci.

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Ethanol-induced cerebellar hypoplasia is associated with inhibition of insulin-stimulated survival signaling. The present work explores the mechanisms of impaired insulin signaling in a rat model of fetal alcohol syndrome. Real-time quantitative RT-PCR demonstrated reduced expression of the insulin gene in cerebella of ethanol-exposed pups. Although receptor expression was unaffected, insulin and insulin-like growth factor (IGF-I) receptor tyrosine kinase (RTK) activities were reduced by ethanol exposure, and these abnormalities were associated with increased PTP1b activity. In addition, glucose transporter molecule expression and steady-state levels of ATP were reduced in ethanol-exposed cerebellar tissue. Cultured cerebellar granule neurons from ethanol-exposed pups had reduced expression of genes encoding insulin, IGF-II, and the IGF-I and IGF-II receptors, and impaired insulin- and IGF-I-stimulated glucose uptake and ATP production. The results demonstrate that ethanol inhibits insulin-mediated actions in the developing brain by reducing local insulin production and insulin RTK activation, leading to inhibition of glucose transport and ATP production.

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“…An early study involving prenatal ethanol exposure indicated a retention of climbing fiber synapses on the soma rather than the normal progression to dendritic locations (Mohamed et al, 1987). A recent study with prenatal ethanol exposure in mice indicated that the climbing fiber induced complex spike firing rate of the Purkinje cells was normal (Servais et al, 2007).…”

mentioning

confidence: 99%

Developmental alterations in olivary climbing fiber distribution following postnatal ethanol exposure in the rat

et al. 2010

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Ethanol exposure during postnatal days (PN) 4-6 in rats alters cerebellar development resulting in significant loss of Purkinje cells. There is little knowledge, however, on what happens to the neurons that survive. In this study, rat pups were treated with a daily dose of ethanol (either 3.6 or 4.5 g/kg body weight) delivered by intragastric intubation on PN4, PN4-6, or PN7-9. Then the interactions between climbing fibers and Purkinje cell were examined on PN14 using confocal microscopy. Mid-vermal cerebellar sections were stained with antibodies to calbindin-D28k (to visualize Purkinje cells) and vesicular glutamate transporter 2 (VGluT2, to visualize climbing fibers). Confocal z-stack images were obtained from Lobule 1 and analyzed with Imaris software to quantify the staining of the two antibodies. The VGluT2 immunostaining was significantly reduced in the PN4 and PN4-6 ethanol groups for the 4.5 g/kg dose level, compared to controls, indicating that the cerebellar circuitry was significantly altered following developmental ethanol exposure. Not only were there fewer Purkinje cells following ethanol exposure, but the surviving neurons had significantly fewer VGluT2-labeled synapses. These alterations in the synaptic integrity were both dose dependent and temporally dependent.

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Altered Purkinje cell maturation in rats exposed prenatally to ethanol

Cited by 17 publications

References 23 publications

Chronic gestational exposure to ethanol causes insulin and IGF resistance and impairs acetylcholine homeostasis in the brain

Chronic gestational exposure to ethanol causes insulin and IGF resistance and impairs acetylcholine homeostasis in the brain

Ethanol inhibits insulin expression and actions in the developing brain

Developmental alterations in olivary climbing fiber distribution following postnatal ethanol exposure in the rat

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