Impeded cerebellar development and reduced serum thyroxine levels associated with fetal alcohol intoxication

Kornguth, Steven; Rutledge, J. J.; Sunderland, E.; Siegel, Frank L.; Carlson, Ian H.; Smollens, J.; Juhl, U.; Young, Bruce W.

doi:10.1016/0006-8993(79)90785-6

Cited by 98 publications

(22 citation statements)

References 36 publications

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“…Prolonged exposure to alcohol during gestation and lactation leads to a pattern of abnormal development in newborns, including cerebellar damage [102,103,104,105,106]. Alcohol exposure results in abnormal development of the postnatal cerebellum [107,108,109]. On cerebellar slices, ethanol reduces the speed of granule cell migration in the EGL, ML and IGL in a dose-dependent manner [110].…”

Section: Impact Of Environmental Conditions Pollutants Nutrientsmentioning

confidence: 99%

Postnatal Migration of Cerebellar Interneurons

et al. 2017

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Due to its continuing development after birth, the cerebellum represents a unique model for studying the postnatal orchestration of interneuron migration. The combination of fluorescent labeling and ex/in vivo imaging revealed a cellular highway network within cerebellar cortical layers (the external granular layer, the molecular layer, the Purkinje cell layer, and the internal granular layer). During the first two postnatal weeks, saltatory movements, transient stop phases, cell-cell interaction/contact, and degradation of the extracellular matrix mark out the route of cerebellar interneurons, notably granule cells and basket/stellate cells, to their final location. In addition, cortical-layer specific regulatory factors such as neuropeptides (pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin) or proteins (tissue-type plasminogen activator (tPA), insulin growth factor-1 (IGF-1)) have been shown to inhibit or stimulate the migratory process of interneurons. These factors show further complexity because somatostatin, PACAP, or tPA have opposite or no effect on interneuron migration depending on which layer or cell type they act upon. External factors originating from environmental conditions (light stimuli, pollutants), nutrients or drug of abuse (alcohol) also alter normal cell migration, leading to cerebellar disorders.

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Section: Impact Of Environmental Conditions Pollutants Nutrientsmentioning

confidence: 99%

Postnatal Migration of Cerebellar Interneurons

et al. 2017

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“…Prenatal alcohol exposure impedes cerebral and cerebellar growth (Bauer-Moffett and Altman, 1975, 1977, Kornguth et al, 1979, Samson and Diaz, 1981, Sulik et al, 1981, Barron et al, 1988, Bonthius and West, 1990), and induces brain growth deficits (Sari and Gozes, 2006) through an apoptotic mechanism (Ikonomidou et al, 2000). Little is known, however, about the underlying signaling pathways of the apoptotic mechanism.…”

Section: Introductionmentioning

confidence: 99%

A novel peptide, colivelin, prevents alcohol-induced apoptosis in fetal brain of C57BL/6 mice: signaling pathway investigations

et al. 2009

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Fetal alcohol exposure is known to induce cell death through apoptosis. We found that colivelin (CLN), a novel peptide with the sequence SALLRSIPAPAGASRLLLLTGEIDLP, prevents this apoptosis. Our initial experiment revealed that CLN enhanced the viability of primary cortical neurons exposed to alcohol. We then used a mouse model of fetal alcohol exposure to identify the intracellular mechanisms underlying these neuroprotective effects. On embryonic day 7 (E7), weightmatched pregnant females were assigned to the following groups: (1) ethanol liquid diet (ALC) 25% (4.49%, v/v) ethanol derived calories; (2) pair-fed control; (3) normal chow; (4) ALC combined with administration (i.p.) of CLN (20 μg/20 g body weight); and (5) pair-fed combined with administration (i.p.) of CLN (20 μg/20 g body weight). On E13, fetal brains were collected and assayed for TUNEL staining, caspase-3 colorimetric assay, ELISA, and MSD electrochemiluminescence. CLN blocked the alcohol-induced decline in brain weight and prevented alcohol-induced: apoptosis, activation of caspase-3 and increases of cytosolic cytochrome c, and decreases of mitochondrial cytochrome c. Analysis of proteins in the upstream signaling pathway revealed that CLN down-regulated the phosphorylation of the c-Jun N-terminal kinase. Moreover, CLN prevented alcohol-induced reduction in phosphorylation of BAD protein. Thus, CLN appears to act directly on upstream signaling proteins to prevent alcohol-induced apoptosis. Further assessment of these proteins and their signaling mechanisms is likely to enhance development of neuroprotective therapies.

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“…The most vulnerable period of cerebellar development in humans is during the third trimester (Clarren, 1986). The equivalent time of development in mice is during the early postnatal period (Kornguth et al, 1979), and alcohol exposure results in abnormal development of the postnatal cerebellum (Kornguth et al, 1979;Sakata-Haga et al, 2001;Dikranian et al, 2005). In particular, the numbers of granule cells in the internal granular layer (IGL), where postmigratory granule cells reside and make synaptic connections with mossy fiber terminals, were significantly reduced in the alcohol-treated animals (Borges and Lewis, 1983), suggesting that alcohol affects the migration of immature granule cells from their birthplace to their final destination.…”

Section: Introductionmentioning

confidence: 99%

Reversal of Neuronal Migration in a Mouse Model of Fetal Alcohol Syndrome by Controlling Second-Messenger Signalings

Kumada¹,

Lakshmana²,

Komuro³

2006

J. Neurosci.

131

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The brains of fetal alcohol syndrome patients exhibit impaired neuronal migration, but little is known about the mechanisms underlying this abnormality. Here we show that Ca 2ϩ signaling and cyclic nucleotide signaling are the central targets of alcohol action in neuronal cell migration. Acute administration of ethanol reduced the frequency of transient Ca 2ϩ elevations in migrating neurons and cGMP levels and increased cAMP levels. Experimental manipulations of these second-messenger pathways, through stimulating Ca 2ϩ and cGMP signaling or inhibiting cAMP signaling, completely reversed the action of ethanol on neuronal migration in vitro as well as in vivo. Each second messenger has multiple but distinct downstream targets, including Ca 2ϩ /calmodulin-dependent protein kinase II, calcineurin, protein phosphatase 1, Rho GTPase, mitogen-activated protein kinase, and phosphoinositide 3-kinase. These results demonstrate that the aberrant migration of immature neurons in the fetal brain caused by maternal alcohol consumption may be corrected by controlling the activity of these second-messenger pathways.

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Impeded cerebellar development and reduced serum thyroxine levels associated with fetal alcohol intoxication

Cited by 98 publications

References 36 publications

Postnatal Migration of Cerebellar Interneurons

Postnatal Migration of Cerebellar Interneurons

A novel peptide, colivelin, prevents alcohol-induced apoptosis in fetal brain of C57BL/6 mice: signaling pathway investigations

Reversal of Neuronal Migration in a Mouse Model of Fetal Alcohol Syndrome by Controlling Second-Messenger Signalings

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