Maternal Alcohol Consumption Increases Sphingosine Levels in the Brains of Progeny Mice

Dasgupta, Somsankar; Adams, Jeanette; Hogan, Edward L.

doi:10.1007/s11064-007-9445-3

Cited by 15 publications

(12 citation statements)

References 72 publications

(76 reference statements)

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“…8, 21 Our results suggested that this may be the result of aberrant development of NCC-derived tissues. We focused on meninges, as this tissue complex is derived from NCCs.…”

Section: Resultsmentioning

confidence: 69%

Prenatal alcohol exposure triggers ceramide-induced apoptosis in neural crest-derived tissues concurrent with defective cranial development

Wang

Bieberich

2010

Cell Death Dis

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Fetal alcohol syndrome (FAS) is caused by maternal alcohol consumption during pregnancy. The reason why specific embryonic tissues are sensitive toward ethanol is not understood. We found that in neural crest-derived cell (NCC) cultures from the first branchial arch of E10 mouse embryos, incubation with ethanol increases the number of apoptotic cells by fivefold. Apoptotic cells stain intensely for ceramide, suggesting that ceramide-induced apoptosis mediates ethanol damage to NCCs. Apoptosis is reduced by incubation with CDP-choline (citicoline), a precursor for the conversion of ceramide to sphingomyelin. Consistent with NCC cultures, ethanol intubation of pregnant mice results in ceramide elevation and increased apoptosis of NCCs in vivo. Ethanol also increases the protein level of prostate apoptosis response 4 (PAR-4), a sensitizer to ceramide-induced apoptosis. Prenatal ethanol exposure is concurrent with malformation of parietal bones in 20% of embryos at day E18. Meninges, a tissue complex derived from NCCs, is disrupted and generates reduced levels of TGF-β1, a growth factor critical for bone and brain development. Ethanol-induced apoptosis of NCCs leading to defects in the meninges may explain the simultaneous presence of cranial bone malformation and cognitive retardation in FAS. In addition, our data suggest that treatment with CDP-choline may alleviate the tissue damage caused by alcohol.

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“…8, 21 Our results suggested that this may be the result of aberrant development of NCC-derived tissues. We focused on meninges, as this tissue complex is derived from NCCs.…”

Section: Resultsmentioning

confidence: 69%

Prenatal alcohol exposure triggers ceramide-induced apoptosis in neural crest-derived tissues concurrent with defective cranial development

Wang

Bieberich

2010

Cell Death Dis

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“…Activity of the sphingolipid metabolism enzyme, i.e., acid sphingomyelinase (ASM), has been reported to be increased in alcohol-dependent patients [43]. Alcohol consumption can increase sphingosine levels in the rat brains [44]. Additionally, there are numerous functional variants in SERINC2 including rare variants (Table 3), common variants and frameshift variants such as Indels and CNVs (see NCBI dbSNPs).…”

Section: Discussionmentioning

confidence: 99%

Rare SERINC2 variants are specific for alcohol dependence in individuals of European descent

Zuo

Wang

Zhang

et al. 2013

Pharmacogenetics and Genomics

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Objectives We previously reported a top-ranked risk gene [i.e., serine incorporator 2 gene (SERINC2)] for alcohol dependence in the subjects of European descent by analyzing the common variants in a genome-wide association study. In the present study, we comprehensively examined the rare variants [minor allele frequency (MAF) < 0.05] in the NKAIN1-SERINC2 region, in order to confirm our previous finding. Methods A discovery sample (1,409 European-American cases with alcohol dependence and 1,518 European-American controls) and a replication sample (6,438 European-Australian family subjects with 1,645 alcohol dependent probands) underwent association analysis. A total of 39,903 subjects from 19 other cohorts with 11 different neuropsychiatric and neurological disorders served as contrast groups. The entire NKAIN1-SERINC2 region was imputed in all cohorts using the same reference panels of genotypes that included rare variants from the whole-genome sequencing data. We stringently cleaned the phenotype and genotype data, and obtained a total of about 220 SNPs in the subjects with European descent and about 450 SNPs in the subjects with African descent with 0

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“…It is well established that sphingosine concentrations are tightly regulated inside the cell (Hannun and Obeid, 2008; Lahiri and Futerman, 2007). Bulk concentration of free sphingosine in mouse brain was estimated to be 0.5 μM (Dasgupta et al., 2007) whereas estimates in rat pituitary cells gave a value of ∼5 μM (Blom et al., 2006). A recent study demonstrated the presence of sphingosine kinase in synapses arguing that production of sphingosine and its further phosphorylation must take place in these secretory compartments (Kajimoto et al., 2007).…”

Section: Discussionmentioning

confidence: 99%

Sphingosine Facilitates SNARE Complex Assembly and Activates Synaptic Vesicle Exocytosis

Darios

Wasser

Shakirzyanova

et al. 2009

Neuron

141

167

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SummarySynaptic vesicles loaded with neurotransmitters fuse with the plasma membrane to release their content into the extracellular space, thereby allowing neuronal communication. The membrane fusion process is mediated by a conserved set of SNARE proteins: vesicular synaptobrevin and plasma membrane syntaxin and SNAP-25. Recent data suggest that the fusion process may be subject to regulation by local lipid metabolism. Here, we have performed a screen of lipid compounds to identify positive regulators of vesicular synaptobrevin. We show that sphingosine, a releasable backbone of sphingolipids, activates synaptobrevin in synaptic vesicles to form the SNARE complex implicated in membrane fusion. Consistent with the role of synaptobrevin in vesicle fusion, sphingosine upregulated exocytosis in isolated nerve terminals, neuromuscular junctions, neuroendocrine cells and hippocampal neurons, but not in neurons obtained from synaptobrevin-2 knockout mice. Further mechanistic insights suggest that sphingosine acts on the synaptobrevin/phospholipid interface, defining a novel function for this important lipid regulator.

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Maternal Alcohol Consumption Increases Sphingosine Levels in the Brains of Progeny Mice

Cited by 15 publications

References 72 publications

Prenatal alcohol exposure triggers ceramide-induced apoptosis in neural crest-derived tissues concurrent with defective cranial development

Prenatal alcohol exposure triggers ceramide-induced apoptosis in neural crest-derived tissues concurrent with defective cranial development

Rare SERINC2 variants are specific for alcohol dependence in individuals of European descent

Sphingosine Facilitates SNARE Complex Assembly and Activates Synaptic Vesicle Exocytosis

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