Glial-derived neurotrophic factor (GDNF) prevents ethanol-induced apoptosis and JUN kinase phosphorylation

McAlhany, Robert E.; West, John C; Miranda, Rajesh C.

doi:10.1016/s0165-3806(99)00171-6

Cited by 99 publications

(86 citation statements)

References 67 publications

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“…Rodent cell culture models and tumor-derived cell lines also have been used extensively to understand the effects of ethanol on neuronal survival and differentiation, i.e., events that occur during the third trimester. Using these models, we and others, have shown that, in differentiated neural tissue, part of alcohol's neurotoxicity may be caused by the induction of death mechanisms (18)(19)(20)(21), the loss of growth and survival factors (22)(23)(24)(25)(26)(27)(28), alterations in neuronal migration (29), and in neurotransmitters systems (30), among others. Further, in vitro studies found that the state of differentiation of the cells determined the degree of sensitivity to alcohol insult (31,32), confirming in vivo work showing windows of vulnerability that reflected maturation of the neurons (16,33,34).…”

Section: Effects Of Alcohol During Brain Growth and Developmentmentioning

confidence: 99%

Modeling the Impact of Alcohol on Cortical Development in a Dish: Strategies from Mapping Neural Stem Cell Fate

Miranda

Santillano

Camarillo

et al. 2008

Alcohol

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SummaryDuring the second trimester period, neuroepithelial stem cells give birth to millions of new neuroblasts, which migrate away from their germinal zones to populate the developing brain and terminally differentiate into neurons. During this period, large numbers of cells are also eliminated by programmed cell death. Therefore, the second trimester constitutes an important critical period for neuronal proliferation, migration, differentiation and apoptosis. Substantial evidence indicates that teratogens like ethanol can interfere with neuronal maturation. However, there is a paucity of good model systems to study early, second trimester events. In vivo models are inherently interpretatively complex because cell proliferation, migration, differentiation, and death mechanisms occur concurrently in regions like the cerebral cortex. This temporal overlap of multiple developmental critical periods makes it difficult to evaluate the relative vulnerability of any individual critical period. Our laboratory has elected to utilize fetal rodent cerebral corticalderived neurosphere cultures as an experimental model of the second-trimester ventricular neuroepithelium. This model has enabled us to use flow cytometric approaches to identify neuroepithelial stem cell and progenitor sub-populations and to show that ethanol accelerates the maturation of neural stem cells. We have also developed a simplified mitogen-withdrawal/matrixadhesion paradigm to model the exit of neuroepithelial cells from the ventricular zone towards the subventricular zone and cortical plate, and their maturation into multipolar neurons. We can treat neurosphere cultures with ethanol to mimic exposure during the period of neuroepithelial proliferation and by using the step-wise maturation model, ask questions about the impact of prior ethanol exposure on the subsequent maturation of neurons as they migrate and undergo terminal differentiation. The combination of neurosphere culture and stepwise maturation models will enable us to dissect out the contributions of specific developmental critical periods to the overall teratology of a drug of abuse like ethanol.

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Section: Effects Of Alcohol During Brain Growth and Developmentmentioning

confidence: 99%

Modeling the Impact of Alcohol on Cortical Development in a Dish: Strategies from Mapping Neural Stem Cell Fate

Miranda

Santillano

Camarillo

et al. 2008

Alcohol

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“…It has been reported that alcohol induces death in astroglia and neuroblastoma cells and that ethanol consumption during CNS development leads to substantial neuronal loss in multiple brain regions. [2][3][4] Electrophysiological studies suggest that alcohol disrupts learning and memory formation by compromising hippocampal functions. 16) At physiologically relevant concentrations, ethanol was shown to diminish the amplitude of stimulationevoked spikes in hippocampal slices, suggesting a suppressive effect of alcohol on cell activity.…”

Section: Discussionmentioning

confidence: 99%

“…Alcohol consumption is known to cause substantial neuronal loss in several regions of the brain, [2][3][4] and to exert various effects on the central nervous system (CNS). 5) It has been reported that alcohol induces death in a variety of cells including astroglia 2) and neuroblastoma cells in vitro 4) and that it triggers apoptotic neurodegeneration in the developing rat brain in vivo.…”

mentioning

confidence: 99%

“…5) It has been reported that alcohol induces death in a variety of cells including astroglia 2) and neuroblastoma cells in vitro 4) and that it triggers apoptotic neurodegeneration in the developing rat brain in vivo. 3) In addition, alcohol intake during the developmental stage has been associated with deficits in learning and memory, 6,7) and alcohol abuse has been shown to induce behavioral disorders during adolescence.…”

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confidence: 99%

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Effect of Puerariae radix on c-Fos Expression in Hippocampus of Alcohol-Intoxicated Juvenile Rats.

Jang

Shin

Lee

et al. 2003

Biological & Pharmaceutical Bulletin

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“…We chose SKNSH neuroblastoma cells as an alternative to CGN cultures because SKNSH cells are transfected by plasmid-based vectors with a high efficiency. SKNSH cells are relevant to these studies because, like CGN, they are of neuronal origin and vulnerable to alcohol-induced cell death in a dose dependent manner (McAlhany, et al, 2000;McAlhany et al, 1997).…”

Section: Forskolin Activates a Nnos-promoter Construct Containing Crementioning

confidence: 99%

Stimulation of the cAMP pathway protects cultured cerebellar granule neurons against alcohol-induced cell death by activating the neuronal nitric oxide synthase (nNOS) gene

Karaçay

Pantazis

et al. 2007

Brain Research

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Neuronal loss is a key component of fetal alcohol syndrome pathophysiology. Therefore, identification of molecules and signaling pathways that ameliorate alcohol-induced neuronal death is important. We have previously reported that neuronal nitric oxide synthase (nNOS) can protect developing cerebellar granule neurons (CGN) against alcohol-induced death both in vitro and in vivo. However, the upstream signal controlling nNOS expression in CGN is unknown. Activated cAMP response element binding protein (CREB) has been strongly linked to the survival of multiple cell types, including CGN. Furthermore, the promoter of the nNOS gene contains two cAMP response elements (CRE). Using cultures of CGN, we tested the hypothesis that cAMP mediates nNOS activation and the protective effect of nNOS against alcohol-induced cell death. Forskolin, an activator of the cAMP pathway, stimulated expression of a reporter gene under the control of the nNOS promoter, and this stimulation was substantially reduced when the two CREs were mutated. Forskolin increased nNOS mRNA levels several-fold, increased production of nitric oxide, and abolished alcohol's toxic effect in wild type CGN. Furthermore, forskolin's protective effect was substantially reduced in CGN cultures genetically deficient for nNOS (from nNOS−/− mice). Delivery of nNOS cDNA using a replication-deficient adenoviral vector into nNOS−/− CGN abolished alcohol-induced neuronal death. In addition, over-expression of nNOS in wild type CGN ameliorated alcohol-induced cell death. These results indicate that the neuroprotective effect of the cAMP pathway is mediated, in part, by the pathway's downstream target, the nNOS gene.

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Glial-derived neurotrophic factor (GDNF) prevents ethanol-induced apoptosis and JUN kinase phosphorylation

Cited by 99 publications

References 67 publications

Modeling the Impact of Alcohol on Cortical Development in a Dish: Strategies from Mapping Neural Stem Cell Fate

Modeling the Impact of Alcohol on Cortical Development in a Dish: Strategies from Mapping Neural Stem Cell Fate

Effect of Puerariae radix on c-Fos Expression in Hippocampus of Alcohol-Intoxicated Juvenile Rats.

Stimulation of the cAMP pathway protects cultured cerebellar granule neurons against alcohol-induced cell death by activating the neuronal nitric oxide synthase (nNOS) gene

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