Glutathione content as a potential mediator of the vulnerability of cultured fetal cortical neurons to ethanol-induced apoptosis

Shivani Kaushal Maffi, Mary Latha Rathinam, Priscilla P. Cherian, William Pate, Rhoda Hamby-Mason, Steven Schenker, George I. Henderson

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Ethanol ingestion during pregnancy elicits damage to the developing brain, some of which appears to result from enhanced apoptotic death of neurons. A consistent characteristic of this phenomenon is a highly differing sensitivity to ethanol within specific neuron populations. One possible explanation for this "selective vulnerability" could be cellular variations in glutathione (GSH) homeostasis. Prior studies have illustrated that ethanol elicits apoptotic death of neurons in the developing brain, that oxidative stress may be an underlying mechanism, and that GSH can be neuroprotective. In the present study, both multiphoton microscopy and flow cytometry demonstrate a striking heterogeneity in GSH content within cortical neuron populations. Ethanol differentially elicits apoptotic death and oxidative stress in these neurons. When neuron GSH content is reduced by treatment with butathione sulfoxamine, the ethanol-mediated enhancement of reactive oxygen species is exacerbated. Sorting of cells into high- and low-GSH populations further exemplifies ethanol-mediated oxidative stress whereby apoptotic indices are preferentially elevated in the low-GSH population. Western blot analysis of the low-GSH subpopulations shows higher ethanol-mediated expression of active caspase 3 and 24-kDa PARP-1 fragments compared with the high-GSH subpopulation. In addition, neuronal content of 4-hydroxynonenal adducts is higher in low-GSH neurons in response to ethanol. These studies suggest that GSH content is an important predictor of neuronal sensitivity to ethanol-mediated oxidative stress and subsequent cell death. The data support the proposition that the differences in proapoptotic responses to ethanol within specific neuron populations reflect a heterogeneity of neuron GSH content.

Original languageEnglish (US)
Pages (from-to)1064-1076
Number of pages13
JournalJournal of Neuroscience Research
Volume86
Issue number5
DOIs
StatePublished - Apr 2008

Fingerprint

Glutathione
Ethanol
Apoptosis
Neurons
Oxidative Stress
Population
Brain
Caspase 3
Microscopy
Reactive Oxygen Species
Flow Cytometry
Homeostasis
Cell Death
Eating
Western Blotting
Pregnancy

Keywords

  • Alcohol
  • Apoptosis
  • FASD
  • Glutathione
  • Neuron
  • Oxidative stress

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Maffi, S. K., Rathinam, M. L., Cherian, P. P., Pate, W., Hamby-Mason, R., Schenker, S., & Henderson, G. I. (2008). Glutathione content as a potential mediator of the vulnerability of cultured fetal cortical neurons to ethanol-induced apoptosis. Journal of Neuroscience Research, 86(5), 1064-1076. https://doi.org/10.1002/jnr.21562

Glutathione content as a potential mediator of the vulnerability of cultured fetal cortical neurons to ethanol-induced apoptosis. / Maffi, Shivani Kaushal; Rathinam, Mary Latha; Cherian, Priscilla P.; Pate, William; Hamby-Mason, Rhoda; Schenker, Steven; Henderson, George I.

In: Journal of Neuroscience Research, Vol. 86, No. 5, 04.2008, p. 1064-1076.

Research output: Contribution to journalArticle

Maffi, SK, Rathinam, ML, Cherian, PP, Pate, W, Hamby-Mason, R, Schenker, S & Henderson, GI 2008, 'Glutathione content as a potential mediator of the vulnerability of cultured fetal cortical neurons to ethanol-induced apoptosis', Journal of Neuroscience Research, vol. 86, no. 5, pp. 1064-1076. https://doi.org/10.1002/jnr.21562
Maffi, Shivani Kaushal ; Rathinam, Mary Latha ; Cherian, Priscilla P. ; Pate, William ; Hamby-Mason, Rhoda ; Schenker, Steven ; Henderson, George I. / Glutathione content as a potential mediator of the vulnerability of cultured fetal cortical neurons to ethanol-induced apoptosis. In: Journal of Neuroscience Research. 2008 ; Vol. 86, No. 5. pp. 1064-1076.
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