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Allopregnanolone attenuates N-methyl-D-aspartate-induced excitotoxicity and apoptosis in the human NT2 cell line in culture.

Publication ,  Journal Article
Lockhart, EM; Warner, DS; Pearlstein, RD; Penning, DH; Mehrabani, S; Boustany, R-M
Published in: Neurosci Lett
August 2, 2002

Progesterone modulates gamma-aminobutyric acid and excitatory amino acid neurotransmitter systems and has neuroprotective properties in models of hypoxia-ischemia. This study examined the in vitro effects of allopregnanolone, the active progesterone metabolite, in models of N-methyl-D-aspartate (NMDA)-induced necrosis and apoptosis. Cultured NT2 neurons were exposed to 1 mM NMDA. Lactate dehydrogenase (LDH) release was measured 24 h later. NMDA at a concentration of 1 mM produced a 39 +/- 19% release of total LDH. Exposure to 10 microM allopregnanolone prior to NMDA exposure reduced LDH release by 51% (P = 0.0028). NMDA stimulated apoptotic cell changes defined by terminal dUTP nick-end labeling (TUNEL) and 5,5', 6,6'-tetrachloro-1,1,3,3'-tetra ethlybenzimidazolycarbocyanide iodide staining were reduced to baseline values by both 10 microM allopregnanolone and 100 microM MK-801. Pretreatment with allopregnanolone (0-10 microM) reduced the percentage of TUNEL-positive cells in a dose-dependent manner (EC(50) = 2.7 +/- 0.1 nM). Physiologic concentrations of allopregnanolone provided protection against both necrotic and apoptotic injury induced by NMDA excitotoxicity.

Duke Scholars

Published In

Neurosci Lett

DOI

ISSN

0304-3940

Publication Date

August 2, 2002

Volume

328

Issue

1

Start / End Page

33 / 36

Location

Ireland

Related Subject Headings

  • Tumor Cells, Cultured
  • Progesterone
  • Pregnanolone
  • Pregnancy
  • Neurotoxins
  • Neuroprotective Agents
  • Neurons
  • N-Methylaspartate
  • Mitochondria
  • Membrane Potentials
 

Citation

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MLA
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Lockhart, E. M., Warner, D. S., Pearlstein, R. D., Penning, D. H., Mehrabani, S., & Boustany, R.-M. (2002). Allopregnanolone attenuates N-methyl-D-aspartate-induced excitotoxicity and apoptosis in the human NT2 cell line in culture. Neurosci Lett, 328(1), 33–36. https://doi.org/10.1016/s0304-3940(02)00448-2
Lockhart, Ellen M., David S. Warner, Robert D. Pearlstein, Donald H. Penning, Saeed Mehrabani, and Rose-Mary Boustany. “Allopregnanolone attenuates N-methyl-D-aspartate-induced excitotoxicity and apoptosis in the human NT2 cell line in culture.Neurosci Lett 328, no. 1 (August 2, 2002): 33–36. https://doi.org/10.1016/s0304-3940(02)00448-2.
Lockhart EM, Warner DS, Pearlstein RD, Penning DH, Mehrabani S, Boustany R-M. Allopregnanolone attenuates N-methyl-D-aspartate-induced excitotoxicity and apoptosis in the human NT2 cell line in culture. Neurosci Lett. 2002 Aug 2;328(1):33–6.
Lockhart, Ellen M., et al. “Allopregnanolone attenuates N-methyl-D-aspartate-induced excitotoxicity and apoptosis in the human NT2 cell line in culture.Neurosci Lett, vol. 328, no. 1, Aug. 2002, pp. 33–36. Pubmed, doi:10.1016/s0304-3940(02)00448-2.
Lockhart EM, Warner DS, Pearlstein RD, Penning DH, Mehrabani S, Boustany R-M. Allopregnanolone attenuates N-methyl-D-aspartate-induced excitotoxicity and apoptosis in the human NT2 cell line in culture. Neurosci Lett. 2002 Aug 2;328(1):33–36.
Journal cover image

Published In

Neurosci Lett

DOI

ISSN

0304-3940

Publication Date

August 2, 2002

Volume

328

Issue

1

Start / End Page

33 / 36

Location

Ireland

Related Subject Headings

  • Tumor Cells, Cultured
  • Progesterone
  • Pregnanolone
  • Pregnancy
  • Neurotoxins
  • Neuroprotective Agents
  • Neurons
  • N-Methylaspartate
  • Mitochondria
  • Membrane Potentials