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[Effects of neuroactive steroid allopregnanolone on the damage of cortical neurons]

Xian-Hui Li1, Xin-Chang Zhang, Gang Wang

  • 1Department of Molecular Biology, Medical College of Chinese People's Armed Police Force, Tianjing 300162, China. lixianhuiwj@163.com

Zhongguo Ying Yong Sheng Li Xue Za Zhi = Zhongguo Yingyong Shenglixue Zazhi = Chinese Journal of Applied Physiology
|August 18, 2011
PubMed
Abstract

Insights

Neurosteroid allopregnanolone protects mouse neurons from N-methyl-D-aspartate (NMDA) toxicity. It increases beta-aminobutyric acid receptor beta2 subunit (beta2-GABA-R) expression and Akt phosphorylation, reducing neuronal apoptosis.

Area of Science:

  • Neuroscience
  • Neuropharmacology
  • Cell Biology

Background:

  • N-methyl-D-aspartate (NMDA) receptor overactivation can lead to excitotoxicity and neuronal cell death.
  • Neuroactive steroids, such as allopregnanolone, have demonstrated neuroprotective properties.
  • Understanding the mechanisms underlying neuroprotection is crucial for developing therapeutic strategies.

Purpose of the Study:

  • To elucidate the protective mechanism of allopregnanolone against NMDA-induced toxicity in primary mouse cortical neurons.
  • To investigate the role of beta-aminobutyric acid receptor beta2 subunit (beta2-GABA-R) and Akt signaling pathway in allopregnanolone's neuroprotective effects.

Main Methods:

  • Primary mouse cortical neurons were treated with allopregnanolone and/or NMDA.
  • Quantitative analysis of beta2-GABA-R mRNA expression using RT-PCR.
  • Assessment of Akt phosphorylation via Western blot.
  • Evaluation of apoptosis markers (cleaved-PARP, cleaved-caspase-3, cleaved-caspase-9) using Western blot and DNA fragmentation analysis.

Main Results:

  • Allopregnanolone treatment significantly increased beta2-GABA-R mRNA expression and Akt phosphorylation in cortical neurons.
  • Pretreatment with allopregnanolone attenuated NMDA-induced apoptosis, evidenced by reduced levels of cleaved-PARP, cleaved-caspase-3, and cleaved-caspase-9.
  • The neuroprotective effect was observed at a final allopregnanolone concentration of 5 x 10(-6) mol/L.

Conclusions:

  • Allopregnanolone exhibits neuroprotective effects against NMDA-induced excitotoxicity in primary mouse cortical neurons.
  • The mechanism involves the upregulation of beta2-GABA-R expression and enhanced Akt phosphorylation.
  • These findings suggest allopregnanolone as a potential therapeutic agent for conditions involving NMDA receptor-mediated neurodegeneration.

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