Neuroprotective actions of pyridoxine

Krishnamurti Dakshinamurti, S. K. Sharma, Jonathan D. Geiger

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Electroencephalographic recordings in cerebral cortex of mice given a single sub-convulsive dose of domoic acid exhibited typical spike and wave discharges. Administration of the anti-epileptic drugs sodium valproate, nimodipine, or 5α-pregnan 3α-ol-20-one as well as pyridoxine simultaneously with or after domoic acid treatment resulted in significantly less spike and wave activity. Administration of these same drugs 45 min prior to the administration of domoic acid also significantly reduced EEG background. Mechanistically, sodium valproate and pyridoxine significantly attenuated domoic acid-induced increase in levels of glutamate, increase in levels of calcium influx, decrease in levels of γ-aminobutyric acid and increase in levels of the protooncogenes c-fos, jun-B and jun-D. In hippocampal cells, domoic acid-induced increases in glutamate and calcium influx were significantly decreased by pyridoxal phosphate or nimodipine. Similarly in neuroblastoma-glioma hybrid cells (NG 108/15), pyridoxine attenuated domoic acid-induced increases in glutamate, influx of extracellular calcium, and enhanced induction of oncoproteins regardless of whether cells were undifferentiated, differentiated or de-differentiated. Pyridoxine has anti-seizure and neuroprotective actions mediated through mechanisms similar to those targeted by current therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)225-229
Number of pages5
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1647
Issue number1-2
DOIs
Publication statusPublished - Apr 11 2003

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Keywords

  • Calcium influx
  • Domoic acid
  • Neuroprotection
  • Neurotoxicity
  • Oncoprotein
  • Pyridoxine

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology

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