Methylcobalamin attenuates the hypoxia/hypoglycemia- or glutamate-induced reduction in hippocampal fiber spikes in vitro

Yasuharu Yamamoto, Shigenobu Shibata, Chiaki Hara, Shigenori Watanabe

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The effects of methylcobalamin, a vitamin B12 analogue, on the hypoxia/hypoglycemia- or glutamate-induced reduction in hippocampal CA1 presynaptic fiber spikes elicited by Schaffer collateral stimulation in rat brain slices were evaluated. Hippocampal slices were exposed to 15 min of hypoxia/hypoglycemia, and then these slices were returned to oxygenated and glucose-containing buffer for 3 h. Hypoxia/hypoglycemia reduced CA1 presynaptic potentials in vitro. Treatment with 10 μM methylcobalamin attenuated the impairment of CA1 presynaptic potentials induced by hypoxia/hypoglycemia or glutamate application (10 mM). Daily injection of methylcobalamin (0.5 mg/kg i.p./day) for 3 days in vivo also attenuated the hypoxia/hypoglycemia- or glutamate-induced reduction in presynaptic potentials in hippocampal slices. Pretreatment with cyanocobalamin at 10 μM failed to attenuate the impairment of CA1 presynaptic potentials. However, daily injection of cyanocobalamin (0.5 mg/kg i.p./day) for 3 days caused a protective action against the hypoxia/hypoglycemia- or glutamate-induced functional deficit. Furthermore, co-treatment of l-arginine (100 μM), a substrate for nitric oxide synthase, with methylcobalamin in vitro reversed the methylcobalamin-induced functional recovery. The present results demonstrate that methylcobalamin application in vivo or in vitro leads to functional recovery from hypoxia/hypoglycemia- or glutamate-induced impairment of CA1 presynaptic potentials. Neuroprotection was obtained by in vivo application of cyanocobalamin, but not by its in vitro application. It is reported that in vivo injected cyanocobalamin converted to methylcobalamin in the hepatic cells. Therefore, the results suggest that a transmethylation reaction in the hippocampal regions may be involved in the methylcobalamin-induced functional recovery from ischemic impairment.

Original languageEnglish
Pages (from-to)335-340
Number of pages6
JournalEuropean Journal of Pharmacology
Volume281
Issue number3
DOIs
Publication statusPublished - 1995 Aug 15

Keywords

  • Glutamate
  • Hippocampus
  • Hypoxia/hypoglycemia
  • Ischemia
  • Neuroprotection
  • Vitamin B

ASJC Scopus subject areas

  • Pharmacology

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