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

    Fingerprint

    Hypoglycemia
    Glutamic Acid
    Vitamin B 12
    Injections
    In Vitro Techniques
    mecobalamin
    Hypoxia
    Nitric Oxide Synthase
    Arginine
    Hepatocytes
    Hippocampus
    Buffers
    Glucose
    Brain
    Therapeutics

    Keywords

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

    ASJC Scopus subject areas

    • Pharmacology
    • Cellular and Molecular Neuroscience

    Cite this

    Methylcobalamin attenuates the hypoxia/hypoglycemia- or glutamate-induced reduction in hippocampal fiber spikes in vitro. / Yamamoto, Yasuharu; Shibata, Shigenobu; Hara, Chiaki; Watanabe, Shigenori.

    In: European Journal of Pharmacology, Vol. 281, No. 3, 15.08.1995, p. 335-340.

    Research output: Contribution to journalArticle

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