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Huperzine A, a potential therapeutic agent for dementia, reduces neuronal cell death caused by glutamate

Ved, Haresh S.1,3; Koenig, Michael L.2; Dave, Jitendra R.2; Doctor, Bhupendra P.1

Neuropharmacology and Neurotoxicology

HUPERZINE A, a potential therapeutic agent for Alzheimer's disease, inhibits acetylcholinesterase in primary cultures derived from forebrain, hippocampus, cortex and cerebellum of embryonic rat brain. Glutamate induces cell death in cultures from all these brain regions. Maximum cell toxicity was observed in cerebellar cultures. Pretreatment of cell cultures with Huperzine A reduced cell toxicity, as evidenced by cytotoxicity assay and general morphology. Huperzine A pretreatment also reduced glutamate-induced calcium mobilization, but did not affect elevations in intraneuronal free Ca2+ ([Ca]i) caused by KCl or (–)Bay K 8644. The data suggest that Huperzine A could be a potent neuroprotective agent not only where cholinergic neurons are impaired, but also under conditions in which glutamatergic functions are compromised.

1Division of Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA

2Division of Neurosciences, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.

3Corresponding Author: Haresh S. Ved

ACKNOWLEDGEMENTS: The authors wish to thank Bob Burge for the statistical analysis of the data, and Mary Kay Gentry and Dr Raymond Genovese for critical review of this manuscript.

Received 4 December 1996; accepted 10 Decembe 1996

© Lippincott-Raven Publishers.