The “Dark Side” of Endocannabinoids: A Neurotoxic Role for Anandamide

Journal of Cerebral Blood Flow and Metabolism - Tập 24 Số 5 - Trang 564-578 - 2004
Ibolja Černak1, Robert Vink2,3, JoAnne E. Natale2,4, Bogdan A. Stoica2,4, Midhun Paul2,4, Vilen Movsesyan2,4, Farid Ahmed2,4, Susan M. Knoblach2,4, Stanley T. Fricke2,4, Alan I. Faden2,4
1Department of Neuroscience, Georgetown University Medical Center, Washington DC 20057, USA
2Department of Neuroscience, Georgetown University Medical Center, Washington D.C., U.S.A.
3Department of Pathology, University of Adelaide, Australia
4Georgetown University

Tóm tắt

Endocannabinoids, including 2-arachidonoylglycerol and anandamide ( N-arachidonoylethanolamine; AEA), have neuroprotective effects in the brain through actions at CB1 receptors. However, AEA also binds to vanilloid (VR1) receptors and induces cell death in several cell lines. Here we show that anandamide causes neuronal cell death in vitro and exacerbates cell loss caused by stretch-induced axonal injury or trophic withdrawal in rat primary neuronal cultures. Administered intracerebroventricularly, AEA causes sustained cerebral edema, as reflected by diffusion-weighted magnetic resonance imaging, regional cell loss, and impairment in long-term cognitive function. These effects are mediated, in part, through VR1 as well as through calpain-dependent mechanisms, but not through CB1 receptors or caspases. Central administration of AEA also significantly upregulates genes involved in proinflammatory/microglial-related responses. Thus, anandamide produces neurotoxic effects both in vitro and in vivo through multiple mechanisms independent of the CB1 receptor.

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Thông tin xuất bản

Journal of Cerebral Blood Flow and Metabolism

Tập 24 Số 5

564-578

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