The "Dark Side" of Endocannabinoids: A Neurotoxic Role for Anandamide

Ibolja Cernak, Robert Vink, JoAnne E Natale, Bogdan Stoica, Paul M. Lea IV, Vilen Movsesyan, Farid Ahmed, Susan M. Knoblach, Stanley T. Fricke, Alan I. Faden

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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 CBI 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.

Original languageEnglish (US)
Pages (from-to)564-578
Number of pages15
JournalJournal of Cerebral Blood Flow and Metabolism
Volume24
Issue number5
StatePublished - May 2004
Externally publishedYes

Fingerprint

Endocannabinoids
Cannabinoid Receptor CB1
Cell Death
Diffusion Magnetic Resonance Imaging
Calpain
Brain Edema
Neuroprotective Agents
Caspases
Cognition
Up-Regulation
Cell Line
Wounds and Injuries
Brain
Genes
anandamide
In Vitro Techniques

Keywords

  • Anandamide
  • Cell death
  • Cognitive deficit
  • Endocannabinoids
  • Magnetic resonance imaging
  • Microarray

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

Cernak, I., Vink, R., Natale, J. E., Stoica, B., Lea IV, P. M., Movsesyan, V., ... Faden, A. I. (2004). The "Dark Side" of Endocannabinoids: A Neurotoxic Role for Anandamide. Journal of Cerebral Blood Flow and Metabolism, 24(5), 564-578.

The "Dark Side" of Endocannabinoids : A Neurotoxic Role for Anandamide. / Cernak, Ibolja; Vink, Robert; Natale, JoAnne E; Stoica, Bogdan; Lea IV, Paul M.; Movsesyan, Vilen; Ahmed, Farid; Knoblach, Susan M.; Fricke, Stanley T.; Faden, Alan I.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 24, No. 5, 05.2004, p. 564-578.

Research output: Contribution to journalArticle

Cernak, I, Vink, R, Natale, JE, Stoica, B, Lea IV, PM, Movsesyan, V, Ahmed, F, Knoblach, SM, Fricke, ST & Faden, AI 2004, 'The "Dark Side" of Endocannabinoids: A Neurotoxic Role for Anandamide', Journal of Cerebral Blood Flow and Metabolism, vol. 24, no. 5, pp. 564-578.
Cernak I, Vink R, Natale JE, Stoica B, Lea IV PM, Movsesyan V et al. The "Dark Side" of Endocannabinoids: A Neurotoxic Role for Anandamide. Journal of Cerebral Blood Flow and Metabolism. 2004 May;24(5):564-578.
Cernak, Ibolja ; Vink, Robert ; Natale, JoAnne E ; Stoica, Bogdan ; Lea IV, Paul M. ; Movsesyan, Vilen ; Ahmed, Farid ; Knoblach, Susan M. ; Fricke, Stanley T. ; Faden, Alan I. / The "Dark Side" of Endocannabinoids : A Neurotoxic Role for Anandamide. In: Journal of Cerebral Blood Flow and Metabolism. 2004 ; Vol. 24, No. 5. pp. 564-578.
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