Tetrahydrocannabinol-induced apoptosis of cultured cortical neurones is associated with cytochrome c release and caspase-3 activation

Veronica A. Campbell

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)

Abstract

Δ9-Tetrahydrocannabinol (THC), the principal psychoactive component of marijuana, is associated with impaired cognition and altered cortical function. THC transduces its central effects via activation of the G-protein linked cannabinoid receptor CB1. In this study we report that THC induces morphological degenerative changes in cultured cortical neurones, such as membrane blebbing and formation of apoptotic bodies, that are consistent with the apoptotic pathway of cell death. The THC-induced apoptosis was blocked by the CB1 receptor antagonist AM251 and pertussis toxin (PTX), suggesting that this effect of THC involves receptor-mediated activation of the G-protein subtypes Gi or Go. THC also promoted translocation of mitochondrial cytochrome c to the cytosol and increased the activity of the cysteine protease caspase-3, in a PTX-sensitive manner. The results from this study suggest that coupling of THC to a PTX-sensitive G-protein promotes cytochrome c release, caspase-3 activation and subsequent degeneration of cultured cortical neurones. This apoptotic pathway may underlie the compromised neuronal function that is associated with marijuana usage.

Original languageEnglish
Pages (from-to)702-709
Number of pages8
JournalNeuropharmacology
Volume40
Issue number5
DOIs
Publication statusPublished - 2001
Externally publishedYes

Keywords

  • Apoptosis
  • Caspase-3
  • Cortical neurones
  • Cytochrome c
  • Pertussis toxin
  • Tetrahydrocannabinol

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