Neuroscience 2003 Abstract
| Presentation Number: | 355.9 |
|---|---|
| Abstract Title: | Protective effect of cannabinoids on N-methyl-<smcap>D</smcap>-aspartate-induced excitotoxic cell death in the AF5 centrial nervous system (CNS) cell line. |
| Authors: |
Chen, J.*1
; Lee, C. T.1
; Errico, S.1
; Deng, X.1
; Cadet, J. L.1
; Freed, W. J.1
1Cell. NeuroBiol. Res. Br., NIDA, Natl. Inst. of Hlth., DHHS, Baltimore, MD |
| Primary Theme and Topics |
Development - Trophic Factors and Developmental Cell Death -- Trophic factors and cell death |
| Session: |
355. Trophic Factors & Cell Death II Poster |
| Presentation Time: | Monday, November 10, 2003 8:00 AM-9:00 AM |
| Location: | Morial Convention Center - Hall F-I, Board # B81 |
| Keywords: | CELL CULTURE, EXCITATORY AMINO ACID, CELL DEATH, NEUROPROTECTION |
Excitotoxicity associated with the N-methyl-D-aspartate (NMDA) receptor is thought to be involved in several neurodegenerative disorders. The cannabinoids exert many of their actions in brain through the CB1 cannabinoid receptor. We have examined the effect of cannabinoids on NMDA-induced excitotoxicity in the rat AF5 CNS cell line (Truckenmiller et al., Exp. Neurol., 2002). AF5 cells were briefly exposed to NMDA (5 mM -10 mM) and returned to culture medium for 22 hr. NMDA produced a dose-dependent decrease in viability as determined by mitochondrial tetrazolium formazan (MTT). Immunocytochemistry demonstrated that AF5 cells express NMDA receptor 1, and expression was increased following exposure to NMDA. Single-stranded DNA and caspase-3 staining indicated that NMDA induced apoptotic cell death. Western blotting showed that AF5 cells express the CB1 receptor. The synthetic cannabinoid agonist WIN55212-2 and delta-9 tetrahydrocannabinol (THC) were examined for protection against NMDA-induced excitoxicity. AF5 cells were incubated with 5 um WIN 55212 or 3 um THC for 6 hr prior to NMDA. At 3 uM THC had no cytotoxic effect and enhanced cell survival: AF5 cells were completely protected from 7.5 mM NMDA and 50% protection was observed from 10 mM NMDA treatment. Single–stranded DNA staining confirmed that 3 uM THC inhibited NMDA–induced apoptosis. In contrast, WIN 55212-2 did not protect against NMDA-induced excitoxicity. Both THC and WIN 55212-2 are agonists for both the CB1 and the peripheral CB2 receptor. Therefore, THC may exert neuroprotective effects through mechanisms that do not involve the known cannabinoid receptors. These data suggest that the AF5 cell line may be a useful model for investigating the molecular effects of cannabinoids and mechanisms of apoptosis in the CNS.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
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