Neuroscience 2002 Abstract
| Presentation Number: | 892.5 |
|---|---|
| Abstract Title: | TETRAHYDROCANNABINOL INDUCES APOPTOSIS IN CORTICAL NEURONES. |
| Authors: |
Downer, E. J.*1
; Campbell, V. A.1
1Physiology Dept., Trinity College, Dublin, Ireland |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Neurotoxicity -- Apoptosis |
| Session: |
892. Neurotoxicity: apoptosis--disease mechanisms and oxidative mechanisms Poster |
| Presentation Time: | Thursday, November 7, 2002 8:00 AM-9:00 AM |
| Location: | Hall A2-B3 Y-2 |
| Keywords: |
E. Downer and V. Campbell. * Dept. of Physiology, Trinity College Dublin, Ireland.
Δ9-Tetrahydrocannabinol (THC), the principle psychoactive component of marijuana, elicits diverse psychological effects in humans. At a cellular level THC has been shown to have both neurotoxic1 and neuroprotective effects2. The aim of this study was to examine the role of the stress activated protein kinase (SAPK) c-jun N-terminal kinase (JNK) in THC-induced neurotoxicity in cortical neurones.
Treatment of cultured cortical neurones with THC (5µM) for 2h resulted in a 49% increase in genomic DNA strand breaks as assessed by TUNEL staining (p<0.01, paired t-test, n=10). Use of a fluorogenic assay has revealed that caspase-3 activity is increased from 13±6 pmol AFC produced/mg/min (mean±SEM) to 24±8 pmol AFC produced/mg/min following treatment of neurones with THC for 2h. Western Blot analysis showed that cell death was preceded by JNK activation (p<0.05, ANOVA, n=6). The specific role of JNK in this system was assessed by downregulating JNK protein expression using antisense oligonucleotides complementary to the mRNA encoding JNK1/2. Treatment of neurones with JNK antisense (4µM) for 6hr reduced both JNK1 and JNK2 expression. Following JNK downregulation, the stimulatory effect of THC on caspase-activity and DNA fragmentation was significantly reduced (p<0.01, paired t-test, n=6).
These results support the hypothesis that THC neurotoxicity involves the activation of JNK. This study suggests that this biochemical pathway may contribute to the behavioural pathology associated with marijuana abuse.
1: Downer, E. et al., (2001) Neuroreport 12(18), 3973-78
2: Hampson, A.J. et al., (2000) Ann NY Acad Sci 899, 274-282.
Δ9-Tetrahydrocannabinol (THC), the principle psychoactive component of marijuana, elicits diverse psychological effects in humans. At a cellular level THC has been shown to have both neurotoxic1 and neuroprotective effects2. The aim of this study was to examine the role of the stress activated protein kinase (SAPK) c-jun N-terminal kinase (JNK) in THC-induced neurotoxicity in cortical neurones.
Treatment of cultured cortical neurones with THC (5µM) for 2h resulted in a 49% increase in genomic DNA strand breaks as assessed by TUNEL staining (p<0.01, paired t-test, n=10). Use of a fluorogenic assay has revealed that caspase-3 activity is increased from 13±6 pmol AFC produced/mg/min (mean±SEM) to 24±8 pmol AFC produced/mg/min following treatment of neurones with THC for 2h. Western Blot analysis showed that cell death was preceded by JNK activation (p<0.05, ANOVA, n=6). The specific role of JNK in this system was assessed by downregulating JNK protein expression using antisense oligonucleotides complementary to the mRNA encoding JNK1/2. Treatment of neurones with JNK antisense (4µM) for 6hr reduced both JNK1 and JNK2 expression. Following JNK downregulation, the stimulatory effect of THC on caspase-activity and DNA fragmentation was significantly reduced (p<0.01, paired t-test, n=6).
These results support the hypothesis that THC neurotoxicity involves the activation of JNK. This study suggests that this biochemical pathway may contribute to the behavioural pathology associated with marijuana abuse.
1: Downer, E. et al., (2001) Neuroreport 12(18), 3973-78
2: Hampson, A.J. et al., (2000) Ann NY Acad Sci 899, 274-282.
Supported by Health Research Board Ireland
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2002 Neuroscience Meeting Planner. Orlando, FL: Society for Neuroscience, 2002. Online.
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