Neuroscience 2004 Abstract
| Presentation Number: | 690.14 |
|---|---|
| Abstract Title: | The apoptotic actions of tetrahydrocannabinol in the rat cortex vary with post-natal development. |
| Authors: |
Downer, E. J.*1
; Campbell, V. A.1
1Dept. of Physiology, Trinity Col. Inst. of Neurosci., Trinity Col., Dublin, Ireland |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Addiction and Drugs of Abuse -- Cannabinoids |
| Session: |
690. Drugs of Abuse: Cannabinoids Poster |
| Presentation Time: | Tuesday, October 26, 2004 9:00 AM-10:00 AM |
| Location: | San Diego Convention Center - Hall A-H, Board # EEE10 |
| Keywords: | cannabinoids, neurotoxicity |
Δ9-Tetrahydrocannabinol (THC), the psychoactive ingredient of cannabis, induces apoptosis in cultured cortical neurons prepared from neonatal rats1. However there is no evidence to suggest that THC is toxic to adult neurons2. This study was aimed at determining if post-natal development of the rat cortex influenced the ability of THC to activate components of the THC-induced apoptotic cascade in the rat cortex in vivo.
Neonatal (4 day-old) and adult (3 month-old) male Wistar rats were anaesthetized by intraperitoneal injection of urethane (1.5g/kg). The THC group received subcutaneous injections of 10mg/kg THC in vehicle and the control group received injections of vehicle only (5% absolute alcohol, 5% Cremophor EL and 90% saline). Three hours later rats were killed humanely, half the cortex dissected and cortical slices prepared, and the other half brain frozen and prepared for cryostat sections. JNK activity was assessed by immunocytochemistry. Caspase-3 activity was measured using a fluorogenic assay and neuronal DNA fragmentation monitored using TUNEL.
THC increased caspase-3 activity from 396.94±53.37 to 717.52±77.25 pmol/AFC produced/mg/min (Mean±SEM, p<0.05, ANOVA, n=9) in neonatal, but not adult, rats. Immunocytochemical analysis of cryostats sections revealed a marked increased in positive staining for TUNEL (n=4), JNK (n=4) and caspase-3 (n=4) immunoreactive cells in the cortex of neonatal rats treated with THC as compared to controls. THC treatment had no effect on the level of DNA fragmentation, caspase-3 and JNK activity in the adult cortex.
These results suggest that the neonatal cortex may be more susceptible to the apoptotic effects of THC, and suggest that THC signaling may be differentially regulated during post-natal development.
1: Downer, E.J. et al., (2003) Br. J. Pharm. 140, 547-57
2: Galve-Roperh, I. et al., (2000) Nat. Med. 6(3), 313-319.
Neonatal (4 day-old) and adult (3 month-old) male Wistar rats were anaesthetized by intraperitoneal injection of urethane (1.5g/kg). The THC group received subcutaneous injections of 10mg/kg THC in vehicle and the control group received injections of vehicle only (5% absolute alcohol, 5% Cremophor EL and 90% saline). Three hours later rats were killed humanely, half the cortex dissected and cortical slices prepared, and the other half brain frozen and prepared for cryostat sections. JNK activity was assessed by immunocytochemistry. Caspase-3 activity was measured using a fluorogenic assay and neuronal DNA fragmentation monitored using TUNEL.
THC increased caspase-3 activity from 396.94±53.37 to 717.52±77.25 pmol/AFC produced/mg/min (Mean±SEM, p<0.05, ANOVA, n=9) in neonatal, but not adult, rats. Immunocytochemical analysis of cryostats sections revealed a marked increased in positive staining for TUNEL (n=4), JNK (n=4) and caspase-3 (n=4) immunoreactive cells in the cortex of neonatal rats treated with THC as compared to controls. THC treatment had no effect on the level of DNA fragmentation, caspase-3 and JNK activity in the adult cortex.
These results suggest that the neonatal cortex may be more susceptible to the apoptotic effects of THC, and suggest that THC signaling may be differentially regulated during post-natal development.
1: Downer, E.J. et al., (2003) Br. J. Pharm. 140, 547-57
2: Galve-Roperh, I. et al., (2000) Nat. Med. 6(3), 313-319.
Supported by Health Research Board Ireland and Enterprise Ireland
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2004 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2004. Online.
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