Neuroscience 2004 Abstract
| Presentation Number: | 341.6 |
|---|---|
| Abstract Title: | Cannabinoids are neuroprotective in mouse models of ALS. |
| Authors: |
Abood, M. E.*1
; Raman, C.1
; Kim, K.1
; Rizvi, G.1
; McAllister, S.1
; Moore, D. H.2
1Forbes Norris ALS Res Ctr, California Pacific Med Ctr, San Francisco, CA 2Geraldine Brush Cancer Res Inst., California Pacific Med Ctr, San Francisco, CA |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Neurodegenerative Disorders -- ALS |
| Secondary Theme and Topics | Neurological and Psychiatric Conditions<br />- Addiction and Drugs of Abuse<br />-- Cannabinoids |
| Session: |
341. ALS IV Poster |
| Presentation Time: | Sunday, October 24, 2004 2:00 PM-3:00 PM |
| Location: | San Diego Convention Center - Hall A-H, Board # UU18 |
| Keywords: | MOTONEURON, EXCITOTOXICITY, OXIDATIVE STRESS |
Effective treatment for amyotrophic lateral sclerosis (ALS) remains elusive. Two of the primary hypotheses underlying motor neuron vulnerability are susceptibility to excitotoxicity and oxidative damage. We have found that delta-9-tetrahydrocannabinol (THC) inhibits both excitotoxic and oxidative damage in spinal cord cultures and slows progression and improves survival in the ALS mouse model (hSODG93A transgenic mice) even when administered after onset of disease signs. Mice were treated daily beginning on day 75 (when tremors were first observed) with 20 mg/kg THC or with 40 mg/kg cannabidiol i.p. or with vehicle. Treatment with THC resulted in a 7 day extension of survival. There was a trend toward increased survival in female mice treated with cannabidiol, but this did not reach statistical significance. Male mice showed no improvement with cannabidiol. Female mice lived significantly longer than male mice. We present an improved method for the analysis of disease progression in the ALS mouse model. The use of a non-linear mixed effects model for data analysis increased statistical power to detect a large range of effects and to test separately for delayed disease onset and rate of disease progression. THC attenuates direct excitotoxicity produced by kainate as effectively as NBQX, an AMPA/Kainate receptor antagonist. However, the rank order of efficacy differs from other systems in that THC and anandamide are most efficacious whereas CP55,940 is ineffective against direct application of kainate. These data suggest alternate mechanisms of action for cannabinoid compounds. THC was also extremely effective at reducing oxidative damage produced by TBH in mixed spinal cord cultures; however this was not CB1 receptor mediated. As THC is well tolerated, it and other cannabinoids may prove to be novel therapeutic targets for the treatment of ALS.
Supported by NS041639
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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