Cannabis receptor influences nerve damage

C
Rossi S, Bozzali M, Bari M, Mori F, Studer V, Motta C, Buttari F, Cercignani M, Gravina P, Mastrangelo N, Castelli M, Mancino R, Nucci C, Sottile F, Bernardini S, Maccarrone M, Centonze D Association between a Genetic Variant of Type-1 Cannabinoid Receptor and Inflammatory Neurodegeneration in Multiple Sclerosis.PLoS One. 2013 ;8(12):e82848. 

Genetic ablation of type-1 cannabinoid receptors (CB1Rs) exacerbates the neurodegenerative damage of experimental autoimmune encephalomyelitis, the rodent model of multiple sclerosis (MS). To address the role on CB1Rs in the pathophysiology of human MS, we first investigated the impact of AAT trinucleotide short tandem repeat polymorphism of CNR1 gene on CB1R cell expression, and secondly on the inflammatory neurodegeneration process responsible for irreversible disability in MS patients. We found that MS patients with long AAT repeats within the CNR1 gene (≥12 in both alleles) had more pronounced neuronal degeneration in response to inflammatory white matter damage both in the optic nerve and in the cortex. Optical Coherence Tomography (OCT), in fact, showed more severe alterations of the retinal nerve fibre layer (RNFL) thickness and of the macular volume (MV) after an episode of optic neuritis in MS patients carrying the long AAT genotype of CNR1. MS patients with long AAT repeats also had magnetic resonance imaging (MRI) evidence of increased gray matter damage in response to inflammatory lesions of the white matter, especially in areas with a major role in cognition. In parallel, visual abilities evaluated at the low contrast acuity test, and cognitive performances were negatively influenced by the long AAT CNR1 genotype in our sample of MS patients. Our results demonstrate the biological relevance of the (AAT)n CNR1 repeats in the inflammatory neurodegenerative damage of MS.
This study suggests that genetic variant of the cannabinoid receptor have be associated with more nerve damage and follows on from a previous study. How does is gene variant have this effect. we have shown, in mice, if you do not have this receptor you loose nerves. suggesting if you stimulate the receptor you can save nerves…same the CUPID study could not support this view.

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MouseDoctor

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  • It needs to be shown that the genetic variant of CB1 correlates to a reduction in function/expression but these results suggest it may. More evidence that cannabinoid therapy should have a neuroprotective effect in MS and as MD says such a shame the CUPID study was unable to show this due to methodological flaws.

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