Association between a genetic variant of type-1 cannabinoid receptor and inflammatory neurodegeneration in multiple sclerosis

Silvia Rossi, Marco Bozzali, Monica Bari, Francesco Mori, Valeria Studer, Caterina Motta, Fabio Buttari, Mara Cercignani, Paolo Gravina, Nicolina Mastrangelo, Maura Castelli, Raffaele Mancino, Carlo Nucci, Fabrizio Sottile, Sergio Bernardini, Mauro Maccarrone, Diego Centonze

Research output: Contribution to journalArticle

Abstract

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 fiber 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.

Original languageEnglish
Article numbere82848
JournalPLoS One
Volume8
Issue number12
DOIs
Publication statusPublished - Dec 31 2013

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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. (2013). Association between a genetic variant of type-1 cannabinoid receptor and inflammatory neurodegeneration in multiple sclerosis. PLoS One, 8(12), [e82848]. https://doi.org/10.1371/journal.pone.0082848