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

14 Citations (Scopus)

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

Fingerprint

Cannabinoid Receptors
sclerosis
Multiple Sclerosis
Optics
Genes
Optical tomography
Magnetic resonance
Ablation
Polymorphism
Microsatellite Repeats
Imaging techniques
Fibers
optics
cognition
Genotype
Optic Neuritis
Aptitude
Autoimmune Experimental Encephalomyelitis
cannabinoid receptors
genotype

ASJC Scopus subject areas

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

Cite this

Association between a genetic variant of type-1 cannabinoid receptor and inflammatory neurodegeneration in multiple sclerosis. / Rossi, Silvia; Bozzali, Marco; Bari, Monica; Mori, Francesco; Studer, Valeria; Motta, Caterina; Buttari, Fabio; Cercignani, Mara; Gravina, Paolo; Mastrangelo, Nicolina; Castelli, Maura; Mancino, Raffaele; Nucci, Carlo; Sottile, Fabrizio; Bernardini, Sergio; Maccarrone, Mauro; Centonze, Diego.

In: PLoS One, Vol. 8, No. 12, e82848, 31.12.2013.

Research output: Contribution to journalArticle

Rossi, Silvia ; Bozzali, Marco ; Bari, Monica ; Mori, Francesco ; Studer, Valeria ; Motta, Caterina ; Buttari, Fabio ; Cercignani, Mara ; Gravina, Paolo ; Mastrangelo, Nicolina ; Castelli, Maura ; Mancino, Raffaele ; Nucci, Carlo ; Sottile, Fabrizio ; Bernardini, Sergio ; Maccarrone, Mauro ; Centonze, Diego. / Association between a genetic variant of type-1 cannabinoid receptor and inflammatory neurodegeneration in multiple sclerosis. In: PLoS One. 2013 ; Vol. 8, No. 12.
@article{2ed7b2183372466583fdce59d229a5a9,
title = "Association between a genetic variant of type-1 cannabinoid receptor and inflammatory neurodegeneration in multiple sclerosis",
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.",
author = "Silvia Rossi and Marco Bozzali and Monica Bari and Francesco Mori and Valeria Studer and Caterina Motta and Fabio Buttari and Mara Cercignani and Paolo Gravina and Nicolina Mastrangelo and Maura Castelli and Raffaele Mancino and Carlo Nucci and Fabrizio Sottile and Sergio Bernardini and Mauro Maccarrone and Diego Centonze",
year = "2013",
month = "12",
day = "31",
doi = "10.1371/journal.pone.0082848",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - Association between a genetic variant of type-1 cannabinoid receptor and inflammatory neurodegeneration in multiple sclerosis

AU - Rossi, Silvia

AU - Bozzali, Marco

AU - Bari, Monica

AU - Mori, Francesco

AU - Studer, Valeria

AU - Motta, Caterina

AU - Buttari, Fabio

AU - Cercignani, Mara

AU - Gravina, Paolo

AU - Mastrangelo, Nicolina

AU - Castelli, Maura

AU - Mancino, Raffaele

AU - Nucci, Carlo

AU - Sottile, Fabrizio

AU - Bernardini, Sergio

AU - Maccarrone, Mauro

AU - Centonze, Diego

PY - 2013/12/31

Y1 - 2013/12/31

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84894281274&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84894281274&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0082848

DO - 10.1371/journal.pone.0082848

M3 - Article

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e82848

ER -