P2Y12 receptor protein in cortical gray matter lesions in multiple sclerosis

Susanna Amadio, Cinzia Montilli, Roberta Magliozzi, Giorgio Bernardi, Richard Reynolds, Cinzia Volonté

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Although Multiple Sclerosis (MS) is regarded as a white matter disease, the incidence of demyelination and axonal injury is prominent also in gray matter. In MS, extracellular adenosine triphosphate (ATP) is an important mediator of central nervous system pathology via its ability to cause oligodendrocyte excitotoxicity. We have analyzed the distribution pattern of all ionotropic P2X and metabotropic P2Y receptors for ATP in postmortem samples of the cerebral cortex from healthy human subjects as well as MS patients. We focus particularly on the P2Y12 subtype that is highly enriched in oligodendrocytes. We correlate the expression of this receptor to the extent of gray matter demyelination and pathological alterations occurring during secondary progressive MS. Using triple immunofluorescence and confocal analysis, we show that in sections of cerebral cortex from postmortem MS brains, the P2Y 12 protein is present in myelin and interlaminar astrocytes but absent from protoplasmic astrocytes residing in the deeper cortical layers, from microglia/macrophages, and from intact demyelinated axons. We report that a decreased P2Y12 receptor immunoreactivity in proximity to the lesions is directly correlated with the extent of demyelination found in all types of gray matter cortical plaques (I-III) and subcortical white matter. Our study provides further insights into the pathogenetic features of MS and suggests that the loss of purinergic P2Y12 receptors might be detrimental to tissue integrity.

Original languageEnglish
Pages (from-to)1263-1273
Number of pages11
JournalCerebral Cortex
Volume20
Issue number6
DOIs
Publication statusPublished - 2010

Fingerprint

Multiple Sclerosis
Demyelinating Diseases
Oligodendroglia
Proteins
Astrocytes
Cerebral Cortex
Purinergic P2Y12 Receptors
Adenosine Triphosphate
Chronic Progressive Multiple Sclerosis
Leukoencephalopathies
Microglia
Myelin Sheath
Fluorescent Antibody Technique
Axons
Healthy Volunteers
Central Nervous System
Macrophages
Gray Matter
Pathology
Incidence

Keywords

  • Astrocyte
  • Demyelination
  • Extracellular ATP
  • Oligodendrocyte
  • Purinergic receptor

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

P2Y12 receptor protein in cortical gray matter lesions in multiple sclerosis. / Amadio, Susanna; Montilli, Cinzia; Magliozzi, Roberta; Bernardi, Giorgio; Reynolds, Richard; Volonté, Cinzia.

In: Cerebral Cortex, Vol. 20, No. 6, 2010, p. 1263-1273.

Research output: Contribution to journalArticle

Amadio, Susanna ; Montilli, Cinzia ; Magliozzi, Roberta ; Bernardi, Giorgio ; Reynolds, Richard ; Volonté, Cinzia. / P2Y12 receptor protein in cortical gray matter lesions in multiple sclerosis. In: Cerebral Cortex. 2010 ; Vol. 20, No. 6. pp. 1263-1273.
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