P2Y12 receptor protein in cortical gray matter lesions in multiple sclerosis.
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 P2Y(12) 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 P2Y(12) 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 P2Y(12) receptors might be detrimental t…
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This signaling is disrupted by the degeneration of the interlaminar processes in multiple sclerosis patients.
“This signaling is disrupted by the degeneration of the interlaminar processes in MS patients (Amadio et al., 2010).”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Amadio et al., 2010
Astrocytes play key roles in both the destructive and regenerative phases of multiple sclerosis, mostly thanks to purinergic signaling.
“Astrocytes play key roles in both the destructive and regenerative phases of MS, mostly thanks to the purinergic signaling.”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Amadio et al., 2010
The purinergic receptor P2Y12 is localized to myelin and ILAs but not protoplasmic astrocytes, suggesting a role in long-distance signaling within the different cortical layers.
“Amadio et al. (2010) localized the purinergic receptor P2Y12 to myelin and ILAs but not protoplasmic astrocytes, suggesting a role in long-distance signaling within the different cortical layers.”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Amadio et al. (2010)
Multiple sclerosis starts as an autoimmune inflammatory reaction against myelin, leading to oligodendrocyte and neuronal axon degeneration in both white and gray matter.
“Multiple sclerosis (MS) starts as an autoimmune inflammatory reaction against myelin, leading to oligodendrocyte and neuronal axon degeneration in both white and gray matter (Amadio et al., 2010).”
From Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain (2024) · cites this paper as Amadio et al., 2010
Cites
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Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism
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“…as a white matter disease, the incidence of demyelination and oligodendrocyte or neuron/ axon injury is prominent and widespread in gray matter (Peterson et al. 2001; Vercellino et al. 2005; Wegner et al. 2006; Magliozzi et al. 2007; Pirko et al. 2007; Gilmore et al. 2009; reviewed in Boët al.”
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Microglia and Neuroinflammation: What Place for P2RY12?
Gómez Morillas, A., Besson, V. C., & Lerouet, D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041636 · Cited by 214 · see citing works
P2Y12 expression and function in alternatively activated human microglia
Moore, C. S., Ase, A. R., Kinsara, A., Rao, V. T. S., Michell-Robinson, M., Leong, S. Y., Butovsky, O., Ludwin, S. K., Séguéla, P., Bar-Or, A., et al. (2015) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000000080 · Cited by 212 · see citing works
Walker, D. G., Tang, T. M., Mendsaikhan, A., Tooyama, I., Serrano, G. E., Sue, L. I., Beach, T. G., & Lue, L.-F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21020678 · Cited by 128 · see citing works
Purinergic Receptors in Neurological Diseases With Motor Symptoms: Targets for Therapy
Oliveira-Giacomelli, Á., Naaldijk, Y., Sardá-Arroyo, L., Gonçalves, M. C. B., Corrêa-Velloso, J., Pillat, M. M., de Souza, H. D. N., & Ulrich, H. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00325 · Cited by 50 · see citing works
Interlaminar and varicose-projection astrocytes: toward a new understanding of the primate brain
Ciani, C., & Falcone, C. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1477753 · Cited by 11 · see citing works
- Authors
- Amadio, S., Montilli, C., Magliozzi, R., Bernardi, G., Reynolds, R., & Volonte, C.
- Affiliations
- Fondazione Santa Lucia (IT)
- Hammersmith Hospital (GB)
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-09-26
- Volume
- 20
- Issue
- 6
- Pages
- 1263-1273
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2134722155
- Cited by
- 73
- References
- 3
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 3 · 2018: 10 · 2017: 2 · 2016: 7 · 2015: 5 · 2014: 5 · 2013: 5 · 2012: 7
- FWCI
- 2.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- P2Y12 receptor, multiple sclerosis, oligodendrocytes, extracellular ATP, purinergic signaling, secondary progressive multiple sclerosis, astrocytes, myelin
- MeSH terms
- Adult, Aged, Aged, 80 and over, Astrocytes, Cerebral Cortex, Female, Humans, Male, Middle Aged, Multiple Sclerosis, Myelin Sheath, Biomarkers, Receptors, Purinergic P2, Receptors, Purinergic P2Y12
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