Platelet glutamate uptake and Th1 cells inversely correlate in relapsing/remitting and in progressive multiple sclerosis.
Benign multiple sclerosis
Excitotoxicity, glutamate EAAT
Inflammation
Platelets & lympho-monocytes
Journal
Multiple sclerosis and related disorders
ISSN: 2211-0356
Titre abrégé: Mult Scler Relat Disord
Pays: Netherlands
ID NLM: 101580247
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
07
06
2019
revised:
06
02
2020
accepted:
10
02
2020
pubmed:
25
2
2020
medline:
23
3
2021
entrez:
25
2
2020
Statut:
ppublish
Résumé
High affinity sodium-dependent Excitatory Amino Acid Transporters (EAAT), present in glial and neuron cells, clear around 90% of the synaptic cleft released glutamate, and their impaired activity seem to be critical for many neurodegenerative disorders, including Multiple Sclerosis (MS). These transporters are also present in human platelets, and they show molecular and biochemical characteristics similar to those in the CNS. The aim of this study was to investigate whether EAAT-dependent uptake is present also at the peripheral level in blood of MS patients. Moreover, since platelets (plt) and peripheral blood mononuclear cells (PBMC) share the same intra-corporeal fluid, they might be reciprocally influenced, and the glutamate uptake modulation might be useful as a peripheral "trait-marker" to characterize different clinical courses of MS RESULTS: : Reduced uptake values were found in MS patients compared to healthy controls (HC), as well as significant differences were found across MS clinical courses. Representative saturation curves showed that Vmax was significantly decreased for patients compared to HC. Conversely, dissociation constant of the two reactions appeared similar for MS and HC subjects. Furthermore, clinical forms of MS with mild (benign) prognosis was not affected as fa as concern EAAT uptake. Gender, age, and drug treatments did not impact glutamate uptake efficiency. Interestingly, a negative correlation between EAAT activity and percentage of Th1 cells (CD4+IFNγ+ and CD4+TBET+IFNγ+ cells) was observed, suggesting a relationship between EAAT impairment and a pro-inflammatory environment. Interestingly, as shown in the CNS, a relationship between clinical, inflammatory MS features and glutamate clearance can be also assessed in platelets. Moreover, glutamate uptake activity might be an useful biomarker to characterize patients with benign prognosis.
Sections du résumé
BACKGROUND
BACKGROUND
High affinity sodium-dependent Excitatory Amino Acid Transporters (EAAT), present in glial and neuron cells, clear around 90% of the synaptic cleft released glutamate, and their impaired activity seem to be critical for many neurodegenerative disorders, including Multiple Sclerosis (MS). These transporters are also present in human platelets, and they show molecular and biochemical characteristics similar to those in the CNS.
OBJECTIVES
OBJECTIVE
The aim of this study was to investigate whether EAAT-dependent uptake is present also at the peripheral level in blood of MS patients. Moreover, since platelets (plt) and peripheral blood mononuclear cells (PBMC) share the same intra-corporeal fluid, they might be reciprocally influenced, and the glutamate uptake modulation might be useful as a peripheral "trait-marker" to characterize different clinical courses of MS RESULTS: : Reduced uptake values were found in MS patients compared to healthy controls (HC), as well as significant differences were found across MS clinical courses. Representative saturation curves showed that Vmax was significantly decreased for patients compared to HC. Conversely, dissociation constant of the two reactions appeared similar for MS and HC subjects. Furthermore, clinical forms of MS with mild (benign) prognosis was not affected as fa as concern EAAT uptake. Gender, age, and drug treatments did not impact glutamate uptake efficiency. Interestingly, a negative correlation between EAAT activity and percentage of Th1 cells (CD4+IFNγ+ and CD4+TBET+IFNγ+ cells) was observed, suggesting a relationship between EAAT impairment and a pro-inflammatory environment.
CONCLUSIONS
CONCLUSIONS
Interestingly, as shown in the CNS, a relationship between clinical, inflammatory MS features and glutamate clearance can be also assessed in platelets. Moreover, glutamate uptake activity might be an useful biomarker to characterize patients with benign prognosis.
Identifiants
pubmed: 32092504
pii: S2211-0348(20)30083-3
doi: 10.1016/j.msard.2020.102007
pii:
doi:
Substances chimiques
Glutamate Plasma Membrane Transport Proteins
0
Glutamic Acid
3KX376GY7L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102007Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest All the authors have no potential conflicts of interest relevant to this manuscript and they approve the manuscript. The research has been approved by the local ethics committee, in accordance with Helsinki Declaration.