Cerebrospinal fluid, brain, and spinal cord levels of L-aspartate signal excitatory neurotransmission abnormalities in multiple sclerosis patients and experimental autoimmune encephalomyelitis mouse model.
Mice
Animals
Encephalomyelitis, Autoimmune, Experimental
/ metabolism
Multiple Sclerosis
/ metabolism
Aspartic Acid
/ cerebrospinal fluid
D-Aspartic Acid
/ metabolism
Spinal Cord
/ metabolism
Brain
/ metabolism
Synaptic Transmission
Excitatory Amino Acids
/ metabolism
Glutamic Acid
/ metabolism
Cytokines
/ metabolism
NMDA receptors
aspartate
cerebrospinal fluid
inflammation
multiple sclerosis
Journal
Journal of neurochemistry
ISSN: 1471-4159
Titre abrégé: J Neurochem
Pays: England
ID NLM: 2985190R
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
revised:
17
04
2023
received:
21
02
2023
accepted:
28
05
2023
medline:
24
7
2023
pubmed:
19
6
2023
entrez:
19
6
2023
Statut:
ppublish
Résumé
The neuroinflammatory process characterizing multiple sclerosis (MS) is associated with changes in excitatory synaptic transmission and altered central concentrations of the primary excitatory amino acid, L-glutamate (L-Glu). Recent findings report that cerebrospinal fluid (CSF) levels of L-Glu positively correlate with pro-inflammatory cytokines in MS patients. However, to date, there is no evidence about the relationship between the other primary excitatory amino acid, L-aspartate (L-Asp), its derivative D-enantiomer, D-aspartate, and the levels of pro-inflammatory and anti-inflammatory cytokines in the CSF of MS. In the present study, we measured by HPLC the levels of these amino acids in the cortex, hippocampus, cerebellum, and spinal cord of mice affected by experimental autoimmune encephalomyelitis (EAE). Interestingly, in support of glutamatergic neurotransmission abnormalities in neuroinflammatory conditions, we showed reduced L-Asp levels in the cortex and spinal cord of EAE mice and increased D-aspartate/total aspartate ratio within the cerebellum and spinal cord of these animals. Additionally, we found significantly decreased CSF levels of L-Asp in both relapsing-remitting (n = 157) MS (RR-MS) and secondary progressive/primary progressive (n = 22) (SP/PP-MS) patients, compared to control subjects with other neurological diseases (n = 40). Importantly, in RR-MS patients, L-Asp levels were correlated with the CSF concentrations of the inflammatory biomarkers G-CSF, IL-1ra, MIP-1β, and Eotaxin, indicating that the central content of this excitatory amino acid, as previously reported for L-Glu, reflects a neuroinflammatory environment in MS. In keeping with this, we revealed that CSF L-Asp levels were positively correlated with those of L-Glu, highlighting the convergent variation of these two excitatory amino acids under inflammatory synaptopathy occurring in MS.
Substances chimiques
Aspartic Acid
30KYC7MIAI
D-Aspartic Acid
4SR0Q8YD1X
Excitatory Amino Acids
0
Glutamic Acid
3KX376GY7L
Cytokines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
534-546Informations de copyright
© 2023 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.
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