Affiliation:
1. Department of Agricultural Sciences University of Naples “Federico II” Portici Italy
2. CEINGE Biotecnologie Avanzate “Franco Salvatore” Naples Italy
3. Unit of Neurology, IRCCS Neuromed Pozzilli Italy
4. Faculty of Psychology, Uninettuno Telematic International University Rome Italy
5. Section of Neurology, Department of Medicine and Surgery University of Perugia Perugia Italy
6. Department of Environmental, Biological and Pharmaceutical Sciences and Technologies University of Campania "Luigi Vanvitelli" Caserta Italy
7. Clinical Neuroimmunology Unit Institute of Experimental Neurology Division of Neuroscience, San Raffaele Scientific Institute Milan Italy
8. Department of Systems Medicine University of Rome Tor Vergata Rome Italy
Abstract
AbstractThe 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.image
Funder
Fondazione Italiana Sclerosi Multipla
Ministero della Salute
Ministero dell’Istruzione, dell’Università e della Ricerca
Subject
Cellular and Molecular Neuroscience,Biochemistry