Alterations of glutamate release in the spinal cord of mice with experimental autoimmune encephalomyelitis.
We have investigated the spontaneous and the depolarisation-induced release of [(3)H]D-aspartate ([(3)H]D-ASP), a non-metabolisable analogue of glutamate, in spinal cord slices, synaptosomes and gliosomes from mice with experimental autoimmune encephalomyelitis (EAE) at 13, 21 and 55 days post-immunisation (d.p.i.), representing onset, peak and chronic phases of the pathology. At 13 and 21 d.p.i., the KCl-evoked, calcium-dependent overflow of [(3)H]D-ASP in spinal cord slices was significantly lower (30-40%), whereas at 55 d.p.i. it was significantly higher (30%), than that elicited in matched controls. When the release was measured from spinal cord synaptosomes and gliosomes in superfusion, a different picture emerged. The spontaneous and the KCl(15 mM)-induced release of [(3)H]D-ASP were significantly increased both in synaptosomes (17% and 45%, respectively) and gliosomes (26% and 25%, respectively) at 21, but not at 13, d.p.i. At 55 d.p.i., the KCl-induced [(3)H]D-ASP release was significantly increased (40%) only in synaptosomes. Finally, uptake of [(3)H]D-ASP was markedly (50-60%) increased in spinal cord synaptosomes, but not in gliosomes, obtained from EAE mice at 21 d.p.i., whereas no differences could be detected at 13 d.p.i. Our data indicate that glutamatergic neurotransmission is altered in the spinal cord of EAE mice.
Marte
Antonella
A
Department of Experimental Medicine, University of Genoa, Genoa, Italy.
Cavallero
Anna
A
Morando
Sara
S
Uccelli
Antonio
A
Raiteri
Maurizio
M
Fedele
Ernesto
E
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006023:Glycoproteins / Q000276:immunology; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein; D009457:Neuroglia / Q000187:drug effects / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D010446:Peptide Fragments / Q000276:immunology; D011189:Potassium Chloride / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D014316:Tritium; D001224:Aspartic Acid; D018698:Glutamic Acid; D011189:Potassium Chloride