Memantine abrogates neurological deficits, but not CNS inflammation, in Lewis rat experimental autoimmune encephalomyelitis.
Memantine, a clinically employed drug with N-methyl-D-aspartate (NMDA) receptor antagonistic effects, dose-dependently ameliorates neurological deficits in Lewis rat experimental autoimmune encephalomyelitis (EAE). Interestingly, this therapeutic effect was not due to dampened CNS inflammation, as assessed by immunohistochemical evaluation of spinal cord tissue. Furthermore, numbers of interferon gamma (IFN gamma) mRNA expressing cells were not decreased, as assessed by in situ hybridization. Systemic immunity in terms of numbers of IFN gamma secreting cells in response to immunodominant myelin basic protein (MBP) peptides ex vivo was not reduced, and non-toxic doses of memantine did not affect lymphocyte proliferation or IFN gamma secretion in vitro. Considering these findings, we hypothesize that effector mechanisms responsible for reversible neurological deficits in EAE may involve NMDA receptors, and this highlights neurons as targets during autoimmune neuroinflammation.
Wallström
E
E
Department of Medicine, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
Diener
P
P
Ljungdahl
A
A
Khademi
M
M
Nilsson
C G
CG
Olsson
T
T
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D004676:Myelin Basic Protein / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology
D018691:Excitatory Amino Acid Antagonists; D004676:Myelin Basic Protein; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D007371:Interferon-gamma; D008559:Memantine