Local infusion of interleukin-6 attenuates the neurotoxic effects of NMDA on rat striatal cholinergic neurons.
The potential neuroprotective effects of IL-6 against the excitotoxic neuronal loss induced by N-methyl-D-aspartate (NMDA) have been studied. Infusion into the rat striatum of excitotoxic amounts (250 nmol) of NMDA resulted in a 45% decrease in striatal choline acetyl transferase activity (ChAT; a marker of cholinergic neurons) and glutamate decarboxylase (GAD, a marker of GABAergic neurons) at 2 days post-injection. Co-infusion of 10 U of IL-6 reduced the loss of ChAT activity to 21% but failed to prevent the loss of GAD activity. IL-6 per se, up to the dose of 500 U, failed to affect ChAT or GAD activities. The in vivo effects of IL-6 are not mediated by a direct antagonism of NMDA toxicity, since IL-6 (up to a concentration of 500 and 5000 U/ml, respectively) did not antagonize either the increase in cyclic GMP levels resulting from NMDA receptor activation in cerebellar slices or the glutamate-induced release of lactate dehydrogenase, an index of neurotoxicity, by cultured cortical neurons. These results suggest that the increase in IL-6 levels observed in experimental brain lesions may play a role in the protection and regeneration of cholinergic neurons.
Toulmond
S
S
Synthelabo Recherche-LERS, Biology Department, Bagneux, France.
Vige
X
X
Fage
D
D
Benavides
J
J
D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000473:pathology*; D000242:Cyclic AMP / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000633:toxicity; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D009474:Neurons / Q000187:drug effects*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013238:Stereotaxic Techniques
D015850:Interleukin-6; D016202:N-Methylaspartate; D000242:Cyclic AMP; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase