Increased neuronal cell survival after L-deprenyl treatment in experimental thiamine deficiency.
Experimental thiamine deficiency results in a reproducible pattern of selective neuronal cell death. Events such as blood-brain barrier breakdown, N-methyl-D-aspartic acid (NMDA) receptor-mediated excitotoxicity, and increased reactive oxygen species have been implicated in thiamine deficiency-induced neural loss. L-deprenyl protects dopaminergic, noradrenergic, and acetylcholinergic neurons from neurotoxic, mechanical, and excitotoxic damage. In the present study, the effects of l-deprenyl on neuronal cell survival were examined in rats made thiamine deficient by daily administration of the central thiamine antagonist pyrithiamine (0.5 mg/kg s.c.). Rats assigned to thiamine deficient or control groups received daily injections of l-deprenyl (0.25, 0.5, or 1.0 mg/kg/day i.p.) or vehicle until they reached a state of severe thiamine deficiency (loss of righting reflex). At this stage, thiamine status was restored by daily injections of thiamine (10 mg/kg s.c.) for 3 days, after which the animals were killed, and their brains were processed for neuronal cell counts (cresyl violet staining), astrocytic proliferation [glial fibrillary acidic protein (GFAP) immunohistochemistry], and monoamine oxidase B (MAO-B) activity. All rats receiving l-deprenyl (all doses) had significantly decreased neuronal cell loss in thalamic nuclei, in the inferior colliculus, and in the inferior olive and had a concomitant decrease in reactive astrocytic proliferation compared with the thiamine-deficient, vehicle-treated rats. The neuroprotective effects of l-deprenyl in thiamine deficiency induced brain damage most likely result from its properties other than its effects as an MAO-B inhibitor.
Todd
K G
KG
Neuroscience Research Unit, Andre-Viallet Clinical Research Centre, Hôpital St-Luc (University of Montreal), Quebec, Canada.
Butterworth
R F
RF
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002452:Cell Count / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D011745:Pyrithiamine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000627:therapeutic use*; D013832:Thiamine Deficiency / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*
D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D011745:Pyrithiamine