Neuronal sparing and behavioral effects of the antiapoptotic drug, (-)deprenyl, following kainic acid administration.
(-)Deprenyl is an irreversible inhibitor of monoamine oxidase B (MAO-B) frequently used as an adjunct therapy in the treatment of Parkinson's Disease. Recent evidence, however, has found that deprenyl's metabolites are associated with an antiapoptotic action within certain neuronal populations. Interestingly, deprenyl's antiapoptotic actions appear not to depend upon the inhibition of MAO-B. Due to a paucity of information surrounding (-)deprenyl's ability to spare neurons in vivo, a series of studies was conducted to further investigate this phenomenon within an apoptotic neuronal death model: kainic acid induced excitotoxicity. Results indicated that (-)deprenyl increased hippocampal neuronal survival compared to saline-matched controls following kainic acid insult. Furthermore, it was discovered that (-)deprenyl treatment could be stopped 14 days following CNS insult by kainate, with evidence of neuronal sparing still present by day 28. In open-field locomotor activity testing of kainate-treated animals, those given subsequent (-)deprenyl treatment showed habituation curves similar to control subjects, while saline-treated animals did not. Given deprenyl's antiapoptotic actions, it is proposed that (-)deprenyl may be beneficial in the treatment of a variety of neurodegenerative diseases where evidence of apoptosis exists, such as Parkinson's and Alzheimer's Disease, by slowing the disease process itself.
Gelowitz
D L
DL
Department of Psychiatry, University of Cincinnati, OH 45267-0559, USA.
Paterson
I A
IA
D000818:Animals; D017209:Apoptosis; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage* / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007608:Kainic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000494:pharmacology*