N-methyl,N-propargyl-2-phenylethylamine (MPPE), an analog of deprenyl, increases neuronal cell survival in thiamin deficiency encephalopathy

Wernicke encephalopathy (WE) is a neurological disorder attributable to thi amin deficiency (TD). Severe TD, in humans and animals, results in highly s elective lesions with a symmetrical distribution in brain regions including the mammillary bodies, thalamus, inferior colliculi, periaqueductal and pe riventricular regions, and inferior olivary nuclei. Experimental TD in the rat provides a robust and reproducible model that allows investigations of mechanisms underlying both apoptotic and necrotic neuronal death. (-)-Depre nyl (DEP), a selective monoamine oxidase B (MAO-B) inhibitor, has been repo rted to be clinically effective in the treatment of neurodegenerative disor ders and to have neuroprotective and/or neurorescue properties in a variety of ex vivo and in vitro paradigms, including experimental TD. Because the metabolites of DEP, amphetamine, and methamphetamine may have adverse behav ioral effects, a DEP analog, N-methyl,N-propargyl-2-phenylethylamine (MPPE) that is not metabolized to amphetamine or methamphetamine was examined in the present studies. Results showed that TD rats treated with MPPE had sign ificantly increased neuronal cell counts compared to vehicle-treated TD rat s. MPPE, like DEP, also significantly decreased the density of reactive ast rocytes and the infiltration of microglia/macrophages. Chronic treatment wi th DEP or MPPE resulted in significant inhibition of MAO-A acid MAO-B activ ity compared to VEH-treated animals. Thus, MPPE, an inhibitor of MAO activi ty, was shown to be neuroprotective in the TD model of neuronal cell death. (C) 2001 Wiley-Liss. Inc.