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D-Deprenyl Protects Nigrostriatal Neurons Against 1-Methyl-4-Phenyl-1,2,3,6- Tetrahydropyridine-Induced Dopaminergic Neurotoxicity

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Title D-Deprenyl Protects Nigrostriatal Neurons Against 1-Methyl-4-Phenyl-1,2,3,6- Tetrahydropyridine-Induced Dopaminergic
Neurotoxicity
 
Creator Muralikrishnan, Dhanasekharan
Samanta Roy, Supriti
Mohanakumar, K P
 
Subject Infectious Diseases and Immunology
 
Description Selegiline (L-deprenyl) is believed to render protection against l-methyl-
4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-neurotoxicity to a significant extent via a
free radical scavenging mechanism, which is independent of its ability to inhibit monoamine
oxidase-B (MAO-B) in the brain. We investigated the hydroxyl radical (.OH)
scavenging action and neuroprotective effect of D-deprenyl, its less active isomer, in
MPTP-induced dopaminergic neurotoxicity in mice to test whether the chemical structure
of the molecule or its biological effects contribute to this property. To achieve this
goal we studied the effects of D-deprenyl on: (1) .OH production in a Fenton reaction; (2)
MPTP-induced .OH generation and dopamine (DA) depletion in vivo, employing a
sensitive HPLC-electrochemical procedure; and (3) formation of MPP� in vivo in the
striatum following systemic administration of MPTP, employing an HPLC-photodiode
array detection system. D-deprenyl inhibited ferrous citrate-induced .OH in vitro (0.45
�M) and MPTP-induced .OH in vivo in substantia nigra (SN) and in the striatum (1.0
mg/kg, i.p.). D-deprenyl did not, but L-deprenyl (0.5 mg/kg dose) did significantly inhibit
formation of MPP� in the striatum 90 min following systemic MPTP injection. It failed
to affect MAO-B activity at 0.5 mg/kg in the striatum, but effectively blocked MPTPinduced
striatal DA depletion. The potency of D-deprenyl to scavenge MPTP-induced
.OH in vivo and to render protection against the dopaminergic neurotoxicity without
affecting dopamine turnover, MAO-B activity, or formation of MPP� in the brain
indicates a direct involvement of .OH in the neurotoxic action of MPTP and antioxidant
effect in the neuroprotective action of deprenyl.
 
Date 2003
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1187/1/27_SYN_2003.pdf
Muralikrishnan, Dhanasekharan and Samanta Roy, Supriti and Mohanakumar, K P (2003) D-Deprenyl Protects Nigrostriatal Neurons Against 1-Methyl-4-Phenyl-1,2,3,6- Tetrahydropyridine-Induced Dopaminergic Neurotoxicity. Synapse, 50 (1). pp. 7-13.
 
Relation http://dx.doi.org/10.1002/syn.10239
http://www.eprints.iicb.res.in/1187/