Attenuation of 1-methyl-4-phenylpyridinium (MPP+) neurotoxicity by deprenyl in organotypic canine substantia nigra cultures

Journal of Neural Transmission
D E SchmidtW O Whetsell

Abstract

Systemic administration of MPTP to experimental animals induces neurodegeneration of dopaminergic neurons in the central nervous system. MPTP crosses the blood-brain barrier where it is taken up by astrocytes and converted to MPP+ by monamine oxidase-B (MAO-B). Subsequently, MPP+ is selectively taken up by dopaminergic neurons upon which it exerts intracellular neurotoxic effects. Systemic administration of the selective MAO-B inhibitor deprenyl prevents the conversion of MPTP to MPP+ and by this mechanism is able to protect against MPTP neurotoxicity. Deprenyl has also been reported to exert neuroprotective effects that are independent of its MAO-B inhibitory properties, but since MPP+ itself does not cross the blood-brain barrier it is difficult to directly study the MAO-B independent in vivo effects of MPP+ itself. One approach is to use organotypic tissue cultures of the canine substantia nigra (CSN) which permit administration of precise concentrations of pharmacological agents directly to mature, well-developed and metabolically active dopaminergic neurons. These neurons as well as other components of the cultures exhibit morphological and biochemical characteristics identical to their in vivo counterparts. This study was...Continue Reading

References

Feb 1, 1992·Journal of Neuroscience Research·P T Salo, W G Tatton
Jan 1, 1991·Acta Neurologica Scandinavica. Supplementum·V V MyllyläE H Heinonen
Jan 1, 1983·Modern Problems of Pharmacopsychiatry·W BirkmayerM B Youdim
Jan 1, 1981·Journal of Neural Transmission·W O WhetsellM D Yahr
Nov 15, 1994·European Journal of Pharmacology·E KoutsilieriW D Rausch
Aug 1, 1994·Journal of the Neurological Sciences·Y IwasakiM Kinoshita
Jun 13, 1996·European Journal of Pharmacology·E KoutsilieriP Riederer

❮ Previous
Next ❯

Related Concepts

Related Feeds

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.