Resistance to striatal dopamine depletion induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice expressing human mutant Cu,Zn superoxide dismutase

Neurosci Lett. 2002 Jun 7;325(2):124-8. doi: 10.1016/s0304-3940(02)00252-5.

Abstract

Recent data indicate that overexpression of the enzyme Cu,Zn superoxide dismutase (SOD1) in mice confers neuroprotection against various dopamine neurotoxins like 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), methamphetamine, 6-hydroxydopamine and methylenedioxymethamphetamine. In the present study we investigated whether a mutant form of SOD1 (G93A), occurring in humans affected by amyotrophic lateral sclerosis, leads to a differential vulnerability of nigrostriatal dopaminergic neurons to the chronic dopamine depletion induced by the selective neurotoxin MPTP. Our results indicate that overexpression of both wild-type and human mutant SOD1 induces comparable neuroprotective effects against striatal dopaminergic depletion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology*
  • Animals
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism*
  • Dopamine / deficiency*
  • Dopamine Agents / pharmacology*
  • Humans
  • Mice
  • Mice, Transgenic
  • Mutation* / physiology*
  • Neuroprotective Agents / metabolism*
  • Neurotoxins / pharmacology*
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / metabolism*
  • Superoxide Dismutase-1

Substances

  • Dopamine Agents
  • Neuroprotective Agents
  • Neurotoxins
  • SOD1 protein, human
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Dopamine