Functional impairment of nigrostriatal neurons progresses following withdrawal of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

A. Albanese, B. Gregori, D. Carretta, P. Tonali

Research output: Contribution to journalArticlepeer-review

Abstract

C57 BL/6 mice were rendered severely parkinsonian by exposure to high doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The fluorescent retrograde tracer Fast Blue was injected into the neostriatum one (group A) or five weeks (group B) following exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neurons located in the substantia nigra pars compacta and in the centre median parafascicular complex were analysed. There was no variation in the number and distribution of Fast Blue-labelled perikarya located in the centre median-parafascicular complex, which are insensitive to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. No variation was seen in the number of Nissl-stained perikarya located in the substantia nigra pars compacta, indicating that neurons had not degenerated. The number and the density of Fast Blue retrogradely-labelled neurons located in the same region were decreased in group A by 41% and in group B by 55%. Fast Blue labelling provided a measure of functional impairment in viable neurons. The Fast Blue-to-Nissl cell ratio was 55% in controls and declined to 20% in group A and to 17% in group B mice. The present study shows that (i) functional inactivation of viable neurons can be measured by using a fluorescent retrograde tracer following exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and (ii) inactivation of retrograde axonal transport progresses from one to five weeks following withdrawal of the toxin. Fluorescent retrograde probes may be used to measure the anatomical substrate of recovery induced by drugs or by brain grafts in parkinsonian animals.

Original languageEnglish
Pages (from-to)1185-1191
Number of pages7
JournalNeuroscience
Volume75
Issue number4
DOIs
Publication statusPublished - Nov 1 1996

Keywords

  • 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • axonal transport
  • mouse
  • retrograde fluorescent tracers
  • substantia nigra
  • thalamus

ASJC Scopus subject areas

  • Neuroscience(all)

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