Occurrence of neuronal inclusions combined with increased nigral expression of α-synuclein within dopaminergic neurons following treatment with amphetamine derivatives in mice

Francesco Fornai, Paola Lenzi, Michela Ferrucci, Gloria Lazzeri, Adolfo Bandettini Di Poggio, Gianfranco Natale, Carla L. Busceti, Francesca Biagioni, Mario Giusiani, Stefano Ruggieri, Antonio Paparelli

Research output: Contribution to journalArticlepeer-review

Abstract

In recent years several clinical and research findings have demonstrated the involvement of the presynaptic protein α-synuclein in a variety of neurodegenerative disorders which are known as synucleinopathies. Although the function of this protein in the physiology of the cell remains unknown, it is evident that both genetic alterations or a mere overexpression of the native molecule produces a degeneration of nigral dopamine-containing neurons leading to movement disorders, as demonstrated in inherited Parkinson's disease. In the present study, we investigated whether widely abused drugs such as methamphetamine and methylenedioxymethamphetamine (ecstasy), which are known to damage the nigrostriatal dopamine pathway of mice, increase the expression of α-synuclein within dopamine neurons of the substantia nigra pars compacta. The results of this study demonstrate that nigrostriatal dopamine denervation and occurrence of intracellular inclusions in nigral neurons produced by amphetamine derivatives are related to increased expression of α-synuclein within dopamine neurons of the substantia nigra. This lends substance to the hypothesis that increased amounts of native α-synuclein may be per se a detrimental factor for the dopamine neurons.

Original languageEnglish
Pages (from-to)405-413
Number of pages9
JournalBrain Research Bulletin
Volume65
Issue number5
DOIs
Publication statusPublished - May 15 2005

Keywords

  • Ecstasy
  • Methamphetamine
  • Methylenedioxymethamphetamine
  • Parkinson's disease
  • Substantia nigra

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Occurrence of neuronal inclusions combined with increased nigral expression of α-synuclein within dopaminergic neurons following treatment with amphetamine derivatives in mice'. Together they form a unique fingerprint.

Cite this