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

• Published in: Brain research bulletin 2005-05, Vol.65 (5), p.405-413
• Main Authors: Fornai, Francesco, Lenzi, Paola, Ferrucci, Michela, Lazzeri, Gloria, Poggio, Adolfo Bandettini di, Natale, Gianfranco, Busceti, Carla L., Biagioni, Francesca, Giusiani, Mario, Ruggieri, Stefano, Paparelli, Antonio
• Format: Article
• Language: English
• Subjects: 3,4-Dihydroxyphenylacetic Acid - metabolism; Adrenergic Uptake Inhibitors - pharmacology; Alkanes - pharmacology; alpha-Synuclein; Amides - pharmacology; Amphetamine - pharmacology; Analysis of Variance; Animals; Blotting, Western - methods; Dopamine - metabolism; Dopamine Uptake Inhibitors - pharmacology; Ecstasy; Gene Expression Regulation - drug effects; Glutamate Decarboxylase - metabolism; Homovanillic Acid - metabolism; Immunohistochemistry - methods; Inclusion Bodies - drug effects; Inclusion Bodies - metabolism; Isoenzymes - metabolism; Methamphetamine; Methylenedioxymethamphetamine; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission - methods; N-Methyl-3,4-methylenedioxyamphetamine - pharmacology; Nerve Tissue Proteins - metabolism; Neurons - drug effects; Neurons - metabolism; Neurons - ultrastructure; Parkinson's disease; Substantia nigra; Substantia Nigra - cytology; Substantia Nigra - drug effects; Synucleins; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2005.02.022

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.