title: Occurrence of neuronal inclusions combined with increased nigral expression of alpha-synuclein within dopaminergic neurons following treatment with amphetamine derivatives in mice.
abstract: In recent years several clinical and research findings have demonstrated the involvement of the presynaptic protein alpha-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 alpha-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 alpha-synuclein within dopamine neurons of the substantia nigra. This lends substance to the hypothesis that increased amounts of native alpha-synuclein may be per se a detrimental factor for the dopamine neurons.
authors.affiliation: Department of Human Morphology and Applied Biology, University of Pisa, Via Roma 55, 56126 Pisa, Italy. f.fornai@med.unipi.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Fornai
authors.forename: Paola
authors.initials: P
authors.lastname: Lenzi
authors.forename: Michela
authors.initials: M
authors.lastname: Ferrucci
authors.forename: Gloria
authors.initials: G
authors.lastname: Lazzeri
authors.forename: Adolfo Bandettini
authors.initials: AB
authors.lastname: di Poggio
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Natale
authors.forename: Carla L
authors.initials: CL
authors.lastname: Busceti
authors.forename: Francesca
authors.initials: F
authors.lastname: Biagioni
authors.forename: Mario
authors.initials: M
authors.lastname: Giusiani
authors.forename: Stefano
authors.initials: S
authors.lastname: Ruggieri
authors.forename: Antonio
authors.initials: A
authors.lastname: Paparelli
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000473:Alkanes / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D002479:Inclusion Bodies / Q000187:drug effects* / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission / Q000379:methods; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D013378:Substantia Nigra / Q000166:cytology* / Q000187:drug effects; D051843:Synucleins; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051844:alpha-Synuclein
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000473:Alkanes; D000577:Amides; D018765:Dopamine Uptake Inhibitors; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; C497605:Snca protein, mouse; D051843:Synucleins; D051844:alpha-Synuclein; C477079:methyl neodecanamide; D015102:3,4-Dihydroxyphenylacetic Acid; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine; D006719:Homovanillic Acid