Occurrence of neuronal inclusions combined with increased nigral expression of alpha-synuclein within dopaminergic neurons following treatment with amphetamine derivatives in mice.
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.
Fornai
Francesco
F
Department of Human Morphology and Applied Biology, University of Pisa, Via Roma 55, 56126 Pisa, Italy. f.fornai@med.unipi.it
Lenzi
Paola
P
Ferrucci
Michela
M
Lazzeri
Gloria
G
di Poggio
Adolfo Bandettini
AB
Natale
Gianfranco
G
Busceti
Carla L
CL
Biagioni
Francesca
F
Giusiani
Mario
M
Ruggieri
Stefano
S
Paparelli
Antonio
A
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
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