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Occurrence of neuronal inclusions combined with increased nigral expression of alpha-synuclein within dopaminergic neurons following treatment with amphetamine derivatives in mice.
Brain Res Bull. 2005 May 15; 65(5):405-13.BR

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.

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Authors+Show Affiliations

Fornai F
Department of Human Morphology and Applied Biology, University of Pisa, Via Roma 55, 56126 Pisa, Italy. f.fornai@med.unipi.it
Lenzi P
No affiliation info available
Ferrucci M
No affiliation info available
Lazzeri G
No affiliation info available
di Poggio AB
No affiliation info available
Natale G
No affiliation info available
Busceti CL
No affiliation info available
Biagioni F
No affiliation info available
Giusiani M
No affiliation info available
Ruggieri S
No affiliation info available
Paparelli A
No affiliation info available

MeSH

3,4-Dihydroxyphenylacetic AcidAdrenergic Uptake InhibitorsAlkanesAmidesAmphetamineAnalysis of VarianceAnimalsBlotting, WesternDopamineDopamine Uptake InhibitorsGene Expression RegulationGlutamate DecarboxylaseHomovanillic AcidImmunohistochemistryInclusion BodiesIsoenzymesMiceMice, Inbred C57BLMicroscopy, Electron, TransmissionN-Methyl-3,4-methylenedioxyamphetamineNerve Tissue ProteinsNeuronsSubstantia NigraSynucleinsTyrosine 3-Monooxygenasealpha-Synuclein

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

15833595

Citation

Fornai, Francesco, et al. "Occurrence of Neuronal Inclusions Combined With Increased Nigral Expression of Alpha-synuclein Within Dopaminergic Neurons Following Treatment With Amphetamine Derivatives in Mice." Brain Research Bulletin, vol. 65, no. 5, 2005, pp. 405-13.
Fornai F, Lenzi P, Ferrucci M, et al. Occurrence of neuronal inclusions combined with increased nigral expression of alpha-synuclein within dopaminergic neurons following treatment with amphetamine derivatives in mice. Brain Res Bull. 2005;65(5):405-13.
Fornai, F., Lenzi, P., Ferrucci, M., Lazzeri, G., di Poggio, A. B., Natale, G., Busceti, C. L., Biagioni, F., Giusiani, M., Ruggieri, S., & Paparelli, A. (2005). Occurrence of neuronal inclusions combined with increased nigral expression of alpha-synuclein within dopaminergic neurons following treatment with amphetamine derivatives in mice. Brain Research Bulletin, 65(5), 405-13.
Fornai F, et al. Occurrence of Neuronal Inclusions Combined With Increased Nigral Expression of Alpha-synuclein Within Dopaminergic Neurons Following Treatment With Amphetamine Derivatives in Mice. Brain Res Bull. 2005 May 15;65(5):405-13. PubMed PMID: 15833595.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Occurrence of neuronal inclusions combined with increased nigral expression of alpha-synuclein within dopaminergic neurons following treatment with amphetamine derivatives in mice. AU - Fornai,Francesco, AU - Lenzi,Paola, AU - Ferrucci,Michela, AU - Lazzeri,Gloria, AU - di Poggio,Adolfo Bandettini, AU - Natale,Gianfranco, AU - Busceti,Carla L, AU - Biagioni,Francesca, AU - Giusiani,Mario, AU - Ruggieri,Stefano, AU - Paparelli,Antonio, PY - 2004/11/30/received PY - 2005/02/02/revised PY - 2005/02/11/accepted PY - 2005/4/19/pubmed PY - 2005/6/18/medline PY - 2005/4/19/entrez SP - 405 EP - 13 JF - Brain research bulletin JO - Brain Res Bull VL - 65 IS - 5 N2 - 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. SN - 0361-9230 UR - https://www.unboundmedicine.com/medline/citation/15833595/Occurrence_of_neuronal_inclusions_combined_with_increased_nigral_expression_of_alpha_synuclein_within_dopaminergic_neurons_following_treatment_with_amphetamine_derivatives_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0361-9230(05)00072-9 DB - PRIME DP - Unbound Medicine ER -