title: Mechanisms involved in the formation of dopamine-induced intracellular bodies within striatal neurons.
abstract: Recent studies demonstrated that methamphetamine (METH) produces intracellular bodies which are reminiscent of those occurring during degenerative disorders. In vivo studies demonstrate the occurrence of these morphological alterations both in the dopamine (DA) neurons of the substantia nigra and striatal cells. These consist of neuronal bodies staining for a variety of antigens belonging to the ubiquitin-proteasome pathway. The formation of these intracellular bodies both in the substantia nigra and PC12 cells depends on the presence of endogenous DA. In the present study, we analyze the mechanisms which lead to METH-induced intracellular bodies within non-dopaminergic striatal neurons. We found that METH is no longer able to produce inclusions in vivo, in striatal cells, when striatal DA is lost. Similarly, in vitro, in primary striatal cell cultures which do not possess DA, METH administration does not produce inclusions. On the other hand, administration of DA to striatal cell cultures produces neuronal inclusions and cell death, which are both related to the inhibition of the ubiquitin-proteasome system and activation of specific-DA receptors. In line with this, we produced subcellular alterations by administering dopamine agonists.
authors.affiliation: Department of Human Morphology and Applied Biology, University of Pisa, Pisa, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Lazzeri
authors.forename: Paola
authors.initials: P
authors.lastname: Lenzi
authors.forename: Carla L
authors.initials: CL
authors.lastname: Busceti
authors.forename: Michela
authors.initials: M
authors.lastname: Ferrucci
authors.forename: Alessandra
authors.initials: A
authors.lastname: Falleni
authors.forename: Valeria
authors.initials: V
authors.lastname: Bruno
authors.forename: Antonio
authors.initials: A
authors.lastname: Paparelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Fornai
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology* / Q000293:injuries; D004298:Dopamine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D002479:Inclusion Bodies / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D016627:Oxidopamine / Q000633:toxicity; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D025801:Ubiquitin / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; D018765:Dopamine Uptake Inhibitors; D017382:Reactive Oxygen Species; D025801:Ubiquitin; D051844:alpha-Synuclein; D008694:Methamphetamine; D016627:Oxidopamine; D046988:Proteasome Endopeptidase Complex; D004298:Dopamine