Mechanisms involved in the formation of dopamine-induced intracellular bodies within striatal neurons

Gloria Lazzeri, Paola Lenzi, Carla L. Busceti, Michela Ferrucci, Alessandra Falleni, Valeria Bruno, Antonio Paparelli, Francesco Fornai

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1414-1427
Number of pages14
JournalJournal of Neurochemistry
Volume101
Issue number5
DOIs
Publication statusPublished - Jun 2007

Keywords

  • Dopamine receptors
  • Electron microscopy
  • Methamphetamine
  • Striatal inclusions
  • Ubiquitin
  • Ubiquitin-proteasome system

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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