Distribution of α- and γ-synucleins in the adult rat brain and their modification by high-dose cocaine treatment

Maria S. Brenz Verca, Amine Bahi, Frederic Boyer, George C. Wagner, Jean Luc Dreyer

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53 Citations (Scopus)

Abstract

Synucleins have attracted much attention because of their involvement in several neurodegenerative disorders. In a screening for genes differentially expressed after high-dose cocaine exposure, we found γ-synuclein as a major upregulated candidate in the tegmentum. Overexpression of both α- and γ-synuclein after drug treatment was confirmed by means of microarrays, yielding an increase in the hippocampus, the striatum and the tegmentum (2.65 x, 1.96 x and 3.5 x, respectively, for α-synuclein vs. 2. 7 x, 1.96 x and 7.16 x for γ-synuclein), but no change in the nucleus accumbens. Investigation of the distribution of mRNA (by in situ hybridization) and of the proteins (by immunocytochemistry) shows in both cases a clearly distinct pattern of expression for α- and γ-synuclein. α-synuclein displays a very characteristic distribution, confined to specific nuclei, whereas γ-synuclein is more widely expressed throughout the brain. mRNA of both α- and γ-synucleins display a complementary pattern of expression all over the cortex. In contrast to γ-synuclein, α-synuclein is neuronal, being only found in NeuN-expressing cells, and is expressed in the basal ganglia (faintly) and in the substantia nigra compacta where it is highly correlated with tyrosine hydroxylase. Immunocytochemistry shows that γ-synuclein generally colocalizes with glial fibrillary acidic protein-expressing cells and is abundant in the red nucleus, the substantia nigra reticulata and the anterior commissure, while γ-synuclein mRNA labels the matrix compartments of the caudate-putamen. The role of synucleins in relation to cocaine-induced plasticity or neurotoxicity is discussed.

Original languageEnglish
Pages (from-to)1923-1938
Number of pages16
JournalEuropean Journal of Neuroscience
Volume18
Issue number7
DOIs
Publication statusPublished - Oct 2003

Keywords

  • Cocaine
  • Dopamine
  • Drugs of abuse
  • Reward
  • Synuclein

ASJC Scopus subject areas

  • Neuroscience(all)

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