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

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 gamma-synuclein as a major upregulated candidate in the tegmentum. Overexpression of both alpha- and gamma-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 alpha-synuclein vs. 2.7 x, 1.96 x and 7.16 x for gamma-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 alpha- and gamma-synuclein. alpha-synuclein displays a very characteristic distribution, confined to specific nuclei, whereas gamma-synuclein is more widely expressed throughout the brain. mRNA of both alpha- and gamma-synucleins display a complementary pattern of expression all over the cortex. In contrast to gamma-synuclein, alpha-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 gamma-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 gamma-synuclein mRNA labels the matrix compartments of the caudate-putamen. The role of synucleins in relation to cocaine-induced plasticity or neurotoxicity is discussed.