Distribution of alpha- and gamma-synucleins in the adult rat brain and their modification by high-dose cocaine treatment.
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.
Brenz Verca
Maria S
MS
Max-Planck Institute of Psychiatry, München, Germany.
Bahi
Amine
A
Boyer
Frederic
F
Wagner
George C
GC
Dreyer
Jean-Luc
JL
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry; D002452:Cell Count; D003042:Cocaine / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051843:Synucleins; D014018:Tissue Distribution; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051844:alpha-Synuclein; D051845:gamma-Synuclein
D000779:Anesthetics, Local; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C497606:Snca protein, rat; D051843:Synucleins; D051844:alpha-Synuclein; D051845:gamma-Synuclein; D014446:Tyrosine 3-Monooxygenase; D010751:Phosphopyruvate Hydratase; D003042:Cocaine