Hyperactivation of midbrain dopaminergic system in schizophrenia could be attributed to the down-regulation of dysbindin.
Extraordinal activation of nigrostriatal and mesolimbic dopaminergic systems (midbrain dopaminergic system) is thought to be one of the most important etiologies for schizophrenia, though the reason why unusual hyperactivation of the dopaminergic system occurs in the schizophrenic brain is quite obscure. Dysbindin, one of the most susceptible genes for schizophrenia, has been reported to be reduced in the schizophrenic brain. In situ hybridization analysis showed the mRNA expression of dysbindin in the mouse substantia nigra. Furthermore, suppression of dysbindin expression in PC12 cells resulted in an increase of the expression of SNAP25, which plays an important role in neurotransmitter release, and increased the release of dopamine. On the other hand, up-regulation of dysbindin expression in PC12 cells showed a tendency to decrease the expression of SNAP25. These data suggest that dysbindin might regulate the dopamine release of the dopaminergic system via modulation of the expression of SNAP25.
Kumamoto
Natsuko
N
Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Matsuzaki
Shinsuke
S
Inoue
Kiyoshi
K
Hattori
Tsuyoshi
T
Shimizu
Shoko
S
Hashimoto
Ryota
R
Yamatodani
Atsushi
A
Katayama
Taiichi
T
Tohyama
Masaya
M
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D015536:Down-Regulation; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005786:Gene Expression Regulation; D006801:Humans; D017403:In Situ Hybridization; D008636:Mesencephalon / Q000378:metabolism*; D051379:Mice; D018377:Neurotransmitter Agents / Q000235:genetics / Q000378:metabolism; D016716:PC12 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D050825:Synaptosomal-Associated Protein 25; D004298:Dopamine