Dopamine and the phosphorylated dopamine transporter are increased in the diacylglycerol kinase η-knockout mouse brain

FEBS Letters

article

Maho Asami¹  Yuji Suzuki¹  Fumio Sakane¹ 

[1] Department of Chemistry, Graduate School of Science, Chiba University

关键词: bipolar disorder;    diacylglycerol kinase;    dopamine;    Parkinson's disease;    protein kinase C;    schizophrenia;   

DOI  :  10.1002/1873-3468.14059

来源: John Wiley & Sons Ltd.

【 摘 要 】

The molecular mechanisms generating the mania-like abnormal behaviors caused by diacylglycerol (DG) kinase (DGK) η deficiency remain unclear. Here, we found that DGKη knockout markedly increased dopamine (DA) levels in the midbrain (DA-producing region, 2.8-fold) and cerebral cortex (DA projection region, 1.2-fold). Moreover, DGKη deficiency significantly augmented phosphorylated DA transporter (DAT) levels (1.4-fold increase), which induce DA efflux to the synaptic cleft, in the cerebral cortex. Moreover, phosphorylation levels of protein kinase C-β, which is activated by DG and involved in DAT phosphorylation, were also increased. DAT expressed in Neuro-2a cells recruited DGKη to the plasma membrane and colocalized with it. These results strongly suggest that dopaminergic hyperfunction caused by DGKη deficiency in the brain leads to mania-like behaviors.

【 授权许可】

Unknown