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

Abstract

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.

Molecular signature of excessive female aggression: study of stressed mice with genetic inactivation of neuronal serotonin synthesis

“…High levels of expression were observed in brain regions implicated in cognition and emotionality. While inactivation of Dgkh in mice increases levels of dopamine in the midbrain (Asami et al 2021 ), variants of DGKH were associated with ADHD and bipolar disorder (Weber et al 2011 ; Whalley et al 2012 ). Taken together, the upregulation of Dgkh gene may contribute to the observed increased aggression and anxiety-like behavior by impacting both serotoninergic and dopaminergic transmission.…”

Phosphatidylinositol 4,5‐bisphosphate‐specific phospholipase C β1 selectively binds dipalmitoyl and distearoyl phosphatidic acids via Lys946 and Lys951

“…COS‐7 cells were cultured in Dulbecco's modified Eagle's medium (DMEM; Wako Pure Chemical Industries, Tokyo, Japan) supplemented with 10% fetal bovine serum (FBS) (Thermo Fisher Scientific, Waltham, MA), 100 units/ml penicillin (Wako Pure Chemical Industries), and 100 μg/ml streptomycin (Wako Pure Chemical Industries). The cells were maintained at 37°C in an atmosphere containing 5% CO 2 and transfected as described previously (Asami et al, 2021).…”