PI4KIIIβ-Mediated Phosphoinositides Metabolism Regulates Function of the VTA Dopaminergic Neurons and Depression-Like Behavior

Author:

Sang YuqiORCID,Niu Chenxu,Xu Jiaxi,Zhu Tiantian,You Shuangzhu,Wang Jing,Zhang Ludi,Du Xiaona,Zhang Hailin

Abstract

Phosphoinositides, including phosphatidylinositol-4,5-bisphosphate (PIP2), play a crucial role in controlling key cellular functions such as membrane and vesicle trafficking, ion channel, and transporter activity. Phosphatidylinositol 4-kinases (PI4K) are essential enzymes in regulating the turnover of phosphoinositides. However, the functional role of PI4Ks and mediated phosphoinositide metabolism in the central nervous system has not been fully revealed. In this study, we demonstrated that PI4KIIIβ, one of the four members of PI4Ks, is an important regulator of VTA dopaminergic neuronal activity and related depression-like behavior of mice by controlling phosphoinositide turnover. Our findings provide new insights into possible mechanisms and potential drug targets for neuropsychiatric diseases, including depression. Both sexes were studied in basic behavior tests, but only male mice could be used in the social defeat depression model.

Funder

MOST | National Natural Science Foundation of China

Science Fund for Creative Research Groups

Basic Research Fund for Provincial Universities

Publisher

Society for Neuroscience

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