TY  - JOUR
PY  - 2022//
TI  - Depressive patient-derived GABA interneurons reveal abnormal neural activity associated with HTR2C
JO  - EMBO molecular medicine
A1  - Lu, Kaiqin
A1  - Hong, Yuan
A1  - Tao, Mengdan
A1  - Shen, Luping
A1  - Zheng, Zhilong
A1  - Fang, Kaiheng
A1  - Yuan, Fang
A1  - Xu, Min
A1  - Wang, Chun
A1  - Zhu, Dongya
A1  - Guo, Xing
A1  - Liu, Yan
SP  - ePub
EP  - ePub
VL  - ePub
IS  - ePub
N2  - Major depressive disorder with suicide behavior (sMDD) is a server mood disorder, bringing tremendous burden to family and society. Although reduced gamma amino butyric acid (GABA) level has been observed in postmortem tissues of sMDD patients, the molecular mechanism by which GABA levels are altered remains elusive. In this study, we generated induced pluripotent stem cells (iPSC) from five sMDD patients and differentiated the iPSCs to GABAergic interneurons (GINs) and ventral forebrain organoids. sMDD GINs exhibited altered neuronal morphology and increased neural firing, as well as weakened calcium signaling propagation, compared with controls. Transcriptomic sequencing revealed that a decreased expression of serotoninergic receptor 2C (5-HT2C) may cause the defected neuronal activity in sMDD. Furthermore, targeting 5-HT2C receptor, using a small molecule agonist or genetic approach, restored neuronal activity deficits in sMDD GINs. Our findings provide a human cellular model for studying the molecular mechanisms and drug discoveries for sMDD.<p />  <p>Language: en</p>
LA  - en
SN  - 1757-4676
UR  - http://dx.doi.org/10.15252/emmm.202216364
ID  - ref1
ER  -