Transcriptomics

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Depressive patient-derived GABA interneurons reveal abnormal neural activity associated with HTR2C


ABSTRACT: Major depressive disorder with suicide behavior (sMDD) is a severe mood disorder, bringing tremendous burden to family and society. Although reduced gamma aminobutyric 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 and ventral forebrain organoids. sMDD GINs exhibited altered neuronal morphology and increased neural firing, as well as weakened calcium signaling propagation, compared to controls. Transcriptomic sequencing revealed a decreased expression of serotoninergic receptor 2C (5-HT2C) may cause the defected neuronal acitivity 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE208438 | GEO | 2022/11/06

REPOSITORIES: GEO

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