Adenylyl Cyclase 8 in Dorsal CA1 Neurons Prevents Depressive-Like Behaviors by Maintaining Neuronal Excitability and Glutamatergic Neurotransmission Through TIP39-PTH2R Signaling.

ABSTRACT: Depression, a common neuropsychiatric disorder, profoundly disrupts individuals' daily lives. Although the pathogenesis of depression is intensively investigated for decades, its underlying mechanisms remain elusive. Here, dysfunctional adenylyl cyclase 8 (Adcy8) is identified as a critical risk factor for the development of depression. Adcy8 expression is selectively decreased in the hippocampus, but not in the cortex, thalamus, and hypothalamus, of mice exposed to chronic stress. Adcy8 conditional knockout (CKO) in excitatory neurons, particularly dorsal CA1 (dCA1) neurons, resulted in pronounced depressive-like behaviors. Depletion of Adcy8 in dCA1 neurons reduces neuronal excitability and glutamatergic neurotransmission. Further mechanistic studies reveal a remarkable inhibition of the

SUBMITTER: Liu ZJ 

PROVIDER: S-EPMC12915128 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature