Adcy8, also known as adenylyl cyclase 8, is a key enzyme involved in the production of cyclic AMP (cAMP) in a Ca2+-stimulated manner. It participates in the cAMP signaling pathway and calcium signaling pathway, playing an important role in various biological processes [1,2]. Genetic models, such as gene knockout mice, have been valuable tools in studying its function.

In Adcy8-/- mice, studies have shown distinct roles in synaptic and cognitive flexibility. At the Schaffer collateral-CA1 synapses, these mice display normal long-term potentiation (LTP) following high-frequency stimulation, but have deficits in synaptic depotentiation that are dependent on the induction protocol. ADCY8 is specifically required for reversal memory formation [1]. In addition, Adcy8 knockout mice are glucose intolerant after oral or intraperitoneal glucose administration, and insulin secretion is diminished in their islets, indicating its role in glucose homeostasis [3].

In conclusion, Adcy8 is crucial for regulating synaptic and cognitive flexibility, as well as glucose homeostasis. The use of Adcy8 knockout mouse models has significantly contributed to understanding its role in these biological processes, providing insights into potential mechanisms underlying cognitive and metabolic disorders [1,3].

References:

1. Zhang, Ming, Wang, Hongbing. 2023. Ca2+-stimulated ADCY1 and ADCY8 regulate distinct aspects of synaptic and cognitive flexibility. In Frontiers in cellular neuroscience, 17, 1215255. doi:10.3389/fncel.2023.1215255. https://pubmed.ncbi.nlm.nih.gov/37465213/

2. Zheng, Qiangqiang, Min, Shihui, Zhou, Qinghua. . Identification of potential diagnostic and prognostic biomarkers for LUAD based on TCGA and GEO databases. In Bioscience reports, 41, . doi:10.1042/BSR20204370. https://pubmed.ncbi.nlm.nih.gov/34017995/

3. Raoux, Matthieu, Vacher, Pierre, Papin, Julien, Magnan, Christophe, Lang, Jochen. 2014. Multilevel control of glucose homeostasis by adenylyl cyclase 8. In Diabetologia, 58, 749-57. doi:10.1007/s00125-014-3445-z. https://pubmed.ncbi.nlm.nih.gov/25403481/