Potential mechanisms of HBOT associated CREB activation and degradation: CREB activates its downstream genes when phosphorylated, while PP1 catalyzes the dephosphorylation of CREB. PP1γ is the core subunit of PP1. In hypoxia, PP1γ is repressed, leading to over-phosphorylation of CREB, followed by CREB ubiquitination and degradation by 26s proteasome. HBOT may reverse this process by reactivating PP1γ and blocking CREB degradation. Thus, phosphorylated CREB activates the downstream genes (BDNF, Bcl-2, VGF, et al.) to promote neurogenesis. Abbreviation: PP1γ, protein phosphatase-1; CREB, cAMP response element-binding; Ub, ubiquitin; CRE, cAMP response elements; CBP, CREB binding protein.