Caffeine-induced protein kinase A activation restores cognitive deficits induced by sleep deprivation by regulating < em > O < /em > -GlcNAc cycling in adult zebrafish

In this study, intraperitoneal caffeine administration significantly ameliorated the learning and memory (L/M) deficits induced by SD and reduced aggressive behaviors in adult zebrafish. SD led to a reduction in PKA phosphorylation, phosphorylated-cAMP response element-binding protein (p-CREB) and c-Fos expression in zebrafish brain. Notably, these alterations were effectively reversed by caffeine. Additionally, caffeine mitigated neuroinflammation induced by SD, as evident from suppression of the SD-mediated increase in GFAP and NF-κB activation. Caffeine restored normal O-GlcNAcylation and O-GlcNAc transferase (OGT) levels while reversing the increased expression of O-GlcNAcase (OGA) in zebrafish brain after SD. Intriguingly, rolipram, a selective phosphodiesterase 4 (PDE4) inhibitor, effectively mitigated cognitive deficits, restored p-CREB and c-Fos levels, and attenuated the increase in GFAP in brain induced by SD. Additionally, rolipram reversed the decrease in O-GlcNAcylation and OGT expression as well as elevation of OGA expression following SD. Treatment with H89, a PKA inhibitor, significantly impaired the L/M functions of zebrafish compared to the control group, inducing a decrease in O-GlcNAcylation and OGT expression and, conversely, increase in OGA expression. The H89-induced changes in O-GlcNAc cycling and L/M dysfunction were effectively reversed by glucosamine treatment. H89 suppressed, while caffeine and rolipram promoted O-GlcNAc cycling in Neuro2a cells. ...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Source Type: research