PUBLICATION
Caffeine-induced protein kinase A activation restores cognitive deficits induced by sleep deprivation by regulating O-GlcNAc cycling in adult zebrafish
- Authors
- Tran, T.T., Park, J., Kim, D.Y., Han, I.O.
- ID
- ZDB-PUB-240206-2
- Date
- 2024
- Source
- American journal of physiology. Cell physiology 326(3): C978-C989 (Journal)
- Registered Authors
- Keywords
- O-GlcNAc transferase, caffeine, cognition, hexosamine, rolipram
- MeSH Terms
-
- Caffeine/pharmacology
- Animals
- Cognition
- Cyclic AMP-Dependent Protein Kinases/metabolism
- Sleep Deprivation*/drug therapy
- Cognitive Dysfunction*/drug therapy
- Sulfonamides*
- Zebrafish/metabolism
- N-Acetylglucosaminyltransferases/genetics
- N-Acetylglucosaminyltransferases/metabolism
- Rolipram
- Protein Processing, Post-Translational
- Acetylglucosamine/metabolism
- Isoquinolines*
- PubMed
- 38314722 Full text @ Am. J. Physiol. Cell Physiol.
Citation
Tran, T.T., Park, J., Kim, D.Y., Han, I.O. (2024) Caffeine-induced protein kinase A activation restores cognitive deficits induced by sleep deprivation by regulating O-GlcNAc cycling in adult zebrafish. American journal of physiology. Cell physiology. 326(3):C978-C989.
Abstract
Sleep deprivation (SD) is widely acknowledged as a significant risk factor for cognitive impairment. 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. Our collective findings underscore the interplay between PKA signaling and O-GlcNAc cycling in regulation of cognitive function in the brain, offering potential therapeutic targets for cognitive deficits associated with SD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping