1. A single dose of glycogen phosphorylase inhibitor improves cognitive functions of aged mice and affects the concentrations of metabolites in the brain.
- Author
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Pudełko-Malik N, Drulis-Fajdasz D, Pruss Ł, Mielko-Niziałek KA, Rakus D, Gizak A, and Młynarz P
- Subjects
- Animals, Mice, Male, Aging metabolism, Aging drug effects, Enzyme Inhibitors pharmacology, Enzyme Inhibitors administration & dosage, Hippocampus metabolism, Hippocampus drug effects, Imino Furanoses pharmacology, Mice, Inbred C57BL, Arabinose, Sugar Alcohols, Cognition drug effects, Glycogen Phosphorylase metabolism, Glycogen Phosphorylase antagonists & inhibitors, Brain metabolism, Brain drug effects
- Abstract
Inhibition of glycogen phosphorylase (Pyg) - a regulatory enzyme of glycogen phosphorolysis - influences memory formation in rodents. We have previously shown that 2-week intraperitoneal administration of a Pyg inhibitor BAY U6751 stimulated the "rejuvenation" of the hippocampal proteome and dendritic spines morphology and improved cognitive skills of old mice. Given the tedious nature of daily intraperitoneal drug administration, in this study we investigated whether a single dose of BAY U6751 could induce enduring behavioral effects. Obtained results support the efficacy of such treatment in significantly improving the cognitive performance of 20-22-month-old mice. Metabolomic analysis of alterations observed in the hippocampus, cerebellum, and cortex reveal that the inhibition of glycogen phosphorolysis impacts not only glucose metabolism but also various other metabolic processes., (© 2024. The Author(s).)
- Published
- 2024
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