Berberine Ameliorates Cognitive Disorder via GSK3β/PGC-1α Signaling in APP/PS1 Mice.

Abstract

Previous studies have revealed that Berberine (BBR) had therapeutic effects on Alzheimer's disease (AD). However, the underlying mechanism of BBR in the treatment of AD is unclear. The study was to investigate whether berberine ameliorates cognitive disorder in AD by regulating on GSK3β/PGC-1α signaling pathway. APP/PS1 mice were treated with BBR (50 mg/kg and 100 mg/kg) for 4 mo, and the cognitive function of mice was tested by Morris water maze. The levels of inflammatory cytokines IL-1β, TNF-α, and IL-6 in hippocampus of mice were detected by ELISA kits. The damage of neuronal in hippocampal CA1 was detected by Nissl staining. The tau and GSK3β protein were detected by western blot. The results showed that BBR treatment obviously improved spatial cognitive function of APP/PS1 mice. Meanwhile, the pro-inflammatory cytokines were decreased in hippocampus by the administration of BBR. Additionally, BBR significantly alleviated neuronal damage and reduced the levels of hyperphosphorylated tau at sites of Thr205 and Thr231 in hippocampus. Importantly, BBR inhibited the activity of GSK3β and increased the expression of PGC-1α. Consequently, our results demonstrates that BBR could improve the cognitive function by inhibiting the tau hyperphosphorylation and neuroinflammation. These beneficial effects of BBR may be attributed to the regulation of GSK3β/PGC-1α signaling pathway in APP/PS1 mice. These findings reveal a vital role for GSK3β/PGC-1α signaling pathway in retarding cognitive disorder, indicating that PGC-1α might be a potential target for the treatment of AD.

• Authors: Meng Yang, Jing Wang
• Journal: Journal of nutritional science and vitaminology (J Nutr Sci Vitaminol (Tokyo)) Vol. 68 Issue 3 Pg. 228-235 ( 2022) ISSN: 1881-7742 [Electronic] Japan
• PMID: 35768254 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Ppargc1a protein, mouse
• Berberine
• Glycogen Synthase Kinase 3 beta

Topics

• Alzheimer Disease (drug therapy, metabolism)
• Animals
• Berberine (pharmacology)
• Cognition
• Cognitive Dysfunction (drug therapy, metabolism)
• Cytokines
• Disease Models, Animal
• Glycogen Synthase Kinase 3 beta (metabolism)
• Mice
• Mice, Transgenic
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (metabolism)
• Signal Transduction