Low-Dose Lithium Supplementation Influences GSK3β Activity in a Brain Region Specific Manner in C57BL6 Male Mice

• DOI: 10.3233/jad-220813
• Publication Date: 2022-12-02T15:42:38Z
• Authors: Rachel K. Fenech; Sophie I. Hamstra; Michael S. Finch; Chantal R. Ryan; Daniel M. Marko; Brian D. Roy; Val A. Fajardo; Rebecca E.K. MacP...
• Keywords: Male; 0301 basic medicine; Glycogen Synthase Kinase 3 beta; Drinking Water; Brain; Lithium; 3. Good health; Mice, Inbred C57BL; Mice; Glycogen Synthase Kinase 3; 03 medical and health sciences; Alzheimer Disease; Dietary Supplements; Animals; Phosphorylation

Lithium, a commonly used treatment for bipolar disorder, has been shown to have neuroprotective effects other conditions including Alzheimer's disease via the inhibition of enzyme glycogen synthase kinase-3 (GSK3). However, dose-dependent adverse lithium are well-documented, highlighting need determine if low doses can reliably reduce GSK3 activity.The purpose this study was evaluate low-dose supplementation on activity in brain an early, diet-induced model.Male C57BL/6J mice were divided into either 6-week or 12-week study. In study, fed chow diet with lithium-supplemented drinking water (10 mg/kg/day) 6 weeks. Alternatively, diet, high-fat (HFD), HFD 12 Prefrontal cortex and hippocampal tissues collected analysis.Results demonstrated reduced prefrontal as early weeks supplementation, absence inhibitory phosphorylation changes. Further, obese model well improved insulin sensitivity.Collectively, these data provide evidence inhibit brain. Moreover, results indicate that be inhibited despite any changes phosphorylation. These findings contribute overall greater understanding lithium's ability influence its potential prophylactic.