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Voluntary wheel running combined with low-dose lithium supplementation improves novel object recognition in male
Emily N Copeland1, Ahmad Mohammad2, Bradley J Baranowski2
1Department of Kinesiology, Brock University, St. Catharines, ON, Canada; Department of Health Sciences, Brock University, St. Catharines, ON, Canada.
Background:
Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder caused by a mutation to the dystrophin gene. Cognitive dysfunction is a lesser-known symptom of DMD; however, approximately one-third of patients experience it. Though the mechanisms underlying these dysfunctions are unknown, research points towards an Alzheimer's disease (AD)-like pathology in clinical and preclinical work. In a recent study, we previously demonstrated that inhibiting glycogen synthase kinase 3 (GSK3) through a combination of low-dose lithium supplementation and voluntary wheel running (VWR) improved muscle quality and function in the mdx mouse model of DMD. Interestingly, both VWR and GSK3 inhibition with lithium can exert neuroprotective effects against Alzheimer's pathology; however, whether this treatment can also benefit cognitive function in mdx mice remains unknown.
Methods:
Here, we conducted a brief follow-up study to determine whether inhibiting GSK3 with a combination of low-dose lithium supplementation and VWR would enhance novel object recognition in mdx mice, while also investigating potential mechanisms, including beta-secretase activity, Tau phosphorylation, and sarco(endo)plasmic reticulum calcium ATPase (SERCA) activity.
Results:
Our findings show that lithium and VWR treatment, on average, improved novel object recognition in mdx mice-a result that may be linked to enhanced SERCA activity within the hippocampus but not to any changes in beta-secretase activity or tau phosphorylation.
Conclusion:
Taken together, these data point to the potential benefits of Li and VWR on cognitive function in mdx mice, highlighting the need for future research aimed at teasing out the potential mechanisms.
Insights
This study investigated if lithium and voluntary wheel running (VWR) improve cognitive function in Duchenne muscular dystrophy (DMD) mice. The treatment enhanced object recognition, possibly by increasing SERCA activity in the hippocampus.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Duchenne muscular dystrophy (DMD) is a genetic disorder affecting muscle, often accompanied by cognitive dysfunction.
- Research suggests an Alzheimer's disease (AD)-like pathology may underlie cognitive issues in DMD.
- Previous work showed lithium and voluntary wheel running (VWR) improve muscle function in DMD models.
Purpose of the Study:
- To determine if combined lithium and VWR treatment enhances cognitive function in mdx mice (a DMD model).
- To investigate the underlying mechanisms, focusing on beta-secretase activity, Tau phosphorylation, and SERCA activity.
Main Methods:
- Mdx mice were treated with low-dose lithium and VWR.
- Novel object recognition tests were used to assess cognitive function.
- Biochemical assays measured beta-secretase activity, Tau phosphorylation, and SERCA activity.
Main Results:
- Lithium and VWR treatment improved novel object recognition in mdx mice.
- This cognitive improvement correlated with enhanced sarco(endo)plasmic reticulum calcium ATPase (SERCA) activity in the hippocampus.
- No significant changes were observed in beta-secretase activity or Tau phosphorylation.
Conclusions:
- Combined lithium and VWR treatment shows potential for improving cognitive function in DMD.
- Enhanced SERCA activity may be a key mechanism mediating these cognitive benefits.
- Further research is needed to fully elucidate the neuroprotective mechanisms involved.
