The Possibility of the "Muscle-Brain Connection" Taught by Mice

📖 Literature Information and Abstract Translation

Cognition from the Partnership Between Body and Brain: Adaptation of Memory

[Background/Objective] Cognitive impairment is a major challenge for the elderly because it progresses rapidly and effective treatments are limited. Elderly individuals with sarcopenia are at a higher risk of dementia. This scoping review aims to clarify whether muscle is a mediator of cognitive function based on pre-clinical evidence.

[Methods] PubMed, Embase, and Web of Science were searched up to February 2, 2022, using the keywords (muscle) AND (cognition OR dementia OR Alzheimer) AND (mouse OR rat OR animal). This study used PRISMA guidelines.

[Results] A total of 17 pre-clinical studies were selected from 7,638 studies.

■ Muscle atrophy/muscle injury → Effects on memory, etc.
・Four studies reported that muscle atrophy or muscle injury in mice, regardless of the presence of Alzheimer's disease (AD), harms memory, functional factors, and neurons in the brain.

■ Exercise → Metabolites → Contribution to increased BDNF levels
・Three studies observed that exercise causes muscles to secrete factors such as lactate, fibronectin type III domain-containing protein 5 (FNDC5), and cathepsin B, which play important roles in cognitive function and the elevation of brain-derived neurotrophic factor (BDNF) levels.

■ Electrical stimulation/intramuscular injection → Neurogenesis effects + alpha
・Muscle-targeted therapies, including electrical stimulation and intramuscular injections, showed effective remote effects on the hippocampus.
・Six studies showed that muscle-specific overexpression of scFv59 and neprilysin, or knockdown of myostatin, alleviated AD symptoms.

■ Growth factor manipulation → Deficits in hippocampal neurogenesis
・One study showed that muscle insulin resistance also leads to deficits in hippocampal neurogenesis in MKR mice.

[Conclusion] Skeletal muscle is involved in the mediation of cognitive function. Evidence for this was established by muscle atrophy and injury, myokines, and brain responses (changes in neuron count, functional factors, and other AD pathological features) to muscle-targeted therapies. Translational potential of this paper: This study summarizes current evidence on how muscle influences cognitive function at the molecular level and supports the potential of muscle-specific therapy as a clinical strategy to prevent cognitive impairment.

🌱 So What?: What did I find interesting?

Exercise maintains and improves cognitive function.
It is one of the representative effects of "Exercise is Medicine".
I have read many related papers so far.

However, in studies targeting humans, only comprehensive effects can be verified.
What does that mean?

To know these things, extremely invasive interventions such as injections, resections, and electrical stimulation are required.
It would not be possible to apply these methods to humans.
That is what mice allow us to do.
Animal experiments are positioned at a very low level in terms of evidence hierarchy.

However, I think there are optimal areas for each.
Experiments using mice are powerful for knowing the detailed mechanisms like this time.
I want to express my heartfelt gratitude to the mice.
And it is our duty as humans to make full use of those results.

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