Five review articles: New insights on how exercise can prevent neurodegenerative diseases

A growing body of evidence is finding that exercise can improve brain function and delay or prevent the onset of neurodegenerative diseases such as Alzheimer's and Parkinson's disease
.
While the underlying mechanisms are unknown, recent research suggests that activation of exercise-induced peripheral systems such as muscles, gut, liver, and adipose tissue may affect neuroplasticity
.
A special issue of Brain Plasticity presents new research and insights on
the role of neuroplasticity and peripheral factors in cognitive health.

Dr.
Henriette van Praag, co-guest editor and journal editor-in-chief of the Charles E.
Schmidt School of Medicine and Brain Institute at Florida Atlantic University, explains, "At least a dozen peripheral factors have been identified as influencing neuronutrient levels, neurogenesis in adults, inflammation, synaptic plasticity, and memory function
.
"

Cathepsin B (CTSB), a muscle factor and brain-derived neurotrophic factor (BNDF), has been found to have powerful neuroprotective effects
.
In a new study published in a special issue, researchers looked at whether increasing aerobic exercise intensity increased the amount of
CTSB and BDNF circulating in the blood.
Sixteen young, healthy subjects completed treadmill-based aerobic exercise at maximum capacity, then at
40%, 60%, and 80% capacity, respectively.

Circulating CTSB and BDNF were detected in blood samples taken after each exercise, and CTSB protein, BDNF protein, and mRNA expression
were detected in bone tissue.
The researchers found that high-intensity exercise boosted circulating CTSB in young people immediately after exercise, and skeletal muscle tissue expressed information and proteins
of CTSB and BDNF.

"CTSB and BDNF are promising therapeutic targets that can delay the onset and progression of cognitive impairment," said
lead researcher Jacob M.
Haus, Ph.
D.
, of the University of Michigan's College of Kinesiology.
"Future research needs to elucidate the mechanisms
that regulate their release, treatment, and specific roles of fiber types in skeletal muscle tissue.
"

The special issue also shares new research that CTSB may play a role in cognitive control by modulating processing speed, with both moderate-intensity and high-intensity interval exercise increasing serum BDNF levels and working memory performance
in young adult women.

Five review articles cover organ-to-organ crosstalk
between muscles, liver, adipose tissue, gut microbiota, and the brain.
While exercise is known to protect the central nervous system, it has only recently been discovered that it depends on the endocrine capacity
of skeletal muscles.
In their review, Dr.
Mamta Rai and Dr.
Fabio Demontis from the Department of Developmental Neurobiology at St.
Jude Children's Research Hospital highlight the influence of muscle factors, metabolites, and other nontraditional factors that mediate the effects
of muscle-brain and muscle-retinal communication on neurogenesis, neurotransmitter synthesis, protein balance, mood, sleep, cognitive function, and post-exercise eating behavior.

They also raised the possibility that
harmful muscle factors caused by inactive and muscle disease states could become a new focus of therapeutic interventions.
"We propose that modulating muscle-to-central nervous system signaling by modulating muscle factors and muscle metabolites may combat age-related neurodegeneration and brain diseases
affected by systemic signals," they said.

Men and women have different biological responses to physical activity and different
vulnerabilities to the onset, progression and outcome of neurodegenerative diseases.
A review by Dr.
Constanza J.
Cortes of the University of Alabama at Birmingham and Dr.
Zurine De Miguel of California State University discusses emerging research on sex differences in the immune system's response to exercise as a potential mechanism by
which physical activity affects the brain.

"Individual findings suggest that women's immune response to exercise may be enhanced, but more research is needed," Dr.
Cortez and Dr.
DeMiguel observed
.
"Interdisciplinary studies integrating neuroscience, exercise physiology and geriatrics are needed to explain sex differences in cognitive aging and age-related neurodegenerative diseases and to develop new therapeutic targets
.
"

Study the interactions between the brain and adipose tissue, specifically a hormone that can cross the blood-brain barrier, which has been shown to improve neuronal function in animal models of Alzheimer's disease; There is growing evidence that neurogenesis can be regulated by the gut microbiota; and studies on the effects of exercise and diet on hippocampal BDNF signaling, which provide recommendations
for the treatment of neurodegenerative diseases.

"The research collected in this issue confirms the importance of exercise for memory function," said
Christian D.
Wrann, Ph.
D.
, D.
D.
, guest editor of DVM, Massachusetts General Hospital and Harvard Medical School.
"We are delighted to share this exciting special issue
with you.
In the coming years, more systemic molecules related to the brain may be discovered and may provide the basis for new treatments for
neurodegenerative diseases.
”