Summary: Weight-bearing leg exercise sends signals to the brain that are essential for producing healthy neural cells, new research reports.
Source: Frontiers.
New research demonstrates that neurological health depends not only on signals from the brain to muscles but also on feedback from the body’s large leg muscles back to the brain. Published in Frontiers in Neuroscience, the study offers important insights into why patients with motor neuron disease, multiple sclerosis, spinal muscular atrophy and other movement-limiting neurological conditions often deteriorate rapidly when mobility is lost.
“Our findings show that people who cannot perform load-bearing activities—such as bedridden patients or astronauts on extended missions—lose more than muscle mass; their cellular metabolism and nervous system health are also affected,” explains Dr. Raffaella Adami of Università degli Studi di Milano, Italy.
The researchers investigated how reduced use of leg muscles affects the brain by restricting mice from using their hind legs while allowing normal use of the front legs for 28 days. The animals ate, groomed and behaved normally, showing no signs of stress. At the end of the study the team analyzed the subventricular zone (SVZ) of the brain, a region that supports neural stem cells and contributes to ongoing neurogenesis in many mammals.
Mice with limited hind-leg use showed a 70 percent reduction in neural stem cell numbers compared with freely moving controls. In addition, neurons and oligodendrocytes—cells that support and insulate nerve fibers—failed to reach full maturity when weight-bearing exercise was severely reduced. In short, reduced leg use impaired the brain’s ability to generate and mature essential neural cells.
The study highlights that weight-bearing leg activity sends critical physiological signals to the brain, helping maintain neural stem cell production and healthy cell maturation. Cutting back on such exercise undermines the generation of new nerve cells, weakening the brain’s capacity to adapt to stress and environmental challenges.
“Human bodies are designed to be active: to walk, run, sit and lift using our leg muscles,” says Adami. “Neurological health is a two-way system, not simply the brain issuing commands to muscles.”
To probe the mechanisms behind these effects, the team analyzed single-cell changes. They found that reduced activity lowers systemic oxygen levels, creating a more anaerobic environment and shifting metabolic pathways. Exercise restriction also altered expression of specific genes, including CDK5Rap1, which plays a key role in mitochondrial function—the energy-producing machinery inside cells. These changes create additional feedback loops linking muscle use, metabolism, and neural health.
These findings have broad implications. They shed light on the harmful consequences of sedentary lifestyles for cardiovascular and neurological health and offer new perspectives on progressive conditions such as spinal muscular atrophy, multiple sclerosis, and motor neuron disease. The research suggests that loss of load-bearing movement itself may accelerate or worsen neurological decline in people living with these disorders.
Co-author Dr. Daniele Bottai, also from Università degli Studi di Milano, reflects on the clinical motivation for the work: “I have studied neurological diseases for many years. We wanted to know whether the progression of conditions like spinal muscular atrophy is driven solely by genetic lesions or spinal cord damage, or whether reduced movement itself is a major factor that worsens outcomes.”
The study underscores the critical role of movement, particularly load-bearing leg activity, in preserving neural stem cell function and metabolic balance in the brain. The results also carry practical implications for long-duration spaceflight: without gravity and routine load-bearing exercise, astronauts may face neurological risks in addition to well-known musculoskeletal and cardiovascular challenges.
“You could say our health is literally grounded on Earth in ways we are only beginning to understand,” Bottai concludes.
Funding: Support provided by Asamsi ONLUS, Italy and Vertical Foundation.
Source: Emma Duncan, Frontiers.
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Open access research titled “Reduction of Movement in Neurological Diseases: Effects on Neural Stem Cells Characteristics” by Raffaella Adami et al., published in Frontiers in Neuroscience, May 23, 2018. DOI: 10.3389/fnins.2018.00336
Frontiers. “Leg Exercise is Critical to Brain and Nervous System Health.” NeuroscienceNews, May 23, 2018.
Abstract
Reduction of Movement in Neurological Diseases: Effects on Neural Stem Cells Characteristics
Prolonged reductions in movement—whether due to chronic illness or extended spaceflight—can impair both muscle and brain function. This study examines how sustained muscle disuse affects neural stem cells (NSCs) in the subventricular zone. NSCs from mice with restricted hind-limb use showed reduced proliferation, altered cell-cycle dynamics, and incomplete differentiation. The results indicate a clear link between loss of load-bearing movement, altered brain metabolism, and impaired NSC properties, offering new insight into how immobility may contribute to negative neurological outcomes.