The effect of age and exercise on the proprioceptive and vestibular system

Battilana, Fabienne. The effect of age and exercise on the proprioceptive and vestibular system. 2019, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: http://edoc.unibas.ch/diss/DissB_13225

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Aging is a physiological process associated with decreased mental abilities but also declining muscle function, posture and balance. Consequently, every third elderly person above 60 falls at least once per year, greatly affecting quality of life and independence. Body posture, gait and balance can be improved by physical activity. However, it is not at all understood why and how exercise improves balance function because the neuropathological mechanisms underlying age-associated balance disorders are not well understood.
Two main sensory systems complement each other in guiding proper balance: The vestibular system, residing in the inner ear, monitors gravitational forces while the proprioceptive system tracks the velocity and force of the muscle movement. Motor neurons, responsible for initiating muscle contractions, receive monosynaptic feedback from both sensory systems. Thus, direct and functional vestibular and proprioceptive feedback to motor neurons are indispensable for proper balance. It is already well understood that the neuromuscular system experiences age-associated changes affecting muscle mass and force and that exercise is beneficial to counteract aging. However, a comprehensive overview about synaptic connectivity between motor neurons and vestibular and proprioceptive system in aging is so far lacking. Furthermore, the effects of exercise on vestibular and proprioceptive spinal circuits in aging are also unknown.
Here, we used anterograde and retrograde neuronal and synaptic tracing approaches combined with balance and gait phenotypic assessment of aged exercised mice to relate declining balance to alterations in the morphology and synaptic networks of the proprioceptive and vestibular system. To that end, mice of different ages were trained for 6 to 12 weeks on treadmill and running wheels.
As expected from epidemiological studies done in humans, balance and gait of aged exercised mice were superior to aged sedentary mice, for some parameters statistically indistinguishable from 7-month-old control mice. These results show that exercise done late in life is sufficient to substantially improve balance and gait in aged mice. Interestingly, loss of balance with age was accompanied by morphological changes on the level of muscle spindles concomitant with decreased proprioceptive input to motor neurons. However, we did not observe any improvement in muscle spindle morphology or proprioceptive input to motor neurons with training, showing that exercise likely does not modulate the proprioceptive system. Since also the vestibular system is crucial for maintaining balance, we next asked if the improvements in gait and balance in response to exercise could be mediated by the vestibular system. Interestingly, vestibular input to motor neurons in aged mice was substantially decreased even more than the proprioceptive input suggesting that decreased vestibular signalling with age could be the main driver for age-associated loss of balance. Strikingly, vestibular input to motor neurons in aged exercised mice was significantly higher than in aged sedentary mice, strongly indicating that balance improvement in response to exercise is due to increased vestibular input to motor neurons.
The mechanism of increased vestibular synapses on the level of motor neurons due to exercise is unknown, but could involve neurotrophic-factor-induced axonal sprouting. Interestingly, exercise improves recovery from spinal cord injury by promoting axonal sprouting and synapse formation and elevates neurotrophic factors, able to induce synapses formation and axonal sprouting, in the spinal cord.
Therefore, we propose that exercise elevates synaptic vestibular input to motor neurons by releasing neurotrophic factors promoting axonal sprouting and synapse formation in the spinal cord, which ameliorates loss of balance in aged mice.
Advisors:Handschin, Christoph and Rüegg, Markus A.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Associated Research Groups > Pharmakologie (Handschin)
UniBasel Contributors:Battilana, Fabienne and Handschin, Christoph and Rüegg, Markus A.
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:13225
Thesis status:Complete
Number of Pages:1 Online-Ressource (129 Seiten)
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edoc DOI:
Last Modified:12 Jun 2021 04:30
Deposited On:21 Aug 2019 08:50

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