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Jones, Eleanor J. (2024) Understanding neuromuscular responses to pharmacological and exercise interventions: Manipulating motor unit plasticity in humans to improve muscle function. PhD thesis, University of Nottingham.

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Abstract

Sarcopenia, the loss of muscle mass and strength observed with ageing, presents a challenge to the growing ageing population and healthcare services. Motor unit (MU) numbers decrease with age but have remodelling potential, with the ability to rescue denervated fibres via axonal sprouting and reinnervation. Exercise interventions targeting the ageing musculoskeletal system, particularly resistance exercise training (RET), have showed promise in ameliorating declining function, however, blunted hypertrophic responses in the muscles of the older population demonstrate the need for further investigation of the neuromuscular system to develop optimal interventions.

In Chapter 2 of this thesis, intramuscular and high-density surface electromyography (EMG) were used to assess the effects of concentric (CON) and eccentric (ECC) loading on MU properties. Only ECC led to an increase in MU firing rate (FR) while changes to membrane excitability were observed with CON only. These findings demonstrates that MU features are altered following exercise-induced fatigue in an exercise modality dependant manner which is important when considering interventional strategies.

Chapter 3 further investigated physiological parameters associated with muscle fatigue, specifically the effects of an isometric fatiguing contraction on MU properties (via EMG), and muscle microvascular blood flow (MBF) using contrast enhanced ultrasound (CEUS). During the contraction, FR initially decreased before increasing in the later phase accompanied by increases in common synaptic input to motoneurons, and force variability. No change in MBF was observed, indicating this was not responsible for MU or functional changes with fatigue.

In Chapter 4, the effect of 6-weeks unilateral RET in older males on force control and underlying MU properties was assessed. RET resulted in increased strength (via 1-repetition maximum) and improved knee extensor force control. However, no changes in FR variability or common inputs to the vastus lateralis were observed, indicating an alternative mechanism is responsible for these beneficial effects of RET.

To follow on, in Chapter 5 the effect of 6-weeks unilateral RET on MU properties with or without administration of a mammalian target of rapamycin (mTOR) inhibitor (Rapamune) in older people was investigated. Rapamune did not prevent exercise-induced strength gains or MU remodelling but did prevent reductions in MU potential size and neuromuscular junction transmission instability which was observed in the placebo group.

Overall, the findings of this work provide fundamental information on changes in MU properties during and in response to different acute and chronic exercise challenges in older adults, including RET with mTOR inhibition. This is important knowledge for developing future exercise interventions targeting sarcopenia.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Piasecki, Mathew Phillips, Bethan
Keywords:	Sarcopenia; Ageing; Exercise interventions; Neuromuscular system; Hypertrophic responses; Motor unit numbers
Subjects:	W Medicine and related subjects (NLM Classification) > WE Muscoskeletal system
Faculties/Schools:	UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID:	77119
Depositing User:	Jones, Eleanor
Date Deposited:	31 Jul 2024 04:40
Last Modified:	31 Jul 2024 04:40
URI:	https://eprints.nottingham.ac.uk/id/eprint/77119

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