Human neuromuscular junction: anatomical features and the effects of increasing age
dc.contributor.advisor
Gillingwater, Tom
dc.contributor.advisor
Jones, Ross
dc.contributor.advisor
Faller, Kiterie
dc.contributor.author
Ramadan, Abdullah Fahad
dc.contributor.sponsor
King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia
dc.date.accessioned
2026-05-28T09:46:37Z
dc.date.issued
2026-05-28
dc.description.abstract
The neuromuscular junction (NMJ) is a specialised chemical synapse that mediates communication between motor neurons and skeletal muscle fibres, playing a critical role in voluntary motor control. Despite its functional importance, our understanding of human NMJ morphology remains limited, particularly in terms of ageing and nanostructured details. This thesis addresses key gaps in human NMJ research through investigating anatomical characterisation, age-associated structural changes in human upper limb muscles, and applying a new super-resolution (SR) technique to reveal fine structures.
In the first part of this study, NMJs were systematically analysed in upper limb muscles obtained from healthy adult donors. Using immunohistochemistry (IHC) staining and confocal microscopy, a baseline morphological profile was established.
The second part explored age-related changes of the NMJ, focusing on terminal Schwann cells (TSCs) and voltage-gated sodium channels (NaV1.4) besides the basic presynaptic and postsynaptic elements. Aged NMJs exhibited subtle structural alterations, including changes in TSCs architecture and disruption in NaV1.4 expression, suggesting progressive synaptic decline with preserved overall integrity. These findings indicate that human NMJ ageing changes diverge from the rodent scenario, where the latter reveals a progressive structural denervation in response to ageing.
The final part of the thesis introduced and validated Expansion Microscopy (ExM) as a novel technique for NMJs imaging at nanoscale resolution. ExM results are enabled by isotropic tissue expansion, capturing synaptic details in three-dimensional visualisation. As a recent SR technique, the ExM is cost-effective, accessible and applicable.
Collectively, these three studies represent the aims of the thesis, provide a comprehensive and novel anatomical account of the human NMJ. They offer critical reference data, reveal patterns of structural ageing, and establish a powerful imaging platform for future research.
dc.identifier.uri
https://era.ed.ac.uk/handle/1842/44760
dc.identifier.uri
https://doi.org/10.7488/era/7275
dc.language.iso
en
dc.relation.hasversion
Jones, R.A., Ramadan, A., Qutifan, S. and Gillingwater, T.H. (2024) 'Comment on 'Neuromuscular Impairment at Different Stages of Human Sarcopenia' by Sarto et al', J Cachexia Sarcopenia Muscle, 15(6), 2885-2886, available: http://dx.doi.org/10.1002/jcsm.13624
dc.relation.hasversion
Ramadan, A., Sheard, T.M.D., Alhindi, A., Rust, P.A., Jones, R.A., Gillingwater, T.H. and Jayasinghe, I. (2025) 'Protocol for applying expansion microscopy to the study of mammalian neuromuscular junctions', STAR Protoc, 7(1), 104272, available: http://dx.doi.org/10.1016/j.xpro.2025.104272
dc.subject
neuromuscular junction (NMJ)
dc.subject
Ageing
dc.subject
Super-resolution microscopy
dc.title
Human neuromuscular junction: anatomical features and the effects of increasing age
dc.title.alternative
On the human neuromuscular junction: anatomical features and the effects of increasing age
dc.type
Thesis
dc.type.qualificationlevel
Doctoral
dc.type.qualificationname
PhD Doctor of Philosophy
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