NMJ maintenance and repair in aging

Taetzsch, Thomas; Valdez, Gregorio

doi:10.1016/j.cophys.2018.05.007

Cited by 54 publications

(38 citation statements)

References 73 publications

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“…Importantly, synapse dysfunction and synaptic loss at the NMJ are reversible, whereas loss of neuronal function in the spinal cord is not. As a result, a growing community has begun to investigate NMJ‐targeted regenerative therapies to restore mobility (Homan & Meriney, ; Legay & Mei, ; Taetzsch & Valdez, ).…”

Section: Introductionmentioning

confidence: 99%

Neuronal substrates alter the migratory responses of nonmyelinating Schwann cells to controlled brain‐derived neurotrophic factor gradients

Singh

Robles

Vázquez

2020

J Tissue Eng Regen Med

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Neurodegeneration and dysfunction cause mobility impairment and/or paralysis in millions of adults, worldwide. Motor deficit and recovery in adults depend upon the plasticity of the neuromuscular junction (NMJ), a tripartite, biochemical synapse that transduces electrical impulses from the brain into voluntary contraction of skeletal muscle. Nonmyelinating Schwann cells (nmSCs) of the NMJ have been increasingly recognized as active synaptic partners with motor neurons and muscle and have become recent therapeutic targets for regeneration. nmSC synaptic transmission, plasticity, and growth are strongly modulated by brain-derived neurotrophic factor (BDNF), whose regenerative abilities have been explored through emerging biomaterials and tissue-engineered systems, as well as via clinical trials. Experimental models engineered to investigate integrated NMJ response(s) to local gradients of BDNF will both advance our understanding of key modulators of synaptic activity, postinjury, and aid in the development of NMJ-targeted, regenerative therapies to restore mobility. The current study examined the ability of nmSCs to respond to microfluidically controlled BDNF signaling upon different haptotactic substrates of motor neurons (MNs) and laminin adhesion coating. Tests seeding nmSCs sequentially with MNs illustrated that sequential seeding reported a fivefold increase in levels of tropomyosin receptor kinase B expression in response to BDNF signaling and a nearly fivefold increase in migration distance along BDNF gradients. By contrast, concurrent seeding of MNs and nmSCs upon laminin adhesion coating illustrated a difference in migration distance of less than one third-fold over control. Our findings are among the first to examine migratory responses of nmSCs for regenerative strategies and highlight the potential to restabilize NMJ synaptic activity by affecting nmSC behaviors through therapeutic BDNF and seeding with MNs.

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Section: Introductionmentioning

confidence: 99%

Neuronal substrates alter the migratory responses of nonmyelinating Schwann cells to controlled brain‐derived neurotrophic factor gradients

Singh

Robles

Vázquez

2020

J Tissue Eng Regen Med

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“…Studies in young and older rats have revealed that aging alters the morphology of each cellular component of the NMJ, including the increased extent of overlap between the nerve terminal and motor end-plate at the level of type IIb fibres [108], and the increased length and number of pre-synaptic nerve terminals and branching complexity [107]. Additionally, because of agerelated pre-synaptic alterations, it has been found that synaptic vesicles are aggregated along non-synaptic regions of aged motor axons, which may result in a reduction in the density of active zones along with the alterations in acetylcholine stores and releases [109,110]. The functional consequences of the morphological remodelling of NMJ with aging include impaired neuromuscular transmission and junctional stability [94,110], which may lead to impulse blocking and more variable transmission of the action potential from the motor neuron to the muscle fibre [111,112].…”

Section: Effect Of Aging On Neuromuscular Junctionsmentioning

confidence: 99%

“…Additionally, because of agerelated pre-synaptic alterations, it has been found that synaptic vesicles are aggregated along non-synaptic regions of aged motor axons, which may result in a reduction in the density of active zones along with the alterations in acetylcholine stores and releases [109,110]. The functional consequences of the morphological remodelling of NMJ with aging include impaired neuromuscular transmission and junctional stability [94,110], which may lead to impulse blocking and more variable transmission of the action potential from the motor neuron to the muscle fibre [111,112]. These transmissions/communications signals between the terminal motor neuron and myofiber are modulated by different types of molecules.…”

Section: Effect Of Aging On Neuromuscular Junctionsmentioning

confidence: 99%

Age-related Changes in Motor Function (I). Mechanical and Neuromuscular Factors

2020

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This two-part narrative review aims to provide an insight into the age-related mechanical and neuromuscular factors contributing to: (1) decreased maximal muscle strength and power; (2) decreased force control; and (3) increased fatigability. Structural and functional changes from the macro-level of the muscle-tendon unit to the micro-level of the single muscle fibre have been reviewed and are described. At the muscle-tendon unit level, muscle volume, thickness and cross-sectional area, as well as pennation angle and fascicle length all decrease as part of the natural ageing process. These changes negatively affect muscle quality, muscle and tendon stiffness and Young’s modulus and account for impairment in motor performance. A progressive age-related alteration in neuromuscular function is also well-established, with reduction in number and firing rate of the motor unit, contractile velocity and specific tension of muscle fibres, and stability of neuromuscular junction. These could be the result of structural alterations in the: (i) motor neuron, with number reduced, size and collateral sprouting increased; (ii) neuromuscular junction, with decreased post-synaptic junctional fold and density of active zones and increased pre-synaptic branching and post-synaptic area; and (iii) muscle fibre, with decreased number and size and increased type I and co-expression of myosin heavy chain.

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“…The other possible etiology of NMJ fragmentation with aging can be explained by the appearance of neuronal lesions or complete motor neuron death leading to muscle fiber denervation followed by reinnervation of the same post-synaptic apparatus by a new neuronal sprout from neighboring neurons. Finally, the rearrangement of molecular events could lead to a slow and constant decay of synaptic regions with age progression [12,13].…”

Section: Ecmmentioning

confidence: 99%

An Overview of Neuromuscular Junction Aging Findings in Human and Animal Studies

Khosa

Trikamji

Khosa

et al. 2019

CAS

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Background: Aging is a complex irreversible process that is not only related to an individual’s genetic make-up but also to lifestyle choices and environmental exposures. Like every other structure in human body, the Neuromuscular Junction (NMJ) is not averse to aging. Objectives: The prime objective is to analyse the microscopic and macroscopic changes at the NMJs with aging. Methods: For the purpose of review we evaluated data from resources like Pubmed, Ovid, UCLA libraries and USC libraries. Results: We review various morphological, physiological, immunological, and biochemical changes in NMJs with aging and their management. Conclusion: The alterations in NMJs secondary to aging are inevitable. It is vital that neurologists clearly understand the pathophysiology of NMJ aging and differentiate between physiological and pathological effects of aging. With the current knowledge of science, the changes in NMJ aging can be better prevented rather than cured.

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NMJ maintenance and repair in aging

Cited by 54 publications

References 73 publications

Neuronal substrates alter the migratory responses of nonmyelinating Schwann cells to controlled brain‐derived neurotrophic factor gradients

Neuronal substrates alter the migratory responses of nonmyelinating Schwann cells to controlled brain‐derived neurotrophic factor gradients

Age-related Changes in Motor Function (I). Mechanical and Neuromuscular Factors

An Overview of Neuromuscular Junction Aging Findings in Human and Animal Studies

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