Neural Junction 7 Letters

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Neural Junction 7 Letters

Feature Papers represent the most advanced research with significant potential for high impact in the field. Full-length articles are submitted by individual invitation or recommendation of scientific editors and undergo peer review before publication.

Neuromuscular Connectomes Across Development Reveal Synaptic Ordering Rules

A Feature Paper can be either an original research article, a substantial new research study often involving several techniques or approaches, or a comprehensive review paper with concise and precise updates of the latest advances in the field that systematically reviews the most interesting advances in scientific research. literature. This type of paper provides an outlook on future research directions or possible applications.

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Department of Anatomy, Histology, Forensic Medicine and Orthopedics (DAHFMO) – Department of Histology and Medical Embryology, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 00161 Rome, Italy

Department of Biological Sciences and Public Health, Department of Histology and Embryology, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy

A Non Canonical Notch Complex Regulates Adherens Junctions And Vascular Barrier Function

Received: 27 April 2021 / Revised: 19 May 2021 / Accepted: 22 May 2021 / Published: 24 May 2021

(This article belongs to a special issue of The Role of Skeletal Muscle in Neuromuscular Disease: From Cellular and Molecular Players to Therapeutic Interventions)

As we age, physical abilities decline, leading to reduced mobility and loss of independence. Although many factors contribute to the physiopathological effects of aging, an important event appears to be related to the impaired integrity of the neuromuscular system that connects the brain and skeletal muscles through motoneurons and neuromuscular junctions (NMJs). NMJs undergo severe functional, morphological and molecular changes during aging and eventually degenerate. The result of this decline is an inexorable decline in skeletal muscle mass and strength, a condition commonly known as sarcopenia. Additionally, several studies have highlighted how an age-related change in reactive oxygen species (ROS) homeostasis can contribute to changes in the morphology and stability of the neuromuscular junction, leading to a reduction in fiber number and innervation. A growing body of evidence supports the involvement of epigenetic modifications in age-dependent NMJ changes. In particular, DNA methylation, histone modification, and miRNA-dependent gene expression represent major epigenetic mechanisms that play a key role in NMJ remodeling. It is shown that environmental and lifestyle factors such as physical exercise and nutrition, which are susceptible to changes during aging, can modulate epigenetic phenomena and moderate age-related changes in the NMJ. This review aims to highlight recent epigenetic findings related to NMJ dysregulation during aging and the role of physical activity and nutrition as possible interventions to mitigate or delay age-related neuromuscular decline.

Aging; ROS; oxidative stress; ALS; skeletal muscle; nutrition; aging with exercise; ROS; oxidative stress; ALS; skeletal muscle; nutrition; exercises

Magnetic Tunnel Junction As An On Chip Temperature Sensor

A decline in physical ability and reduced mobility are hallmarks of aging. Although several phenomena are known to contribute to muscle loss during aging, including a low-grade chronic inflammatory state [1], reduced protein synthesis [2], mitochondrial dysfunction [3], and impaired satellite cell function [4], it is generally accepted that the decline of neural functions is one of the main factors leading to the pathological condition known as sarcopenia [5, 6, 7]. Indeed, the nervous system not only controls muscle contraction and voluntary movements [8] but also influences myoblast orientation [9], skeletal muscle fiber specification, and myosin heavy chain (MHC) isoform expression [10]. Skeletal muscle fibers are classified as fast or slow according to motor neuron activity, their different oxidative capacities and ATPase activities [11]. These properties can be altered by motor unit decline, muscle fiber denervation and NMJ changes [12]. Indeed, the slow-twitch muscle phenotype is supported by tonic motor neuron activity, whereas infrequent motor neuron firing leads to fast fiber formation [12]. In addition, cross-reinnervation experiments have shown that fast muscles switch to slow when reinnervated by a slow nerve, whereas slow muscles switch to fast once reinnervated by a fast nerve [ 13 , 14 ]. It is reported by Klitgaard et al. that the co-expression of different MHC isoforms in a single muscle fiber increases with age, suggesting a continuous shift in muscle fiber type [15], and muscles in older individuals have been shown to contain more slow-twitch muscle fibers that reduce contractility [16]. This also promotes endplate fragmentation and functional denervation [17].

The inability of aged motor axons to efficiently reinnervate muscle fibers after bouts of degeneration [18] contributes to muscle fiber atrophy and motor neuron loss. Loss of motor neurons accompanied by loss of muscle fibers may result in subsequent age-related increases in intermuscular fat and connective tissue [19, 20], less degree of muscle fiber bundling [21], and reduced muscle size [6, 22].

One possible mechanism for this progressive impairment of the reinnervation process appears to be related to age-related degeneration of the NMJ. The NMJ is a synaptic junction where the peripheral nervous system contacts skeletal muscle fibers and thus controls basic processes such as breathing and voluntary body movements [8]. In this critical region, significant deterioration has been observed with advancing age, including fragmentation of the postsynaptic apparatus, denervation, multiple innervation, and axon sprouting [ 23 , 24 , 25 ]. Interestingly, similar defects characterize several severe motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggesting that strategies aimed at preserving NMJ integrity may be key to understanding critical components associated with aging and ALS [26, 27].

Although skeletal muscle fibers are characterized by having many nuclei, only those located near the NMJ are important for the transcription of genes involved in NMJ structure, function, and maintenance [ 28 , 29 , 30 ]. Proper localization of synaptic nuclei at the NMJ requires interplay between the cytoskeleton and several nuclear envelope proteins to efficiently transmit cytoskeletal forces to the nucleus to regulate signaling pathways, chromatin organization, and gene expression [31, 32, 33, 34]. Lamin A/C, an intermediate filament involved in establishing a continuous physical connection between the nuclear lamina and the cytoskeleton [35, 36, 37, 38], has been shown to be reduced in old muscle and its mutations are involved in premature aging disorders [39, 40, 41]. In particular, a recent paper published by Gao et al. demonstrated that a muscle-specific mutation of lamin A/C leads to progressive denervation, AChR cluster fragmentation, and neuromuscular dysfunction [ 42 ]. These results demonstrate that lamin A/C is critical in NMJ maintenance and suggest that changes in the cytoskeleton-nuclear network may contribute to NMJ degeneration in aging muscle.

Microglia Monitor And Protect Neuronal Function Through Specialized Somatic Purinergic Junctions

Increasing evidence supports the involvement of epigenetic modifications in age-dependent morphological and functional alterations of the NMJ [25, 43, 44]. In particular, DNA methylation, histone modification, and miRNA-dependent gene expression represent major epigenetic mechanisms that play an essential role in NMJ remodeling [ 45 , 46 , 47 ]. This review aims to highlight recent epigenetic findings related to NMJ dysregulation during aging and the role of physical activity and nutrition as possible interventions to mitigate or delay age-related neuromuscular decline.

Three main elements make up the NMJ: a presynaptic motor nerve terminal filled with synaptic vesicles containing the neurotransmitter acetylcholine (ACh); synaptic cleft; and the deeply folded postsynaptic membrane of the muscle fiber, also referred to as the end plate, where the acetylcholine receptors (AChRs) are located. When the action potential reaches the presynaptic element, voltage-gated calcium channels open, allowing calcium to trigger the delivery of ACh into the synaptic cleft. Acetylcholine triggers the AChR located in the postsynaptic membrane to generate an action potential, which subsequently activates voltage-gated dihydropyridine receptors (DHPR) located in the sarcolemma and subsequently ryanodine receptors (RyR) located in the sarcoplasmic reticulum membrane. The nerve ending is covered by specialized glial cells, called terminal Schwann cells (tSCs), which produce a basal lamina that fuses with the muscle fiber lamina at the NMJ boundary [ 48 , 49 , 50 ]. In addition, fibroblast-like cells, known as cranocytes or perisynaptic fibroblasts, form a loose covering over the NMJ and participate in nerve repair and regeneration, thus representing other key players in neuromuscular functionality [50, 51] (Figure 1).

During aging, NMJs undergo dramatic morphological, functional, and molecular changes that lead to their eventual degeneration [ 52 , 53 , 54 ]. At the level of the presynaptic region, an increased diameter of the axon and a larger area of ​​the nerve terminal were observed [23, 55]. However, this effect is not accompanied by increased stores of Ah, because it is