scholarly journals Early postnatal elimination of slow-type motor neurons induces progressive muscle atrophy and kinetic tremor

Author(s):  
Tenkei Koyama ◽  
Lisa Ohgaki ◽  
Kai Kamishima ◽  
Tomoyuki Yamanaka ◽  
Shigeyoshi Itohara ◽  
...  
PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e74908 ◽  
Author(s):  
Stephan Gysi ◽  
Christa Rhiner ◽  
Stephane Flibotte ◽  
Donald G. Moerman ◽  
Michael O. Hengartner

Author(s):  
Valentina Pegoraro ◽  
Antonio Merico ◽  
Corrado Angelini

Amyotrophic lateral sclerosis (ALS) is a rare, progressive, neurodegenerative disorder caused by degeneration of upper and lower motor neurons. The disease process leads from lower motor neuron involvement to progressive muscle atrophy, weakness, fasciculations for the upper motor neuron involvement to spasticity. Muscle atrophy in ALS is caused by a dysregulation in the molecular network controlling fast and slow muscle fibres. Denervation and reinnervation processes in skeletal muscle occur in the course of ALS and are modulated by rehabilitation. MicroRNAs (miRNAs) are small non-coding RNAs that modulate a wide range of biological functions under various pathophysiological conditions. MiRNAs can be secreted by various cell types and they are markedly stable in body fluids. MiR-1, miR-133 a, miR-133b, and miR-206 are called “myomiRs” and are considered markers of myogenesis during muscle regeneration and neuromuscular junction stabilization or sprouting. We observed a positive effect of a standard aerobic exercise rehabilitative protocol conducted for six weeks in 18 ALS patients during hospitalization in our center. We correlated clinical scales with molecular data on myomiRs. After six weeks of moderate aerobic exercise, myomiRNAs were down-regulated, suggesting an active proliferation of satellite cells in muscle and increased neuromuscular junctions. Our data suggest that circulating miRNAs modulate during skeletal muscle recovery in response to physical rehabilitation in ALS.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Vartika Mishra ◽  
Diane B. Re ◽  
Virginia Le Verche ◽  
Mariano J. Alvarez ◽  
Alessandro Vasciaveo ◽  
...  

Abstract Cell-to-cell communications are critical determinants of pathophysiological phenotypes, but methodologies for their systematic elucidation are lacking. Herein, we propose an approach for the Systematic Elucidation and Assessment of Regulatory Cell-to-cell Interaction Networks (SEARCHIN) to identify ligand-mediated interactions between distinct cellular compartments. To test this approach, we selected a model of amyotrophic lateral sclerosis (ALS), in which astrocytes expressing mutant superoxide dismutase-1 (mutSOD1) kill wild-type motor neurons (MNs) by an unknown mechanism. Our integrative analysis that combines proteomics and regulatory network analysis infers the interaction between astrocyte-released amyloid precursor protein (APP) and death receptor-6 (DR6) on MNs as the top predicted ligand-receptor pair. The inferred deleterious role of APP and DR6 is confirmed in vitro in models of ALS. Moreover, the DR6 knockdown in MNs of transgenic mutSOD1 mice attenuates the ALS-like phenotype. Our results support the usefulness of integrative, systems biology approach to gain insights into complex neurobiological disease processes as in ALS and posit that the proposed methodology is not restricted to this biological context and could be used in a variety of other non-cell-autonomous communication mechanisms.


1976 ◽  
Vol 13 (6) ◽  
pp. 428-435 ◽  
Author(s):  
M. Vandevelde ◽  
C. E. Greene ◽  
E. J. Hoff

A young cat had signs of tetraparesis that progressed to tetraplegia within a few weeks. Clinically, there was lower motor neuron disease with areflexia and muscle atrophy in all limbs. Degeneration of the motor neurons in the spinal cord was seen on histological examination. Ultrastructurally, the degeneration of nerve cells was characterized by abnormal proliferation of neurofilaments. These findings were compared to other motor neuron diseases and neurofibrillary accumulations in man and animals.


2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Yu-Ting Zhang ◽  
Hui Jin ◽  
Jun-Hua Wang ◽  
Lan-Yu Wen ◽  
Yang Yang ◽  
...  

Spinal cord injury (SCI) often results in death of spinal neurons and atrophy of muscles which they govern. Thus, following SCI, reorganizing the lumbar spinal sensorimotor pathways is crucial to alleviate muscle atrophy. Tail nerve electrical stimulation (TANES) has been shown to activate the central pattern generator (CPG) and improve the locomotion recovery of spinal contused rats. Electroacupuncture (EA) is a traditional Chinese medical practice which has been proven to have a neural protective effect. Here, we examined the effects of TANES and EA on lumbar motor neurons and hindlimb muscle in spinal transected rats, respectively. From the third day postsurgery, rats in the TANES group were treated 5 times a week and those in the EA group were treated once every other day. Four weeks later, both TANES and EA showed a significant impact in promoting survival of lumbar motor neurons and expression of choline acetyltransferase (ChAT) and ameliorating atrophy of hindlimb muscle after SCI. Meanwhile, the expression of neurotrophin-3 (NT-3) in the same spinal cord segment was significantly increased. These findings suggest that TANES and EA can augment the expression of NT-3 in the lumbar spinal cord that appears to protect the motor neurons as well as alleviate muscle atrophy.


2001 ◽  
Vol 204 (18) ◽  
pp. 3201-3208 ◽  
Author(s):  
Robert H. Fitts ◽  
Danny R. Riley ◽  
Jeffrey J. Widrick

SUMMARY Our purpose is to summarize the major effects of space travel on skeletal muscle with particular emphasis on factors that alter function. The primary deleterious changes are muscle atrophy and the associated decline in peak force and power. Studies on both rats and humans demonstrate a rapid loss of cell mass with microgravity. In rats, a reduction in muscle mass of up to 37% was observed within 1 week. For both species, the antigravity soleus muscle showed greater atrophy than the fast-twitch gastrocnemius. However, in the rat, the slow type I fibers atrophied more than the fast type II fibers, while in humans, the fast type II fibers were at least as susceptible to space-induced atrophy as the slow fiber type. Space flight also resulted in a significant decline in peak force. For example, the maximal voluntary contraction of the human plantar flexor muscles declined by 20–48% following 6 months in space, while a 21% decline in the peak force of the soleus type I fibers was observed after a 17-day shuttle flight. The reduced force can be attributed both to muscle atrophy and to a selective loss of contractile protein. The former was the primary cause because, when force was expressed per cross-sectional area (kNm−2), the human fast type II and slow type I fibers of the soleus showed no change and a 4% decrease in force, respectively. Microgravity has been shown to increase the shortening velocity of the plantar flexors. This increase can be attributed both to an elevated maximal shortening velocity (V0) of the individual slow and fast fibers and to an increased expression of fibers containing fast myosin. Although the cause of the former is unknown, it might result from the selective loss of the thin filament actin and an associated decline in the internal drag during cross-bridge cycling. Despite the increase in fiber V0, peak power of the slow type I fiber was reduced following space flight. The decreased power was a direct result of the reduced force caused by the fiber atrophy. In addition to fiber atrophy and the loss of force and power, weightlessness reduces the ability of the slow soleus to oxidize fats and increases the utilization of muscle glycogen, at least in rats. This substrate change leads to an increased rate of fatigue. Finally, with return to the 1g environment of earth, rat studies have shown an increased occurrence of eccentric contraction-induced fiber damage. The damage occurs with re-loading and not in-flight, but the etiology has not been established.


2021 ◽  
Vol 134 (12) ◽  
Author(s):  
Eleonora Giagnorio ◽  
Claudia Malacarne ◽  
Renato Mantegazza ◽  
Silvia Bonanno ◽  
Stefania Marcuzzo

ABSTRACT Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of both upper and lower motor neurons (MNs). The main clinical features of ALS are motor function impairment, progressive muscle weakness, muscle atrophy and, ultimately, paralysis. Intrinsic skeletal muscle deterioration plays a crucial role in the disease and contributes to ALS progression. Currently, there are no effective treatments for ALS, highlighting the need to obtain a deeper understanding of the molecular events underlying degeneration of both MNs and muscle tissue, with the aim of developing successful therapies. Muscle tissue is enriched in a group of microRNAs called myomiRs, which are effective regulators of muscle homeostasis, plasticity and myogenesis in both physiological and pathological conditions. After providing an overview of ALS pathophysiology, with a focus on the role of skeletal muscle, we review the current literature on myomiR network dysregulation as a contributing factor to myogenic perturbations and muscle atrophy in ALS. We argue that, in view of their critical regulatory function at the interface between MNs and skeletal muscle fiber, myomiRs are worthy of further investigation as potential molecular targets of therapeutic strategies to improve ALS symptoms and counteract disease progression.


2017 ◽  
Author(s):  
Tianqi Xu ◽  
Jing Huo ◽  
Shuai Shao ◽  
Michelle Po ◽  
Taizo Kawano ◽  
...  

Descending signals from the brain play critical roles in controlling and modulating locomotion kinematics. In the Caenorhabditis elegans nervous system, descending AVB premotor interneurons exclusively form gap junctions with B-type motor neurons that drive forward locomotion. We combined genetic analysis, optogenetic manipulation, and computational modeling to elucidate the function of AVB-B gap junctions during forward locomotion. First, we found that some B-type motor neurons generated intrinsic rhythmic activity, constituting distributed central pattern generators. Second, AVB premotor interneurons drove bifurcation of B-type motor neuron dynamics, triggering their transition from stationary to oscillatory activity. Third, proprioceptive couplings between neighboring B-type motor neurons entrained the frequency of body oscillators, forcing coherent propagation of bending waves. Despite substantial anatomical differences between the worm motor circuit and those in higher model organisms, we uncovered converging principles that govern coordinated locomotion.Significance StatementA deep understanding of the neural basis of motor behavior must integrate neuromuscular dynamics, mechanosensory feedback, as well as global command signals, to predict behavioral dynamics. Here, we report on an integrative approach to defining the circuit logic underlying coordinated locomotion in C. elegans. Our combined experimental and computational analysis revealed that (1) motor neurons in C. elegans could function as intrinsic oscillators; (2) Descending inputs and proprioceptive couplings work synergistically to facilitate the sequential activation of motor neuron activities, allowing bending waves to propagate efficiently along the body. Our work thus represents a key step towards an integrative view of animal locomotion.


2015 ◽  
Vol 25 (4) ◽  
pp. 237 ◽  
Author(s):  
Sandra Zampieri ◽  
Simone Mosole ◽  
Stefan Löfler ◽  
Hannah Fruhmann ◽  
Samantha Burggraf ◽  
...  

Sarcopenia is the age-related loss of muscle mass and function, reducing force generation and mobility in the elderlies. Contributing factors include a severe decrease in both myofiber size and number as well as a decrease in the number of motor neurons innervating muscle fibers (mainly of fast type) which is sometimes accompanied by reinnervation of surviving slow type motor neurons (motor unit remodeling). Reduced mobility and functional limitations characterizing aging can promote a more sedentary lifestyle for older individuals, leading to a vicious circle further worsening muscle performance and the patients' quality of life, predisposing them to an increased risk of disability, and mortality. Several longitudinal studies have shown that regular exercise may extend life expectancy and reduce morbidity in aging people. Based on these findings, the Interreg IVa project aimed to recruit sedentary seniors with a normal life style and to train them for 9 weeks with either leg press (LP) exercise or electrical stimulation (ES). Before and at the end of both training periods, all the subjects were submitted to mobility functional tests and muscle biopsies from the Vastus Lateralis muscles of both legs. No signs of muscle damage and/or of inflammation were observed in muscle biopsies after the training. Functional tests showed that both LP and ES induced improvements of force and mobility of the trained subjects. Morphometrical and immunofluorescent analyses performed on muscle biopsies showed that ES significantly increased the size of fast type muscle fibers (p<0.001), together with a significant increase in the number of Pax7 and NCAM positive satellite cells (p<0.005). A significant decrease of slow type fiber diameter was observed in both ES and LP trained subjects (p<0.001). Altogether these results demonstrate the effectiveness of physical exercise either voluntary (LP) or passive (ES) to improve the functional performances of aging muscles. Here ES is demonstrated to be a safe home-based method to counteract fast type fiber atrophy, typically associated with aging skeletal muscle.


Sign in / Sign up

Export Citation Format

Share Document