scholarly journals Analysis of retrograde transport in motor neurons reveals common endocytic carriers for tetanus toxin and neurotrophin receptor p75NTR

2002 ◽  
Vol 156 (2) ◽  
pp. 233-240 ◽  
Author(s):  
Giovanna Lalli ◽  
Giampietro Schiavo
Keyword(s):  
Motor Neurons ◽  
Tetanus Toxin ◽  
Experimental System ◽  
Retrograde Transport ◽  
Endocytic Pathway ◽  
Neurotrophin Receptor ◽  
Tubular Structures ◽  
Growth And Survival ◽  
Membrane Compartments ◽  
The Central Nervous System

Axonal retrograde transport is essential for neuronal growth and survival. However, the nature and dynamics of the membrane compartments involved in this process are poorly characterized. To shed light on this pathway, we established an experimental system for the visualization and the quantitative study of retrograde transport in living motor neurons based on a fluorescent fragment of tetanus toxin (TeNT HC). Morphological and kinetic analysis of TeNT HC retrograde carriers reveals two major groups of organelles: round vesicles and fast tubular structures. TeNT HC carriers lack markers of the classical endocytic pathway and are not acidified during axonal transport. Importantly, TeNT HC and NGF share the same retrograde transport organelles, which are characterized by the presence of the neurotrophin receptor p75NTR. Our results provide the first direct visualization of retrograde transport in living motor neurons, and reveal a novel retrograde route that could be used both by physiological ligands (i.e., neurotrophins) and TeNT to enter the central nervous system.

scholarly journals The Expression and Significance of Metallothioneins in Murine Organs and Tissues Following Mercury Vapour Exposure

2003 ◽  
Vol 31 (5) ◽  
pp. 514-523 ◽  
Author(s):  
Roger Kevin Stankovic ◽  
Victor Lee ◽  
Murat Kekic ◽  
Clive Harper
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Motor System ◽  
Grey Matter ◽  
Retrograde Transport ◽  
Ventral Root ◽  
Mercury Vapour ◽  
Wild Type ◽  
Double Knockout ◽  
The Central Nervous System

The fate of inspired mercury vapour (Hg0) is critical in the central nervous system (CNS) where it can circumvent the blood—brain barrier (BBB) at the neuromuscular junction (NMJ) and accumulate indefinitely in motor neurons by retrograde transport. The detoxification of systemic Hg0 by lung and liver requires investigation. We exposed 129/Sv wild-type (Wt) and 129/Sv MT-I, II double knockout (KO) mice to 500 μg Hg0/m3 for 4 hours to investigate the expression of MT in the lung, liver, and spinal cord following Hg0 exposure using unexposed groups as controls. There were congestive changes in liver and lung of both Wt and MT-KO groups of Hg0-treated mice; these changes appeared more pronounced in the MT-KO group. Motor neurons in the spinal cord did not show any pathological changes. Based on expression of MT, liver appears to have a major role in trapping and stabilising mercury. In the spinal cord, MT was expressed in all white matter astrocytes and in some grey matter astrocytes. Notably, motor neurons did not express MT, and the presence of MT could not be demonstrated in the axons of the ventral root. The absence of MT expression in motor neurons and their axons suggests the dependence of the motor system on the detoxifying capacity of liver MTs.

scholarly journals Flux of signalling endosomes undergoing axonal retrograde transport is encoded by presynaptic activity and TrkB

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Tong Wang ◽  
Sally Martin ◽  
Tam H. Nguyen ◽  
Callista B. Harper ◽  
Rachel S. Gormal ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Hippocampal Neurons ◽  
Super Resolution ◽  
Retrograde Transport ◽  
Synaptic Activity ◽  
Neurotrophin Receptor ◽  
Independent Manner ◽  
Cholera Toxin Subunit B ◽  
Super Resolution Microscopy ◽  
Subunit B

AbstractAxonal retrograde transport of signalling endosomes from the nerve terminal to the soma underpins survival. As each signalling endosome carries a quantal amount of activated receptors, we hypothesized that it is the frequency of endosomes reaching the soma that determines the scale of the trophic signal. Here we show that upregulating synaptic activity markedly increased the flux of plasma membrane-derived retrograde endosomes (labelled using cholera toxin subunit-B: CTB) in hippocampal neurons cultured in microfluidic devices, and liveDrosophilalarval motor neurons. Electron and super-resolution microscopy analyses revealed that the fast-moving sub-diffraction-limited CTB carriers contained the TrkB neurotrophin receptor, transiently activated by synaptic activity in a BDNF-independent manner. Pharmacological and genetic inhibition of TrkB activation selectively prevented the coupling between synaptic activity and the retrograde flux of signalling endosomes. TrkB activity therefore controls the encoding of synaptic activity experienced by nerve terminals, digitalized as the flux of retrogradely transported signalling endosomes.

scholarly journals The Skeletal Muscle Emerges as a New Disease Target in Amyotrophic Lateral Sclerosis

2021 ◽  
Vol 11 (7) ◽  
pp. 671
Author(s):  
Oihane Pikatza-Menoio ◽  
Amaia Elicegui ◽  
Xabier Bengoetxea ◽  
Neia Naldaiz-Gastesi ◽  
Adolfo López de Munain ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amyotrophic Lateral Sclerosis ◽  
Muscle Tissue ◽  
Motor Neurons ◽  
Neurodegenerative Disorder ◽  
Disease Onset ◽  
Fine Tuning ◽  
Current State ◽  
The Central Nervous System ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that leads to progressive degeneration of motor neurons (MNs) and severe muscle atrophy without effective treatment. Most research on ALS has been focused on the study of MNs and supporting cells of the central nervous system. Strikingly, the recent observations of pathological changes in muscle occurring before disease onset and independent from MN degeneration have bolstered the interest for the study of muscle tissue as a potential target for delivery of therapies for ALS. Skeletal muscle has just been described as a tissue with an important secretory function that is toxic to MNs in the context of ALS. Moreover, a fine-tuning balance between biosynthetic and atrophic pathways is necessary to induce myogenesis for muscle tissue repair. Compromising this response due to primary metabolic abnormalities in the muscle could trigger defective muscle regeneration and neuromuscular junction restoration, with deleterious consequences for MNs and thereby hastening the development of ALS. However, it remains puzzling how backward signaling from the muscle could impinge on MN death. This review provides a comprehensive analysis on the current state-of-the-art of the role of the skeletal muscle in ALS, highlighting its contribution to the neurodegeneration in ALS through backward-signaling processes as a newly uncovered mechanism for a peripheral etiopathogenesis of the disease.

scholarly journals Anatomy and Neural Pathways Modulating Distinct Locomotor Behaviors in Drosophila Larva

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 90
Author(s):  
Swetha B. M. Gowda ◽  
Safa Salim ◽  
Farhan Mohammad
Keyword(s):  
Motor Neurons ◽  
Model Systems ◽  
Neural Pathways ◽  
Animal Movements ◽  
Drosophila Larvae ◽  
The Central Nervous System ◽  
Drosophila Larva ◽  
Locomotor Behaviors ◽  
Basic Level

The control of movements is a fundamental feature shared by all animals. At the most basic level, simple movements are generated by coordinated neural activity and muscle contraction patterns that are controlled by the central nervous system. How behavioral responses to various sensory inputs are processed and integrated by the downstream neural network to produce flexible and adaptive behaviors remains an intense area of investigation in many laboratories. Due to recent advances in experimental techniques, many fundamental neural pathways underlying animal movements have now been elucidated. For example, while the role of motor neurons in locomotion has been studied in great detail, the roles of interneurons in animal movements in both basic and noxious environments have only recently been realized. However, the genetic and transmitter identities of many of these interneurons remains unclear. In this review, we provide an overview of the underlying circuitry and neural pathways required by Drosophila larvae to produce successful movements. By improving our understanding of locomotor circuitry in model systems such as Drosophila, we will have a better understanding of how neural circuits in organisms with different bodies and brains lead to distinct locomotion types at the organism level. The understanding of genetic and physiological components of these movements types also provides directions to understand movements in higher organisms.

scholarly journals Targeted axonal import (TAxI) peptide delivers functional proteins into spinal cord motor neurons after peripheral administration

2016 ◽  
Vol 113 (9) ◽  
pp. 2514-2519 ◽  
Author(s):  
Drew L. Sellers ◽  
Jamie M. Bergen ◽  
Russell N. Johnson ◽  
Heidi Back ◽  
John M. Ravits ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Unmet Need ◽  
Nerve Roots ◽  
Biologic Drugs ◽  
Administration Routes ◽  
Macromolecular Drugs ◽  
The Central Nervous System ◽  
Clinical Potential

A significant unmet need in treating neurodegenerative disease is effective methods for delivery of biologic drugs, such as peptides, proteins, or nucleic acids into the central nervous system (CNS). To date, there are no operative technologies for the delivery of macromolecular drugs to the CNS via peripheral administration routes. Using an in vivo phage-display screen, we identify a peptide, targeted axonal import (TAxI), that enriched recombinant bacteriophage accumulation and delivered protein cargo into spinal cord motor neurons after intramuscular injection. In animals with transected peripheral nerve roots, TAxI delivery into motor neurons after peripheral administration was inhibited, suggesting a retrograde axonal transport mechanism for delivery into the CNS. Notably, TAxI-Cre recombinase fusion proteins induced selective recombination and tdTomato-reporter expression in motor neurons after intramuscular injections. Furthermore, TAxI peptide was shown to label motor neurons in the human tissue. The demonstration of a nonviral-mediated delivery of functional proteins into the spinal cord establishes the clinical potential of this technology for minimally invasive administration of CNS-targeted therapeutics.

Characterization of Myoelectric Signals Using System Identification Techniques

2004 ◽  
Author(s):  
Jeffrey T. Bingham ◽  
Marco P. Schoen
Keyword(s):  
System Identification ◽  
Motor Neurons ◽  
Current System ◽  
Electrical Potential ◽  
Computer Software ◽  
The Body ◽  
Myoelectric Signals ◽  
Hand Motion ◽  
The Central Nervous System

Human muscle motion is initiated in the central nervous system where a nervous signal travels through the body and the motor neurons excite the muscles to move. These signals, termed myoelectric signals, can be measured on the surface of the skin as an electrical potential. By analyzing these signals it is possible to determine the muscle actions the signals elicit, and thus can be used in manipulating smart prostheses and teleoperation of machinery. Due to the randomness of myoelectric signals, identification of the signals is not complete, therefore the goal of this project is to complete a study of the characterization of one set of hand motions using current system identification methods. The gripping motion of the hand and the corresponding myoelectric signals are measured and the data captured with a personal computer. Using computer software the captured data are processed and finally subjected to several system identification routines. Using this technique it is possible to construct a mathematical model that correlates the myoelectric signals with the matching hand motion.

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