scholarly journals Novel Mechanisms of Spinal Cord Plasticity in a Mouse Model of Motoneuron Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Rosario Gulino ◽  
Rosalba Parenti ◽  
Massimo Gulisano
Keyword(s):  
Spinal Cord ◽  
Synaptic Plasticity ◽  
Mouse Model ◽  
Toxin B ◽  
Spinal Plasticity ◽  
Important Regulator ◽  
Dependent Modification ◽  
Spinal Cord Repair ◽  
Activity Dependent ◽  
Lateral Sclerosis

A hopeful spinal cord repairing strategy involves the activation of neural precursor cells. Unfortunately, their ability to generate neurons after injury appears limited. Another process promoting functional recovery is synaptic plasticity. We have previously studied some mechanisms of spinal plasticity involving BDNF, Shh, Notch-1, Numb, and Noggin, by using a mouse model of motoneuron depletion induced by cholera toxin-B saporin. TDP-43 is a nuclear RNA/DNA binding protein involved in amyotrophic lateral sclerosis. Interestingly, TDP-43 could be localized at the synapse and affect synaptic strength. Here, we would like to deepen the investigation of this model of spinal plasticity. After lesion, we observed a glial reaction and an activity-dependent modification of Shh, Noggin, and Numb proteins. By using multivariate regression models, we found that Shh and Noggin could affect motor performance and that these proteins could be associated with both TDP-43 and Numb. Our data suggest that TDP-43 is likely an important regulator of synaptic plasticity, probably in collaboration with other proteins involved in both neurogenesis and synaptic plasticity. Moreover, given the rapidly increasing knowledge about spinal cord plasticity, we believe that further efforts to achieve spinal cord repair by stimulating the intrinsic potential of spinal cord will produce interesting results.

scholarly journals Selective neuronal degeneration in MATR3 S85C knock-in mouse model of early-stage ALS

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ching Serena Kao ◽  
Rebekah van Bruggen ◽  
Jihye Rachel Kim ◽  
Xiao Xiao Lily Chen ◽  
Cadia Chan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mouse Model ◽  
Motor Neurons ◽  
Neuronal Degeneration ◽  
Early Stage ◽  
Motor Impairment ◽  
Preclinical Research ◽  
Cell Degeneration ◽  
Promising Tool ◽  
Lateral Sclerosis

Abstract A missense mutation, S85C, in the MATR3 gene is a genetic cause for amyotrophic lateral sclerosis (ALS). It is unclear how the S85C mutation affects MATR3 function and contributes to disease. Here, we develop a mouse model that harbors the S85C mutation in the endogenous Matr3 locus using the CRISPR/Cas9 system. MATR3 S85C knock-in mice recapitulate behavioral and neuropathological features of early-stage ALS including motor impairment, muscle atrophy, neuromuscular junction defects, Purkinje cell degeneration and neuroinflammation in the cerebellum and spinal cord. Our neuropathology data reveals a loss of MATR3 S85C protein in the cell bodies of Purkinje cells and motor neurons, suggesting that a decrease in functional MATR3 levels or loss of MATR3 function contributes to neuronal defects. Our findings demonstrate that the MATR3 S85C mouse model mimics aspects of early-stage ALS and would be a promising tool for future basic and preclinical research.

scholarly journals ALS-Associated SOD1(G93A) Decreases SERCA Pump Levels and Increases Store-Operated Ca2+ Entry in Primary Spinal Cord Astrocytes from a Transgenic Mouse Model

2019 ◽  
Vol 20 (20) ◽  
pp. 5151 ◽  
Author(s):  
Norante ◽  
Peggion ◽  
Rossi ◽  
Martorana ◽  
De Mario ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mouse Model ◽  
Motor Neurons ◽  
Neurodegenerative Disorder ◽  
Nervous System Function ◽  
Serca Pump ◽  
Selective Death ◽  
First Time ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective death of motor neurons (MNs), probably by a combination of cell- and non-cell-autonomous processes. The past decades have brought many important insights into the role of astrocytes in nervous system function and disease, including the implication in ALS pathogenesis possibly through the impairment of Ca2+-dependent astrocyte-MN cross-talk. In this respect, it has been recently proposed that altered astrocytic store-operated Ca2+ entry (SOCE) may underlie aberrant gliotransmitter release and astrocyte-mediated neurotoxicity in ALS. These observations prompted us to a thorough investigation of SOCE in primary astrocytes from the spinal cord of the SOD1(G93A) ALS mouse model in comparison with the SOD1(WT)-expressing controls. To this purpose, we employed, for the first time in the field, genetically-encoded Ca2+ indicators, allowing the direct assessment of Ca2+ fluctuations in different cell domains. We found increased SOCE, associated with decreased expression of the sarco-endoplasmic reticulum Ca2+-ATPase and lower ER resting Ca2+ concentration in SOD1(G93A) astrocytes compared to control cells. Such findings add novel insights into the involvement of astrocytes in ALS MN damage.

scholarly journals Clinical Testing and Spinal Cord Removal in a Mouse Model for Amyotrophic Lateral Sclerosis (ALS)

10.3791/3936 ◽  
2012 ◽  
Author(s):  
René Günther ◽  
Martin Suhr ◽  
Jan C. Koch ◽  
Mathias Bähr ◽  
Paul Lingor ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
Clinical Testing ◽  
Lateral Sclerosis

Impaired Pentose Phosphate Pathway in the Spinal Cord of the hSOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

2019 ◽  
Vol 56 (8) ◽  
pp. 5844-5855 ◽  
Author(s):  
Tesfaye Wolde Tefera ◽  
Katherine Bartlett ◽  
Shirley S. Tran ◽  
Mark P. Hodson ◽  
Karin Borges
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
Pentose Phosphate Pathway ◽  
Pentose Phosphate ◽  
Lateral Sclerosis
Sign in / Sign up

Export Citation Format

Share Document