scholarly journals A high-fat jelly diet restores bioenergetic balance and extends lifespan in the presence of motor dysfunction and lumbar spinal cord motor neuron loss in TDP-43A315Tmutant C57BL6/J mice

2016 ◽  
Vol 9 (9) ◽  
pp. 1029-1037 ◽  
Author(s):  
Karen S. Coughlan ◽  
Luise Halang ◽  
Ina Woods ◽  
Jochen H. M. Prehn
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Motor Dysfunction ◽  
Lumbar Spinal Cord ◽  
High Fat ◽  
Neuron Loss ◽  
Motor Neuron Loss ◽  
Lumbar Spinal ◽  
Spinal Cord Motor Neuron

Lasting paraplegia caused by loss of lumbar spinal cord interneurons in rats: no direct correlation with motor neuron loss

2000 ◽  
Vol 93 (2) ◽  
pp. 266-275 ◽  
Author(s):  
Bassam Hadi ◽  
Y. Ping Zhang ◽  
Darlene A. Burke ◽  
Christopher B. Shields ◽  
David S. K. Magnuson
Keyword(s):  
Spinal Cord ◽  
Locomotor Activity ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Lumbar Spinal Cord ◽  
Neuron Loss ◽  
Content Type ◽  
Motor Neuron Loss ◽  
Lumbar Spinal ◽  
Fine Print

Object. The aims of this study were to investigate further the role played by lumbar spinal cord interneurons in the generation of locomotor activity and to develop a model of spinal cord injury suitable for testing neuron replacement strategies. Methods. Adult rats received intraspinal injections of kainic acid (KA). Locomotion was assessed weekly for 4 weeks by using the Basso, Beattie, and Bresnahan (BBB) 21-point locomotor scale, and transcranial magnetic motor evoked potentials (MMEPs) were recorded in gastrocnemius and quadriceps muscles at 1 and 4 weeks. No changes in transcranial MMEP latency were noted following KA injection, indicating that the descending motor pathways responsible for these responses, including the alpha motor neurons, were not compromised. Rats in which KA injections included much of the L-2 segment (10 animals) showed severe locomotor deficits, with a mean BBB score of 4.5 ± 3.6 (± standard deviation). Rats that received lesions rostral to the L-2 segment (four animals) were able to locomote and had a mean BBB score of 14.6 ± 2.6. Three rats that received only one injection bilaterally centered at L-2 (three animals) had a mean BBB score of 3.2 ± 2. Histological examination revealed variable loss of motor neurons limited to the injection site. There was no correlation between motor neuron loss and BBB score. Conclusions. Interneuron loss centered on the L-2 segment induces lasting paraplegia independent of motor neuron loss and white matter damage, supporting earlier suggestions that circuitry critical to the generator of locomotor activity (the central pattern generator) resides in this area. This injury model may prove ideal for studies of neuron replacement strategies.

scholarly journals Bisperoxovanadium promotes motor neuron survival and neuromuscular innervation in amyotrophic lateral sclerosis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Junmei Wang ◽  
Lydia Tierney ◽  
Ranjeet Mann ◽  
Thomas Lonsway ◽  
Chandler L. Walker
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Lumbar Spinal Cord ◽  
Therapeutic Effects ◽  
Spinal Cord Tissue ◽  
Neuron Loss ◽  
Neuroprotective Therapy ◽  
Motor Neuron Loss ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis (ALS) is the most common motor neuron (MN) disease, with no present cure. The progressive loss of MNs is the hallmark of ALS. We have previously shown the therapeutic effects of the phosphatase and tensin homolog (PTEN) inhibitor, potassium bisperoxo (picolinato) vanadium (bpV[pic]), in models of neurological injury and demonstrated significant neuroprotective effects on MN survival. However, accumulating evidence suggests PTEN is detrimental for MN survival in ALS. Therefore, we hypothesized that treating the mutant superoxide dismutase 1 G93A (mSOD1G93A) mouse model of ALS during motor neuron degeneration and an in vitro model of mSOD1G93A motor neuron injury with bpV(pic) would prevent motor neuron loss. To test our hypothesis, we treated mSOD1G93A mice intraperitoneally daily with 400 μg/kg bpV(pic) from 70 to 90 days of age. Immunolabeled MNs and microglial reactivity were analyzed in lumbar spinal cord tissue, and bpV(pic) treatment significantly ameliorated ventral horn motor neuron loss in mSOD1G93A mice (p = 0.003) while not significantly altering microglial reactivity (p = 0.701). Treatment with bpV(pic) also significantly increased neuromuscular innervation (p = 0.018) but did not affect muscle atrophy. We also cultured motor neuron-like NSC-34 cells transfected with a plasmid to overexpress mutant SOD1G93A and starved them in serum-free medium for 24 h with and without bpV(pic) and downstream inhibitor of Akt signaling, LY294002. In vitro, bpV(pic) improved neuronal viability, and Akt inhibition reversed this protective effect (p < 0.05). In conclusion, our study indicates systemic bpV(pic) treatment could be a valuable neuroprotective therapy for ALS.

scholarly journals Early Phrenic Motor Neuron Loss and Transient Respiratory Abnormalities after Unilateral Cervical Spinal Cord Contusion

2013 ◽  
Vol 30 (12) ◽  
pp. 1092-1099 ◽  
Author(s):  
Charles Nicaise ◽  
David M. Frank ◽  
Tamara J. Hala ◽  
Michèle Authelet ◽  
Roland Pochet ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Cervical Spinal Cord ◽  
Neuron Loss ◽  
Motor Neuron Loss ◽  
Spinal Cord Contusion

scholarly journals Blood–Spinal Cord Barrier Pericyte Reductions Contribute to Increased Capillary Permeability

2012 ◽  
Vol 32 (10) ◽  
pp. 1841-1852 ◽  
Author(s):  
Ethan A Winkler ◽  
Jesse D Sengillo ◽  
Robert D Bell ◽  
Joseph Wang ◽  
Berislav V Zlokovic
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Capillary Permeability ◽  
Serum Proteins ◽  
Brain Regions ◽  
Proper Function ◽  
Neuron Loss ◽  
Junction Protein ◽  
Motor Neuron Loss ◽  
Blood Spinal Cord Barrier

The blood–spinal cord barrier (BSCB) regulates molecular exchange between blood and spinal cord. Pericytes are presumed to be important cellular constituents of the BSCB. However, the regional abundance and vascular functions of spinal cord pericytes have yet to be determined. Utilizing wild-type mice, we show that spinal cord pericyte capillary coverage and number compared with the brain regions are reduced most prominently in the anterior horn. Regional pericyte variations are highly correlated with: (1) increased capillary permeability to 350 Da, 40,000 Da, and 150,000 Da, but not 2,000,000 Da fluorescent vascular tracers in cervical, thoracic, and lumbar regions and (2) diminished endothelial zonula occludens-1 (ZO-1) and occludin tight junction protein expression. Pericyte-deficient mutations ( Pdgfrβ F7/F7 mice) resulted in additional pericyte reductions in spinal cord capillaries leading to overt BSCB disruption to serum proteins, accumulation in motor neurons of cyotoxic thrombin and fibrin and motor neuron loss. Barrier disruption in perciyte-deficient mice coincided with further reductions in ZO-1 and occludin. These data suggest that pericytes contribute to proper function of the BSCB at the capillary level. Regional reductions in spinal cord pericytes may provide a cellular basis for heightened spinal cord barrier capillary permeability and motor neuron loss.

scholarly journals Muscle Atrophy and Motor Neuron Degeneration in Human NEDL1 Transgenic Mice

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Lin Zhang ◽  
Seiki Haraguchi ◽  
Tadayuki Koda ◽  
Kenji Hashimoto ◽  
Akira Nakagawara
Keyword(s):  
Spinal Cord ◽  
Transgenic Mice ◽  
Motor Neuron ◽  
Muscle Atrophy ◽  
Lumbar Spinal Cord ◽  
Wild Type ◽  
Proteasome Pathway ◽  
Familial Als ◽  
Motor Abnormalities ◽  
Lumbar Spinal

Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disease. Approximately 20% cases of familial ALS show the mutation in the superoxide dismutase-1 (SOD1) gene. We previously demonstrated that homologue to E6AP carboxyl terminus- (HECT-) type ubiquitin protein E3 ligase (NEDL1) physically bind to mutated SOD1 protein but not wild-type SOD1 and promote the degradation of mutated SOD1 protein through ubiquitin-mediated proteasome pathway. To further understand the role of NEDL1 involved in the pathogenesis of familial ALS, we generated transgenic mice with human NEDL1 cDNA. The transgenic mice with human NEDL1 expression showed motor dysfunctions in rotarod, hanging wire, and footprint pattern examination. Histological studies indicated degeneration of neurons in the lumbar spinal cord and muscle atrophy. The number of activated microglia in the spinal cord of transgenic mice was significantly higher than that of wild-type mice, suggesting that inflammation might be observed in the spinal cord of transgenic mice. In conclusion, these findings suggest that the human NEDL1 transgenic mice might develop ALS-like symptoms, showing signs of motor abnormalities, accompanied with significant reduction in muscle strength.

scholarly journals Blood-spinal cord barrier leakage is independent of motor neuron pathology in ALS

2019 ◽  
Author(s):  
Sarah Waters ◽  
Birger V. Dieriks ◽  
Molly E. V. Swanson ◽  
Yibin Zhang ◽  
Natasha L. Grimsey ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Lower Motor Neuron ◽  
Spinal Cord Tissue ◽  
Thoracic Spinal Cord ◽  
Neuron Loss ◽  
Thoracic Spinal ◽  
Potential Biomarker ◽  
Motor Neuron Loss ◽  
Blood Spinal Cord Barrier

AbstractBackgroundAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving progressive degeneration of upper and lower motor neurons. Both lower motor neuron loss and the deposition of phosphorylated TDP-43 inclusions display regional patterning along the spinal cord. The blood-spinal cord barrier (BSCB) ordinarily restricts entry into the spinal cord parenchyma of blood components that are neurotoxic, but in ALS there is evidence for barrier breakdown. Here we sought to examine whether BSCB breakdown, motor neuron loss, and TDP-43 proteinopathy display the same regional patterning across and along the spinal cord.MethodsWe measured cerebrospinal fluid (CSF) hemoglobin in living ALS patients (n=87 controls, n=236 ALS) as a potential biomarker of BSCB and blood-brain barrier leakage. We then immunostained cervical, thoracic, and lumbar post mortem spinal cord tissue (n=5 controls, n=13 ALS) and employed semi-automated imaging and analysis to quantify and map lower motor neuron loss and phosphorylated TDP-43 inclusion load against hemoglobin leakage.ResultsMotor neuron loss and TDP-43 proteinopathy were seen at all three levels of the ALS spinal cord, with most abundant TDP-43 deposition in the ventral grey (lamina IX) of the cervical and lumbar cord. In contrast, hemoglobin leakage was observed along the ALS spinal cord axis but was most severe in the dorsal grey and white matter in the thoracic spinal cord.ConclusionsOur data show that leakage of the blood-spinal cord barrier occurs during life but at end-stage its distribution is independent from the major motor neuron pathology and is unlikely to be a major contributor to pathogenesis in ALS.

scholarly journals Blood-spinal cord barrier leakage is independent of motor neuron pathology in ALS

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sarah Waters ◽  
Molly E. V. Swanson ◽  
Birger V. Dieriks ◽  
Yibin B. Zhang ◽  
Natasha L. Grimsey ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Lower Motor Neuron ◽  
Spinal Cord Tissue ◽  
Thoracic Spinal Cord ◽  
Neuron Loss ◽  
Thoracic Spinal ◽  
Potential Biomarker ◽  
Motor Neuron Loss ◽  
Blood Spinal Cord Barrier

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving progressive degeneration of upper and lower motor neurons. The pattern of lower motor neuron loss along the spinal cord follows the pattern of deposition of phosphorylated TDP-43 aggregates. The blood-spinal cord barrier (BSCB) restricts entry into the spinal cord parenchyma of blood components that can promote motor neuron degeneration, but in ALS there is evidence for barrier breakdown. Here we sought to quantify BSCB breakdown along the spinal cord axis, to determine whether BSCB breakdown displays the same patterning as motor neuron loss and TDP-43 proteinopathy. Cerebrospinal fluid hemoglobin was measured in living ALS patients (n = 87 control, n = 236 ALS) as a potential biomarker of BSCB and blood–brain barrier leakage. Cervical, thoracic, and lumbar post-mortem spinal cord tissue (n = 5 control, n = 13 ALS) were then immunolabelled and semi-automated imaging and analysis performed to quantify hemoglobin leakage, lower motor neuron loss, and phosphorylated TDP-43 inclusion load. Hemoglobin leakage was observed along the whole ALS spinal cord axis and was most severe in the dorsal gray and white matter in the thoracic spinal cord. In contrast, motor neuron loss and TDP-43 proteinopathy were seen at all three levels of the ALS spinal cord, with most abundant TDP-43 deposition in the anterior gray matter of the cervical and lumbar cord. Our data show that leakage of the BSCB occurs during life, but at end-stage disease the regions with most severe BSCB damage are not those where TDP-43 accumulation is most abundant. This suggests BSCB leakage and TDP-43 pathology are independent pathologies in ALS.

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