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 Tail Nerve Electrical Stimulation and Electro-Acupuncture Can Protect Spinal Motor Neurons and Alleviate Muscle Atrophy after Spinal Cord Transection in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Yu-Ting Zhang ◽  
Hui Jin ◽  
Jun-Hua Wang ◽  
Lan-Yu Wen ◽  
Yang Yang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Muscle Atrophy ◽  
Motor Neurons ◽  
Lumbar Spinal Cord ◽  
Hindlimb Muscle ◽  
Neurotrophin 3 ◽  
Spinal Cord Segment ◽  
Cord Injury ◽  
Lumbar Spinal

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.

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 Decreased GLT-1 and increased SOD1 and HO-1 expression in astrocytes contribute to lumbar spinal cord vulnerability of SOD1-G93A transgenic mice

FEBS Letters ◽  
2010 ◽  
Vol 584 (8) ◽  
pp. 1615-1622 ◽  
Author(s):  
Yansu Guo ◽  
Weisong Duan ◽  
Zhongyao Li ◽  
Jing Huang ◽  
Yunxia Yin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Transgenic Mice ◽  
Lumbar Spinal Cord ◽  
Lumbar Spinal ◽  
G93a Transgenic Mice

Ultrastructural diversity of inclusions and aggregations in the lumbar spinal cord of SOD1-G93A transgenic mice

2010 ◽  
Vol 1353 ◽  
pp. 234-244 ◽  
Author(s):  
Yansu Guo ◽  
Chunyan Li ◽  
Dongxia Wu ◽  
Shuyu Wu ◽  
Cheng Yang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Transgenic Mice ◽  
Lumbar Spinal Cord ◽  
Lumbar Spinal ◽  
G93a Transgenic Mice
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