scholarly journals Blocking the mitochondrial apoptotic pathway preserves motor neuron viability and function in a mouse model of amyotrophic lateral sclerosis

2010 ◽  
Vol 120 (10) ◽  
pp. 3673-3679 ◽  
Author(s):  
Nichole A. Reyes ◽  
Jill K. Fisher ◽  
Kathryn Austgen ◽  
Scott VandenBerg ◽  
Eric J. Huang ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
Motor Neuron ◽  
Apoptotic Pathway ◽  
Mitochondrial Apoptotic Pathway ◽  
And Function ◽  
Lateral Sclerosis

Survival motor neuron deficiency enhances progression in an amyotrophic lateral sclerosis mouse model

2009 ◽  
Vol 34 (3) ◽  
pp. 511-517 ◽  
Author(s):  
Bradley J. Turner ◽  
Nicholas J. Parkinson ◽  
Kay E. Davies ◽  
Kevin Talbot
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
Motor Neuron ◽  
Survival Motor Neuron ◽  
Lateral Sclerosis

scholarly journals Resveratrol Ameliorates Motor Neuron Degeneration and Improves Survival in SOD1G93AMouse Model of Amyotrophic Lateral Sclerosis

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Lin Song ◽  
Liang Chen ◽  
Xiaojie Zhang ◽  
Jia Li ◽  
Weidong Le
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Neuroprotective Effect ◽  
Disease Onset ◽  
Succinic Dehydrogenase ◽  
Immunofluorescent Staining ◽  
Nissl Staining ◽  
Apoptotic Pathway ◽  
Resveratrol Treatment ◽  
Lateral Sclerosis

Resveratrol has recently been used as a supplemental treatment for several neurological and nonneurological diseases. It is not known whether resveratrol has neuroprotective effect on amyotrophic lateral sclerosis (ALS). To assess the effect of resveratrol on the disease, we tested this agent on an ALS model ofSOD1G93Atransgenic mouse. Rotarod measurement was performed to measure the motor function of the ALS mice. Nissl staining and SMI-32 immunofluorescent staining were used to determine motor neurons survival in the spinal cord of the ALS mice. Hematoxylin-eosin (H&E), succinic dehydrogenase (SDH), and cytochrome oxidase (COX) staining were applied to pathologically analyze the skeletal muscles of the ALS mice. We found that resveratrol treatment significantly delayed the disease onset and prolonged the lifespan of the ALS mice. Furthermore, resveratrol treatment attenuated motor neuron loss, relieved muscle atrophy, and improved mitochondrial function of muscle fibers in the ALS mice. In addition, we demonstrated that resveratrol exerted these neuroprotective effects mainly through increasing the expression of Sirt1, consequently suppressing oxidative stress and downregulating p53 and its related apoptotic pathway. Collectively, our findings suggest that resveratrol might provide a promising therapeutic intervention for ALS.

scholarly journals Dissociation of disease onset, progression and sex differences from androgen receptor levels in a mouse model of amyotrophic lateral sclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Doris Tomas ◽  
Victoria M. McLeod ◽  
Mathew D. F. Chiam ◽  
Nayomi Wanniarachchillage ◽  
Wah C. Boon ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Sex Differences ◽  
Androgen Receptor ◽  
Mouse Model ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Disease Onset ◽  
Disease Course ◽  
Male Mice ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder caused by loss of motor neurons. ALS incidence is skewed towards males with typically earlier age of onset and limb site of onset. The androgen receptor (AR) is the major mediator of androgen effects in the body and is present extensively throughout the central nervous system, including motor neurons. Mutations in the AR gene lead to selective lower motor neuron degeneration in male spinal bulbar muscular atrophy (SBMA) patients, emphasising the importance of AR in maintaining motor neuron health and survival. To evaluate a potential role of AR in onset and progression of ALS, we generated SOD1G93A mice with either neural AR deletion or global human AR overexpression. Using a Cre-LoxP conditional gene knockout strategy, we report that neural deletion of AR has minimal impact on the disease course in SOD1G93A male mice. This outcome was potentially confounded by the metabolically disrupted Nestin-Cre phenotype, which likely conferred the profound lifespan extension observed in the SOD1G93A double transgenic male mice. In addition, overexpression of human AR produced no benefit to disease onset and progression in SOD1G93A mice. In conclusion, the disease course of SOD1G93A mice is independent of AR expression levels, implicating other mechanisms involved in mediating the sex differences in ALS. Our findings using Nestin-Cre mice, which show an inherent metabolic phenotype, led us to hypothesise that targeting hypermetabolism associated with ALS may be a more potent modulator of disease, than AR in this mouse model.

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