Histological Bulbar Manifestations in the ALS Rat

Kashlan, Osama N.; Kashlan, Bader N.; Oh, Sang Su; McGinley, Lisa M.; Chen, Kevin S.; Kupfer, Robbi A.; Erman, Audrey B.; Sakowski, Stacey A.; Feldman, Eva L.

doi:10.1159/000377725

Cited by 7 publications

(6 citation statements)

References 15 publications

(21 reference statements)

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“…This modest but significant difference in tongue force during the training sessions during the last week of testing was consistent with our finding of GG denervation in the SOD1-G93A rats. It is also consistent with a recent report of modest but significant hypoglossal motor neuron loss and tongue muscle NMJ denervation in SOD1-G93A rats 12 . It is possible that differences in lifespan due to genetic drift accounted for the disparity between reported findings of NMJ denervation and hypoglossal motor neuron loss in SOD1-G93A rats.…”

Section: Discussionsupporting

confidence: 93%

“…It is also consistent with a recent report of modest but significant hypoglossal motor neuron loss and tongue muscle NMJ denervation in SOD1-G93A rats. 12 It is possible that differences in lifespan caused by genetic drift accounted for the disparity between reported findings of NMJ denervation and hypoglossal motor neuron loss in SOD1-G93A rats. The SOD1-G93A rats in our study and in the Kashlan et al 12 study reached end stage later (~30 and 27 weeks, respectively) than those in the Llado et al 11 study (18 weeks).…”

Section: Discussionmentioning

confidence: 96%

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Effects of Tongue Force Training on Bulbar Motor Function in the Female SOD1-G93A Rat Model of Amyotrophic Lateral Sclerosis

Shuler

Kumar

et al. 2016

Neurorehabil Neural Repair

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Background The use of exercise in Amyotrophic Lateral Sclerosis (ALS) is controversial. Although moderate exercise appears to be beneficial for limb muscles in ALS, the effects of exercise on bulbar muscles such as the tongue have not been studied. Objective The aim of this study was to determine the effects of tongue force training on bulbar motor function in the SOD1-G93A rat model of ALS. Methods We compared the effects of tongue force training on bulbar motor function and neuromuscular junction (NMJ) innervation in female SOD1-G93A rats and age-matched female wild-type controls. Half of each group underwent afternoon tongue force training sessions, while all rats were tested under minimal force conditions in the mornings. Results Tongue force did not differ between the SOD1-G93A rats and healthy controls during the morning testing sessions, nor was it affected by training. Surprisingly, decreases in tongue motility, the number of licks per session, and body weight were greater in the tongue force-trained SOD1-G93A rats. Forelimb grip force, survival, and denervation of the genioglossus muscle did not differ between the trained and untrained SOD1-G93A rats. Genioglossus innervation was correlated with changes in tongue force but not tongue motility in SOD1-G93A rats at end stage. Conclusions The results indicate a potential deleterious effect of tongue force training on tongue motility in female SOD1-G93A rats. The lack of relationship between genioglossus innervation and tongue motility suggest that factors other than lower motor neuron integrity likely accounted for this effect.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 96%

Effects of Tongue Force Training on Bulbar Motor Function in the Female SOD1-G93A Rat Model of Amyotrophic Lateral Sclerosis

Shuler

Kumar

et al. 2016

Neurorehabil Neural Repair

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“…They develop UMN and LMN degeneration and similar neuropathological findings. SOD1 G93A rats also have motor neuron (MN) loss in trigeminal, facial and hypoglossal nuclei which correspond to features of bulbar ALS [ 83 ]. Rats are of particular interest for ALS research because of their size which facilitate intra-thecal or intra cerebro-ventricular injection for preclinical trials.…”

Section: Reviewmentioning

confidence: 99%

From animal models to human disease: a genetic approach for personalized medicine in ALS

Picher-Martel

Valdmanis

Gould

et al. 2016

acta neuropathol commun

124

104

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Amyotrophic Lateral Sclerosis (ALS) is the most frequent motor neuron disease in adults. Classical ALS is characterized by the death of upper and lower motor neurons leading to progressive paralysis. Approximately 10 % of ALS patients have familial form of the disease. Numerous different gene mutations have been found in familial cases of ALS, such as mutations in superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP-43), fused in sarcoma (FUS), C9ORF72, ubiquilin-2 (UBQLN2), optineurin (OPTN) and others. Multiple animal models were generated to mimic the disease and to test future treatments. However, no animal model fully replicates the spectrum of phenotypes in the human disease and it is difficult to assess how a therapeutic effect in disease models can predict efficacy in humans. Importantly, the genetic and phenotypic heterogeneity of ALS leads to a variety of responses to similar treatment regimens. From this has emerged the concept of personalized medicine (PM), which is a medical scheme that combines study of genetic, environmental and clinical diagnostic testing, including biomarkers, to individualized patient care. In this perspective, we used subgroups of specific ALS-linked gene mutations to go through existing animal models and to provide a comprehensive profile of the differences and similarities between animal models of disease and human disease. Finally, we reviewed application of biomarkers and gene therapies relevant in personalized medicine approach. For instance, this includes viral delivering of antisense oligonucleotide and small interfering RNA in SOD1, TDP-43 and C9orf72 mice models. Promising gene therapies raised possibilities for treating differently the major mutations in familial ALS cases.

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“…In this nucleus, only few degenerating hallmarks have been observed, such as pyknotic nuclei or Bunina bodies [1]. The apparent resistance of the oculomotor and Onuf's nuclei contrasts with the progressive degeneration of spinal, hypoglossal and trigeminal MNs responsible for the locomotion, swallowing and the control of the jaw musculature, respectively [33,34] (Figure 1).…”

Section: Onuf/oculomotor Versus Spinal/hypoglossal Mnsmentioning

confidence: 99%

Selective Vulnerability of Neuronal Subtypes in ALS: A Fertile Ground for the Identification of Therapeutic Targets

Rochat¹,

Bernard-Marissal²,

Schneider³

2016

Update on Amyotrophic Lateral Sclerosis

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It is well defined that subpopulations of motoneurons have different vulnerability to the pathology causing amyotrophic lateral sclerosis (ALS). In the spinal cord, the fast fatigable motoneurons have been shown to be the first to degenerate, followed by fatigue-resistant and slow motoneurons. In contrast motoneurons located in the Onuf's and oculomotor nuclei appear to be resistant to disease. With a focus on research mainly done on mice overexpressing the mutated human superoxide dismutase (SOD1) protein, we review recent studies exploring the mechanisms that underlie the selective vulnerability of the various motoneuron subtypes. By comparing differences in gene expression between these populations, it has been possible to identify factors, which critically determine the survival of motoneurons and the neuromuscular function in the pathologic context of ALS. Furthermore, we discuss the contribution of non-cell autonomous processes, involving glial cells and the skeletal muscle, in the neurodegenerative process. Exploring the cause of neurodegeneration from the angle of the selective neuronal vulnerability has recently led to the identification of novel targets, which open opportunities for therapeutic intervention against ALS.

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Histological Bulbar Manifestations in the ALS Rat

Cited by 7 publications

References 15 publications

Effects of Tongue Force Training on Bulbar Motor Function in the Female SOD1-G93A Rat Model of Amyotrophic Lateral Sclerosis

Effects of Tongue Force Training on Bulbar Motor Function in the Female SOD1-G93A Rat Model of Amyotrophic Lateral Sclerosis

From animal models to human disease: a genetic approach for personalized medicine in ALS

Selective Vulnerability of Neuronal Subtypes in ALS: A Fertile Ground for the Identification of Therapeutic Targets

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