Adipose-derived stem cell conditioned medium impacts asymptomatic peripheral neuromuscular denervation in the mutant superoxide dismutase (G93A) transgenic mouse model of amyotrophic lateral sclerosis.

Adipose-derived stem cell conditioned medium impacts asymptomatic peripheral neuromuscular denervation in the mutant superoxide dismutase (G93A) transgenic mouse model of amyotrophic lateral sclerosis. Restor Neurol Neurosci. 2018 Jul 13;: Authors: Walker LC, Meadows MR, Du Y, March LK, Jones JK Abstract BACKGROUND: Amyotrophic lateral sclerosis (ALS) is devastating, leading to paralysis and death. Disease onset begins pre-symptomatically through spinal motor neuron (MN) axon die-back from musculature at ∼47 days of age in the mutant superoxide dismutase 1 (mSOD1G93A) transgenic ALS mouse model. This period may be optimal to assess potential therapies. We previously demonstrated that post-symptomatic adipose-derived stem cell conditioned medium (ASC-CM) treatment is neuroprotective in mSOD1G93A mice. We hypothesized that early disease onset treatment could ameliorate neuromuscular junction (NMJ) disruption. OBJECTIVE: To determine whether pre-symptom administration of ASC-CM prevents early NMJ disconnection. METHODS: We confirmed the NMJ denervation time course in mSOD1G93A mice using co-labeling of neurofilament and post-synaptic acetylcholine receptors (AchR) by α-bungarotoxin. We determined whether ASC-CM ameliorates early NMJ loss in mSOD1G93A mice by systemically administering 200μl ASC-CM or vehicle medium daily from postnatal days 35 to 47 and quantifying intact NMJs through co-labeling of neurofilament and synaptophysin with &...
Source: Restorative Neurology and Neuroscience - Category: Neurology Tags: Restor Neurol Neurosci Source Type: research

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Mir-17∼92 Confers Motor Neuron Subtype Differential Resistance to ALS-Associated Degeneration. Cell Stem Cell. 2019 May 21;: Authors: Tung YT, Peng KC, Chen YC, Yen YP, Chang M, Thams S, Chen JA Abstract Progressive degeneration of motor neurons (MNs) is the hallmark of amyotrophic lateral sclerosis (ALS). Limb-innervating lateral motor column MNs (LMC-MNs) seem to be particularly vulnerable and are among the first MNs affected in ALS. Here, we report association of this differential susceptibility with reduced expression of the mir-17∼92 cluster in LMC-MNs prior to disease onset. Reduced mir-...
Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research
Publication date: Available online 9 May 2019Source: Stem Cell ReportsAuthor(s): Ilary Allodi, Jik Nijssen, Julio Aguila Benitez, Christoph Schweingruber, Andrea Fuchs, Gillian Bonvicini, Ming Cao, Ole Kiehn, Eva HedlundSummaryOculomotor neurons, which regulate eye movement, are resilient to degeneration in the lethal motor neuron disease amyotrophic lateral sclerosis (ALS). It would be highly advantageous if motor neuron resilience could be modeled in vitro. Toward this goal, we generated a high proportion of oculomotor neurons from mouse embryonic stem cells through temporal overexpression of PHOX2A in neuronal prog...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
Contributors : Jik Nijssen ; Julio Aguila ; Ilary Allodi ; Eva HedlundSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusOculomotor neurons, which regulate eye movement, are resilient to degeneration in the lethal motor neuron disease amyotrophic lateral sclerosis (ALS). It would be highly advantageous if motor neuron resilience could be modeled in vitro. Towards this goal, we generated a high proportion of oculomotor neurons from mouse embryonic stem cells through temporal overexpression of Phox2a in neuronal progenitors. We demonstrate, using immunocytochemistry and RNA sequencing, tha...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
Contributors : Julio Aguila Benitez ; Jik Nijssen ; Christoph Schweingruber ; Eva HedlundSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensOculomotor neurons, which regulate eye movement, are resilient to degeneration in the lethal motor neuron disease amyotrophic lateral sclerosis (ALS). It would be highly advantageous if motor neuron resilience could be modeled in vitro. Towards this goal, we generated a high proportion of oculomotor neurons from mouse embryonic stem cells through temporal overexpression of Phox2a in neuronal progenitors. We demonstrate, using electrophysiology, immun...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Conclusion and Perspectives The ARE has been studied for a long time, and about 20 ARE-BPs have been identified since discovery of first ARE-BP, AUF1 (Brewer, 1991; Garcia-Maurino et al., 2017). The specific target mRNAs for different ARE-BPs, as well as their molecular functions on these mRNAs, and contribution of this regulation to specific biological processes are gradually being uncovered. However, with a few exceptions, the molecular mechanisms used by ARE-BPs to regulate their targets are still unknown. In particular, the mechanism to recognize and control specific targets from the large number of transcripts t...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
n A Abstract Amyotrophic lateral sclerosis (ALS) is a fatal disorder characterized by degeneration of the upper and lower motor neuron. Among the at least 25 known genes associated with familial (hereditary) and sporadic ALS, mutations in fused-in-sarcoma (FUS) and superoxide dismutase 1 (SOD1) have been extensively investigated in the past years, with emphasis on altered excitability of affected neurons. Recently, we reported on hypoexcitability and increased cell death in a FUS/SOD1-ALS-induced pluripotent stem cell-derived motor neuron model, which was partly reversible by a treatment with the potassium channel...
Source: The Journal of Clinical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: J Clin Pharmacol Source Type: research
Conclusion and Perspectives The IL-6/JAK/STAT signaling cascade plays a dominant role in skeletal muscle pathophysiology. IL-6 autocrine, paracrine, and endocrine functions assign to its downstream effectors pivotal importance in skeletal muscle-wasting-associated diseases and other multiple system diseases where muscle acts in communication with other organs. Targeting the components of the JAK/STAT pathway recently emerged as a strategic approach for the treatment of inflammatory diseases and human cancer. This review highlights the opposite outcomes on muscle biology caused by the amount of local and systemic release ...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Conclusion The key problem with the ND field is the lack of understanding in the events preceding the development of protein-based markers – such as Tau – currently used to diagnose NDs. By this stage, the diseases become more difficult to treat. SncRNAs play an important regulatory role in the maintenance of the homeostatic brain. Therefore, changes in their concentration levels can be indicative of mechanistic changes that could precede protein-based markers. One single sncRNA biomarker is unlikely to differentiate between diseases. However, a combination of sncRNA biomarkers could be illustrative of the me...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Conclusions: We demonstrated in the SOD1G93A model of ALS that increased levels of several cytokines were associated with a shorter lifespan. However, their role as prognostic biomarkers is unclear as their expression was very variable depending on both the disease stage and the subject. Nevertheless, cytokines may be potential therapeutic targets. Introduction Amyotrophic Lateral Sclerosis (ALS) is one of the most common rare diseases of unknown origin that leads to progressive motor neuron degeneration and muscle denervation (1). In particular, it has been described that either distal axonopathy or neuromuscular ju...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
AbstractMutations insuperoxide dismutase 1 (SOD1) cause amyotrophic lateral sclerosis (ALS). Disease pathogenesis is linked to destabilization, disorder and aggregation of the SOD1 protein. However, the non-genetic factors that promote disorder and the subsequent aggregation of SOD1 have not been studied. Mainly located to the reducing cytosol, mature SOD1 contains an oxidized disulfide bond that is important for its stability. Since O2 is required for formation of the bond, we reasoned that low O2 tension might be a risk factor for the pathological changes associated with ALS development. By combining biochemical approach...
Source: Acta Neuropathologica - Category: Neurology Source Type: research
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