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The Metabolic Disturbances of Motoneurons Exposed to Glutamate

AbstractGlutamate-induced excitotoxicity is considered as one of the major pathophysiological factors of motoneuron death in amyotrophic lateral sclerosis and other motoneuron diseases. In order to expand our knowledge on mechanisms of glutamate-induced excitotoxicity, the present study proposes to determine the metabolic consequences of glutamate and astrocytes in primary enriched motoneuron culture. Using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS), we showed that the presence of astrocytes and glutamate profoundly modified the metabolic profile of motoneurons. Our study highlights for the first time that crosstalk between astrocytes and enriched motoneuron culture induced alterations in phenylalanine, tryptophan, purine, arginine, proline, aspartate, and glutamate metabolism in motoneurons. We observed that astrocytes modulate the sensitivity of motoneurons to glutamate, since metabolites altered by glutamate in motoneurons cultured alone were different (except 5-hydroxylysine) from those altered in co-cultured motoneurons. Our findings provide new insight into the metabolic alterations associated to astrocytes and glutamate in motoneurons and provide opportunities to identify novel therapeutic targets.
Source: Molecular Neurobiology - Category: Neurology Source Type: research

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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that always affects the respiratory muscles. It is characterized by degeneration of motor neurons in the brain and spinal cord. Respiratory complications are the most common causes of death in ALS and typically occur within 3 to 5  years of diagnosis. Because ALS affects both upper and lower motor neurons, it causes hyperreflexia, spasticity, muscle fasciculations, muscle atrophy, and weakness. It ultimately progresses to functional quadriplegia. ALS most commonly begins in the limbs, but in about one-third of cases it begin s in the bulba...
Source: Clinics in Chest Medicine - Category: Respiratory Medicine Authors: Source Type: research
Authors: Asai H, Inoue K, Sakuma E, Shinohara Y, Ueki T Abstract It has recently been established that microglial activation is involved in the pathophysiology of various neurological and psychiatric disorders such as amyotrophic lateral sclerosis and schizophrenia. The pathological molecular machineries underlying microglial activation and its accelerating molecules have been precisely described in the diseased central nervous system (CNS). However, to date, the details of physiological mechanism, which represses microglial activation, are still to be elucidated. Our latest report demonstrated that serum- and gluc...
Source: International Journal of Physiology, Pathophysiology and Pharmacology - Category: Physiology Tags: Int J Physiol Pathophysiol Pharmacol Source Type: research
In conclusion, we here demonstrated for the first time that human TARDBP mutated MNs can be successfully obtained exploiting the reprogramming and differentiation ability of peripheral blood cells, an easily accessible source from any patient.
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Publication date: 15 June 2018 Source:Life Sciences, Volume 203 Author(s): Qing-Qing Tao, Qiao Wei, Zhi-Ying Wu Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disorder, characterized by the selective degeneration of upper and lower motor neurons. The common clinical symptoms of ALS are caused by the degeneration and dysfunction of motor neurons. With the progression of our understanding of the pathogenesis of the disease, an increasing number of extramotor phenotypes have been linked to ALS. It has long been believed that sensory neurons localized in the dorsal root ganglia are not involved in ALS. In...
Source: Life Sciences - Category: Biology Source Type: research
Conclusions These results demonstrate the safety and potential benefit of expanded autologous Treg infusions, warranting further clinical trials in patients with ALS. The correlation between Treg suppressive function and disease progression underscores the significance of using Treg suppressive function as an indicator of clinical status. Classification of evidence This study provides Class IV evidence. This is a phase I trial with no controls.
Source: Neurology Neuroimmunology and Neuroinflammation - Category: Neurology Authors: Tags: All Immunology, Amyotrophic lateral sclerosis, All Clinical trials, Class IV Article Source Type: research
Misfolding and aggregation of Cu, Zn Superoxide dismutase (SOD1) is involved in the neurodegenerative disease, amyotrophic lateral sclerosis. Many studies have shown that metal-depleted, monomeric form of SOD1 displays substantial local unfolding dynamics and is the precursor for aggregation. Here, we have studied the structure and dynamics of different apo monomeric SOD1 variants associated with unfolding and aggregation in aqueous trifluoroethanol (TFE) through experiments and simulation. TFE induces partially unfolded β-sheet-rich extended conformations in these SOD1 variants, which subsequently develops aggregates...
Source: Biochemical Journal - Category: Biochemistry Authors: Tags: Research Articles Source Type: research
This study demonstrates, for the first time, that the presence of mutated SOD1 protein affects the MHC class I molecules expression, altering the presynaptic input in motoneurons. Nevertheless, a positive MHC class I immunolabeling was evident in glial cells around facial injured motoneurons, underlying an involvement of these cells in synaptic stripping. This study contributes to better understand the involvement of the mutated SOD1 protein in the vulnerability of motoneurons after damage.
Source: European Journal of Histochemistry - Category: Biomedical Science Source Type: research
Contributors : Tassa K Saldi   ; Patrick Gonzales ; Alfonso Garrido-Lecca ; Vishantie Dostal ; Christine M Roberts ; Lenoard Petrucelli ; Christopher D LinkSeries Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencing ; OtherOrganism : Caenorhabditis elegansTDP-1 is the  C. elegans ortholog of mammalian TDP-43, which is strongly implicated in the etiology of Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS). We discovered that deletion of the tdp-1 gene results in enhanced transcriptional gene silencing leadin...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Other Caenorhabditis elegans Source Type: research
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Source: Neuron - Category: Neuroscience Source Type: research
Purpose The goals of this study were to (a) classify speech movements of patients with amyotrophic lateral sclerosis (ALS) in presymptomatic and symptomatic phases of bulbar function decline relying solely on kinematic features of lips and jaw and (b) identify the most important measures that detect the transition between early and late bulbar changes.Method One hundred ninety-two recordings obtained from 64 patients with ALS were considered for the analysis. Feature selection and classification algorithms were used to analyze lip and jaw movements recorded with Optotrak Certus (Northern Digital Inc.) during a sentence tas...
Source: Journal of Speech, Language, and Hearing Research - Category: Speech-Language Pathology Source Type: research
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