scholarly journals Embryonic Exposure to the Environmental Neurotoxin BMAA Negatively Impacts Early Neuronal Development and Progression of Neurodegeneration in the Sod1-G93R Zebrafish Model of Amyotrophic Lateral Sclerosis

2017 ◽  
pp. kfx020 ◽  
Author(s):  
Samantha Powers ◽  
Samantha Kwok ◽  
Emily Lovejoy ◽  
Tom Lavin ◽  
Roger Sher
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neuronal Development ◽  
Zebrafish Model ◽  
Embryonic Exposure ◽  
Lateral Sclerosis

A novel alternative splicing event rescues the mutant tardbp phenotype in a zebrafish model of TDP-43 related Amyotrophic Lateral Sclerosis (ALS) (P03.180)

Neurology ◽  
2012 ◽  
Vol 78 (Meeting Abstracts 1) ◽  
pp. P03.180-P03.180
Author(s):  
C. Hewamadduma ◽  
A. Grierson ◽  
C. Moens ◽  
L. Pan ◽  
T. Ma ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Alternative Splicing ◽  
Zebrafish Model ◽  
Lateral Sclerosis

scholarly journals LncRNAs Associated with Neuronal Development and Oncogenesis Are Deregulated in SOD1-G93A Murine Model of Amyotrophic Lateral Sclerosis

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 809
Author(s):  
Federica Rey ◽  
Stefania Marcuzzo ◽  
Silvia Bonanno ◽  
Matteo Bordoni ◽  
Toniella Giallongo ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neuronal Development ◽  
Specific Area ◽  
Stage Disease ◽  
Non Coding Rnas ◽  
Disease Modifying Agents ◽  
Inherited Mutations ◽  
Brain And Spinal Cord ◽  
Early Phases ◽  
Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease caused in 10% of cases by inherited mutations considered “familial”. An ever-increasing amount of evidence is showing a fundamental role for RNA metabolism in ALS pathogenesis, and long non-coding RNAs (lncRNAs) appear to play a role in ALS development. Here, we aim to investigate the expression of a panel of lncRNAs (linc-Enc1, linc–Brn1a, linc–Brn1b, linc-p21, Hottip, Tug1, Eldrr, and Fendrr) which could be implicated in early phases of ALS. Via Real-Time PCR, we assessed their expression in a murine familial model of ALS (SOD1-G93A mouse) in brain and spinal cord areas of SOD1-G93A mice in comparison with that of B6.SJL control mice, in asymptomatic (week 8) and late-stage disease (week 18). We highlighted a specific area and pathogenetic-stage deregulation in each lncRNA, with linc-p21 being deregulated in all analyzed tissues. Moreover, we analyzed the expression of their human homologues in SH-SY5Y-SOD1-WT and SH-SY5Y-SOD1-G93A, observing a profound alteration in their expression. Interestingly, the lncRNAs expression in our ALS models often resulted opposite to that observed for the lncRNAs in cancer. These evidences suggest that lncRNAs could be novel disease-modifying agents, biomarkers, or pathways affected by ALS neurodegeneration.

scholarly journals BDNF-dependent modulation of axonal transport is selectively impaired in ALS

2021 ◽  
Author(s):  
Andrew P. Tosolini ◽  
James N. Sleigh ◽  
Sunaina Surana ◽  
Elena R. Rhymes ◽  
Stephen D. Cahalan ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Axonal Transport ◽  
Neuronal Development ◽  
Therapeutic Interventions ◽  
Wild Type ◽  
Disease Pathogenesis ◽  
Sciatic Nerves ◽  
Lateral Sclerosis ◽  
Selective Impairment ◽  
Stimulation Of

AbstractAxonal transport ensures long-range delivery of essential cargoes between proximal and distal compartments of neurons, and is needed for neuronal development, function, and survival. Deficits in axonal transport have been detected at pre-symptomatic stages in mouse models of amyotrophic lateral sclerosis (ALS), suggesting that impairments are fundamental for disease pathogenesis. However, the precise mechanisms responsible for the transport deficits and whether they preferentially affect α-motor neuron (MN) subtypes remain unresolved. Here, we report that stimulation of wild-type neurons with brain-derived neurotrophic factor (BDNF) enhances trafficking of signalling endosomes specifically in fast MNs (FMNs). In early symptomatic SOD1G93A mice, FMNs display selective impairment of axonal transport and develop an insensitivity to BDNF stimulation, with pathology upregulating classical non-pro-survival receptors in muscles and sciatic nerves. Altogether, these data indicate that cell- and non-cell autonomous BDNF signalling is impaired in vulnerable SOD1G93A MNs, thus identifying a new key deficit in ALS amenable for future therapeutic interventions.

A novel alternative splicing event rescues the mutant tardbp phenotype in a zebrafish model of TDP-43 related Amyotrophic Lateral Sclerosis (ALS) (IN9-2.001)

Neurology ◽  
2012 ◽  
Vol 78 (Meeting Abstracts 1) ◽  
pp. IN9-2.001-IN9-2.001
Author(s):  
C. Hewamadduma ◽  
A. Grierson ◽  
C. Moens ◽  
L. Pan ◽  
T. Ma ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Alternative Splicing ◽  
Zebrafish Model ◽  
Lateral Sclerosis

scholarly journals Integrated Hypoxia Signaling and Oxidative Stress in Developmental Neurotoxicity of Benzo[a]Pyrene in Zebrafish Embryos

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 731 ◽  
Author(s):  
Yi-Chen Lin ◽  
Chang-Yi Wu ◽  
Chin-Hwa Hu ◽  
Tun-Wen Pai ◽  
Yet-Ran Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Target Genes ◽  
Neuronal Development ◽  
Posterior Commissure ◽  
Zebrafish Model ◽  
Embryonic Exposure ◽  
Ventral Thalamus ◽  
Polycyclic Aromatic ◽  
Transcriptional Changes ◽  
And Function

Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon formed by the incomplete combustion of organic matter. Environmental B[a]P contamination poses a serious health risk to many organisms because the pollutant may negatively affect many physiological systems. As such, chronic exposure to B[a]P is known to lead to locomotor dysfunction and neurodegeneration in several organisms. In this study, we used the zebrafish model to delineate the acute toxic effects of B[a]P on the developing nervous system. We found that embryonic exposure of B[a]P downregulates shh and isl1, causing morphological hypoplasia in the telencephalon, ventral thalamus, hypothalamus, epiphysis and posterior commissure. Moreover, hypoxia-inducible factors (hif1a and hif2a) are repressed upon embryonic exposure of B[a]P, leading to reduced expression of the Hif-target genes, epo and survivin, which are associated with neural differentiation and maintenance. During normal embryogenesis, low-level oxidative stress regulates neuronal development and function. However, our experiments revealed that embryonic oxidative stress is greatly increased in B[a]P-treated embryos. The expression of catalase was decreased and sod1 expression increased in B[a]P-treated embryos. These transcriptional changes were coincident with increased embryonic levels of H2O2 and malondialdehyde, with the levels in B[a]P-treated fish similar to those in embryos treated with 120-μM H2O2. Together, our data suggest that reduced Hif signaling and increased oxidative stress are involved in B[a]P-induced acute neurotoxicity during embryogenesis.

Loss of function of C9orf72 causes motor deficits in a zebrafish model of Amyotrophic Lateral Sclerosis

2013 ◽  
pp. n/a-n/a ◽  
Author(s):  
Sorana Ciura ◽  
Serena Lattante ◽  
Isabelle Le Ber ◽  
Morwena Latouche ◽  
Hervé Tostivint ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Deficits ◽  
Loss Of Function ◽  
Zebrafish Model ◽  
Lateral Sclerosis

Automated Acoustic Analysis of Oral Diadochokinesis to Assess Bulbar Motor Involvement in Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 63 (1) ◽  
pp. 59-73 ◽  
Author(s):  
Panying Rong
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Acoustic Analysis ◽  
Speaking Rate ◽  
Disease Stage ◽  
Healthy Controls ◽  
Tongue Movement ◽  
Major Barrier ◽  
Syllable Repetition ◽  
Oral Diadochokinesis ◽  
Lateral Sclerosis

Purpose The purpose of this article was to validate a novel acoustic analysis of oral diadochokinesis (DDK) in assessing bulbar motor involvement in amyotrophic lateral sclerosis (ALS). Method An automated acoustic DDK analysis was developed, which filtered out the voice features and extracted the envelope of the acoustic waveform reflecting the temporal pattern of syllable repetitions during an oral DDK task (i.e., repetitions of /tɑ/ at the maximum rate on 1 breath). Cycle-to-cycle temporal variability (cTV) of envelope fluctuations and syllable repetition rate (sylRate) were derived from the envelope and validated against 2 kinematic measures, which are tongue movement jitter (movJitter) and alternating tongue movement rate (AMR) during the DDK task, in 16 individuals with bulbar ALS and 18 healthy controls. After the validation, cTV, sylRate, movJitter, and AMR, along with an established clinical speech measure, that is, speaking rate (SR), were compared in their ability to (a) differentiate individuals with ALS from healthy controls and (b) detect early-stage bulbar declines in ALS. Results cTV and sylRate were significantly correlated with movJitter and AMR, respectively, across individuals with ALS and healthy controls, confirming the validity of the acoustic DDK analysis in extracting the temporal DDK pattern. Among all the acoustic and kinematic DDK measures, cTV showed the highest diagnostic accuracy (i.e., 0.87) with 80% sensitivity and 94% specificity in differentiating individuals with ALS from healthy controls, which outperformed the SR measure. Moreover, cTV showed a large increase during the early disease stage, which preceded the decline of SR. Conclusions This study provided preliminary validation of a novel automated acoustic DDK analysis in extracting a useful measure, namely, cTV, for early detection of bulbar ALS. This analysis overcame a major barrier in the existing acoustic DDK analysis, which is continuous voicing between syllables that interferes with syllable structures. This approach has potential clinical applications as a novel bulbar assessment.

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