Understanding mechanisms that lead to selective motor neuron degeneration requires visualization and cellular identification of vulnerable neurons. Here we report generation and characterization of UCHL1-eGFP and hSOD1(G93A)-UeGFP mice, novel reporter lines for cortical and spinal motor neurons. Corticospinal motor neurons (CSMN) and a subset of spinal motor neurons (SMN) are genetically labeled in UCHL1-eGFP mice, which express eGFP under the UCHL1 promoter. eGFP expression is stable and continues through P800 in vivo. Retrograde labeling, molecular marker expression, electrophysiological analysis, and cortical circuit mapping confirmed CSMN identity of eGFP(+) neurons in the motor cortex. Anatomy, molecular marker expression, and electrophysiological analysis revealed that the eGFP expression is restricted to a subset of small-size SMN that are slow-twitch α and γ motor neurons. Crossbreeding of UCHL1-eGFP and hSOD1(G93A) lines generated hSOD1(G93A)-UeGFP mice, which displayed the disease phenotype observed in a hSOD1(G93A) mouse model of ALS. eGFP(+) SMN showed resistance to degeneration in hSOD1(G93A)-UeGFP mice, and their slow-twitch α and γ motor neuron identity was confirmed. In contrast, eGFP(+) neurons in the motor cortex of hSOD1(G93A)-UeGFP mice recapitulated previously reported progressive CSMN loss and apical dendrite degeneration. Our findings using these two novel reporter lines revealed accumulation of autophagosomes along the apical dendrites of vulnerable CSMN at P60, early symptomatic stage, suggesting autophagy as a potential intrinsic mechanism for CSMN apical dendrite degeneration.
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http://dx.doi.org/10.1523/JNEUROSCI.2787-12.2013 | DOI Listing |
Biochem Biophys Res Commun
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Department of Cancer Pathology, Faculty of Medicine, Hokkaido University, Sapporo, Japan; World Premier International Research Center Initiative, Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo, Japan. Electronic address:
Parkinson's disease (PD) is a neurodegenerative disease primarily affecting the central nervous system and impacting both the motor system and non-motor systems. Although administration of L-DOPA is effective, it is not a fundamental treatment and has side effects such as diurnal fluctuation and dyskinesia, highlighting the need for new treatment methods. There is a growing interest in dopaminergic neuron transplantation as a potential treatment.
View Article and Find Full Text PDFSensors (Basel)
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Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100032, China.
Investigating the physiological mechanisms in the motor cortex during rehabilitation exercises is crucial for assessing stroke patients' progress. This study developed a single-channel Jansen neural mass model to explore the relationship between model parameters and motor cortex mechanisms. Firstly, EEG signals were recorded from 11 healthy participants under 20%, 40%, and 60% maximum voluntary contraction, and alpha rhythm power spectral density characteristics were extracted using the Welch power spectrum method.
View Article and Find Full Text PDFInt J Mol Sci
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Department of Molecular Biology and Genetics, Çanakkale Onsekiz Mart University, Çanakkale 17100, Turkey.
Fucosidosis is a rare lysosomal storage disease caused by α-L-fucosidase deficiency following a mutation in the gene. This enzyme is responsible for breaking down fucose-containing glycoproteins, glycolipids, and oligosaccharides within the lysosome. Mutations in result in either reduced enzyme activity or complete loss of function, leading to the accumulation of fucose-rich substrates in lysosomes.
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Department of Information Technology, Aylol University College, Yarim 547, Yemen.
Background: Neurodegenerative diseases (NGD) encompass a range of progressive neurological conditions, such as Alzheimer's disease (AD) and Parkinson's disease (PD), characterised by the gradual deterioration of neuronal structure and function. This degeneration manifests as cognitive decline, movement impairment, and dementia. Our focus in this investigation is on PD, a neurodegenerative disorder characterized by the loss of dopamine-producing neurons in the brain, leading to motor disturbances.
View Article and Find Full Text PDFGene Ther
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Departments of Pediatrics and Neurology, Emory University, Atlanta, 30322, Georgia.
Spinal muscular atrophy (SMA) is a progressive disease that affects motor neurons, with symptoms usually starting in infancy or early childhood. Recent breakthroughs in treatments targeting SMA have improved both lifespan and quality of life for infants and children with the disease. Given the impact of these treatments, it is essential to develop methods for managing treatment-induced changes in disease characteristics.
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