scholarly journals Highly Efficient Conversion of Motor Neuron-Like NSC-34 Cells into Functional Motor Neurons by Prostaglandin E2

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1741
Author(s):  
Hiroshi Nango ◽  
Yasuhiro Kosuge ◽  
Masaki Sato ◽  
Yoshiyuki Shibukawa ◽  
Yuri Aono ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Hybrid Cell ◽  
Morphological Differentiation ◽  
Differentiation Markers ◽  
Motor Neuron Diseases ◽  
Protein Levels ◽  
Release Of Acetylcholine ◽  
Islet 1

Motor neuron diseases are a group of progressive neurological disorders that degenerate motor neurons. The neuroblastoma × spinal cord hybrid cell line NSC-34 is widely used as an experimental model in studies of motor neuron diseases. However, the differentiation efficiency of NSC-34 cells to neurons is not always sufficient. We have found that prostaglandin E2 (PGE2) induces morphological differentiation in NSC-34 cells. The present study investigated the functional properties of PGE2-differentiated NSC-34 cells. Retinoic acid (RA), a widely-used agent inducing cell differentiation, facilitated neuritogenesis, which peaked on day 7, whereas PGE2-induced neuritogenesis took only 2 days to reach the same level. Whole-cell patch-clamp recordings showed that the current threshold of PGE2-treated cell action potentials was lower than that of RA-treated cells. PGE2 and RA increased the protein expression levels of neuronal differentiation markers, microtubule-associated protein 2c and synaptophysin, and to the same extent, motor neuron-specific markers HB9 and Islet-1. On the other hand, protein levels of choline acetyltransferase and basal release of acetylcholine in PGE2-treated cells were higher than in RA-treated cells. These results suggest that PGE2 is a rapid and efficient differentiation-inducing factor for the preparation of functionally mature motor neurons from NSC-34 cells.

Motor Neuron Diseases

2014 ◽  
Author(s):  
Elena Ratti ◽  
Merit E. Cudkowicz ◽  
James D Berry
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Viral Infections ◽  
Inflammatory Responses ◽  
Muscular Atrophy ◽  
Experimental Therapy ◽  
Rapid Progression ◽  
Motor Neuron Diseases ◽  
Efficacy Outcome ◽  
Single Disease Entity

The motor neuron diseases (MNDs) are a family of diseases commonly categorized by their propensity to affect upper or lower motor neurons and by their mode of inheritance. The chapter provides some content on infectious MNDs caused by viral infections affecting the motor neurons in the anterior horn of the spinal cord. However, the chapter devotes most of its attention to the inherited and sporadically occurring MNDs. The majority of research into adult MND focuses on amyotrophic lateral sclerosis (ALS) due to its high prevalence, rapid progression, and phenotypical similarities between its inherited form and its sporadic form. As our knowledge of genetic mechanisms underlying ALS pathology has grown, common themes have emerged. These include abnormalities in RNA biology, axonal transport, protein folding, and inflammatory responses. These themes currently drive much of the direction in ALS experimental therapy development. It is clear that MND is complex and involves several different molecular pathways. Given this complexity, ALS might not be a single disease entity, and if this is the case, treatment approaches may need to be targeted to specific pathologies rather than all ALS patients on a broad scale. Chapter content is enhanced by tables outlining the types of MNDs, criteria for supporting a diagnosis, first-line workup, the genes associated with ALS, ALS efficacy outcome measures, symptom management of ALS, and spinal muscular atrophy classification. Mechanisms of ALS are illustrated, and clinical photographs demonstrate symptoms. This chapter contains 252 references. 

Motor Neuron Diseases

2021 ◽  
pp. 752-759
Author(s):  
Eric J. Sorenson
Keyword(s):  
Motor Neuron ◽  
Incidence Rate ◽  
Motor Neurons ◽  
Anterior Horn Cell ◽  
Adult Onset ◽  
Motor Neuron Diseases ◽  
Kii Peninsula ◽  
Geographic Boundaries ◽  
Spinal Muscular Atrophies ◽  
Lateral Sclerosis

The motor neuron disorders are a clinically diverse group of diseases that share a pathologic loss of the motor neurons. The most common adult-onset disorder is amyotrophic lateral sclerosis (ALS). Other forms include the spinal muscular atrophies, infectious motor neuronopathies, and rare focal forms of anterior horn cell loss.Overall, the incidence rate of ALS is believed to be 1.5 to 2.0 cases per 100,000 person-years, and the prevalence rate is 4 to 6 cases per 100,000 population. Other than in sparsely populated geographic clusters (eg, Guam and the Kii Peninsula of Japan), the incidence rate seems consistent across ethnic and geographic boundaries.

scholarly journals Mitochondrial defects in the respiratory complex I contribute to impaired translational initiation via ROS and energy homeostasis in SMA motor neurons

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Maximilian Paul Thelen ◽  
Brunhilde Wirth ◽  
Min Jeong Kye
Keyword(s):  
Protein Synthesis ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Complex I ◽  
Energy Homeostasis ◽  
Muscular Atrophy ◽  
Survival Motor Neuron ◽  
Translational Initiation ◽  
Protein Levels ◽  
Smn Protein

AbstractSpinal muscular atrophy (SMA) is a neuromuscular disease characterized by loss of lower motor neurons, which leads to proximal muscle weakness and atrophy. SMA is caused by reduced survival motor neuron (SMN) protein levels due to biallelic deletions or mutations in the SMN1 gene. When SMN levels fall under a certain threshold, a plethora of cellular pathways are disturbed, including RNA processing, protein synthesis, metabolic defects, and mitochondrial function. Dysfunctional mitochondria can harm cells by decreased ATP production and increased oxidative stress due to elevated cellular levels of reactive oxygen species (ROS). Since neurons mainly produce energy via mitochondrial oxidative phosphorylation, restoring metabolic/oxidative homeostasis might rescue SMA pathology. Here, we report, based on proteome analysis, that SMA motor neurons show disturbed energy homeostasis due to dysfunction of mitochondrial complex I. This results in a lower basal ATP concentration and higher ROS production that causes an increase of protein carbonylation and impaired protein synthesis in SMA motor neurons. Counteracting these cellular impairments with pyruvate reduces elevated ROS levels, increases ATP and SMN protein levels in SMA motor neurons. Furthermore, we found that pyruvate-mediated SMN protein synthesis is mTOR-dependent. Most importantly, we showed that ROS regulates protein synthesis at the translational initiation step, which is impaired in SMA. As many neuropathies share pathological phenotypes such as dysfunctional mitochondria, excessive ROS, and impaired protein synthesis, our findings suggest new molecular interactions among these pathways. Additionally, counteracting these impairments by reducing ROS and increasing ATP might be beneficial for motor neuron survival in SMA patients.

scholarly journals A Systematic Review of Genotype–Phenotype Correlation across Cohorts Having Causal Mutations of Different Genes in ALS

2020 ◽  
Vol 10 (3) ◽  
pp. 58 ◽  
Author(s):  
Owen Connolly ◽  
Laura Le Gall ◽  
Gavin McCluskey ◽  
Colette G Donaghy ◽  
William J Duddy ◽  
...  
Keyword(s):  
Systematic Review ◽  
Amyotrophic Lateral Sclerosis ◽  
Respiratory Failure ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Disease Duration ◽  
Phenotype Correlation ◽  
Motor Neuron Diseases ◽  
Relationship Of ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis is a rare and fatal neurodegenerative disease characterised by progressive deterioration of upper and lower motor neurons that eventually culminates in severe muscle atrophy, respiratory failure and death. There is a concerning lack of understanding regarding the mechanisms that lead to the onset of ALS and as a result there are no reliable biomarkers that aid in the early detection of the disease nor is there an effective treatment. This review first considers the clinical phenotypes associated with ALS, and discusses the broad categorisation of ALS and ALS-mimic diseases into upper and lower motor neuron diseases, before focusing on the genetic aetiology of ALS and considering the potential relationship of mutations of different genes to variations in phenotype. For this purpose, a systematic review is conducted collating data from 107 original published clinical studies on monogenic forms of the disease, surveying the age and site of onset, disease duration and motor neuron involvement. The collected data highlight the complexity of the disease’s genotype–phenotype relationship, and thus the need for a nuanced approach to the development of clinical assays and therapeutics.

Lower Motor Neuron Disease with Accumulation of Neurofilaments in a Cat

1976 ◽  
Vol 13 (6) ◽  
pp. 428-435 ◽  
Author(s):  
M. Vandevelde ◽  
C. E. Greene ◽  
E. J. Hoff
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Histological Examination ◽  
Muscle Atrophy ◽  
Motor Neurons ◽  
Nerve Cells ◽  
Lower Motor Neuron ◽  
Motor Neuron Diseases ◽  
Lower Motor Neuron Disease

A young cat had signs of tetraparesis that progressed to tetraplegia within a few weeks. Clinically, there was lower motor neuron disease with areflexia and muscle atrophy in all limbs. Degeneration of the motor neurons in the spinal cord was seen on histological examination. Ultrastructurally, the degeneration of nerve cells was characterized by abnormal proliferation of neurofilaments. These findings were compared to other motor neuron diseases and neurofibrillary accumulations in man and animals.

scholarly journals Impaired Autophagy in Motor Neurons: A Final Common Mechanism of Injury and Death

Physiology ◽  
2018 ◽  
Vol 33 (3) ◽  
pp. 211-224 ◽  
Author(s):  
Maria A. Gonzalez Porras ◽  
Gary C. Sieck ◽  
Carlos B. Mantilla
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Common Mechanism ◽  
Mechanism Of Injury ◽  
Therapeutic Approaches ◽  
Motor Neuron Diseases ◽  
Digestion Process ◽  
Cord Injury ◽  
Recent Developments ◽  
Health And Disease

Autophagy is a cellular digestion process that contributes to cellular homeostasis and adaptation by the elimination of proteins and damaged organelles. Evidence suggests that dysregulation of autophagy plays a role in neurodegenerative diseases, including motor neuron disorders. Herein, we review emerging evidence indicating the roles of autophagy in physiological motor neuron processes and its function in specific compartments. Moreover, we discuss the involvement of autophagy in the pathogenesis of motor neuron diseases, including spinal cord injury and aging, and recent developments that offer promising therapeutic approaches to mitigate effects of dysregulated autophagy in health and disease.

Retrograde transport and differential accumulation of serum proteins in motor neurons: Implications for motor neuron diseases

Neurology ◽  
1987 ◽  
Vol 37 (5) ◽  
pp. 843-843 ◽  
Author(s):  
T. Yamamoto ◽  
Y. Iwasaki ◽  
H. Konno ◽  
H. Iizuka ◽  
J.-X. Zhao
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Serum Proteins ◽  
Retrograde Transport ◽  
Motor Neuron Diseases

scholarly journals Comparison of independent screens on differentially vulnerable motor neurons reveals alpha-synuclein as a common modifier in motor neuron diseases

PLoS Genetics ◽  
2017 ◽  
Vol 13 (3) ◽  
pp. e1006680 ◽  
Author(s):  
Rachel A. Kline ◽  
Kevin A. Kaifer ◽  
Erkan Y. Osman ◽  
Francesco Carella ◽  
Ariana Tiberi ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Alpha Synuclein ◽  
Motor Neuron Diseases

scholarly journals Assessment of motor neuron pathology and potential compensatory mechanisms in phenotypically normal mice with reduced Survival Motor Neuron levels.

2015 ◽  
Vol 8 (1) ◽  
Author(s):  
Rebecca Xu Xu ◽  
Lyndsay M. Murray M. Murray Murray ◽  
Yves De Repentigny De Repentigny ◽  
Rashmi Kothary Kothary
Keyword(s):  
Motor Neuron ◽  
Mouse Models ◽  
Motor Neurons ◽  
Neuromuscular Junctions ◽  
Muscular Atrophy ◽  
Neuromuscular Disorder ◽  
Survival Motor Neuron ◽  
Compensatory Mechanisms ◽  
Protein Levels ◽  
Smn Protein

Spinal muscular atrophy (SMA) is a destructive pediatric neuromuscular disorder caused by low survival motor neuron (Smn) protein levels due to mutations and deletions within the survival motor neuron 1 (SMN1) gene. Motor neurons are the main pathological targets, and along with neuromuscular junctions (NMJs), they play an early significant role in the pathogenesis of SMA. Previous studies demonstrate that a pathological reduction in Smn levels can lead to significant remodeling defects in both the outgrowth of axonal sprouts and in the nerve-directed clustering of AChRs in mouse models. However, whether this pathological reduction in Smn leads to ubclinical features has not been investigated. Here, we have employed the Smn2B/2B and Smn+/- mouse models to study whether similar SMA pathology is present sub-clinically, and if so whether there is any compensation present. We show a decrease in the motor neuron number in the mouse models, no change in myelin thickness and modest NMJ pathology in both mouse models. Additionally, compensation through the expansion of the motor unit size is suggested.L’amyotrophie spinale (AMS) est un trouble neuromusculaire pédiatrique destructif causé par le niveau bas de protéine du neurone de moteur de survie (NMS) en raison des mutations et des effacements dans le neurone de moteur de survie 1 gène (NMS1). Des neurones du moteur sont les cibles pathologiques principales, et ce, avec des jonctions neuromusculaires (JNMs), ils jouent, en avance, un rôle significatif dans la pathogénie de AMS. Des études précédentes démontrent qu’une réduction pathologique de niveaux de NMS peut mener aux défauts importants de réorganisation tant dans l’excroissance axonale que dans l’agrégation du récepteur de l’acétylcholine (AChR) sous la terminaison nerveuse dans des modèles de souris. Cependant, si cette reduction pathologique de NMS mène aux caractéristiques infracliniques n’a pas été à l’étude. Ici, nous avons employé le NMS2B/2B et NMS +/- des modèles de souris afin de déterminer si une pathologie semblable à l’AMS est présente infracliniquement, ainsi s’il y a présence de quelconque compensation. Nous montrons une diminution dans le nombre des neurones du moteur dans les modèles de souris, aucun changement de l’épaisseur du myelin et une pathologie modeste de JNM dans les deux modèles de souris. De plus, une compensation par l’expansion de la taille d’unité du moteur est suggérée.

Pax-6 is involved in the specification of hindbrain motor neuron subtype

Development ◽  
1997 ◽  
Vol 124 (15) ◽  
pp. 2961-2972 ◽  
Author(s):  
N. Osumi ◽  
A. Hirota ◽  
H. Ohuchi ◽  
M. Nakafuku ◽  
T. Iimura ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neurons ◽  
Neural Tube ◽  
Neural Development ◽  
Abnormal Development ◽  
Pair Rule Gene ◽  
In The Wild ◽  
Rat Strain ◽  
Discrete Domains ◽  
Islet 1

Pax-6 is a member of the vertebrate Pax gene family, which is structurally related to the Drosophila pair-rule gene, paired. In mammals, Pax-6 is expressed in several discrete domains of the developing CNS and has been implicated in neural development, although its precise role remains elusive. We found a novel Small eye rat strain (rSey2) with phenotypes similar to mouse and rat Small eye. Analyses of the Pax-6 gene revealed one base (C) insertion in an exon encoding the region downstream of the paired box of the Pax-6 gene, resulting in generation of truncated protein due to the frame shift. To explore the roles of Pax-6 in neural development, we searched for abnormalities in the nervous system in rSey2 homozygous embryos. rSey2/rSey2 exhibited abnormal development of motor neurons in the hindbrain. The Islet-1-positive motor neurons were generated just ventral to the Pax-6-expressing domain both in the wild-type and mutant embryos. However, two somatic motor (SM) nerves, the abducent and hypoglossal nerves, were missing in homozygous embryos. By retrograde and anterograde labeling, we found no SM-type axonogenesis (ventrally growing) in the mutant postotic hindbrain, though branchiomotor and visceral motor (BM/VM)-type axons (dorsally growing) were observed within the neural tube. To discover whether the identity of these motor neuron subtypes was changed in the mutant, we examined expression of LIM homeobox genes, Islet-1, Islet-2 and Lim-3. At the postotic levels of the hindbrain, SM neurons expressed all the three LIM genes, whereas BM/VM-type neurons were marked by Islet-1 only. In the Pax-6 mutant hindbrain, Islet-2 expression was specifically missing, which resulted in the loss of the cells harboring the postotic hindbrain SM-type LIM code (Islet-1 + Islet-2 + Lim-3). Furthermore, we found that expression of Wnt-7b, which overlapped with Pax-6 in the ventrolateral domain of the neural tube, was also specifically missing in the mutant hindbrain, while it remained intact in the dorsal non-overlapping domain. These results strongly suggest that Pax-6 is involved in the specification of subtypes of hindbrain motor neurons, presumably through the regulation of Islet-2 and Wnt-7b expression.

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