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Clinics ; 76: e2167, 2021. tab, graf
Article in English | LILACS | ID: biblio-1249576


OBJECTIVES: Leukoaraiosis is described as white matter lesions that are associated with cognitive dysfunction, neurodegenerative disorders, etc. Myelin depletion is a salient pathological feature of, and the loss of oligodendrocytes is one of the most robust alterations evident in, white matter degeneration. Recent studies have revealed that claudin proteins are aberrantly expressed in leukoaraiosis and regulate oligodendrocyte activity. However, the roles of claudin-1 and claudin-3 in oligodendrocytes and leukoaraiosis are still not well-defined. METHODS: Quantitative polymerase chain reaction was used to measure the expression of claudin-1 (CLDN1), claudin-3 (CLDN3), and myelinogenesis-related genes such as myelin basic protein (MBP), proteolipid protein (PLP), oligodendrocyte transcription factor 2 (OLIG2), and SRY-box transcription factor 10 (SOX10) in leukoaraiosis patients (n=122) and healthy controls (n=122). The expression of claudin-1 and claudin-3 was either ectopically silenced or augmented in Oli-neu oligodendrocytes, and colony formation, apoptosis, and migration assays were performed. Finally, the expression of myelin proteins was evaluated by western blotting. RESULTS: Our results revealed that in addition to SOX10, the expression levels of claudin-1, claudin-3, and myelinogenesis-related proteins were prominently downregulated in leukoaraiosis patients, compared to those in healthy controls. Furthermore, the growth and migration of Oli-neu cells were downregulated upon silencing claudin-1 or claudin-3. However, the overexpression of claudin-1 or claudin-3 resulted in the reduction of the degree of apoptosis in Oli-neu cells. In addition, claudin-1 and claudin-3 promoted the expression of MBP, OLIG2, PLP, and SOX10 at the translational level. CONCLUSION: Our data has demonstrated that the abnormal expression of claudin-1 and claudin-3 regulates the pathological progression of leukoaraiosis by governing the viability and myelination of oligodendrocytes. These findings provide novel insights into the regulatory mechanisms underlying the roles of claudin-1 and claudin-3 in leukoaraiosis.

Humans , Leukoaraiosis , Oligodendroglia , Claudin-1 , Claudin-3/genetics , Myelin Sheath
Article in Chinese | WPRIM | ID: wpr-879868


OBJECTIVE@#To study the effect of human oligodendrocyte precursor cell (hOPC) transplantation in the treatment of white matter injury (WMI).@*METHODS@#Neonatal rats were randomly divided into a sham-operation group, a model group, and a transplantation group (@*RESULTS@#The place navigation test using the Morris water maze showed that the model group had a significantly longer escape latency than the sham-operation group, and compared with the model group, the transplantation group had a significant reduction in escape latency (@*CONCLUSIONS@#Intrathecal hOPC transplantation may alleviate neurological injury and promote remyelination in a rat model of WMI.

Animals , Animals, Newborn , Humans , Myelin Sheath , Oligodendrocyte Precursor Cells , Oligodendroglia , Rats , White Matter
Neuroscience Bulletin ; (6): 1397-1411, 2021.
Article in English | WPRIM | ID: wpr-922649


Exposure to chronic hypoxia is considered to be a risk factor for deficits in brain function in adults, but the underlying mechanisms remain largely unknown. Since active myelinogenesis persists in the adult central nervous system, here we aimed to investigate the impact of chronic hypoxia on myelination and the related functional consequences in adult mice. Using a transgenic approach to label newly-generated myelin sheaths (NG2-CreER

Animals , Clemastine , Hypoxia/complications , Mice , Mice, Inbred C57BL , Mice, Transgenic , Myelin Sheath , Oligodendroglia
Neuroscience Bulletin ; (6): 1314-1324, 2021.
Article in English | WPRIM | ID: wpr-922627


The exacerbation of progressive multiple sclerosis (MS) is closely associated with obstruction of the differentiation of oligodendrocyte progenitor cells (OPCs). To discover novel therapeutic compounds for enhancing remyelination by endogenous OPCs, we screened for myelin basic protein expression using cultured rat OPCs and a library of small-molecule compounds. One of the most effective drugs was pinocembrin, which remarkably promoted OPC differentiation and maturation without affecting cell proliferation and survival. Based on these in vitro effects, we further assessed the therapeutic effects of pinocembrin in animal models of demyelinating diseases. We demonstrated that pinocembrin significantly ameliorated the progression of experimental autoimmune encephalomyelitis (EAE) and enhanced the repair of demyelination in lysolectin-induced lesions. Further studies indicated that pinocembrin increased the phosphorylation level of mammalian target of rapamycin (mTOR). Taken together, our results demonstrated that pinocembrin promotes OPC differentiation and remyelination through the phosphorylated mTOR pathway, and suggest a novel therapeutic prospect for this natural flavonoid product in treating demyelinating diseases.

Animals , Cell Differentiation , Flavanones , Mice , Mice, Inbred C57BL , Myelin Sheath/metabolism , Oligodendroglia/metabolism , Rats , Remyelination , Signal Transduction , TOR Serine-Threonine Kinases/metabolism
Int. j. morphol ; 38(6): 1606-1613, Dec. 2020. tab, graf
Article in English | LILACS | ID: biblio-1134486


SUMMARY: Disturbances of sensory and motor nerve conduction velocity in the spinal cord as well as degenerated myelin sheaths are observed in diabetic patients and animal models. Indeed, oligodendrocytes (OLs), which are important neuroglial cells, generate myelin in the central nervous system. Spinal enlargement, including cervical and lumbar enlargements, innervates all limbs. Thus, the purposes of this study were to examine and compare the ultrastructural alterations of OLs in spinal enlargements of streptozotocin (STZ)- induced diabetic rats and controls. Thirteen male Sprague-Dawley rats were induced with STZ in citrate buffer and six control rats were injected with the same buffer solution. All rats were sacrificed after inductions at four (short-term DM) and twenty-four weeks (long-term DM). The selected spinal enlargements were processed for transmission electron microscopy. The OL alterations in both the cervical and lumbar enlargements were apparently the same. In short-term DM, the nuclei of OLs became swelled with chromatin clumping. Cytoplasmic organelles were moderately damaged. In long-term DM, OLs contained shrinkage nuclei with thick heterochromatin clumping. Severely degenerated mitochondria with disrupted cristae and broken membranes were observed. Moreover, distended and fragmented rough endoplasmic reticulum were observed, and large clear areas were present in the cytoplasm. Additionally, the loosening, splitting, and destruction of myelin lamellae were found. This study can provide important preliminary information about the alteration of OLs in the spinal cords of diabetic patients, which might be involve in the impairments of sensory and motor conduction velocities in these individuals.

RESUMEN: En pacientes diabéticos y modelos animales se observan alteraciones de la velocidad de conducción nerviosa sensorial y motora en la médula espinal, así como vainas de mielina degeneradas. De hecho, los oligodendrocitos (OL), que son importantes células neurogliales, generan mielina en el sistema nervioso central. La intumescencia espinal, a nivel cervical y lumbar, inerva los miembros. Por lo tanto, los propósitos de este estudio fueron examinar y comparar las alteraciones ultraestructurales de los OL en la intumescencia espinal de ratas diabéticas inducidas por estreptozotocina (STZ) y controles. Se indujeron trece ratas macho Sprague-Dawley con STZ en tampón citrato y se inyectaron seis ratas de control con la misma solución tampón. Todas las ratas se sacrificaron después de la inducción a las cuatro (DM a corto plazo) y a las veinticuatro semanas (DM a largo plazo). Las ampliaciones de la columna seleccionadas se procesaron para microscopía electrónica de transmisión. Las alteraciones de OL en las intumescencias cervical y lumbar eran aparentemente las mismas. En la DM a corto plazo, los núcleos de los OL se hincharon con la acumulación de cromatina. Los orgánulos citoplasmáticos sufrieron daños moderados. En la DM a largo plazo, los OL contenían núcleos de contracción con aglutinación de heterocromatina gruesa. Se observaron mitocondrias severamente degeneradas con crestas y membranas rotas. Además, se observó un retículo endoplásmico rugoso distendido y fragmentado, y estaban presentes grandes áreas claras en el citoplasma. Además, se encontraron el aflojamiento, la división y la destrucción de las laminillas de mielina. Este estudio puede proporcionar información preliminar importante sobre la alteración de los OL en la médula espinal de los pacientes diabéticos, que podría estar involucrada en las alteraciones de las velocidades de conducción sensorial y motora en estos individuos.

Animals , Male , Rats , Spinal Cord/pathology , Oligodendroglia/pathology , Diabetes Mellitus, Experimental/pathology , Spinal Cord/ultrastructure , Central Nervous System , Oligodendroglia/ultrastructure , Rats, Sprague-Dawley , Microscopy, Electron, Transmission , Myelin Sheath
Int. j. morphol ; 38(5): 1197-1200, oct. 2020. graf
Article in English | LILACS | ID: biblio-1134424


SUMMARY: Histological techniques are the study of animal and human tissues through staining and examining them under a microscope. To demonstrate the axonal degeneration and demyelination in histological studies, the Luxol Fast Blue staining is gold standard techniques. In this study, a new histochemical method based on modified Luxol Fast Blue for the staining of the myelin sheath in sciatic nerve tissues described. The sciatic nerves of rats were removed and then the sciatic nerve was immersed in 10 % formaldehyde for one week and embedded in paraffin block. Next, thin sections (5 µm) were cut, using a microtome and stained with conventional and modified Luxol Fast Blue. Our results showed that a new method of modified Luxol Fast Blue staining can accurately identify the myelin in the sciatic nerve fibers. The current study showed that the Luxol Fast Blue combination with Light Green has a good effect on myelin coloration, and the results of this study are comparable to LFB combination with Sirius red.

RESUMEN: Las técnicas histológicas son el estudio de tejidos animales y humanos mediante tinción y examen bajo un microscopio. Para demostrar la degeneración axonal y la desmielinización en estudios histológicos, la tinción Luxol Fast Blue es una técnica estándar de oro. En este estudio, se describe un nuevo método histoquímico basado en Luxol Fast Blue modificado para la tinción de mielina en los tejidos del nervio ciático. Se seccionaron los nervios ciáticos de ratas y luego el nervio ciático se sumergió en formaldehído al 10 % durante una semana y se fijó en bloque de parafina. Posteriormente, se cortaron secciones delgadas (5 µm) usando un microtomo y se tiñeron con Luxol Fast Blue convencional y modificado. Nuestros resultados mostraron que un nuevo método de tinción Luxol Fast Blue modificado puede identificar con precisión la mielina en las fibras del nervio ciático. El estudio actual mostró que la combinación Luxol Fast Blue con Light Green es un buen efecto sobre la coloración de mielina, y los resultados de este estudio son comparables a la combinación LFB con Sirius red.

Animals , Rats , Sciatic Nerve/anatomy & histology , Staining and Labeling/methods , Myelin Sheath , Paraffin , Histological Techniques , Formaldehyde , Microscopy/methods
Int. j. morphol ; 38(2): 505-512, abr. 2020. graf
Article in English | LILACS | ID: biblio-1056469


Sexual dimorphism exists at all levels of the nervous system. These sex differences could underlie genderrelated differences in behavior and neuropsychological function, as well as the gender differences in the prevalence of various mental disorders such as autism, attention deficit disorders, and schizophrenia. Myelination, on the other hand, is a unique cellular process that can have a dramatic impact on the structure and physiology of an axon and its surrounding tissue. The corpus callosum (CC) is the largest of the brain commissures, which connects the cerebral cortices of the two hemispheres, and provides interhemispheric connectivity for information transfer and processing between cortical regions. Variation in the axonal properties of CC will alter the interhemispheric connectivity. The CC consists of myelinated and unmyelinated axons, glial cells and blood vessels. Several functional studies have reported that the function of CC is associated with its axons density and myelination properties. The sexual dimorphism in the axonal content of the CC has always been controversial; hence, the aim of this study was to analyze the differences in axons' diameter and myelin sheath thickness of the CC between male and female rats. For this purpose, five pairs of adult male and female rats were perfused and the CC were removed and sectioned. Four sections from different subregions of the corpus callosum that represent the genu, anterior body, posterior body, and splenium of the CC were stained and electron microscopic images were captured using stereological guidelines. Later, the axons diameter and myelin sheath thickness for each subregion were calculated and compared between males and females. Our preliminary findings of the present study indicated region specific differences in the myelinated axon thickness and diameter in the CC between male and female rats.

El dimorfismo sexual existe en todos los niveles del sistema nervioso. Estas diferencias de sexo podrían ser la base de las diferencias de comportamiento y función neuropsicológica relacionadas con el sexo, así como las diferencias en la prevalencia de diversos trastornos mentales, como el autismo, los trastornos por déficit de atención y la esquizofrenia. La mielinización, por otro lado, es un proceso celular único que puede tener un impacto dramático en la estructura y fisiología de un axón y su tejido circundante. El cuerpo calloso (CC) es la mayor comisura cerebral, que conecta las cortezas cerebrales de ambos hemisferios, y proporciona la conectividad interhemisférica para la transferencia y el procesamiento de información entre regiones corticales. La variación en las propiedades axonales de CC alterará la conectividad interhemisférica. El CC consiste en axones mielinizados y no mielinizados, células gliales y vasos sanguíneos. Varios estudios funcionales han informado que la función de CC está asociada con la densidad de axones y las propiedades de mielinización. El dimorfismo sexual en el contenido axonal del CC siempre ha sido controvertido; por lo tanto, el objetivo de este estudio fue analizar las diferencias en el diámetro de los axones y el grosor de la vaina de mielina del CC entre ratas macho y hembra. Para este propósito, se perfundieron cinco pares de ratas macho y hembra adultas y se extrajeron y seccionaron las CC. Se tiñeron cuatro secciones de diferentes subregiones del cuerpo calloso que representan el genu, el cuerpo anterior, el cuerpo posterior y el esplenio y se capturaron imágenes de microscopía electrónicas utilizando referencias estereológicas. Posteriormente se calculó el diámetro de los axones y el grosor de la vaina de mielina para cada subregión y se compararon entre machos y hembras. Nuestros hallazgos preliminares del presente estudio indicaron diferencias específicas en el grosor y diámetro del axón mielinizado en el CC entre ratas macho y hembra.

Animals , Male , Female , Rats , Axons/ultrastructure , Sex Characteristics , Corpus Callosum/ultrastructure , Myelin Sheath/ultrastructure , Microscopy, Electron , Corpus Callosum/cytology
Rev. bras. oftalmol ; 79(1): 66-68, Jan.-Feb. 2020. graf
Article in English | LILACS | ID: biblio-1092650


Abstract The presence of retinal myelinated nerve fibers is not a rare finding during routine examinations, and it is usually a benign and isolated finding. However, in some rare cases, it can be associated with other ophthalmological conditions. We describe a case of a patient with the triad myelin nerve fibers, myopia and ambliopia, which configures the Straatsma Syndrome.

Resumo A presença de fibras de mielina é um achado comum durante exames oftalmológicos de rotina. Na maior parte das vezes, tem caráter beningno e é um achado isolado. No entanto, em alguns raros casos, a presença de mielinização pode estar associada a outras condições oftalmológicas. Descrevemos um caso de paciente com a tríade presença de fibras nervosas retinianas mielinizadas, miopia, e ambliopia, configurando a síndrome de Straatsma.

Humans , Female , Middle Aged , Retinal Diseases/diagnosis , Amblyopia/diagnosis , Myopia/diagnosis , Nerve Fibers, Myelinated/pathology , Ophthalmoscopy , Optic Nerve/abnormalities , Visual Acuity , Anisometropia , Tomography, Optical Coherence , Fundus Oculi , Myelin Sheath
Rev. colomb. anestesiol ; 47(3): 180-183, July-Sept. 2019.
Article in English | LILACS, COLNAL | ID: biblio-1020677


Abstract Introduction: It is uncommon to come across patients with neuromuscular diseases in the daily practice of anesthesia, given the low prevalence of those conditions. Charcot-Marie-Tooth (CMT) disease is the most frequently, caused by an inherited abnormal myelin structure pattern. In view of the low prevalence of this condition (1:25,000), there is little information, derived mostly from case reports, about the use of neuroaxial anesthesia in these patients. Case presentation: Description of a patient with underlying CMT disease compromising lower limb mobility, who comes to the emergency service due to lower limb pain. After being diagnosed with an acetabular fracture, the patient underwent orthopedic surgery under spinal anesthesia, selected based on patient comorbidities, and the immediate postoperative follow-up. Results: The anesthetic and surgical procedures proceeded uneventfully and no neuropathic worsening was observed during the next 24 hours. Conclusion: Uneventful neuroaxial anesthesia is reported in a patient with neuromuscular disease. The case contributes to show the benefits and safety of this form of anesthesia when compared with other options.

Resumen Introducción: En la práctica anestésica diaria es raro enfrentarse a pacientes con patologías neuromusculares, dada la poca pre-valencia de dichas patologías. La más frecuente de ellas es la enfermedad de Charcot-Marie-Tooth, en la cual se hereda un patrón alterado en la estructura de la mielina. Debido a la baja prevalencia de esta patología (1:25000), el uso de anestesia neuroaxial en dichos pacientes no cuenta con mucha información, y mucha de ella proviene de reportes de casos. Presentación del caso: Se describe el caso de un paciente con enfermedad de Charcot-Marie-Tooth, de base, con compromiso de la movilidad en miembros inferiores, y quien asiste a urgencias por dolor en miembro inferior. Tras ser diagnosticado con fractura de acetábulo, fue sometido a cirugía ortopédica bajo anestesia raquídea, indicada a la luz de sus comorbilidades, y el posterior seguimiento inmediato. Resultados: Se realiza el procedimiento anestésico y quirúrgico sin complicaciones, y no se presenta empeoramiento de la neuropatía en las 24 horas posteriores. Conclusiones: Se reporta un caso de anestesia neuroaxial en paciente con enfermedad neuromuscular sin incidencias, que ayuda así a ir mostrando los beneficios de la mencionada anestesia y su seguridad frente a otras opciones.

Humans , Male , Middle Aged , Charcot-Marie-Tooth Disease , Orthopedic Procedures , Anesthesia, Spinal , Surgical Procedures, Operative , Aftercare , Lower Extremity , Fractures, Bone , Acetabulum , Myelin Sheath , Neuromuscular Diseases
Saude e pesqui. (Impr.) ; 12(1): 97-106, jan.-abr. 2019. ilus
Article in Portuguese | LILACS | ID: biblio-995593


O objetivo deste trabalho é estudar a morfologia neuronal a partir de modelos animais, fornecer informações biológicas difíceis de serem obtidas em humanos, permitindo estudar condições neuropsiquiátricas como doença de Alzheimer, ansiedade, dentre outras. O presente trabalho descreveu metodologia de estudo para cérebro de roedores, duas técnicas neuroanatômicas, Klüver-Barrera e Golgi-Cox, e seus respectivos processos de quantificação. A técnica de Klüver-Barrera permitiu visualização da substância branca e cinzenta com destaque na bainha de mielina. A técnica de Golgi-Cox, adaptada para realidade de nosso laboratório, mostrou-se eficiente para visualização de neurônios e seus prolongamentos, como dendritos e espinhas dendríticas, permitindo assim a quantificação. A partir de imagens obtidas de microscópio descreveu-se os diferentes passos para quantificação, a determinação de volume de estruturas internas cerebrais (corpo caloso e camada celular do hipocampo) assim como a quantificação das espinhas dendríticas em neurônios piramidais. Os métodos descritos e detalhados poderão ser utilizados em vários campos da neurociência

Neuronal morphology is analyzed in animal models to provide biological information difficult to obtain in humans. The above makes possible the study of neuro-psychiatric, such as Alzheimer´s disease, anxiety and others. Current study described methodology for rodents´ brains, two neuro-anatomic techniques, Klüver-Barrera and Golgi-Cox, and their respective quantification processes. Klüver-Barrera technique visualized the white and gray matter, particularly the myelin sheath. Golgi-Cox technique, adapted for current research, was efficient to visualize neurons and their prolongations, such as dendrites and dendritic spines, with quantification. Images by microscope described the different steps for the quantification, determination of volume of the brain´s internal structures (callous body and the hypocampus´s cell layer) coupled to the quantification of dendritic spines in pyramid neurons. Described and detailed methods will be useful in several fields of neuroscience

Animals , Central Nervous System , Dendritic Spines , Myelin Sheath , Neurosciences
Article in English | WPRIM | ID: wpr-719404


Pelizaeus-Merzbacher disease (PMD) is a progressive and degenerative chromosomal disorder of the central nervous system caused by defective myelin production. Few case reports have been issued on the anesthetic management of PMD, because of its extremely low incidence. We anesthetized a 13-year-old female patient diagnosed with PMD for ophthalmic surgery because of intermittent exotropia. General anesthesia was induced and maintained with propofol and sevoflurane in air and oxygen. Rocuronium was administered to facilitate orotracheal intubation, and residual neuromuscular blockage was reversed with pyridostigmine. Between emergence to 24 hours postoperatively, her muscle power completely recovered and no unpredictable events occurred. Summarizing, anesthesiologists should be concerned about the high possibility of aspiration, spasticity, and seizure during the perioperative period in patients with even mild PMD. Appropriate preoperative evaluation, intraoperative monitoring, and choice of proper anesthetic drugs enable safe anesthesia in patients with PMD.

Adolescent , Anesthesia , Anesthesia, General , Anesthetics , Central Nervous System , Chromosome Disorders , Exotropia , Female , Humans , Incidence , Intubation , Monitoring, Intraoperative , Muscle Spasticity , Myelin Sheath , Oxygen , Pelizaeus-Merzbacher Disease , Perioperative Period , Propofol , Pyridostigmine Bromide , Seizures
Article in Korean | WPRIM | ID: wpr-764671


PURPOSE: The purpose of this study was to identify the effect of ghrelin on memory impairment in a rat model of vascular dementia induced by chronic cerebral hypoperfusion. METHODS: Randomized controlled groups and the posttest design were used. We established the representative animal model of vascular dementia caused by bilateral common carotid artery occlusion and administered 80 µg/kg ghrelin intraperitoneally for 4 weeks. First, behavioral studies were performed to evaluate spatial memory. Second, we used molecular biology techniques to determine whether ghrelin ameliorates the damage to the structure and function of the white matter and hippocampus, which are crucial to learning and memory. RESULTS: Ghrelin improved the spatial memory impairment in the Y-maze and Morris water maze test. In the white matter, demyelination and atrophy of the corpus callosum were significantly decreased in the ghrelin-treated group. In the hippocampus, ghrelin increased the length of hippocampal microvessels and reduced the microvessels pathology. Further, we confirmed angiogenesis enhancement through the fact that ghrelin treatment increased vascular endothelial growth factor (VEGF)-related protein levels, which are the most powerful mediators of angiogenesis in the hippocampus. CONCLUSION: We found that ghrelin affected the damaged myelin sheaths and microvessels by increasing angiogenesis, which then led to neuroprotection and improved memory function. We suggest that further studies continue to accumulate evidence of the effect of ghrelin. Further, we believe that the development of therapeutic interventions that increase ghrelin may contribute to memory improvement in patients with vascular dementia.

Animals , Atrophy , Carotid Artery, Common , Corpus Callosum , Dementia , Dementia, Vascular , Demyelinating Diseases , Ghrelin , Hippocampus , Humans , Learning , Memory Disorders , Memory , Microvessels , Models, Animal , Molecular Biology , Myelin Sheath , Neuroprotection , Pathology , Rats , Spatial Memory , Vascular Endothelial Growth Factor A , Water , White Matter
Article in English | WPRIM | ID: wpr-764168


Hyperglycemia-induced hemichorea (HGHC) is a rare but characteristic hyperkinetic movement disorder involving limbs on one side of the body. In a 75-year-old woman with a left-sided HGHC, conventional brain MR imaging showed very subtle T1-hyperintensity and unique gadolinium enhancement in the basal ganglia contralateral to movements. Multi-parametric MRI was acquired using pulse sequence with quantification of relaxation times and proton density by multi-echo acquisition. Myelin map was reconstructed based on new tissue classification modeling. In this case report of multi-parametric MRI, quantitative measurement of myelin change related to HGHC in brain structures and its possible explanations are presented. This is the first study to demonstrate myelin loss related to hyperglycemic insult in multi-parametric quantitative MR imaging.

Aged , Basal Ganglia , Brain , Classification , Extremities , Female , Gadolinium , Humans , Hyperglycemia , Hyperkinesis , Magnetic Resonance Imaging , Movement Disorders , Myelin Sheath , Protons , Relaxation
Article in English | WPRIM | ID: wpr-763018


Technological advances of mankind, through the development of electrical and communication technologies, have resulted in the exposure to artificial electromagnetic fields (EMF). Technological growth is expected to continue; as such, the amount of EMF exposure will continue to increase steadily. In particular, the use-time of smart phones, that have become a necessity for modern people, is steadily increasing. Social concerns and interest in the impact on the cranial nervous system are increased when considering the area where the mobile phone is used. However, before discussing possible effects of radiofrequency-electromagnetic field (RF-EMF) on the human body, several factors must be investigated about the influence of EMFs at the level of research using in vitro or animal models. Scientific studies on the mechanism of biological effects are also required. It has been found that RF-EMF can induce changes in central nervous system nerve cells, including neuronal cell apoptosis, changes in the function of the nerve myelin and ion channels; furthermore, RF-EMF act as a stress source in living creatures. The possible biological effects of RF-EMF exposure have not yet been proven, and there are insufficient data on biological hazards to provide a clear answer to possible health risks. Therefore, it is necessary to study the biological response to RF-EMF in consideration of the comprehensive exposure with regard to the use of various devices by individuals. In this review, we summarize the possible biological effects of RF-EMF exposure.

Apoptosis , Brain , Cell Phone , Central Nervous System , Electromagnetic Fields , Human Body , In Vitro Techniques , Ion Channels , Magnets , Models, Animal , Myelin Sheath , Nervous System , Neurons , Smartphone
Experimental Neurobiology ; : 679-696, 2019.
Article in English | WPRIM | ID: wpr-785789


Spinal cord injury (SCI) causes axonal damage and demyelination, neural cell death, and comprehensive tissue loss, resulting in devastating neurological dysfunction. Neural stem/progenitor cell (NSPCs) transplantation provides therapeutic benefits for neural repair in SCI, and glial cell line-derived neurotrophic factor (GDNF) has been uncovered to have capability of stimulating axonal regeneration and remyelination after SCI. In this study, to evaluate whether GDNF would augment therapeutic effects of NSPCs for SCI, GDNF-encoding or mock adenoviral vector-transduced human NSPCs (GDNF-or Mock-hNSPCs) were transplanted into the injured thoracic spinal cords of rats at 7 days after SCI. Grafted GDNF-hNSPCs showed robust engraftment, long-term survival, an extensive distribution, and increased differentiation into neurons and oligodendroglial cells. Compared with Mock-hNSPC- and vehicle-injected groups, transplantation of GDNF-hNSPCs significantly reduced lesion volume and glial scar formation, promoted neurite outgrowth, axonal regeneration and myelination, increased Schwann cell migration that contributed to the myelin repair, and improved locomotor recovery. In addition, tract tracing demonstrated that transplantation of GDNF-hNSPCs reduced significantly axonal dieback of the dorsal corticospinal tract (dCST), and increased the levels of dCST collaterals, propriospinal neurons (PSNs), and contacts between dCST collaterals and PSNs in the cervical enlargement over that of the controls. Finally grafted GDNF-hNSPCs substantially reversed the increased expression of voltage-gated sodium channels and neuropeptide Y, and elevated expression of GABA in the injured spinal cord, which are involved in the attenuation of neuropathic pain after SCI. These findings suggest that implantation of GDNF-hNSPCs enhances therapeutic efficiency of hNSPCs-based cell therapy for SCI.

Animals , Axons , Cell Death , Cell Movement , Cell- and Tissue-Based Therapy , Cicatrix , Demyelinating Diseases , gamma-Aminobutyric Acid , Glial Cell Line-Derived Neurotrophic Factor , Humans , Hyperalgesia , Myelin Sheath , Neuralgia , Neurites , Neuroglia , Neurons , Neuropeptide Y , Paraplegia , Pyramidal Tracts , Rats , Regeneration , Spinal Cord Injuries , Spinal Cord , Therapeutic Uses , Transplants , Voltage-Gated Sodium Channels
Experimental Neurobiology ; : 279-288, 2019.
Article in English | WPRIM | ID: wpr-739538


Charcot-Marie Tooth disease type 1A (CMT1A), the major type of CMT, is caused by duplication of peripheral myelin protein 22 (PMP22) gene whose overexpression causes structural and functional abnormalities in myelination. We investigated whether miRNA-mediated regulation of PMP22 expression could reduce the expression level of PMP22, thereby alleviating the demyelinating neuropathic phenotype of CMT1A. We found that several miRNAs were down-regulated in C22 mouse, a CMT1A mouse model. Among them, miR-381 could target 3′ untranslated region (3′UTR) of PMP22 in vitro based on Western botting and quantitative Real Time-PCR (qRT-PCR) results. In vivo efficacy of miR-381 was assessed by administration of LV-miR-381, an miR-381 expressing lentiviral vector, into the sciatic nerve of C22 mice by a single injection at postnatal day 6 (p6). Administration of LV-miR-381 reduced expression level of PMP22 along with elevated level of miR-381 in the sciatic nerve. Rotarod performance analysis revealed that locomotor coordination of LV-miR-381 administered C22 mice was significantly enhanced from 8 weeks post administration. Electrophysiologically, increased motor nerve conduction velocity was observed in treated mice. Histologically, toluidine blue staining and electron microscopy revealed that structural abnormalities of myelination were improved in sciatic nerves of LV-miR-381 treated mice. Therefore, delivery of miR-381 ameliorated the phenotype of peripheral neuropathy in CMT1A mouse model by down-regulating PMP22 expression. These data suggest that miRNA can be used as a potent therapeutic strategy to control diseases with copy number variations such as CMT1A.

Animals , Demyelinating Diseases , In Vitro Techniques , Mice , MicroRNAs , Microscopy, Electron , Myelin Sheath , Neural Conduction , Peripheral Nervous System Diseases , Phenotype , Sciatic Nerve , Tolonium Chloride , Tooth Diseases , Untranslated Regions
Pesqui. vet. bras ; 38(7): 1371-1375, July 2018. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-976464


Sida carpinifolia is a plant responsible for poisoning several species of animals. This paper describes Hypomyelinogenesis in fetuses and neonates of cattle that consumed S. carpinifolia. Neonates manifested ataxia and muscle tremors. Two bovine newborns and four fetuses were necropsied and showed no significant gross changes. Histopathologic findings included vacuolation of pancreatic acinar cells, thyroid follicular cells, hepatocytes, cells of renal tubules and neurons of the fetus and the white matter of the telencephalic frontal lobe of the neonates and also revealed axonal spheroids in the brain of the fetuses and neonates. The lectin-histochemical evaluation shoved staining for the lectins Con-A, WGA and s-WGA. The Luxol Fast Blue staining revealed a marked decrease of myelin in the brain of all the fetuses and a moderate decrease in the neonates. Histologic and lectin-histochemic findings indicate that the consumption of S. carpinifolia by pregnant bovine females can cause hypomyelinogenesis in fetuses and neonates.(AU)

Sida carpinifolia é uma planta responsável por intoxicar várias espécies animais. Este artigo descreve hipomielinogênese em fetos e neonatos de bovinos que consumiram S. carpinifolia. Os neonatos manifestaram ataxia e tremores musculares. Dois neonatos e quatro fetos bovinos foram necropsiados e não havia alterações macroscópicas significativas. Os achados histopatológicos incluíram vacuolização de células acinares do pâncreas, células foliculares da tireoide, hepatócitos, células renais tubulares e neurônios nos fetos. Nos neonatos havia vacuolização na substância branca do lobo frontal telencefálico, além de esferoides axonais no encéfalo dos fetos e dos recém-nascidos. A avaliação lectino-histoquímica demonstrou marcação para as lectinas Con-A, WGA e s-WGA. A coloração de Luxol Fast Blue revelou diminuição acentuada da mielina no telencéfalo de todos os fetos e diminuição moderada nos neonatos. Os achados histológicos e lectina-histoquímicos indicam que o consumo de S. carpinifolia por fêmeas bovinas gestantes pode causar hipomielinogênese em fetos e neonatos.(AU)

Animals , Cattle , Cattle/metabolism , Malvaceae , Myelin Sheath/pathology , Plant Poisoning/veterinary
Laboratory Animal Research ; : 176-184, 2018.
Article in English | WPRIM | ID: wpr-718851


In this study, we observed chronological changes in the immunoreactivity and expression level of myelin basic protein (MBP), one of the most abundant proteins in the central nervous system, in the hippocampus of Zucker diabetic fatty (ZDF) rats and their control littermates (Zucker lean control; ZLC). In the ZLC group, body weight steadily increased with age; the body weight of the ZDF group, however, peaked at 30 weeks of age, and subsequently decreased. Based on the changes of body weight, animals were divided into the following six groups: early (12-week), middle (30-week), and chronic (52-week) diabetic groups and their controls. MBP immunoreactivity was found in the alveus, strata pyramidale, and lacunosum-moleculare of the CA1 region, strata pyramidale and radiatum of the CA3 region, and subgranular zone, polymorphic layer, and molecular layer of the dentate gyrus. MBP immunoreactivity was lowest in the hippocampus of 12-week-old rats in the ZLC group, and highest in 12-week-old rats in the ZDF group. Diabetes increased MBP levels in the 12-week-old group, while MBP immunoreactivity decreased in the 30-week-old group. In the 52-week-old ZLC and ZDF groups, MBP immunoreactivity was detected in the hippocampus, similar to the 30-week-old ZDF group. Western blot results corroborated with immunohistochemical results. These results suggested that changes in the immunoreactivity and expression of MBP in the hippocampus might be a compensatory response to aging, while the sustained levels of MBP in diabetic animals could be attributed to a loss of compensatory responses in oligodendrocytes.

Aging , Animals , Blotting, Western , Body Weight , Central Nervous System , Dentate Gyrus , Hippocampus , Models, Animal , Myelin Basic Protein , Myelin Sheath , Oligodendroglia , Rats
Article in English | WPRIM | ID: wpr-716895


OBJECTIVES: To investigate neurotoxic effect of bone cement (BC) on facial nerve by using electrophysiological and histopathological methods. METHODS: This study included 20 male albino Wistar rats, divided into four equal groups. Group A was designed as the control group, while group B was sham group. In the group C, BC solution was dropped onto the facial nerve trunks of rats and washed with physiological saline after 5 seconds. In the group D, BC solution was dropped onto the facial nerve trunks of rats and after allowing 5 minutes to dry, wounds were closed. Pre- and postoperative (on 4th week) evoked electromyography (EMG) measurements were done. For histopathological assessments, the rats were euthanized and tissue samples of facial nerve and surrounding areas were collected. RESULTS: According to the wave amplitude levels of evoked EMG, postoperative amplitude levels of group D were significantly decreased, compared to preoperative amplitude levels (P=0.043). We found no statistically significant difference in inflammation among the groups. In none of the groups, foreign body reaction and granulation tissue were not detected in any of the groups. In addition, degeneration in axon, myelin, or perineural nets was not detected in any of the groups. CONCLUSION: This study results suggest that BC has no direct toxicity on facial nerve, while it has indirect effects, by decreasing amplitude. Therefore, we conclude that direct contact of BC with nerve should be avoided, and the area should be cleaned by aspiration or washing with physiological saline in case of contact.

Animals , Axons , Bone Cements , Electromyography , Facial Nerve , Foreign-Body Reaction , Granulation Tissue , Humans , Inflammation , Male , Myelin Sheath , Rats , Rats, Wistar , Wounds and Injuries