Study of Cerebellar Tissue Following Induction of Aging in Mice By Di-Galactose / Estudio del Tejido Cerebeloso tras la Inducción del Envejecimiento en Ratones por D-Galactosa

SUMMARY: The cerebellum is a crucial area of the hindbrain that plays an essential role in balancing, excitement control, and subtle and accurate functions. Studies have shown that long-term use of D-galactose in mice, as with the symptoms of aging, causes morphological and functional disorders in the brain. This study was performed to evaluate the changes in the cerebellum cortex tissue and the measurement of reactive oxygen species (ROS) in the cerebellum following the induction of aging in mice by D-galactose. Accordingly, subjects were randomly assigned into two groups: Normal saline group and Aging group (D-galactose). To create an aging model, D- galactose, and saline solution (sodium chloride 0.9 %) were used. After completing the preparation and passage of the tissue, the cerebellum specimens were cut in 5 microns thickness and then stained with hematoxylin-eosin stain and finally examined under a Nikon microscope. Quantitative variables were analyzed by SPSS software using T-test. In the observations of cerebellum tissue samples, in the aged induced group by D-galactose, the most changes were observed in the Neuron purkinjense (Purkinje cells) layer. In the observations of the cerebellum tissue samples of aging group induced by D-galactose, the most changes were observed in the Neuron purkinjense, and the arrangement and placement of these cells were disorientated. The nucleus positioning was not central, and the Neuron purkinjense induced by aging were seen in different morphological forms. Necrosis, Chromatolysis, and Pyknosis were found. Based on the results, D-galactose (induction of aging) causes pathological changes in the cerebellar cortex, especially in the Neuron purkinjense layer.

El cerebelo es un área crucial del rombencéfalo que desempeña un papel esencial en el equilibrio, el control de la excitación y las funciones sutiles y precisas. Los estudios han demostrado que el uso a largo plazo de D-galactosa en ratones, al igual que con los síntomas del envejecimiento, provoca trastornos morfológicos y funcionales en el cerebro. Este estudio se realizó para evaluar los cambios en el tejido de la corteza del cerebelo y la medición de especies reactivas de oxígeno (ROS) en el cerebelo luego de la inducción del envejecimiento en ratones por D-galactosa. En consecuencia, los sujetos fueron asignados aleatoriamente a dos grupos: grupo de solución salina normal y grupo de envejecimiento (D-galactosa). Para crear un modelo de envejecimiento, se utilizaron D-galactosa y solución salina (cloruro de sodio al 0,9 %). Después de completar la preparación y el paso del tejido, las muestras de cerebelo se cortaron en un grosor de 5 µm y luego se tiñeron con tinción de hematoxilina-eosina y finalmente se examinaron bajo un microscopio Nikon. Las variables cuantitativas se analizaron mediante el software SPSS utilizando la prueba T. En las observaciones de muestras de tejido de cerebelo, en el grupo envejecido inducido por D-galactosa, la mayoría de los cambios se observaron en la capa de neuronas purkinjenses (células de Purkinje). En las observaciones de las muestras de tejido del cerebelo del grupo de envejecimiento inducidas por D-galactosa, la mayoría de los cambios se observaron en las neuronas purkinjenses, y la disposición y ubicación de estas células estaban desorientadas. El posicionamiento del núcleo no era central y las neuronas purkinjenses inducidas por el envejecimiento se observaban en diferentes formas morfológicas. Se encontró necrosis, cromatólisis y picnosis. Según los resultados, la D-galactosa (inducción del envejecimiento) provoca cambios patológicos en la corteza cerebelosa, especialmente en la capa de neuronas purkinjenses.

Expression changes of NaV channel subunits correlate with developmental maturation of electrophysiological characteristics of rat cerebellar Purkinje neurons / 南方医科大学学报

OBJECTIVE@#To investigate the variations in the expression of voltage-gated sodium (Nav) channel subunits during development of rat cerebellar Purkinje neurons and their correlation with maturation of electrophysiological characteristics of the neurons.@*METHODS@#We observed the changes in the expression levels of NaV1.1, 1.2, 1.3 and 1.6 during the development of Purkinje neurons using immunohistochemistry in neonatal (5-7 days after birth), juvenile (12-14 days), adolescent (21-24 days), and adult (42-60 days) SD rats. Using whole-cell patch-clamp technique, we recorded the spontaneous electrical activity of the neurons in ex vivo brain slices of rats of different ages to analyze the changes of electrophysiological characteristics of these neurons during development.@*RESULTS@#The expression of NaV subunits in rat cerebellar Purkinje neurons showed significant variations during development. NaV1.1 subunit was highly expressed throughout the developmental stages and increased progressively with age (P < 0.05). NaV1.2 expression was not detected in the neurons in any of the developmental stages (P > 0.05). The expression level of NaV1.3 decreased with development and became undetectable after adolescence (P < 0.05). NaV1.6 expression was not detected during infancy, but increased with further development (P < 0.05). NaV1.1 and NaV1.3 were mainly expressed in the early stages of development. With the maturation of the rats, NaV1.3 expression disappeared and NaV1.6 expression increased in the neurons. NaV1.1 and NaV1.6 were mainly expressed after adolescence. The total NaV protein level increased gradually with development (P < 0.05) and tended to stabilize after adolescence. The spontaneous frequency and excitability of the Purkinje neurons increased gradually with development and reached the mature levels in adolescence. The developmental expression of NaV subunits was positively correlated with discharge frequency (r=0.9942, P < 0.05) and negatively correlated with the excitatory threshold of the neurons (r=0.9891, P < 0.05).@*CONCLUSION@#The changes in the expression levels of NaV subunits are correlated with the maturation of high frequency electrophysiological properties of the neurons, suggesting thatmature NaV subunit expressions is the basis of maturation of electrophysiological characteristics of the neurons.

Noradrenaline modulates the spontaneous firing activities of Purkinje cells via α2-adrenergic receptor in mouse cerebellar cortex / 生理学报

Cerebellar Purkinje cells (PCs) exhibit two types of discharge activities: simple spike (SS) and complex spike (CS). Previous studies found that noradrenaline (NA) can inhibit CS and bidirectionally regulate SS, but the enhancement of NA on SS is overwhelmed by the strong inhibition of excitatory molecular layer interneurons. However, the mechanism underlying the effect of NA on SS discharge frequency is not clear. Therefore, in the present study, we examined the mechanism underlying the increasing effect of NA on SS firing of PC in mouse cerebellar cortex in vivo and in cerebellar slice by cell-attached and whole-cell recording technique and pharmacological methods. GABAA receptor was blocked by 100 µmol/L picrotoxin in the whole process. In vivo results showed that NA significantly reduced the number of spikelets of spontaneous CS and enhanced the discharge frequency of SS, but did not affect the discharge frequency of CS. In vitro experiments showed that NA reduced the number of CS spikelets and after hyperpolarization potential (AHP) induced by electrical stimulation, and increased the discharge frequency of SS. NA also reduced the amplitude of excitatory postsynaptic current (EPSC) of parallel fiber (PF)-PC and significantly increased the paired-pulse ratio (PPR). Application of yohimbine, an antagonist of α2-adrenergic receptor (AR), completely eliminated the enhancing effect of NA on SS. The α2-AR agonist, UK14304, also increased the frequency of SS. The β-AR blocker, propranolol, did not affect the effects of NA on PC. These results suggest that in the absence of GABAA receptors, NA could attenuate the synaptic transmission of climbing fiber (CF)-PC via activating α2-AR, inhibit CS activity and reduce AHP, thus enhancing the SS discharge frequency of PC. This result suggests that NA neurons of locus coeruleus can finely regulate PC signal output by regulating CF-PC synaptic transmission.

Effects of prenatal tobacco smoke on cerebellum histomorphological changes at critical developmental stages in CD-1 mice / Efectos del humo de tabaco en los cambios histomorfológicos del cerebelo en las etapas críticas del desarrollo prenatal en ratones CD-1

SUMMARY: In this study the consequences of prenatal exposure to tobacco smokes on the histo-morphological changes of cerebellum was assessed by comparing the smoker mice to the nonsmoker mice. A total of 30 pregnant cd-1 mice were divided into three groups of 10 mice each and with two replicates per group (5 mice each). Following acclimation for five days, the mice were placed in a special modified smoking machine for 2 hours per day over a two- and three-week period for group two and group three, respectively. Group one was considered as a control group. Mice in the control group were exposed simultaneously to fresh air from the room, while those in the treatment groups were exposed to tobacco smoke from six commercial filter cigarettes, containing 0.8 mg of nicotine, 10 mg of tar, and 10 mg of carbon monoxide, for three 1-hour exposure periods every day for three weeks. The mice in the control group were exposed to room air for three 1-hour periods every day for the same period of three weeks. The results from this study showed a correlation between maternal smoking and histological changes in Neuron purkinjense (Purkinje cells) of the cerebellum. They also showed that prenatal smoking period may have caused more damage in the histology and structure of Neuron purkinjense in some juvenile mice. An increased incidence of morphology damage of the cerebellum's Neuron purkinjense' structures was also observed in fetuses with prolonged exposure to tobacco smoking. Exposure of in utero maternal smoking may interfere with brain biological development parameters, giving rise to structural abnormalities of the cerebellum. This study concluded that tobacco smoke exposure to pregnant mice may affect neurodevelopment which may induce behavioural changes as a result of reduced cerebellar size and function.

RESUMEN: Se evaluaron los efectos producidos por la exposición prenatal al humo de tabaco en ratones expuestos y no expuestos y los cambios histomorfológicos observados en el cerebelo en ambos grupos. Un total de 30 ratones cd-1 preñados se dividieron en tres grupos de 10 ratones cada uno y con dos réplicas por grupo (5 ratones cada uno). Después de la aclimatación durante cinco días, los ratones se colocaron en una máquina de fumar modificada, especial durante 2 horas al día, durante un período de dos y tres semanas para el grupo dos y el grupo tres, respectivamente. El grupo uno se consideró como grupo control. Los ratones del grupo de control fueron expuestos simultáneamente al aire limpio de la habitación, mientras que los grupos de tratamiento fueron expuestos al humo de tabaco de seis cigarrillos comerciales, que contenían 0,8 mg de nicotina, 10 mg de alquitrán y 10 mg de monóxido de carbono. durante tres períodos de 1 hora diariamente, durante tres semanas. Los ratones del grupo de control se expusieron al aire ambiente durante tres períodos de 1 hora todos los días durante el mismo período de tres semanas. Los resultados de este estudio mostraron una correlación entre el tabaquismo materno y los cambios histológicos en las neuronas purkinjenses (células de Purkinje). Se observó además que el período de tabaquismo prenatal puede haber causado mayor daño en la histología y estructura de las neuronas purkinjenses en algunos ratones jóvenes. También se observó una mayor incidencia de daño morfológico de las estructuras de las neuronas purkinjenses del cerebelo en fetos con exposición prolongada al tabaquismo. La exposición al tabaquismo materno en el útero puede interferir con los parámetros de desarrollo biológico del cerebro, dando lugar a anomalías estructurales del cerebelo. Este estudio concluyó que la exposición al humo del tabaco en ratones preñados puede afectar el desarrollo neurológico, lo que puede inducir cambios de comportamiento como resultado de la reducción del tamaño y la función del cerebelo.

Jan Evangelista Purkinje, a brilliant, multifaceted Czech biologist: nerve tissue / Jan Evangelista Purkinje, um brilhante multifacetado biólogo checo: tecido nervoso

Jan Evangelista Purkinje was a Czech physician with an exceptional capacity for innovative thinking, and he was one of the fathers of experimental physiology, experimental pharmacology, experimental psychology, histology, embryology, and physical anthropology. Several achievements are named after him, from his prodigious productivity. Of special interest of this paper was his pioneering role in the rise of experimental physiology, microscopical anatomy, and histological methods by the 1830´s that allowed him define more accurate data concerning the structure of nerve tissue of animals and humans such as the now known "Purkinje's cells" and others cells of the brain. He investigated the structure of neuronal processes, including the dendrites. Purkinje recognized possible functional differences between a variety of types of neurons and speculated about their interrelations. He was one of the great geniuses of science.

Jan Evangelista Purkinje foi um médico checo com excepcional capacidade de pensamento inovador e um dos pais da fisiologia experimental, farmacologia experimental, psicologia experimental, histologia, embriologia e antropologia física. Várias conquistas receberam o nome dele, de sua produtividade prodigiosa. De interesse especial deste trabalho enaltece-se o seu papel pioneiro no surgimento da fisiologia experimental, anatomia microscópica e métodos histológicos na década de 1830. Isso permitiu que ele definisse dados mais precisos sobre a estrutura do tecido nervoso de animais e humanos, como as agora conhecidas "células de Purkinje" e outras células do cérebro. Ele investigou a estrutura dos processos neuronais, incluindo os dendritos. Purkinje reconheceu possíveis diferenças funcionais entre uma variedade de tipos de neurônios e especulou sobre suas inter-relações. Ele foi um dos grandes gênios da ciência.

Rapid and Sparse Labeling of Neurons Based on the Mutant Virus-Like Particle of Semliki Forest Virus / 神经科学通报·英文版

Sparse labeling of neurons contributes to uncovering their morphology, and rapid expression of a fluorescent protein reduces the experiment range. To achieve the goal of rapid and sparse labeling of neurons in vivo, we established a rapid method for depicting the fine structure of neurons at 24 h post-infection based on a mutant virus-like particle of Semliki Forest virus. Approximately 0.014 fluorescent focus-forming units of the mutant virus-like particle transferred enhanced green fluorescent protein into neurons in vivo, and its affinity for neurons in vivo was stronger than for neurons in vitro and BHK21 (baby hamster kidney) cells. Collectively, the mutant virus-like particle provides a robust and convenient way to reveal the fine structure of neurons and is expected to be a helper virus for combining with other tools to determine their connectivity. Our work adds a new tool to the approaches for rapid and sparse labeling of neurons in vivo.

Cerebellar synaptopathy in streptozotocin-induced diabetic rats / Sinaptopatía cerebelosa en ratas diabéticas inducidas por estreptozotocina

SUMMARY: There is an increasing amount of evidence that supports the diabetic complications of the central nervous system structure and function. The cerebellum, which is one of the primary structure derived from the hindbrain, plays an important role in motor control, motor coordination, and non-motor functions, such as cognitive processing. The synapse is a critical structure that regulates neuronal communication, and well-defined afferent and efferent fibre connections in the cerebellum help in maintaining the proper working order. Thus, the present study sought to investigate the long-term effects of diabetes-induced synaptopathy in the cerebellum, using both histological and ultrastructural studies. Twenty Sprague-Dawley male rats were divided randomly into control and diabetic groups, and diabetes was then induced through a single intraperitoneal injection of streptozotocin (60 mg/kg body weight). Six month later, the rats were sacrificed and the cerebellum was removed. Light and electron microscopic examinations showed a degeneration of Purkinje cells (Neuron purkinjense) with shrunken cells, pyknotic nuclei, and synaptopathy, including the reduction in synapse density, number of synaptic vesicles, and maturation of synapses in the molecular layer of diabetic cerebellum. The disruptions in synaptic profiles, which observed in the diabetic condition, could be related to cerebellar dysfunction, thus leading to the defects in coordinated movement, balance, as well as cognitive learning and memory.

RESUMEN: Actualmente existe una creciente evidencia que apoya las complicaciones diabéticas de la estructura y función del sistema nervioso central. El cerebelo, una de las estructuras primarias del cerebro posterior, desempeña un papel importante en el control motor, la coordinación motora y las funciones no motoras, tanto como en el procesamiento cognitivo. La sinapsis es una estructura crítica que regula la comunicación neuronal y las conexiones de fibras aferentes y eferentes bien definidas en el cerebelo, ayudan a mantener el funcionamiento correcto. Por lo tanto, en el presente estudio se investigaron los efectos a largo plazo de la sinaptopatía inducida por la diabetes en el cerebelo, utilizando estudios histológicos y ultraestructurales. Veinte ratas SpragueDawley macho se dividieron al azar en grupos de control y diabetes, se indujó la diabetes a través de una inyección intraperitoneal única de estreptozotocina (60 mg / kg de peso corporal). Seis meses después, se sacrificaron las ratas y se extrajo el cerebelo. Los exámenes de microscopías óptica y electrónica mostraron una degeneración de las neuronas purkinjenses (células de Purkinje), con células reducidas, núcleos picnóticos y sinaptopatía, como también la densidad reducida de sinapsis, el número de vesículas sinápticas y la maduración de las sinapsis en la capa molecular del cerebelo de las ratas diabéticas. Las interrupciones en los perfiles sinápticos, que se observaron en la condición diabética, podrían estar relacionadas con la disfunción cerebelosa, lo que lleva a defectos en el movimiento coordinado, el equilibrio, así como al aprendizaje cognitivo y la memoria.

Treadmill Exercise Improves Motor Function by Suppressing Purkinje Cell Loss in Parkinson Disease Rats / 대한배뇨장애요실금학회지

PURPOSE: Rotenone is the most widely used neurotoxin for the making Parkinson disease (PD) animal model. The neurodegenerative disorder PD shows symptoms, such as slowness of movements, tremor at resting, rigidity, disturbance of gait, and instability of posture. We investigated whether treadmill running improves motor ability using rotenone-caused PD rats. The effect of treadmill running on PD was also assessed in relation with apoptosis of cerebellar Purkinje cells. METHODS: Treadmill running was applied to the rats in the exercise groups for 30 minutes once a day for 4 weeks, starting 4 weeks after birth. We used rota-rod test for the determination of motor coordination and balance. In this experiment, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, immunohistochemistry for calbindin, glial fibrillary acidic protein (GFAP), Iba-1, and western blot analysis for Bax and Bcl-2 were performed. RESULTS: Treadmill running enhanced motor balance and coordination by preventing the loss of Purkinje cells in the cerebellar vermis. Treadmill running suppressed PD-induced expression of GFAP-positive reactive astrocytes and Iba-1-positive microglia, showing that treadmill running suppressed reactive astrogliosis and microglia activation. Treadmill running suppressed TUNEL-positive cell number and Bax expression and enhanced Bcl-2 expression, demonstrating that treadmill running inhibited the progress of apoptosis in the cerebellum of rotenone-induced PD rats. CONCLUSIONS: Treadmill running improved motor ability of the rotenone-induced PD rats by inhibiting apoptosis in the cerebellum. Apoptosis suppressing effect of treadmill running on rotenone-induced PD was achieved via suppression of reactive astrocyte and inhibition of microglial activation.

Unsolved Questions on the Anatomy of the Ventricular Conduction System

We reviewed the anatomical characteristics of the conduction system in the ventricles of human and ungulate hearts and then raised some questions to be answered by clinical and anatomical studies in the future. The ventricular conduction system is a 3-dimensional structure as compared to the 2-dimensional character of the atrial conduction system. The proximal part consisting of the atrioventricular node, the bundle of His and fascicles are groups of conducting cells surrounded by fibrous connective tissue so as to insulate from the underlying myocardium. Their location and morphological characters are well established. The bundle of His is a cord like structure but the left and right fascicles are broad at the proximal and branching at the distal part. The more distal part of fascicles and Purkinje system are linear networks of conducting cells at the immediate subendocardium but the intra-mural network is detected at the inner half of the ventricular wall. The papillary muscle also harbors Purkinje system not in the deeper part. It is hard to recognize histologically in human hearts but conducting cells as well as Purkinje cells are easily recognized in ungulate hearts. Further observation on human and ungulate hearts with myocardial infarct, we could find preserved Purkinje system at the subendocardium in contrast to the damaged system at the deeper myocardium. Further studies are necessary on the anatomical characteristics of this peripheral conduction system so as to correlate the clinical data on hearts with ventricular arrhythmias.

The Emerging Concept of Intrinsic Plasticity: Activity-dependent Modulation of Intrinsic Excitability in Cerebellar Purkinje Cells and Motor Learning

What is memory? How does the brain process the sensory information and modify an organism's behavior? Many neuroscientists have focused on the activity- and experience-dependent modifications of synaptic functions in order to solve these fundamental questions in neuroscience. Recently, the plasticity of intrinsic excitability (called intrinsic plasticity) has emerged as an important element for information processing and storage in the brain. As the cerebellar Purkinje cells are the sole output neurons in the cerebellar cortex and the information is conveyed from a neuron to its relay neurons by forms of action potential firing, the modulation of the intrinsic firing activity may play a critical role in the cerebellar learning. Many voltage-gated and/or Ca²⁺-activated ion channels are involved in shaping the spiking output as well as integrating synaptic inputs to finely tune the cerebellar output. Recent studies suggested that the modulation of the intrinsic excitability and its plasticity in the cerebellar Purkinje cells might function as an integrator for information processing and memory formation. Moreover, the intrinsic plasticity might also determine the strength of connectivity to the sub-cortical areas such as deep cerebellar nuclei and vestibular nuclei to trigger the consolidation of the cerebellar-dependent memory by transferring the information.

Intravenous Anesthetic, Propofol Affects Synaptic Responses in Cerebellar Purkinje Cells

OBJECTIVE: Propofol is an intravenously administered anesthetic that enhances γ-aminobutyric acid-mediated inhibition in the central nerve system. Other mechanisms may also be involved in general anesthesia. Propofol has been implicated in movement disorders. The cerebellum is important for motor coordination and motor learning. The aim of the present study was to investigate the propofol effect on excitatory synaptic transmissions in cerebellar cortex. METHODS: Excitatory postsynaptic currents by parallel fiber stimulation and complex spikes by climbing fiber stimulation were monitored in Purkinje cells of Wister rat cerebellar slice using whole-cell patch-clamp techniques. RESULTS: Decay time, rise time and amplitude of excitatory postsynaptic currents at parallel fiber Purkinje cell synapses and area of complex spikes at climbing fiber Purkinje cell synapses were significantly increased by propofol administration. CONCLUSION: The detected changes of glutamatergic synaptic transmission in cerebellar Purkinje cell, which determine cerebellar motor output, could explain cerebellar mechanism of motor deficits induced by propofol.

Abiotrofia cerebelar em um gato: relato de caso / Cerebellar abiotrophy in a feline: case report

Um caso de abiotrofia cerebelar em um gato com 45 dias de idade foi diagnosticado no Laboratório de Patologia Animal, Hospital Veterinário da Universidade Federal de Campina Grande. O animal apresentava, havia 15 dias, apatia, anorexia, desidratação, ataxia, hipermetria, espasticidade dos membros torácicos e pélvicos, tremores de intenção, nistagmo, opistótono, déficit proprioceptivo e ausência de resposta de ameaça. Clinicamente, havia a suspeita de hipoplasia cerebelar, e, devido ao prognóstico desfavorável, o animal foi eutanasiado. Na necropsia, não foram observadas alterações macroscópicas. Microscopicamente, as lesões estavam restritas ao cerebelo e caracterizavam-se por alterações neurodegenerativas e necróticas, com desaparecimento segmentar dos neurônios de Purkinje. Nessas áreas, também se verificaram espaços em branco, denominado aspecto de cesto vazio, resultantes da perda dos neurônios de Purkinje, além de raros esferoides axonais e proliferação dos astrócitos de Bergmann. Em algumas áreas, a camada granular estava hipocelular e havia moderada gliose multifocal na camada molecular. O diagnóstico de abiotrofia cerebelar foi realizado com base nos dados epidemiológicos, clínicos e, principalmente, pelas alterações histopatológicas dos neurônios de Purkinje características da doença.(AU)

The aim of this report was to describe a case of cerebellar abiotrophy in cat with 45-year-old diagnosed at the Animal Pathology Laboratory, Veterinary Hospital of the Federal University of Campina Grande. The animal had presented 15-day apathy, anorexia, dehydration and neurological signs, characterized by ataxia, hypermetria, spasticity of fore and hindlimbs, intention tremor, nystagmus, opisthotonos, proprioceptive deficits, and absence of threat response. Clinically, cerebellar hypoplasia was suspected and the animal was euthanized due to poor prognosis. During necropsy, gross lesions were not observed. Microscopically the lesions were restricted to the cerebellum and were characterized by neurodegenerative and necrotic damage with segmental disappearance of the Purkinje cells. In these areas, there were also empty spaces, called the empty basket aspect, resulting from the loss of Purkinje cells, as well as rare axonal spheroids and proliferation of Bergmann's astrocytes. In some areas, the granular layer was hypocellular and there was moderate multifocal gliosis in the molecular layer. The diagnosis of cerebellar abiotrophy was based on epidemiological, clinical and mainly on histopathological changes in neurons of Purkinje disease characteristics.(AU)

Effect of electromagnetic field from 2g, 3g and 4g mobile phones on the organization of purkinje cell layer of rat cerebellum

Objective: To study and compare the histomorphological changes induced by second generation [2G], third generation [3G] and fourth generation [4G] mobile phone electromagnetic fields on the organization of Purkinje cell layer of rat cerebellum

Study Design: Laboratory based randomized control trial

Place and Duration of Study: The study was carried out in the Anatomy department, Army Medical College Rawalpindi; in collaboration with animal house, National Institute of Health, Islamabad, from Nov 2014 to Nov 2015

Material and Methods: Forty adult Sprague Dawley rats [20 male, 20 female], weighing 250-350grams,were taken and divided into 4 groups with 10 rats [5 male, 5 female] in each group. Group A served as control and was given normal diet and water ad libitum. Groups B, C and D were exposed to EMF from 2G, 3G and 4G mobile phones respectively, daily for 1 hour for 2 months. The animals were sacrificed on 60th day of the experiment, cerebellums were removed, fixed in 10% formalin, processed and stained with haematoxylin and eosin [H and E] for histological study

Results: It was observed on microscopic examination that EMF from 2G, 3G and 4G mobile phones effected the organization of Purkinje cell layer of cerebellum; being double cell layer in group B and multiple cell layers in groups C and D

Conclusion: It was concluded from current results that radiations from 2G, 3G and 4G mobile phones have deleterious effects on the organization of Purkinje cell layer of cerebellum with 3G and 4G causing more harm as compared to EMF from 2G mobile phones

A Patient Diagnosed with Spinocerebellar Ataxia Type 5 associated with SPTBN2: Case Report / 대한소아신경학회지

Spinocerebellar ataxias (SCAs) are autosomal dominant neurodegenerative disorders which disrupt the afferent and efferent pathways of the cerebellum that cause cerebellar ataxia. Spectrin beta non-erythrocytic 2 (SPTBN2) gene encodes the β-III spectrin protein with high expression in Purkinje cells that is involved in excitatory glutamate signaling through stabilization of the glutamate transporter, and its mutation is known to cause spinocerebellar ataxia type 5. Three years and 5 months old boy with delayed development showed leukodystrophy and cerebellar atrophy in brain magnetic resonance imaging (MRI). Diagnostic exome sequencing revealed that the patient has heterozygous mutation in SPTBN2 (p.Glu1251Gln) which is a causative genetic mutation for spinocerebellar ataxia type 5. With the patient's clinical findings, it seems reasonable to conclude that p.Glu1251Gln mutation of SPTBN2 gene caused spinocerebellar ataxia type 5 in this patient.

Influence of cefuroxime sodium on synaptic plasticity of parallel fiber-Purkinje cells in young rats / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the influence of cefuroxime sodium (CS) on the electrophysiological function of cerebellar Purkinje cells (PCs) in Sprague-Dawley rats.</p><p><b>METHODS</b>Postnatal day 7 (P7) Sprague-Dawley rats were divided into early administration I and II groups (administered from P7 to P14) and late administration group (administered from P14 to P21), and all the groups received intraperitoneally injected CS. The control groups for early and late administration groups were also established and treated with intraperitoneally injected normal saline of the same volume. There were 10 rats in each group. The rats in the early administration I group and early administration control group were sacrificed on P15, and those in the early administration II group, late administration group, and late administration control group were sacrificed on P22. The whole-cell patch-clamp technique was used to record inward current and action potential of PCs on cerebellar slices, as well as the long-term depression (LTD) of excitatory postsynaptic current (EPSC) in PCs induced by low-frequency stimulation of parallel fiber (PF).</p><p><b>RESULTS</b>Compared with the control groups, the early and late administration groups had a slightly higher magnitude of inward current and a slightly higher amplitude of action potential of PCs (P>0.05). All administration groups had a significantly higher degree of EPSC inhibition than the control groups (P<0.01), and the early administration II group had a significantly greater degree of EPSC inhibition than the late administration group (P<0.01).</p><p><b>CONCLUSIONS</b>Early CS exposure after birth affects the synaptic plasticity of PF-PCs in the cerebellum of young rats, which persists after drug withdrawal.</p>

Protective effect of succinic acid on cerebellar Purkinje cells of neonatal rats with convulsion / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the protective effect of succinic acid (SA) on the cerebellar Purkinje cells (PCs) of neonatal rats with convulsion.</p><p><b>METHODS</b>A total of 120 healthy neonatal Sprague-Dawley rats aged 7 days were randomly divided into a neonatal period group and a developmental period group. Each of the two groups were further divided into 6 sub-groups: normal control, convulsion model, low-dose phenobarbital (PB) (30 mg/kg), high-dose PB (120 mg/kg), low-dose SA (30 mg/kg), and high-dose SA (120 mg/kg). Intraperitoneal injection of pentylenetetrazole was performed to establish the convulsion model. The normal control group was treated with normal saline instead. The rats in the neonatal group were sacrificed at 30 minutes after the injection of PB, SA, or normal saline, and the cerebellum was obtained. Those in the developmental group were sacrificed 30 days after the injection of PB, SA, or normal saline, and the cerebellum was obtained. Whole cell patch clamp technique was used to record the action potential (AP) of PCs in the cerebellar slices of neonatal rats; the parallel fibers (PF) were stimulated at a low frequency to induce excitatory postsynaptic current (EPSC). The effect of SA on long-term depression (LTD) of PCs was observed.</p><p><b>RESULTS</b>Compared with the normal control groups, the neonatal and developmental rats with convulsion had a significantly higher AP frequency of PCs (P<0.05), and the developmental rats with convulsion had a significantly decreased threshold stimulus (P<0.01) and a significantly greater inhibition of the amplitude of EPSC in PCs (P<0.05). Compared with the normal control groups, the neonatal and developmental rats with convulsion in the high-dose PB groups had a significantly decreased threshold stimulus (P<0.01), a significantly higher AP frequency of PCs (P<0.05), and a significantly greater inhibition of EPSC in PCs (P<0.05). Compared with the neonatal and developmental rats in the convulsion model groups, those in the high-dose SA groups had a significantly decreased AP frequency of PCs (P<0.05). The developmental rats in the low- and high-dose SA groups had a significantly higher AP threshold than those in the convulsion model group (P<0.05).</p><p><b>CONCLUSIONS</b>The high excitability of PCs and the abnormal PF-PC synaptic plasticity caused by convulsion in neonatal rats may last to the developmental period, which can be aggravated by PB, while SA can reduce the excitability of PCs in neonatal rats with convulsion and repair the short- and long-term abnormalities of LTD of PCs caused by convulsion.</p>

Evaluation of brachial plexus fascicles involvement on infraclavicular block: unfixed cadaver study / Avaliação do envolvimento dos fascículos do plexo braquial no bloqueio por via infraclavicular: estudo em cadáveres não fixados / Evaluación de la implicación de los fascículos del plexo braquial en el bloqueo por vía infraclavicular: estudio en cadáveres no fijos

BACKGROUND AND OBJECTIVES: This study shows how the diffusion of the anesthetic into the sheath occurs through the axillary infraclavicular space and hence proves the efficacy of the anesthetic block of the brachial plexus, and may thereby allow a consolidation of this pathway, with fewer complications, previously attached to the anesthesia. MATERIALS AND METHODS: 33 armpits of adult cadavers were analyzed and unfixed. We injected a solution of neoprene with latex dye in the infraclavicular space, based on the technique advocated by Gusmão et al., and put the corpses in refrigerators for three weeks. Subsequently, the specimens were thawed and dissected, exposing the axillary sheath along its entire length. RESULTS AND DISCUSSION: Was demonstrated involvement of all fasciculus of the plexus in 51.46%. In partial involvement was 30.30%, 18.24% of cases the acrylic was located outside the auxiliary sheath involving no issue. CONCLUSIONS: The results allow us to establish the infraclavicular as an effective and easy way to access plexus brachial, because the solution involved the fascicles in 81.76% partially or totally, when it was injected inside the axillary sheath. We believe that only the use of this pathway access in practice it may demonstrate the efficiency. .

JUSTIFICATIVA E OBJETIVOS: Procuramos demonstrar como ocorre a difusão do anestésico no interior da bainha axilar, quando se utiliza o bloqueio por via infraclavicular, através da fossa infraclavicular e, consequentemente, provar a eficácia dessa via, podendo, com isso, permitir uma consolidação da utilização desse acesso, com redução das complicações. MATERIAS E MÉTODO: Foram utilizadas 33 axilas de cadáveres adultos não fixados. Injetamos uma solução de neoprene látex com corante na fossa infraclavicular, baseando-se na técnica preconizada por Gusmão e col, e colocamos os cadáveres em geladeiras por três semanas. Posteriormente, as peças foram descongeladas e dissecadas, expondo a bainha axilar em toda sua extensão. RESULTADOS E DISCUSSÃO: Foi demonstrado envolvimento de todos os fascículos do plexo em 51,46%. Em 30,30% houve envolvimento parcial, e em 18,24% dos casos o acrílico foi localizado fora da bainha axilar, não envolvendo nenhum fascículo. CONCLUSÕES: Os dados obtidos permitem estabelecer a via infraclavicular como uma via eficaz e de fácil acesso ao plexo braquial, visto que a solução injetada envolveu os fascículos em 81,76% parcialmente ou totalmente, quando era injetada dentro da bainha axilar. Acreditamos que apenas a utilização desta via de acesso na prática poderá demonstrar a eficiência da mesma. .

JUSTIFICACIÓN Y OBJETIVOS: Este estudio intenta demostrar cómo ocurre la difusión del anestésico en el interior de la vaina axilar, cuando se utiliza el bloqueo por vía infraclavicular a través de la fosa infraclavicular, y al mismo tiempo, probar la eficacia de esa vía, pudiendo así permitir una consolidación de la utilización de ese acceso con reducción de las complicaciones. MATERIALES Y MÉTODO: Fueron utilizadas 33 axilas de cadáveres adultos no fijadas. Inyectamos una solución de neopreno látex con colorante en la fosa infraclavicular, con la técnica preconizada por Gusmão et al., y colocamos los cadáveres en frigoríficos durante 3 semanas. Posteriormente, las piezas fueron descongeladas y disecadas, exponiendo la vaina axilar en toda su extensión. RESULTADOS Y DISCUSIÓN: Quedó demostrada la implicación de todos los fascículos del plexo en un 51,46%. En un 30,30% hubo una participación parcial, y en un 18,24% de los casos el acrílico fue ubicado fuera de la vaina axilar sin la participación de ningún fascículo. CONCLUSIONES: Los datos obtenidos permiten establecer la vía infraclavicular como una vía eficaz y de fácil acceso al plexo braquial, visto que la solución inyectada tuvo la participación de los fascículos en un 81,76% parcial o totalmente, cuando se inyectaba dentro de la vaina axilar. Creemos que solamente con la utilización de esta vía de acceso en la práctica podrá quedar demostrada su eficacia. .

Association between overweight and characteristics of young adult students: support for nursing care / Associação entre excesso de peso e características de adultos jovens escolares: subsídio ao cuidado de enfermagem / Asociación entre exceso de peso y características de adultos jóvenes escolares: contribución para el cuidado de enfermería

OBJECTIVE: to verify associations between overweight and the characteristics of young adult students to support nursing care. METHOD: case-control study conducted with young adults from public schools. The sample was composed of 441 participants (147 cases and 294 controls, with and without excess weight, respectively). Sociodemographic and clinical characteristics were collected together with exposure factors and anthropometrics. Multiple logistic regression was used. The study received Institutional Review Board approval. RESULTS: statistically significant association with overweight: non-Caucasian, having a partner; weight gain during adolescence, mother's excess weight, the use of obesogenic medication, augmented diastolic blood pressure, of abdominal circumference and waist/hip ratio. In addition to these, schooling and weight gain during childhood were also included in the multivariate analysis. After adjustment, the final model included: having a partner, weight gain during adolescence, augmented diastolic blood pressure and abdominal circumference. CONCLUSION: the analysis of predictor variables for excess weight among young adult students supports nurses in planning and developing educational practices aimed to prevent this clinical condition, which is a risk factor for other chronic comorbidities, such as cardiovascular diseases. .

OBJETIVO: verificar a associação entre excesso de peso e características de adultos jovens escolares, como subsídio ao cuidado de enfermagem. MÉTODO: estudo caso-controle, realizado com adultos jovens de escolas públicas. Amostra composta por 441 participantes (147 casos e 294 controles, com e sem excesso de peso, respectivamente). Coletaram-se informações sociodemográficas, clínicas, fatores de exposição e antropometria. Utilizou-se regressão logística múltipla. O estudo foi aprovado em comitê de ética. RESULTADOS: detectou-se associação estatística significativa com excesso de peso em: não brancos, ter companheiro(a), ganho ponderal na adolescência, excesso de peso materno, uso de fármacos obesogênicos, pressão arterial diastólica aumentada, circunferência abdominal e relação cintura quadril. Além destas, entraram na análise multivariada as variáveis escolaridade e ganho ponderal na infância. Após etapa de ajuste permaneceram no modelo final: estado civil com companheiro(a), ganho ponderal na adolescência, pressão arterial diastólica aumentada e circunferência abdominal aumentada. CONCLUSÃO: a análise das variáveis preditoras para o excesso de peso em adultos jovens escolares possibilita ao enfermeiro bases para elaboração e planejamento de práticas educativas que visem à prevenção desta condição clínica, visualizada como fator de risco para outras comorbidades de caráter crônico, como as doenças cardiovasculares. .

OBJETIVO: verificar la asociación entre exceso de peso y características de adultos jóvenes escolares como contribución para el cuidado de enfermería. MÉTODO: estudio de caso control realizado con adultos jóvenes de escuelas públicas. Muestra compuesta por 441 participantes (147 casos y 294 controles, con y sin exceso de peso, respectivamente). Se recolectaron características sociodemográficas, clínicas, factores de exposición y antropometría. Se utilizó la regresión logística múltiple. El estudio fue aprobado por comité de ética. RESULTADOS: se detectó asociación estadística significativa con exceso de peso: no blancos, tener compañero, aumento de peso en la adolescencia, exceso de peso materno, uso de medicamentos obesogénicos, presión arterial diastólica aumentada, circunferencia abdominal aumentada y relación cintura-cadera. Además de estas, entraron en el análisis multivariado las variables escolaridad y aumento de peso en la infancia. Después de la etapa de ajuste permanecieron en el modelo final: estado civil con compañero, aumento de peso en la adolescencia, presión arterial diastólica aumentada y circunferencia abdominal aumentada. CONCLUSIÓN: el análisis de las variables de predicción para el exceso de peso en adultos jóvenes escolares suministra al enfermero bases para la elaboración y planificación de prácticas educativas que objetiven la prevención de esta condición clínica, visualizada como factor de riesgo para otras enfermedades concomitantes de carácter crónico, como las enfermedades cardiovasculares. .

Application of Non-invasive Brain Stimulation for Neurorehabilitation: Cerebellar Stimulation

Cerebellum serves an important function in diverse domain of motor, cognition control. Cerebellar non-invasive brain stimulation (NIBS) can provide a better comprehension of cerebellar circuity connecting to primary motor cortex. Cerebellar transcranial magnetic stimulation (TMS) activates Purkinje cells, causing increased inhibition of dentato-thalamo-cortical pathway. Assessing cerebellar-brain inhibition is useful for evaluating normal cerebellar functions and for understanding specific pathophysiology. Transcranial direct current stimulation (tDCS) has the polarity specific effect on cerebellar activity. Both TMS and tDCS can modulate cerebellar functions: motor learning, visuomotor adaptation, motor coordination, working memory and other cognitive domains. Further studies are encouraged to accumulate clinical and molecular evidences of neural plasticity induced by cerebellar NIBS. In the near future, cerebellar NIBS would play a crucial role in the field of neurorehabiliation.

Enhancement of Short-Term Memory by Methyl-6-(Phenylethynyl)-Pyridine in the BTBR T+tf/J Mouse Model of Autism Spectrum Disorder

BACKGROUND: Autism spectrum disorder (ASD) encompasses a range of disorders that are characterized by social and communication deficits and repetitive behaviors. This study evaluated the effect of methyl-6-(phenylethynyl)-pyridine (MPEP), an antagonist of the mGluR5 metabotropic glutamate receptor, on memory enhancement in the BTBR T+tf/J (BTBR) mouse strain, which has been recognized as a model of ASD. METHODS: The pharmacological effects of MPEP on memory and motor coordination were assessed using the Morris water maze and rotarod tests in BTBR and C57BL/6J (B6) mice. Furthermore, we performed morphological analyses of cerebellar foliation in BTBR and B6 mice using hematoxylin and eosin staining. RESULTS: MPEP-treated BTBR mice exhibited improved learning and memory in the Morris water maze test. MPEP administration also improved motor coordination in the rotarod test. However, no significant difference was observed regarding the numbers of Purkinje cells in the cerebella of BTBR versus normal B6 mice. CONCLUSION: This study suggests that the mGluR5 antagonist MPEP has the potential to ameliorate learning and memory dysfunction and impaired motor coordination in BTBR mice. These results further suggest that the BTBR mouse model may be useful in pharmacological studies investigating drugs that could potentially alleviate cognitive dysfunction in ASD.