A cerebellar neuroprosthetic system: computational architecture and in vivo experiments

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Ivan eHerreros Alonso

2014-05-01

Full Text Available Emulating the input-output functions performed by a brain structure opens the possibility for developing neuro-prosthetic systems that replace damaged neuronal circuits. Here, we demonstrate the feasibility of this approach by replacing the cerebellar circuit responsible for the acquisition and extinction of motor memories. Specifically, we show that a rat can undergo acquisition, retention and extinction of the eye-blink reflex even though the biological circuit responsible for this task has been chemically inactivated via anesthesia. This is achieved by first developing a computational model of the cerebellar microcircuit involved in the acquisition of conditioned reflexes and training it with synthetic data generated based on physiological recordings. Secondly, the cerebellar model is interfaced with the brain of an anesthetized rat, connecting the model's inputs and outputs to afferent and efferent cerebellar structures. As a result, we show that the anesthetized rat, equipped with our neuro-prosthetic system, can be classically conditioned to the acquisition of an eye-blink response. However, non-stationarities in the recorded biological signals limit the performance of the cerebellar model. Thus, we introduce an updated cerebellar model and validate it with physiological recordings showing that learning becomes stable and reliable. The resulting system represents an important step towards replacing lost functions of the central nervous system via neuro-prosthetics, obtained by integrating a synthetic circuit with the afferent and efferent pathways of a damaged brain region. These results also embody an early example of science-based medicine, where on the one hand the neuro-prosthetic system directly validates a theory of cerebellar learning that informed the design of the system, and on the other one it takes a step towards the development of neuro-prostheses that could recover lost learning functions in animals and, in the longer term

A Cerebellar Neuroprosthetic System: Computational Architecture and in vivo Test

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Herreros, Ivan; Giovannucci, Andrea [Synthetic Perceptive, Emotive and Cognitive Systems group (SPECS), Universitat Pompeu Fabra, Barcelona (Spain); Taub, Aryeh H.; Hogri, Roni; Magal, Ari [Psychobiology Research Unit, Tel Aviv University, Tel Aviv (Israel); Bamford, Sim [Physics Laboratory, Istituto Superiore di Sanità, Rome (Italy); Prueckl, Robert [Guger Technologies OG, Graz (Austria); Verschure, Paul F. M. J., E-mail: paul.verschure@upf.edu [Synthetic Perceptive, Emotive and Cognitive Systems group (SPECS), Universitat Pompeu Fabra, Barcelona (Spain); Institució Catalana de Recerca i Estudis Avançats, Barcelona (Spain)

2014-05-21

Emulating the input–output functions performed by a brain structure opens the possibility for developing neuroprosthetic systems that replace damaged neuronal circuits. Here, we demonstrate the feasibility of this approach by replacing the cerebellar circuit responsible for the acquisition and extinction of motor memories. Specifically, we show that a rat can undergo acquisition, retention, and extinction of the eye-blink reflex even though the biological circuit responsible for this task has been chemically inactivated via anesthesia. This is achieved by first developing a computational model of the cerebellar microcircuit involved in the acquisition of conditioned reflexes and training it with synthetic data generated based on physiological recordings. Secondly, the cerebellar model is interfaced with the brain of an anesthetized rat, connecting the model’s inputs and outputs to afferent and efferent cerebellar structures. As a result, we show that the anesthetized rat, equipped with our neuroprosthetic system, can be classically conditioned to the acquisition of an eye-blink response. However, non-stationarities in the recorded biological signals limit the performance of the cerebellar model. Thus, we introduce an updated cerebellar model and validate it with physiological recordings showing that learning becomes stable and reliable. The resulting system represents an important step toward replacing lost functions of the central nervous system via neuroprosthetics, obtained by integrating a synthetic circuit with the afferent and efferent pathways of a damaged brain region. These results also embody an early example of science-based medicine, where on the one hand the neuroprosthetic system directly validates a theory of cerebellar learning that informed the design of the system, and on the other one it takes a step toward the development of neuro-prostheses that could recover lost learning functions in animals and, in the longer term, humans.

A Cerebellar Neuroprosthetic System: Computational Architecture and in vivo Test

International Nuclear Information System (INIS)

Herreros, Ivan; Giovannucci, Andrea; Taub, Aryeh H.; Hogri, Roni; Magal, Ari; Bamford, Sim; Prueckl, Robert; Verschure, Paul F. M. J.

2014-01-01

Emulating the input–output functions performed by a brain structure opens the possibility for developing neuroprosthetic systems that replace damaged neuronal circuits. Here, we demonstrate the feasibility of this approach by replacing the cerebellar circuit responsible for the acquisition and extinction of motor memories. Specifically, we show that a rat can undergo acquisition, retention, and extinction of the eye-blink reflex even though the biological circuit responsible for this task has been chemically inactivated via anesthesia. This is achieved by first developing a computational model of the cerebellar microcircuit involved in the acquisition of conditioned reflexes and training it with synthetic data generated based on physiological recordings. Secondly, the cerebellar model is interfaced with the brain of an anesthetized rat, connecting the model’s inputs and outputs to afferent and efferent cerebellar structures. As a result, we show that the anesthetized rat, equipped with our neuroprosthetic system, can be classically conditioned to the acquisition of an eye-blink response. However, non-stationarities in the recorded biological signals limit the performance of the cerebellar model. Thus, we introduce an updated cerebellar model and validate it with physiological recordings showing that learning becomes stable and reliable. The resulting system represents an important step toward replacing lost functions of the central nervous system via neuroprosthetics, obtained by integrating a synthetic circuit with the afferent and efferent pathways of a damaged brain region. These results also embody an early example of science-based medicine, where on the one hand the neuroprosthetic system directly validates a theory of cerebellar learning that informed the design of the system, and on the other one it takes a step toward the development of neuro-prostheses that could recover lost learning functions in animals and, in the longer term, humans.

[Effects of electric stimulation at the cerebellar fastigial nucleus on astrocytes in the hippocampus of neonatal rats with hypoxic-ischemic brain damage].

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Li, Xiao-Li; Jia, Tian-Ming; Luan, Bin; Liu, Tao; Yuan, Yan

2011-04-01

To study the effects of electric stimulation at the cerebellar fastigial nucleus on astrocytes in the hippocampus of neonatal rats with hypoxic-ischemic brain damage (HIBD) and the possible mechanism. One hundred and eighty 7-day-old neonatal Sprague-Dawley rats were randomly divided into three groups: sham-operation (control group) and HIBD with and without electric stimulation (n=60 each). The HIBD model of neonatal rats was prepared by the Rice-Vennucci method. Electric stimulation at the cerebellar fastigial nucleus was given 24 hrs after the operation in the electric stimulation group once daily and lasted for 30 minutes each time. The other two groups were not subjected to electric stimulation but captured to fix in corresponding periods. Rats were sacrificed 3, 7, 14 and 21 days after stimulations to observe the glial fibrillary acidic protein (GFAP) expression by immunohistochemisty and the ultrastructural changes of astrocytes in the hippocampus under an electron microscope. Immunohistochemical analysis showed the expression of GFAP in the HIBD groups with and without electric stimulation increased significantly compared with the control group on day 3, reached the peak on day 7, and the increased expression remained till to day 21. The GFAP expression in the electric stimulation group was significantly lower than that in the untreated HIBD group at all time points. Under the electron microscope, the astrocytes in the untreated HIBD group were swollen and the amount of organelles was reduced, while the swelling of astrocytes was alleviated and the organelles remained in integrity in the electric stimulation group. The electric stimulation at the cerebellar fastigial nucleus can inhibit the excessive proliferation of astrocytes and relieve the structural damage of astrocytes in neonatal rats following HIBD.

Cerebellar level of neurotransmitters in rats exposed to paracetamol during development.

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Blecharz-Klin, Kamilla; Joniec-Maciejak, Ilona; Jawna-Zboińska, Katarzyna; Pyrzanowska, Justyna; Piechal, Agnieszka; Wawer, Adriana; Widy-Tyszkiewicz, Ewa

2016-12-01

The present study was designed to clarify the effect of prenatal and postnatal paracetamol administration on the neurotransmitter level and balance of amino acids in the cerebellum. Biochemical analysis to determine the concentration of neurotransmitters in this brain structure was performed on two-month-old Wistar male rats previously exposed to paracetamol in doses of 5 (P5, n=10) or 15mg/kg (P15, n=10) throughout the entire prenatal period, lactation and until the completion of the second month of life, when the experiment was terminated. Control animals were given tapped water (Con, n=10). The cerebellar concentration of monoamines, their metabolites and amino acids were assayed using High Performance Liquid Chromatography (HPLC). The present experiment demonstrates that prenatal and postnatal paracetamol exposure results in modulation of cerebellar neurotransmission with changes concerning mainly 5-HIAA and MHPG levels. The effect of paracetamol on monoaminergic neurotransmission in the cerebellum is reflected by changes in the level of catabolic end-products of serotonin (5-HIAA) and noradrenaline (MHPG) degradation. Further work is required to define the mechanism of action and impact of prenatal and postnatal exposure to paracetamol in the cerebellum and other structures of the central nervous system (CNS). Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Glucose rapidly decreases plasma membrane GLUT4 content in rat skeletal muscle.

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Marette, A; Dimitrakoudis, D; Shi, Q; Rodgers, C D; Klip, A; Vranic, M

1999-02-01

We have previously demonstrated that chronic hyperglycemia per se decreases GLUT4 glucose transporter expression and plasma membrane content in mildly streptozotocin- (STZ) diabetic rats (Biochem. J. 284, 341-348, 1992). In the present study, we investigated the effect of an acute rise in glycemia on muscle GLUT4 and GLUT1 protein contents in the plasma membrane, in the absence of insulin elevation. Four experimental groups of rats were analyzed in the postabsorptive state: 1. Control rats. 2. Hyperglycemic STZ-diabetic rats with moderately reduced fasting insulin levels. 3. STZ-diabetic rats made normoglycemic with phlorizin treatment. 4. Phlorizin-treated (normoglycemic) STZ-diabetic rats infused with glucose for 40 min. The uniqueness of the latter model is that glycemia can be rapidly raised without any concomitant increase in plasma insulin levels. Plasma membranes were isolated from hindlimb muscle and GLUT1 and GLUT4 proteins amounts determined by Western blot analysis. As predicted, STZ-diabetes caused a significant decrease in the abundance of GLUT4 in the isolated plasma membranes. Normalization of glycemia for 3 d with phlorizin treatment restored plasma membrane GLUT4 content in muscle of STZ-diabetic rats. A sudden rise in glycemia over a period of 40 min caused the GLUT4 levels in the plasma membrane fraction to decrease to those of nontreated STZ-diabetic rats. In contrast to the GLUT4 transporter, plasma membrane GLUT1 abundance was not changed by the acute glucose challenge. It is concluded that glucose can have regulatory effect by acutely reducing plasma membrane GLUT4 protein contents in rat skeletal muscle. We hypothesize that this glucose-induced downregulation of plasma membrane GLUT4 could represent a protective mechanism against excessive glucose uptake under hyperglycemic conditions accompanied by insulin resistance.

The Effect of Salvia Rhytidea Extract on the Number of Cells of Different Layers of Cerebellar Cortex Following Ischemia Reperfusion in Rats

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M Farahmand

2016-09-01

Full Text Available Background & aim: Salvia has anti-oxidant oxygen free radicals which are generated during the interruption and reestablishment of ischemia reperfusion.  The aim of study was to investigate the effect of Salvia Rhytidea extract on the number of cells of different layers of cerebellar cortex following ischemia reperfusion in rats. Methods: In the present experimental study, 35 adult male rats were randomly divided into 7 groups of 5: Group 1 (control-: Sampling without ischemia. Group 2 (control +: Cerebellar ischemia with administration of normal saline. Group 3(sham: Manipulation without ischemia with normal saline administration. Group 4   received (3.2 mg/kg aqueous and alcoholic Salvia extract 2 hours after ischemia. Group 5 received 50 mg/kg silymarin drug, 2 hours after ischemia. Group 6 received 3.2 mg/kg aqueous and alcoholic Salvia extract 72, 48, 24 and 0 h before ischemia and group 7 received silymarin drug (50 mg/kg, 0, 24, 48, and 72, hrs. before ischemia. 24 hrs. following reperfusion, the rats were euthanized and samples of the cerebellum were obtained. By using routine histological technique, the sections were stained by H&E. The measurement of cell count in cerebellar cortex were accomplished. Data were evaluated with One-Way ANOVA and Tukey diagnostic tests. Results: A significant decrease was observed in the number of neural cells in granular layer in the non-treated ischemia group and in the groups which received Salvia extract and silymarin, two hours after the ischemia (p< 0.05. No significant decrease was observed in the number of cells of this layer in the groups which received salvia extract before ischemia. But regarding the cell number of molecular and purkinje layers in above groups, no significant difference was observed compared to the control group (P˃0.05. However, no significant differences was seen in the number of cells layers compared to the control group (P˃0.05. Conclusion: Finally, administration of

Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells

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Wu Kong-Yan

2010-06-01

Full Text Available Abstract Background During cerebellar development, Purkinje cells (PCs form the most elaborate dendritic trees among neurons in the brain, but the mechanism regulating PC arborization remains largely unknown. Geranylgeranyltransferase I (GGT is a prenyltransferase that is responsible for lipid modification of several signaling proteins, such as Rho family small GTPase Rac1, which has been shown to be involved in neuronal morphogenesis. Here we show that GGT plays an important role in dendritic development of PCs. Results We found that GGT was abundantly expressed in the developing rat cerebellum, in particular molecular layer (ML, the region enriched with PC dendrites. Inhibition or down-regulation of GGT using small interference RNA (siRNA inhibited dendritic development of PCs. In contrast, up-regulation of GGT promoted dendritic arborization of PCs. Furthermore, neuronal depolarization induced by high K+ or treatment with brain-derived neurotrophic factor (BDNF promoted membrane association of Rac1 and dendritic development of PCs in cultured cerebellar slices. The effect of BDNF or high K+ was inhibited by inhibition or down-regulation of GGT. Conclusion Our results indicate that GGT plays an important role in Purkinje cell development, and suggest a novel role of GGT in neuronal morphogenesis in vivo.

Cerebellar anatomy as applied to cerebellar microsurgical resections

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Alejandro Ramos

2012-06-01

Full Text Available OBJECTIVE: To define the anatomy of dentate nucleus and cerebellar peduncles, demonstrating the surgical application of anatomic landmarks in cerebellar resections. METHODS: Twenty cerebellar hemispheres were studied. RESULTS: The majority of dentate nucleus and cerebellar peduncles had demonstrated constant relationship to other cerebellar structures, which provided landmarks for surgical approaching. The lateral border is separated from the midline by 19.5 mm in both hemispheres. The posterior border of the cortex is separated 23.3 mm from the posterior segment of the dentate nucleus; the lateral one is separated 26 mm from the lateral border of the nucleus; and the posterior segment of the dentate nucleus is separated 25.4 mm from the posterolateral angle formed by the junction of lateral and posterior borders of cerebellar hemisphere. CONCLUSIONS: Microsurgical anatomy has provided important landmarks that could be applied to cerebellar surgical resections.

Cerebellar projections to the red nucleus and inferior olive originate from separate populations of neurons in the rat: A non-fluorescent double labeling study

NARCIS (Netherlands)

T.M. Teune (Thea); J. van der Burg (Johannes); T.J.H. Ruigrok (Tom)

1995-01-01

textabstractIn the rat, the extent of collateralization of projections from the cerebellar nuclei to the red nucleus and inferior olive was investigated using a retrograde double labeling technique. The combination of tracers selected, cholera toxin-β-subunit and WGA-BSA-gold, not only enabled the

Isolation of plasma membrane-associated membranes from rat liver.

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Suski, Jan M; Lebiedzinska, Magdalena; Wojtala, Aleksandra; Duszynski, Jerzy; Giorgi, Carlotta; Pinton, Paolo; Wieckowski, Mariusz R

2014-02-01

Dynamic interplay between intracellular organelles requires a particular functional apposition of membrane structures. The organelles involved come into close contact, but do not fuse, thereby giving rise to notable microdomains; these microdomains allow rapid communication between the organelles. Plasma membrane-associated membranes (PAMs), which are microdomains of the plasma membrane (PM) interacting with the endoplasmic reticulum (ER) and mitochondria, are dynamic structures that mediate transport of proteins, lipids, ions and metabolites. These structures have gained much interest lately owing to their roles in many crucial cellular processes. Here we provide an optimized protocol for the isolation of PAM, PM and ER fractions from rat liver that is based on a series of differential centrifugations, followed by the fractionation of crude PM on a discontinuous sucrose gradient. The procedure requires ∼8-10 h, and it can be easily modified and adapted to other tissues and cell types.

Ultrastructural immunocytochemical localization of chondroitin sulfate proteoglycan in Bruch's membrane of the rat

DEFF Research Database (Denmark)

Lin, W L; Essner, E; McCarthy, K J

1992-01-01

Two monoclonal antibodies (Mab 4D5 and 2D6) raised against the core protein of a basement membrane chondroitin sulfate proteoglycan from Reichert's membrane of the rat, were used for ultrastructural immunoperoxidase localization of this protein in Bruch's membrane of the rat. Immunoreactivity...

Impairment of DNA synthesis in Gunn rat cerebellum.

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Yamada, N; Sawasaki, Y; Nakajima, H

1977-05-06

Brain DNA synthesis was developmentally investigated in Gunn rat with marked cerebellar hypoplasia due to hereditary hyperbilirubinemia. In this mutant rat, the Purkinje cell was nearly selectively affected in the cerebellar cortex by bilirubin. The impaired DNA synthesis was observed in homozygous (jj) Gunn rat cerebellum, in which the DNA content and [3H]thymidine incorporation rate into DNA decreased after 10 days of age compared to those in the heterozygous (Jj)littermate. In contrast, these impairments were not found in the non-cerebellar parts of the brain and liver of jj Gunn rat. The activity of cerebellar thymidine kinase in jj Gunn rat decreased from a very early stae, being 80% of Jj rat at 6 days, and 50% at 10 days of age. The enzyme activity was not affected in the non-cerebellar parts of the brain. Although bilirubin competitively inhibited cerebellar thymidine kinase activity in vitro (15% at 10(-5) M), such bilirubin level was found to be about 1000-fold that in vivo. Moreover, photo-degradation of bilirubin in jj cerebellum exhibited no improvement in thymidine kinase activity, and the presence of an enzyme inactivator was not suggested in jj cerebellum. These results seem to indicate that the induction of thymidine kinase might be affected in jj Gunn rat cerebellum. The possibility that the impaired DNA synthesis in the external granular cells in jj cerebellum may be due to Purkinje cell damage is discussed.

Neuroprotective Effect of Carnosine on Primary Culture of Rat Cerebellar Cells under Oxidative Stress.

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Lopachev, A V; Lopacheva, O M; Abaimov, D A; Koroleva, O V; Vladychenskaya, E A; Erukhimovich, A A; Fedorova, T N

2016-05-01

Dipeptide carnosine (β-alanyl-L-histidine) is a natural antioxidant, but its protective effect under oxidative stress induced by neurotoxins is studied insufficiently. In this work, we show the neuroprotective effect of carnosine in primary cultures of rat cerebellar cells under oxidative stress induced by 1 mM 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH), which directly generates free radicals both in the medium and in the cells, and 20 nM rotenone, which increases the amount of intracellular reactive oxygen species (ROS). In both models, adding 2 mM carnosine to the incubation medium decreased cell death calculated using fluorescence microscopy and enhanced cell viability estimated by the MTT assay. The antioxidant effect of carnosine inside cultured cells was demonstrated using the fluorescence probe dichlorofluorescein. Carnosine reduced by half the increase in the number of ROS in neurons induced by 20 nM rotenone. Using iron-induced chemiluminescence, we showed that preincubation of primary neuronal cultures with 2 mM carnosine prevents the decrease in endogenous antioxidant potential of cells induced by 1 mM AAPH and 20 nM rotenone. Using liquid chromatography-mass spectrometry, we showed that a 10-min incubation of neuronal cultures with 2 mM carnosine leads to a 14.5-fold increase in carnosine content in cell lysates. Thus, carnosine is able to penetrate neurons and exerts an antioxidant effect. Western blot analysis revealed the presence of the peptide transporter PEPT2 in rat cerebellar cells, which suggests the possibility of carnosine transport into the cells. At the same time, Western blot analysis showed no carnosine-induced changes in the level of apoptosis regulating proteins of the Bcl-2 family and in the phosphorylation of MAP kinases, which suggests that carnosine could have minimal or no side effects on proliferation and apoptosis control systems in normal cells.

Anatomical evidence for direct fiber projections from the cerebellar nucleus interpositus to rubrospinal neurons. A quantitative EM study in the rat combining anterograde and retrograde intra-axonal tracing methods

International Nuclear Information System (INIS)

Dekker, J.J.

1981-01-01

A quantitative electron microscopic (EM) study combining the anterograde intra-axonal transport of radioactive amino acids and the retrograde intra-axonal transport of the enzyme horseradish peroxidase (HRP) was performed in the magnocellular red nucleus of the rat to obtain anatomical evidence as to whether there is a direct projection from the cerebellar nucleus interpositus to the cells in the red nucleus that give rise to the rubrospinal tract. Large asymmetrical synaptic terminals were radioactively labeled in the magnocellular red nucleus following injections of [ 3 H]leucine into the cerebellar nucleus interpositus. In these same animals, the postsynaptic target neurons were labeled with HRP granules after injection of this substance in the rubrospinal tract. A quantitative analysis showed that more than 85% of the large and giant neurons in the magnocellular red nucleus were labeled with HRP granules and also received synaptic contacts from radioactively-labeled terminals. Thus, it can be concluded that in the rat, afferents from the cerebellar nucleus interpositus establish asymmetrical synaptic contacts with large and giant rubrospinal neurons, thus confirming and extending the previous physiological evidence of such direct monosynaptic connections. (Auth.)

The membrane fraction of homogenized rat kidney contains an enzyme that releases epidermal growth factor from the kidney membranes

DEFF Research Database (Denmark)

Nexø, Ebba; Poulsen, Steen Seier

1991-01-01

shows that the membrane fraction of homogenized rat kidney contains an enzyme that releases immuno and receptor reactive EGF from the kidney membranes when incubated at 37 degrees C. Gel filtration shows that the EGF reactivity released from the membranes is similar to the EGF reactivity in rat urine......High levels of epidermal growth factor (EGF) are excreted in the urine and high levels of mRNA for the EGF-precursor have been demonstrated in the kidney. The EGF-precursor is a membrane bound peptide in the kidney, but little is known about the renal processing of the precursor. The present study...

Basement membrane chondroitin sulfate proteoglycans: localization in adult rat tissues

DEFF Research Database (Denmark)

McCarthy, K J; Couchman, J R

1990-01-01

Heparan sulfate proteoglycans have been described as the major proteoglycan component of basement membranes. However, previous investigators have also provided evidence for the presence of chondroitin sulfate glycosaminoglycan in these structures. Recently we described the production...... and characterization of core protein-specific monoclonal antibodies (MAb) against a chondroitin sulfate proteoglycan (CSPG) present in Reichert's membrane, a transient extra-embryonic structure of rodents. This CSPG was also demonstrated to be present in adult rat kidney. We report here the tissue distribution...... of epitopes recognized by these MAb. The ubiquitous presence of these epitopes in the basement membranes of nearly all adult rat tissues demonstrates that at least one CSPG is a constituent of most basement membranes, and by virtue of its unique distribution is distinct from other chondroitin and dermatan...

[Cerebellar cognitive affective syndrome secondary to a cerebellar tumour].

Science.gov (United States)

Domínguez-Carral, J; Carreras-Sáez, I; García-Peñas, J J; Fournier-Del Castillo, C; Villalobos-Reales, J

2015-01-01

Cerebellar cognitive affective syndrome is characterized by disturbances of executive function, impaired spatial cognition, linguistic difficulties, and personality change. The case of an 11 year old boy is presented, with behavior problems, learning difficulties and social interaction problems. In the physical examination he had poor visual contact, immature behavior, reduced expressive language and global motor disability with gait dyspraxia, with no defined cerebellar motor signs. In the neuropsychological evaluation he has a full scale overall intellectual quotient of 84, with signs of cerebellar cognitive affective syndrome. A tumour affecting inferior cerebellar vermis was observed in the magnetic resonance imaging, which had not significantly grown during 5 years of follow up. The cerebellum participates in controlling cognitive and affective functions. Cerebellar pathology must be considered in the differential diagnosis of children with cognitive or learning disorder with associated behavioral and emotional components. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Mechanisms and functional roles of glutamatergic synapse diversity in a cerebellar circuit

NARCIS (Netherlands)

Zampini, Valeria; Liu, Jian K; Diana, Marco A; Maldonado, Paloma P; Brunel, Nicolas; Dieudonné, Stéphane

2016-01-01

Synaptic currents display a large degree of heterogeneity of their temporal characteristics, but the functional role of such heterogeneities remains unknown. We investigated in rat cerebellar slices synaptic currents in Unipolar Brush Cells (UBCs), which generate intrinsic mossy fibers relaying

Neuropharmacologic characterization of strychnine seizure potentiation in the inferior olive lesioned rat

International Nuclear Information System (INIS)

Anderson, M.C.

1988-01-01

Cerebellar stimulation is associated with anticonvulsant activity in several animal models. There are two afferent inputs to cerebellar Purkinje cells: (1) parallel fibers, which relay mossy fiber input, from brainstem, spinal cord, cerebral cortex and cerebellum, and (2) climbing fibers, arising from the inferior olive. Both climbing and parallel fibers release excitatory amino acid neurotransmitters, which stimulate Purkinje cells and cause GABA release in the deep cerebellar nuclei. Climbing fibers also exert tonic inhibition over Purkinje cell activity by producing an absolute refractory period following stimulation, rendering Purkinje cells unresponsive to parallel fibers. Climbing fiber deafferentation by bilateral inferior olive lesions produced a specific decrease in threshold for strychnine-seizures in the rat. Inferior olive lesions produced no change in threshold to seizures induced by picrotoxin, bicuculline or pentylenetetrazole. Inferior olive lesions also produced abnormal motor behavior including, myoclonus, backward locomotion and hyperextension, which was significantly aggravated by strychnine, brucine, picrotoxin, bicuculline and pentylenetetrazole. Inferior olive lesions produced a significant increase in quisqualate sensitive [ 3 H]AMPA ((Rs)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid) binding to cerebellar membranes. AMPA is a glutamate analog with high affinity for quisqualate sensitive receptors

[Modification of red cell membranes with perftoran in papaine emphysema in rats].

Science.gov (United States)

Zoirova, N I; Arifkhanov, S I; Rakhmatullaev, Kh U; Tadzhikhodzhaev, Iu Kh

2006-01-01

Papaine emphysema model on 75 mongrel mature white male rats (10 intact rats were control) was used to study the size, form, surface architechtonics, deformability and state of membrane-receptor erythrocyte complex before and after perftoran intraperitoneal administration. Perftoran emulsion produced a membrane-modulating effect with recovery of hormonal reception sensitivity, PHA-, cAMP-receptor systems as well as restoration of erythrocytic normocytosis and diskocytosis.

Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats

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Fernando B. R. da Silva

2018-05-01

Full Text Available Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures’ morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF, pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.

Effects of ethanol and NAP on cerebellar expression of the neural cell adhesion molecule L1.

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Devon M Fitzgerald

Full Text Available The neural cell adhesion molecule L1 is critical for brain development and plays a role in learning and memory in the adult. Ethanol inhibits L1-mediated cell adhesion and neurite outgrowth in cerebellar granule neurons (CGNs, and these actions might underlie the cerebellar dysmorphology of fetal alcohol spectrum disorders. The peptide NAP potently blocks ethanol inhibition of L1 adhesion and prevents ethanol teratogenesis. We used quantitative RT-PCR and Western blotting of extracts of cerebellar slices, CGNs, and astrocytes from postnatal day 7 (PD7 rats to investigate whether ethanol and NAP act in part by regulating the expression of L1. Treatment of cerebellar slices with 20 mM ethanol, 10(-12 M NAP, or both for 4 hours, 24 hours, and 10 days did not significantly affect L1 mRNA and protein levels. Similar treatment for 4 or 24 hours did not regulate L1 expression in primary cultures of CGNs and astrocytes, the predominant cerebellar cell types. Because ethanol also damages the adult cerebellum, we studied the effects of chronic ethanol exposure in adult rats. One year of binge drinking did not alter L1 gene and protein expression in extracts from whole cerebellum. Thus, ethanol does not alter L1 expression in the developing or adult cerebellum; more likely, ethanol disrupts L1 function by modifying its conformation and signaling. Likewise, NAP antagonizes the actions of ethanol without altering L1 expression.

Back to front: cerebellar connections and interactions with the prefrontal cortex

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Thomas C Watson

2014-02-01

Full Text Available Although recent neuroanatomical evidence has demonstrated closed-loop connectivity between prefrontal cortex and the cerebellum, the physiology of cerebello-cerebral circuits and the extent to which cerebellar output modulates neuronal activity in neocortex during behavior remain relatively unexplored. We show that electrical stimulation of the contralateral cerebellar fastigial nucleus (FN in awake, behaving rats evokes distinct local field potential (LFP responses (onset latency ~13 ms in the prelimbic (PrL subdivision of the medial prefrontal cortex. Trains of FN stimulation evoke heterogeneous patterns of response in putative pyramidal cells in frontal and prefrontal regions in both urethane-anaesthetized and awake, behaving rats. However, the majority of cells showed decreased firing rates during stimulation and subsequent rebound increases; more than 90% of cells showed significant changes in response. Simultaneous recording of on-going LFP activity from FN and PrL while rats were at rest or actively exploring an open field arena revealed significant network coherence restricted to the theta frequency range (5-10 Hz. Granger causality analysis indicated that this coherence was significantly directed from cerebellum to PrL during active locomotion. Our results demonstrate the presence of a cerebello-prefrontal pathway in rat and reveal behaviorally dependent coordinated network activity between the two structures, which could facilitate transfer of sensorimotor information into ongoing neocortical processing during goal directed behaviors.

Moringa oleifera phytochemicals protect the brain against experimental nicotine-induced neurobehavioral disturbances and cerebellar degeneration.

Science.gov (United States)

Omotoso, Gabriel Olaiya; Gbadamosi, Ismail Temitayo; Olajide, Olayemi Joseph; Dada-Habeeb, Shakirat Opeyemi; Arogundade, Tolulope Timothy; Yawson, Emmanuel Olusola

2018-03-01

Nicotine is a neuro-stimulant that has been implicated in the pathophysiology of many brain diseases. The need to prevent or alleviate the resulting dysfunction is therefore paramount, which has also given way to the use of medicinal plants in the management of brain conditions. This study was designed to determine the histomorphological and neurobehavioural changes in the cerebellum of Wistar rats following nicotine insult and how such injuries respond to Moringa intervention. Twenty-four adult male Wistar rats were divided into 4 groups. Group A and B were orally treated with normal saline and Moringa oleifera respectively for twenty-eight days; Group C was treated with nicotine while group D was treated orally with Moringa oleifera and intraperitoneally with nicotine for twenty-eight days. Animals were subjected to the open field test on the last day of treatment. 24 h after last day treatment, the animals were anesthetized and perfusion fixation was carried out. The cerebellum was excised and post-fixed in 4% paraformaldehyde and thereafter put through routine histological procedures. Results revealed cytoarchitectural distortion and extreme chromatolysis in neuronal cells of the cerebellar cortical layers in the nicotine-treated group. The Purkinje cells of the cerebellum of animals in this group were degenerated. There were also reduced locomotor activities in the group. Moringa was able to prevent the chromatolysis, distortion of the cerebellar cortical cells and neurobehavioural deficit. Our result suggests that Moringa oleifera could prevent nicotine-induced cerebellar injury in Wistar rats, with the possibility of ameliorating the clinical features presented in associated cerebellar pathology. Copyright © 2018 Elsevier B.V. All rights reserved.

Identification of the D-1 dopamine receptor subunit in rat striatum after photoaffinity labeling

Energy Technology Data Exchange (ETDEWEB)

Kuno, T; Tanaka, C [Kobe Univ. (Japan). School of Medicine

1982-12-28

When rat striatal membranes, photolabeled with (/sup 3/H)dopamine under assay conditions similar to those used for dopamine-sensitive adenylate cyclase, were subjected to sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, several radioactively labeled bands appeared. Labeling of these bands was reduced in the presence of non-radioactive dopamine during photolysis, but was unaffected by the presence of sulpiride. Haloperidol preferentially reduced the labeling of the main band which had a molecular weight of about 57,000 rather than the other weakly labeled bands. Labeling of this 57,000 dalton protein was not apparent when rat cerebellar membranes were used and was markedly eliminated by kainic acid-induced lesions that destroyed the intrastriatal nerve cell bodies. These results indicate that this 57,000 dalton protein is the binding subunit of the D-1 dopamine receptor.

Identification of immunogenic outer membrane proteins of Haemophilus influenzae type b in the infant rat model system

International Nuclear Information System (INIS)

Hansen, E.J.; Frisch, C.F.; McDade, R.L. Jr.; Johnston, K.H.

1981-01-01

Outer membrane proteins of Haemophilus influenzae type b which are immunogenic in infant rats were identified by a radioimmunoprecipitation method. Intact cells of H. influenzae type b were radioiodinated by a lactoperoxidase-catalyzed procedure, and an outer membrane-containing fraction was prepared from these cells. These radioiodinated outer membranes were mixed with sera obtained from rats convalescing from systemic H. influenzae type b disease induced at 6 days of age, and the resultant (antibody-outer membrane protein antigen) complexes were extracted from these membranes by treatment with nonionic detergent and ethylenediaminetetraacetic acid. These soluble antibody-antigen complexes were isolated by means of adsorption to protein A-bearing staphylococci, and the radioiodinated protein antigens were identified by gel electrophoresis followed by autoradiography. Infant rats were shown to mount a readily detectable antibody response to several different proteins present in the outer membrane of H. influenzae type b. Individual infant rats were found to vary both qualitatively and quantitatively in their immune response to these immunogenic outer membrane proteins

Weaver mutant mouse cerebellar granule cells respond normally to chronic depolarization

DEFF Research Database (Denmark)

Bjerregaard, Annette; Mogensen, Helle Smidt; Hack, N

1997-01-01

We studied the effects of chronic K(+)-induced membrane depolarization and treatment with N-methyl-D-aspartate (NMDA) on cerebellar granule cells (CGCs) from weaver mutant mice and non-weaver litter-mates. The weaver mutation is a Gly-to-Ser substitution in a conserved region of the Girk2 G prote...

Effect of Omega-3 Fatty Acids on Erythrocyte Membrane in Diabetic Rats

OpenAIRE

Hussein, Jihan; Mostafa, Ehab; El-Waseef, Maha; El-Khayat, Zakarya; Badawy, Ehsan; Medhat, Dalia

2011-01-01

Background: Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia resulting from defects in insulin secretion, almost always with a major contribution from insulin resistance which may be affected by cell membrane fatty acids and phospholipids fractions.Aim: To evaluate the effects of omega-3 fatty acids on erythrocyte membrane and also in decreasing oxidative stress in diabetic rats.Material and Methods: Sixty healthy male albino rats weighting 180-200 g divided int...

Studies on the postnatal development of the rat liver plasma membrane following maternal ethanol ingestion

Energy Technology Data Exchange (ETDEWEB)

Rovinski, B

1984-01-01

Studies on the developing rat liver and on the structure and function of the postnatal rat liver plasma membrane were carried out following maternal consumption of alcohol during pregnancy and lactation. A developmental study of alcohol dehydrogenase (ADH) indicated that both the activity and certain kinetic properties of the enzyme from the progeny of alcohol-fed and pair-fed mothers were similar. Fatty liver, however, developed in the alcoholic progeny only after ADH appeared on a day 19 of gestation. Further studies on structural and functional changes were then undertaken on the postnatal development of the rat liver plasma membrane. Radioligand binding studies performed using the hapatic alpha{sub 1}-adrenergic receptor as a plasma membrane probe demonstrated a significant decrease in receptor density in the alcoholic progeny, but no changes in binding affinity. Finally, the fatty acid composition of constituent phospholipids and the cholesterol content of rat liver plasma membranes were determined. All these observations suggest that membrane alterations in the newborn may be partially responsible for the deleterious action(s) of maternal alcoholism at the molecular level.

Tissue Plasminogen Activator Induction in Purkinje Neurons After Cerebellar Motor Learning

Science.gov (United States)

Seeds, Nicholas W.; Williams, Brian L.; Bickford, Paula C.

1995-12-01

The cerebellar cortex is implicated in the learning of complex motor skills. This learning may require synaptic remodeling of Purkinje cell inputs. An extracellular serine protease, tissue plasminogen activator (tPA), is involved in remodeling various nonneural tissues and is associated with developing and regenerating neurons. In situ hybridization showed that expression of tPA messenger RNA was increased in the Purkinje neurons of rats within an hour of their being trained for a complex motor task. Antibody to tPA also showed the induction of tPA protein associated with cerebellar Purkinje cells. Thus, the induction of tPA during motor learning may play a role in activity-dependent synaptic plasticity.

Antioxidant supplementation upregulates calbindin expression in cerebellar Purkinje cells of rat pups subjected to post natal exposure to sodium arsenite.

Science.gov (United States)

Dhar, Pushpa; Kaushal, Parul; Kumar, Pavan

2018-07-01

Optimal cytoplasmic calcium (Ca 2+ ) levels have been associated with adequate cell functioning and neuronal survival. Altered intracellular Ca 2+ levels following impaired Ca 2+ homeostasis could induce neuronal degeneration or even cell death. There are reports of arsenite induced oxidative stress and the associated disturbances in intracellular calcium homeostasis. The present study focused on determining the strategies that would modulate tissue redox status and calcium binding protein (CaBP) (Calbindin D28k-CB) expression affected adversely by sodium arsenite (NaAsO 2 ) exposure (postnatal) of rat pups. NaAsO 2 alone or along with antioxidants (AOXs) (alpha lipoic acid or curcumin) was administered by intraperitoneal (i.p.) route from postnatal day (PND) 1-21 (covering rapid brain growth period - RBGP) to experimental groups and animals receiving sterile water by the same route served as the controls. At the end of the experimental period, the animals were subjected to euthanasia and the cerebellar tissue obtained therefrom was processed for immunohistochemical localization and western blot analysis of CB protein. CB was diffusely expressed in cell body as well as dendritic processes of Purkinje cells (PCs) along the PC Layer (PCL) in all cerebellar folia of the control and the experimental animals. The multilayered pattern of CB +ve cells along with their downregulated expression and low packing density was significantly evident in the arsenic (iAs) alone exposed group as against the controls and AOX supplemented groups. The observations are suggestive of AOX induced restoration of CaBP expression in rat cerebellum following early postnatal exposure to NaAsO 2 . Copyright © 2018 Elsevier B.V. All rights reserved.

Modulation of ASIC channels in rat cerebellar purkinje neurons by ischaemia-related signals

Science.gov (United States)

Allen, Nicola J; Attwell, David

2002-01-01

Acid-sensing ion channels (ASICs), activated by a decrease of extracellular pH, are found in neurons throughout the nervous system. They have an amino acid sequence similar to that of ion channels activated by membrane stretch, and have been implicated in touch sensation. Here we characterize the pH-dependent activation of ASICs in cerebellar Purkinje cells and investigate how they are modulated by factors released in ischaemia. Lowering the external pH from 7.4 activated an inward current at −66 mV, carried largely by Na+ ions, which was half-maximal for a step to pH 6.4 and was blocked by amiloride and gadolinium. The H+-gated current desensitized within a few seconds, but approximately 30% of cells showed a sustained inward current (11% of the peak current) in response to the maintained presence of pH 6 solution. The peak H+-evoked current was potentiated by membrane stretch (which occurs in ischaemia when [K+]o rises) and by arachidonic acid (which is released when [Ca2+]i rises in ischaemia). Arachidonic acid increased to 77% the fraction of cells showing a sustained current evoked by acid pH. The ASIC currents were also potentiated by lactate (which is released when metabolism becomes anaerobic in ischaemia) and by FMRFamide (which may mimic the action of related mammalian RFamide transmitters). These data reinforce suggestions of a mechanosensory aspect to ASIC channel function, and show that the activation of ASICs reflects the integration of multiple signals which are present during ischaemia. PMID:12205186

Fluorescein transport properties across artificial lipid membranes, Caco-2 cell monolayers and rat jejunum.

Science.gov (United States)

Berginc, Katja; Zakelj, Simon; Levstik, Lea; Ursic, Darko; Kristl, Albin

2007-05-01

Membrane transport characteristics of a paracellular permeability marker fluorescein were evaluated using artificial membrane, Caco-2 cell monolayers and rat jejunum, all mounted in side-by-side diffusion cells. Modified Ringer buffers with varied pH values were applied as incubation salines on both sides of artificial membrane, cell culture monolayers or rat jejunum. Passive transport according to pH partition theory was determined using all three permeability models. In addition to that, active transport of fluorescein in the M-S (mucosal-to-serosal) direction through rat jejunum was observed. The highest M-S P(app) values regarding the active transport through the rat jejunum were observed in incubation saline with pH 6.5. Fluorescein transport through the rat jejunum was inhibited by DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid) and alpha-CHC (alpha-cyano-4-hydroxycinnamic acid). Thus, we assume that two pH-dependent influx transporters could be involved in the fluorescein membrane transport through the intestinal (jejunal) epithelium. One is very likely an MCT (monocarboxylic acid cotransporter) isoform, inhibited by specific MCT inhibitor alpha-CHC, while the involvement of the second one with overlapping substrate/inhibitor specificities (most probably a member of the organic anion-transporting polypeptide family, inhibited at least partially by DIDS) could not be excluded.

Questioning the cerebellar doctrine

NARCIS (Netherlands)

Galliano, Elisa; De Zeeuw, Chris I

2014-01-01

The basic principles of cerebellar function were originally described by Flourens, Cajal, and Marr/Albus/Ito, and they constitute the pillars of what can be considered to be the classic cerebellar doctrine. In their concepts, the main cerebellar function is to control motor behavior, Purkinje cells

Effect of dietary zinc deficiency on the endogenous phosphorylation and dephosphorylation of rat erythrocyte membrane

International Nuclear Information System (INIS)

Paterson, P.G.; Allen, O.B.; Bettger, W.J.

1987-01-01

The effect of dietary zinc deficiency on patterns of phosphorylation and dephosphorylation of rat erythrocyte membrane proteins and erythrocyte filterability was examined. Weanling male Wistar rats were fed an egg white-based diet containing less than 1.1 mg zinc/kg diet ad libitum for 3 wk. Control rats were either pair-fed or ad libitum-fed the basal diet supplemented with 100 mg zinc/kg diet. Net phosphorylation and dephosphorylation of erythrocyte membrane proteins were carried out by an in vitro assay utilizing [gamma- 32 P]ATP. The membrane proteins were subsequently separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the 32 P content of gel slices was counted by Cerenkov counting. Erythrocyte filterability was measured as the filtration time of suspensions of erythrocytes, both untreated and preincubated with diamide, under constant pressure. Erythrocyte ghosts from zinc-deficient rats demonstrated greater dephosphorylation of protein bands R1 plus R2 and R7 than pair-fed rats and greater net phosphorylation of band R2.2 than pair-fed or ad libitum-fed control rats (P less than 0.05). Erythrocytes from ad libitum-fed control rats showed significantly longer filtration times than those from zinc-deficient or pair-fed control rats. In conclusion, dietary zinc deficiency alters in vitro patterns of erythrocyte membrane protein phosphorylation and dephosphorylation, whereas the depression in food intake associated with the zinc deficiency increases erythrocyte filterability. 71 references

Changes in the cerebellar and cerebro-cerebellar circuit in type 2 diabetes.

Science.gov (United States)

Fang, Peng; An, Jie; Tan, Xin; Zeng, Ling-Li; Shen, Hui; Qiu, Shijun; Hu, Dewen

2017-04-01

Currently, 422 million adults suffer from diabetes worldwide, leading to tremendous disabilities and a great burden to families and society. Functional and structural MRIs have demonstrated that patients with type 2 diabetes mellitus (T2DM) exhibit abnormalities in brain regions in the cerebral cortex. However, the changes of cerebellar anatomical connections in diabetic patients remains unclear. In the current study, diffusion tensor imaging deterministic tractography and statistical analysis were employed to investigate abnormal cerebellar anatomical connections in diabetic patients. This is the first study to investigate the altered cerebellar anatomical connectivity in T2DM patients. Decreased anatomical connections were found in the cerebellar and cerebro-cerebellar circuits of T2DM patients, providing valuable new insights into the potential neuro-pathophysiology of diabetes-related motor and cognitive deficits. Copyright © 2017. Published by Elsevier Inc.

Effect of docosahexaenoic acid and ascorbate on peroxidation of retinal membranes of ODS rats.

Science.gov (United States)

Wang, Jin-Ye; Sekine, Seiji; Saito, Morio

2003-04-01

Mutant male osteogenic disorder Shionogi (ODS) rats, unable to synthesize ascorbic acid, were fed diets containing a high content of docosahexaenoic acid (DHA) and different amounts of ascorbic acid, to study the effect of DHA on peroxidative susceptibility of the retina and possible antioxidant action of ascorbic acid. ODS rats were fed from 7 weeks of age with diets containing high DHA (6.4% of total energy). A control group received a diet high in linoleic acid. The diets also contained varying amounts of ascorbic acid. Fatty acid compositions and phospholipid hydroperoxides in rod outer segment (ROS) membranes, and retinal ascorbic acid were analyzed. DHA in ROS membranes was significantly increased in rats fed high DHA, compared with the linoleic acid diet. Levels of phospholipid hydroperoxides in the DHA-fed rats were significantly higher than the linoleic acid-fed rats. Ascorbic acid supplementation did not suppress the phospholipid hydroperoxide levels after a high DHA diet, even when the supplement increased the content of retinal ascorbic acid. In conclusion, high DHA feeding induced a marked increase of phospholipid hydroperoxides in ROS membranes of ODS rats. Supplementation of ascorbic acid did not reverse this increase.

Plasticity of Cerebellar Purkinje Cells in Behavioral Training of Body Balance Control

Directory of Open Access Journals (Sweden)

Ray X. Lee

2015-08-01

Full Text Available Neural responses to sensory inputs caused by self-generated movements (reafference and external passive stimulation (exafference differ in various brain regions. The ability to differentiate such sensory information can lead to movement execution with better accuracy. However, how sensory responses are adjusted in regard to this distinguishability during motor learning is still poorly understood. The cerebellum has been hypothesized to analyze the functional significance of sensory information during motor learning, and is thought to be a key region of reafference computation in the vestibular system. In this study, we investigated Purkinje cell (PC spike trains as cerebellar cortical output when rats learned to balance on a suspended dowel. Rats progressively reduced the amplitude of body swing and made fewer foot slips during a 5-min balancing task. Both PC simple (SSs; 17 of 26 and complex spikes (CSs; 7 of 12 were found to code initially on the angle of the heads with respect to a fixed reference. Using periods with comparable degrees of movement, we found that such SS coding of information in most PCs (10 of 17 decreased rapidly during balance learning. In response to unexpected perturbations and under anesthesia, SS coding capability of these PCs recovered. By plotting SS and CS firing frequencies over 15-s time windows in double-logarithmic plots, a negative correlation between SS and CS was found in awake, but not anesthetized, rats. PCs with prominent SS coding attenuation during motor learning showed weaker SS-CS correlation. Hence, we demonstrate that neural plasticity for filtering out sensory reafference from active motion occurs in the cerebellar cortex in rats during balance learning. SS-CS interaction may contribute to this rapid plasticity as a form of receptive field plasticity in the cerebellar cortex between two receptive maps of sensory inputs from the external world and of efference copies from the will center for

Insulin stimulation of phospholipid methylation in isolated rat adipocyte plasma membranes.

OpenAIRE

Kelly, K L; Kiechle, F L; Jarett, L

1984-01-01

Partially purified plasma membranes prepared from rat adipocytes contain N-methyltransferase(s) that utilize(s) S-adenosyl-L-methionine to synthesize phosphatidylcholine from phosphatidylethanolamine. The incorporation of [3H]methyl from S-adenosyl-L-[methyl-3H]methionine into plasma membrane phospholipids was linear with incubation time and plasma membrane protein concentration and was inhibited in a dose-dependent manner by both S-adenosyl-L-homocysteine and 3-deazadenosine. The addition of...

Cerebellar dentate nuclei lesions reduce motivation in appetitive operant conditioning and open field exploration.

Science.gov (United States)

Bauer, David J; Kerr, Abigail L; Swain, Rodney A

2011-02-01

Recently identified pathways from the dentate nuclei of the cerebellum to the rostral cerebral cortex via the thalamus suggest a cerebellar role in frontal and prefrontal non-motor functioning. Disturbance of cerebellar morphology and connectivity, particularly involving these cerebellothalamocortical (CTC) projections, has been implicated in motivational and cognitive deficits. The current study explored the effects of CTC disruption on motivation in male Long Evans rats. The results of two experiments demonstrate that electrolytic lesions of the cerebellar dentate nuclei lower breaking points on an operant conditioning progressive ratio schedule and decrease open field exploration compared to sham controls. Changes occurred in the absence of motor impairment, assessed via lever pressing frequency and rotarod performance. Similar elevated plus maze performances between lesioned and sham animals indicated that anxiety did not influence task performance. Our results demonstrate hedonic and purposive motivational reduction and suggest a CTC role in global motivational processes. These implications are discussed in terms of psychiatric disorders such as schizophrenia and autism, in which cerebellar damage and motivational deficits often present concomitantly. Copyright © 2010 Elsevier Inc. All rights reserved.

Questioning the cerebellar doctrine.

Science.gov (United States)

Galliano, Elisa; De Zeeuw, Chris I

2014-01-01

The basic principles of cerebellar function were originally described by Flourens, Cajal, and Marr/Albus/Ito, and they constitute the pillars of what can be considered to be the classic cerebellar doctrine. In their concepts, the main cerebellar function is to control motor behavior, Purkinje cells are the only cortical neuron receiving and integrating inputs from climbing fiber and mossy-parallel fiber pathways, and plastic modification at the parallel fiber synapses onto Purkinje cells constitutes the substrate of motor learning. Yet, because of recent technical advances and new angles of investigation, all pillars of the cerebellar doctrine now face regular re-examination. In this review, after summarizing the classic concepts and recent disputes, we attempt to synthesize an integrated view and propose a revisited version of the cerebellar doctrine. © 2014 Elsevier B.V. All rights reserved.

Guided bone regeneration in rat mandibular defects using resorbable poly(trimethylene carbonate) barrier membranes

NARCIS (Netherlands)

van Leeuwen, A. C.; Huddleston Slater, J. J. R.; Gielkens, P. F. M.; de Jong, J. R.; Grijpma, D. W.; Bos, R. R. M.

The present study evaluates a new synthetic degradable barrier membrane based on poly(trimethylene carbonate) (PTMC) for use in guided bone regeneration. A collagen membrane and an expanded polytetrafluoroethylene (e-PTFE) membrane served as reference materials. In 192 male Sprague-Dawley rats, a

Guided bone regeneration in rat mandibular defects using resorbable poly(trimethylene carbonate) barrier membranes

NARCIS (Netherlands)

van Leeuwen, A.C.; Huddelston Slater, J.J.R.; Gielkens, P.F.M.; de Jong, J.R.; Grijpma, Dirk W.; Bos, R.R.M.

2012-01-01

The present study evaluates a new synthetic degradable barrier membrane based on poly(trimethylene carbonate) (PTMC) for use in guided bone regeneration. A collagen membrane and an expanded polytetrafluoroethylene (e-PTFE) membrane served as reference materials. In 192 male Sprague–Dawley rats, a

Repeated prenatal exposure to valproic acid results in cerebellar hypoplasia and ataxia.

Science.gov (United States)

Main, Stacey L; Kulesza, Randy J

2017-01-06

Autism spectrum disorder (ASD) is a developmental brain disorder characterized by restricted and repetitive patterns of behavior, social and communication defects, and is commonly associated with difficulties with motor coordination. The etiology of ASD, while mostly idiopathic, has been linked to hereditary factors and teratogens, such as valproic acid (VPA). VPA is used clinically to treat epilepsy, mood disorders, and in the prevention of migraines. The use of VPA during pregnancy significantly increases the risk of ASD in the offspring. Neuropathological studies show decreased cerebellar function in patients with ASD, resulting in gait, balance and coordination impairments. Herein, we have exposed pregnant rats to a repeated oral dose of VPA on embryonic days 10 and 12 and performed a detailed investigation of the structure and function of the cerebellar vermis. We found that throughout all ten lobules of the cerebellar vermis, Purkinje cells were significantly smaller and expression of the calcium binding protein calbindin (CB) was significantly reduced. We also found that dendritic arbors of Purkinje cells were shorter and less complex. Additionally, animals exposed to a repeated dose of VPA performed significantly worse in a number of motor tasks, including beam walking and the rotarod. These results suggest that repeated embryonic exposure to VPA induces significant cerebellar dysfunction and is an effective animal model to study the cerebellar alterations in ASD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

[Relationship between the changes in ischemia/reperfusion cerebro-microvessel basement membrane injury and gelatinase system in senile rat].

Science.gov (United States)

Li, Jian-sheng; Liu, Ke; Liu, Jing-xia; Wang, Ming-hang; Zhao, Yue-wu; Liu, Zheng-guo

2008-11-01

To study the relationship of cerebro-microvessel basement membrane injury and gelatinase system after cerebral ischemia/reperfusion (I/R) in aged rats. Cerebral I/R injury model was reproduced by intraluminal silk ligature thrombosis of the middle cerebral artery occlusion (MCAO). Rats were divided randomly into sham control and I/R groups in young rats [ischemia 3 hours (I 3 h) and reperfusion 6 hours (I/R 6 h), 12 hours (I/R 12 h), 24 hours (I/R 24 h), 3 days (I/R 3 d), 6 days (I/R 6 d)], and sham control group and I/R group in aged rats (I 3 h and I/R 6 h, I/R 12 h, I/R 24 h , I/R 3 d, I/R 6 d). The change in cerebro-cortex microvessel basement membrane structure, basement membrane type IV collagen (Col IV) and laminin (LN) contents, matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) expression in every group were determined with immunohistochemical method and zymogram analysis. With the increase in age, Col IV and LN contents of the microvessel basement membrane were increased, and MMP-2 and MMP-9 expressions were stronger. With prolongation of I/R, the degradation of microvessel basement membrane components (Col IV and LN) was positively correlated with the duration of cerebral I/R. MMP-2 expression was increased gradually, and MMP-9 and TIMP-1 expression increased at the beginning and decreased subsequently. Col IV(I 3 h, I/R 6 h , I/R 12 h), LN (I 3 h, I/R 6-24 h), MMP-2 (I 3 h, I/R 6 h-6 d) and MMP-9 (I 3 h, I/R 6-24 h) expression level in aged rats with I/R injury were higher, and TIMP-1 (I/R 24 h) expression was lower than those in young rats (Pcerebro-microvessel basement membrane in rats is related with MMPs and TIMP. Cerebro-microvessel basement membrane injury is more serious in aged rats than that of young rats. Changes in cerebro-microvessel basement membrane injury in aged rats is related with gelatinase system change.

Cerebro-Cerebellar Functional Connectivity is Associated with Cerebellar Excitation-Inhibition Balance in Autism Spectrum Disorder.

Science.gov (United States)

Hegarty, John P; Weber, Dylan J; Cirstea, Carmen M; Beversdorf, David Q

2018-05-23

Atypical functional connectivity (FC) and an imbalance of excitation-to-inhibition (E/I) have been previously reported in cerebro-cerebellar circuits in autism spectrum disorder (ASD). The current investigation used resting state fMRI and proton magnetic resonance spectroscopy ( 1 H-MRS) to examine the relationships between E/I (glutamate + glutamine/GABA) and FC of the dorsolateral prefrontal cortex and posterolateral cerebellar hemisphere from 14 adolescents/adults with ASD and 12 age/sex/IQ-matched controls. In this pilot sample, cerebro-cerebellar FC was positively associated with cerebellar E/I and listening comprehension abilities in individuals with ASD but not controls. Additionally, a subgroup of individuals with ASD and low FC (n = 5) exhibited reduced E/I and impaired listening comprehension. Thus, altered functional coherence of cerebro-cerebellar circuits in ASD may be related with a cerebellar E/I imbalance.

Real-time cerebellar neuroprosthetic system based on a spiking neural network model of motor learning.

Science.gov (United States)

Xu, Tao; Xiao, Na; Zhai, Xiaolong; Kwan Chan, Pak; Tin, Chung

2018-02-01

Damage to the brain, as a result of various medical conditions, impacts the everyday life of patients and there is still no complete cure to neurological disorders. Neuroprostheses that can functionally replace the damaged neural circuit have recently emerged as a possible solution to these problems. Here we describe the development of a real-time cerebellar neuroprosthetic system to substitute neural function in cerebellar circuitry for learning delay eyeblink conditioning (DEC). The system was empowered by a biologically realistic spiking neural network (SNN) model of the cerebellar neural circuit, which considers the neuronal population and anatomical connectivity of the network. The model simulated synaptic plasticity critical for learning DEC. This SNN model was carefully implemented on a field programmable gate array (FPGA) platform for real-time simulation. This hardware system was interfaced in in vivo experiments with anesthetized rats and it used neural spikes recorded online from the animal to learn and trigger conditioned eyeblink in the animal during training. This rat-FPGA hybrid system was able to process neuronal spikes in real-time with an embedded cerebellum model of ~10 000 neurons and reproduce learning of DEC with different inter-stimulus intervals. Our results validated that the system performance is physiologically relevant at both the neural (firing pattern) and behavioral (eyeblink pattern) levels. This integrated system provides the sufficient computation power for mimicking the cerebellar circuit in real-time. The system interacts with the biological system naturally at the spike level and can be generalized for including other neural components (neuron types and plasticity) and neural functions for potential neuroprosthetic applications.

Ablation of Cerebellar Nuclei Prevents H-Reflex Down-Conditioning in Rats

Science.gov (United States)

Chen, Xiang Yang; Wolpaw, Jonathan R.

2005-01-01

While studies of cerebellar involvement in learning and memory have described plasticity within the cerebellum, its role in acquisition of plasticity elsewhere in the CNS is largely unexplored. This study set out to determine whether the cerebellum is needed for acquisition of the spinal cord plasticity that underlies operantly conditioned…

Fibronectin binding to gangliosides and rat liver plasma membranes

Energy Technology Data Exchange (ETDEWEB)

Matyas, G R; Evers, D C; Radinsky, R; Morre, D J

1986-02-01

Binding of fibronectins to gangliosides was tested directly using several different in vitro models. Using an enzyme-linked immunoabsorbent assay (ELISA), gangliosides were immobilized on polystyrene tubes and relative binding of fibronectin was estimated by alkaline phosphatase activity of conjugated second antibody. Above a critical ganglioside concentration, the gangliosides bound the fibronectin (G/sub T1b/ approx. = G/sub D1b/ approx. = G/sub D1a/ > G/sub M1/ >> G/sub M2/ approx. = G/sub D3/ approx. = G/sub M3/) in approximately the same order of efficiency as they competed for the cellular sites of fibronectin binding in cell attachment assays. Alternatively, these same gangliosides bound to immobilized fibronectin. Rat erythrocytes coated with gangliosides G/sub M1/, G/sub D1a/ or G/sub T1b/ bound more fibronectin than erythrocytes not supplemented with gangliosides. Using fibronectin in which lysine residues were radioiodinated, an apparent K/sub d/ for binding to mixed rat liver gangliosides of 7.8 x 10/sup -9/ M was determined. This value compared favorably with the apparent K/sub d/ for attachment of fibronectin to isolated plasma membranes from rat liver of 3.7 x 10/sup -9/ M for fibronectin modified on the tyrosine residue, or 6.4 x 10/sup -9/ M for fibronectin modified on lysine residues. As shown previously by Grinnell and Minter, fibronectin modified on tyrosine residues did not promote spreading and attachment of CHO cells. It did, however, bind to cells. In contrast, lysine-modified fibronectin both bound to cells and promoted cell attachment. Plasma membranes isolated from hepatic tumors in which the higher gangliosides that bind fibronectin were depleted bound 43-75% less (/sup 125/I)fibronectin than did plasma membranes from control livers. The findings were consistent with binding of fibronectins to gangliosides, including the same gangliosides depleted from cell surfaces during tumorigenesis in the rat.

Quantification of 5-hydroxytryptamine1A receptors in the cerebellum of normal and x-irradiated rats during postnatal development

International Nuclear Information System (INIS)

Matthiessen, L.; Daval, G.; Bailly, Y.; Gozlan, H.; Hamon, M.; Verge, D.

1992-01-01

5-Hydroxytryptamine 1A receptors were studied in rats during the first postnatal month in the normal cerebellum and in the granule cell-deprived cerebellum produced by X-irradiation at postnatal day 5. Quantitative autoradiographic studies on sagittal sections of cerebellar vermis, using [ 125 1]BH-8-MeO-N-PAT as radioligand or specific anti-receptor antibodies, revealed that 5-hydroxytryptamine 1A receptors existed in the molecular/Purkinje cell layer but at variable density from one lobule to another. Thus, in both normal and X-irradiated rats, the posterior lobules were more heavily labelled than the anterior ones, and the density of 5-hydroxytryptamine 1A sites decreased progressively in all the cerebellar folia down to hardly detectable levels at postnatal day 21. However, the intensity of labelling remained higher at postnatal day 8 and postnatal day 12 in X-irradiated rats than in age-paired controls. Measurements of [ 3 H]8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] specific binding to membranes from whole cerebellum confirmed that the density of 5-hydroxytryptamine 1A sites per mg membrane protein (B max ) was higher in X-irradiated animals than in age-paired controls. However, on a ''per cerebellum'' basis, no significant difference could be detected between the total number of 5-hydroxytryptamine 1A sites, which progressively increased in both control and X-irradiated animals during the first postnatal month. These results therefore show that 5-hydroxytryptamine 1A receptors are not located on developing granule cells. (author)

Effect of pinacidil on norepinephrine- and potassium-induced contractions and membrane potential in rat and human resistance vessels and in rat aorta

International Nuclear Information System (INIS)

Videbaek, L.M.; Aalkjaer, C.; Mulvany, M.J.

1988-01-01

The effect of pinacidil on contractile responses to norepinephrine, potassium, and membrane potential was examined in rat and human resistance vessels. In some experiments rat aorta was also used. Pinacidil (0.1-30 microM) caused a concentration-dependent relaxation of norepinephrine-induced contractions in all vessels studied. In the same concentration range, pinacidil had only little effect on potassium (125 mM) activated rat mesenteric and femoral resistance vessels. In denervated rat mesenteric resistance vessels, a depolarization with potassium (125 mM) before superimposing a norepinephrine tone markedly diminished the effect of pinacidil. In resting rat mesenteric resistance vessels, pinacidil (1-10 microM) caused a hyperpolarization of 10-15 mV. In rat aorta, pinacidil (10 microM) caused a significant (p less than 0.001) increase in 86 Rb+ efflux rate constant whereas 1 microM had no effect. The results of these experiments indicate that the vasodilating effect may be caused by a hyperpolarization of the vascular smooth muscle cell membrane

Repeated intermittent alcohol exposure during the third trimester-equivalent increases expression of the GABA(A) receptor δ subunit in cerebellar granule neurons and delays motor development in rats.

Science.gov (United States)

Diaz, Marvin R; Vollmer, Cyndel C; Zamudio-Bulcock, Paula A; Vollmer, William; Blomquist, Samantha L; Morton, Russell A; Everett, Julie C; Zurek, Agnieszka A; Yu, Jieying; Orser, Beverley A; Valenzuela, C Fernando

2014-04-01

Exposure to ethanol (EtOH) during fetal development can lead to long-lasting alterations, including deficits in fine motor skills and motor learning. Studies suggest that these are, in part, a consequence of cerebellar damage. Cerebellar granule neurons (CGNs) are the gateway of information into the cerebellar cortex. Functionally, CGNs are heavily regulated by phasic and tonic GABAergic inhibition from Golgi cell interneurons; however, the effect of EtOH exposure on the development of GABAergic transmission in immature CGNs has not been investigated. To model EtOH exposure during the 3rd trimester-equivalent of human pregnancy, neonatal pups were exposed intermittently to high levels of vaporized EtOH from postnatal day (P) 2 to P12. This exposure gradually increased pup serum EtOH concentrations (SECs) to ∼60 mM (∼0.28 g/dl) during the 4 h of exposure. EtOH levels gradually decreased to baseline 8 h after the end of exposure. Surprisingly, basal tonic and phasic GABAergic currents in CGNs were not significantly affected by postnatal alcohol exposure (PAE). However, PAE increased δ subunit expression at P28 as detected by immunohistochemical and western blot analyses. Also, electrophysiological studies with an agonist that is highly selective for δ-containing GABA(A) receptors, 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol (THIP), showed an increase in THIP-induced tonic current. Behavioral studies of PAE rats did not reveal any deficits in motor coordination, except for a delay in the acquisition of the mid-air righting reflex that was apparent at P15 to P18. These findings demonstrate that repeated intermittent exposure to high levels of EtOH during the equivalent of the last trimester of human pregnancy has significant but relatively subtle effects on motor coordination and GABAergic transmission in CGNs in rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cerebellar abiotrophy in a miniature schnauzer

OpenAIRE

Berry, Michelle L.; Blas-Machado, Uriel

2003-01-01

A 3.5-month-old miniature schnauzer was presented for signs of progressive cerebellar ataxia. Necropsy revealed cerebellar abiotrophy. This is the first reported case of cerebellar abiotrophy in a purebred miniature schnauzer.

Cerebellar abiotrophy in a miniature schnauzer.

Science.gov (United States)

Berry, Michelle L; Blas-Machado, Uriel

2003-08-01

A 3.5-month-old miniature schnauzer was presented for signs of progressive cerebellar ataxia. Necropsy revealed cerebellar abiotrophy. This is the first reported case of cerebellar abiotrophy in a purebred miniature schnauzer.

Evaluation of castor oil-based polyurethane membranes in rat bone-marrow cell culture.

Science.gov (United States)

Cerejo, Sofia de Amorim; Rahal, Sheila Canevese; Lima Neto, João Ferreira de; Voorwald, Fabiana Azevedo; Alvarenga, Fernanda da Cruz Landim e

2011-10-01

To evaluate three methods to isolate rats MSCs and to analyze the potential of a castor oil polyurethane base membrane as a scaffold for MSCs. Four male Wistar rats, aged 20-30 days were used. Bone marrow aspirates from femur and tibia were harvested using DMEM high glucose and heparin. The cell culture was performed in three different ways: direct culture and two types of density gradients. After 15 days, was made the 1st passage and analyzed cell viability with markers Hoerscht 33342 and propidium iodide. The MSCs were characterized by surface markers with the aid of flow cytometry. After this, three types of castor oil polyurethane membranes associated with the MSCs were kept on the 6-well plate for 5 days and were analyzed by optical microscopy to confirm cell aggregation and growth. Separation procedures 1 and 2 allowed adequate isolation of MSCs and favored cell growth with the passage being carried out at 70% confluence after 15 days in culture. The cells could not be isolated using procedure 3. When the 3 castor oil polyurethane membrane types were compared it was possible to observe that the growth of MSCs was around 80% in membrane type 3, 20% in type 2, and 10% in type 1. Both Ficoll-Hypaque densities allow isolation of rat MSCs, and especially castor oil-based membrane type 3 may be used as a scaffold for MSCs.

Quantification of 5-hydroxytryptamine[sub 1A] receptors in the cerebellum of normal and x-irradiated rats during postnatal development

Energy Technology Data Exchange (ETDEWEB)

Matthiessen, L; Daval, G; Bailly, Y [Pierre et Marie Curie Univ., Paris (France). Centre National de la Recherche Scientifique, UA; Gozlan, H; Hamon, M; Verge, D [INSERM, Paris (France). Lab. de Neurobiologie Cellulaire et Fonctionnelle

1992-11-01

5-Hydroxytryptamine[sub 1A] receptors were studied in rats during the first postnatal month in the normal cerebellum and in the granule cell-deprived cerebellum produced by X-irradiation at postnatal day 5. Quantitative autoradiographic studies on sagittal sections of cerebellar vermis, using [[sup 125]1]BH-8-MeO-N-PAT as radioligand or specific anti-receptor antibodies, revealed that 5-hydroxytryptamine[sub 1A] receptors existed in the molecular/Purkinje cell layer but at variable density from one lobule to another. Thus, in both normal and X-irradiated rats, the posterior lobules were more heavily labelled than the anterior ones, and the density of 5-hydroxytryptamine[sub 1A] sites decreased progressively in all the cerebellar folia down to hardly detectable levels at postnatal day 21. However, the intensity of labelling remained higher at postnatal day 8 and postnatal day 12 in X-irradiated rats than in age-paired controls. Measurements of [[sup 3]H]8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] specific binding to membranes from whole cerebellum confirmed that the density of 5-hydroxytryptamine[sub 1A] sites per mg membrane protein (B[sub max]) was higher in X-irradiated animals than in age-paired controls. However, on a ''per cerebellum'' basis, no significant difference could be detected between the total number of 5-hydroxytryptamine[sub 1A] sites, which progressively increased in both control and X-irradiated animals during the first postnatal month. These results therefore show that 5-hydroxytryptamine[sub 1A] receptors are not located on developing granule cells. (author).

Real-time cerebellar neuroprosthetic system based on a spiking neural network model of motor learning

Science.gov (United States)

Xu, Tao; Xiao, Na; Zhai, Xiaolong; Chan, Pak Kwan; Tin, Chung

2018-02-01

Objective. Damage to the brain, as a result of various medical conditions, impacts the everyday life of patients and there is still no complete cure to neurological disorders. Neuroprostheses that can functionally replace the damaged neural circuit have recently emerged as a possible solution to these problems. Here we describe the development of a real-time cerebellar neuroprosthetic system to substitute neural function in cerebellar circuitry for learning delay eyeblink conditioning (DEC). Approach. The system was empowered by a biologically realistic spiking neural network (SNN) model of the cerebellar neural circuit, which considers the neuronal population and anatomical connectivity of the network. The model simulated synaptic plasticity critical for learning DEC. This SNN model was carefully implemented on a field programmable gate array (FPGA) platform for real-time simulation. This hardware system was interfaced in in vivo experiments with anesthetized rats and it used neural spikes recorded online from the animal to learn and trigger conditioned eyeblink in the animal during training. Main results. This rat-FPGA hybrid system was able to process neuronal spikes in real-time with an embedded cerebellum model of ~10 000 neurons and reproduce learning of DEC with different inter-stimulus intervals. Our results validated that the system performance is physiologically relevant at both the neural (firing pattern) and behavioral (eyeblink pattern) levels. Significance. This integrated system provides the sufficient computation power for mimicking the cerebellar circuit in real-time. The system interacts with the biological system naturally at the spike level and can be generalized for including other neural components (neuron types and plasticity) and neural functions for potential neuroprosthetic applications.

Toxic agents causing cerebellar ataxias.

Science.gov (United States)

Manto, Mario

2012-01-01

The cerebellum is particularly vulnerable to intoxication and poisoning, especially so the cerebellar cortex and Purkinje neurons. In humans, the most common cause of a toxic lesion to the cerebellar circuitry is alcohol related, but the cerebellum is also a main target of drug exposure (such as anticonvulsants, antineoplastics, lithium salts, calcineurin inhibitors), drug abuse and addiction (such as cocaine, heroin, phencyclidine), and environmental toxins (such as mercury, lead, manganese, toluene/benzene derivatives). Although data for the prevalence and incidence of cerebellar lesions related to intoxication and poisoning are still unknown in many cases, clinicians should keep in mind the list of agents that may cause cerebellar deficits, since toxin-induced cerebellar ataxias are not rare in daily practice. Moreover, the patient's status may require immediate therapies when the intoxication is life-threatening. 2012 Elsevier B.V. All rights reserved.

The Sodium-Potassium Pump Controls the Intrinsic Firing of the Cerebellar Purkinje Neuron

Science.gov (United States)

Forrest, Michael D.; Wall, Mark J.; Press, Daniel A.; Feng, Jianfeng

2012-01-01

In vitro, cerebellar Purkinje cells can intrinsically fire action potentials in a repeating trimodal or bimodal pattern. The trimodal pattern consists of tonic spiking, bursting, and quiescence. The bimodal pattern consists of tonic spiking and quiescence. It is unclear how these firing patterns are generated and what determines which firing pattern is selected. We have constructed a realistic biophysical Purkinje cell model that can replicate these patterns. In this model, Na+/K+ pump activity sets the Purkinje cell's operating mode. From rat cerebellar slices we present Purkinje whole cell recordings in the presence of ouabain, which irreversibly blocks the Na+/K+ pump. The model can replicate these recordings. We propose that Na+/K+ pump activity controls the intrinsic firing mode of cerbellar Purkinje cells. PMID:23284664

Critical periods during the in situ repair of radiation-induced DNA damage in rat cerebellar neurons and 9L brain tumor cells

International Nuclear Information System (INIS)

Wierowski, J.V.; Thomas, R.R.; Ritter, P.; Wheeler, K.T.

1982-01-01

The consequences of delivering a second 1250-rad dose at various times during and after the repair of DNA damage produced by an initial 1250-rad dose were assessed in intracerebral 9L tumor cells and rat cerebellar neurons by measuring the sedimentation properties of their DNA through alkaline sucrose gradients in zonal rotors with slow gradient reorienting capabilities.In cerebellar neurons, separating the two doses by 15 min resulted in an accumulation of DNA damage as expressed by an increase in the amount of DNA sedimenting >250 S over that obtained from unirradiated controls. Although not statistically different from unirradiated controls, a slight increase in the amount of fast-sedimenting neuronal DNA also occurred when a 1-hr interval between the two doses was investigated. At intervals of 2 hr or more, no such increase in fast-sedimenting neuronal DNA was observed. None of the periods between doses resulted in an accumulation of DNA damage in intracerebral 9L tumor cells. The accumulation of this type of DNA damage in neurons but not in tumor cells suggests that avoidance of a critical period in neuronal DNA repair may someday be an important concept in the design of brain tumor therapy schedules

Hypertensive cerebellar hemorrhage and cerebellar hemorrhage caused by cryptic angioma

International Nuclear Information System (INIS)

Yoshida, Shinichi; Sano, Keiji; Kwak, Suyong; Saito, Isamu.

1981-01-01

A series of 44 patients with hypertensive cerebellar hemorrhage and nine patients with cerebellar hemorrhage caused by small angiomas is described. Hypertensive hemorrhage occurred most frequently in the patients in their seventies, whereas the onset of angioma-caused hemorrhage was often seen below the age of 40. Clinical syndromes of cerebellar hemorrhages can be categorized into three basic types: the vertigo syndrome, cerebellar dysfunction syndrome and brain stem compression syndrome. Patients with small (>= 2 cm in diameter in CT scans) and medium-sized (2 cm = 3 cm) hematomas deteriorated into unresponsive conditions and developed signs of brain stem compression. Surgical mortality was 32% in the hypertensive group, while it was 0% in the angioma group. Mortality as well as morbidity in both groups was strongly influenced by the preoperative status of consciousness. Our results suggest that substantial improvement could be obtained in the overall outcome of this disease by emergency craniectomy and removal of hematomas in all patients with large hematomas regardless of the levels of consciousness and regardless of the causes of bleeding. Furthermore, when clinical information and CT findings are suggestive of a ''cryptic'' angioma as the causative lesion, posterior fossa surgery may be indicated to extirpate the lesion, even if the hematoma is small. (author)

Cerebro-cerebellar circuits in autism spectrum disorder

Directory of Open Access Journals (Sweden)

Anila M. D'Mello

2015-11-01

Full Text Available The cerebellum is one of the most consistent sites of abnormality in autism spectrum disorder (ASD and cerebellar damage is associated with an increased risk of ASD symptoms, suggesting that cerebellar dysfunction may play a crucial role in the etiology of ASD. The cerebellum forms multiple closed-loop circuits with cerebral cortical regions that underpin movement, language, and social processing. Through these circuits, cerebellar dysfunction could impact the core ASD symptoms of social and communication deficits and repetitive and stereotyped behaviors. The emerging topography of sensorimotor, cognitive, and affective subregions in the cerebellum provides a new framework for interpreting the significance of regional cerebellar findings in ASD and their relationship to broader cerebro-cerebellar circuits. Further, recent research supports the idea that the integrity of cerebro-cerebellar loops might be important for early cortical development; disruptions in specific cerebro-cerebellar loops in ASD might impede the specialization of cortical regions involved in motor control, language, and social interaction, leading to impairments in these domains. Consistent with this concept, structural and functional differences in sensorimotor regions of the cerebellum and sensorimotor cerebro-cerebellar circuits are associated with deficits in motor control and increased repetitive and stereotyped behaviors in ASD. In contrast, communication and social impairments are associated with atypical activation and structure in cerebro-cerebellar loops underpinning language and social cognition. Finally, there is converging evidence from structural, functional, and connectivity neuroimaging studies that cerebellar right Crus I/II abnormalities are related to more severe ASD impairments in all domains. We propose that cerebellar abnormalities may disrupt optimization of both structure and function in specific cerebro-cerebellar circuits in ASD.

Cerebro-cerebellar circuits in autism spectrum disorder.

Science.gov (United States)

D'Mello, Anila M; Stoodley, Catherine J

2015-01-01

The cerebellum is one of the most consistent sites of abnormality in autism spectrum disorder (ASD) and cerebellar damage is associated with an increased risk of ASD symptoms, suggesting that cerebellar dysfunction may play a crucial role in the etiology of ASD. The cerebellum forms multiple closed-loop circuits with cerebral cortical regions that underpin movement, language, and social processing. Through these circuits, cerebellar dysfunction could impact the core ASD symptoms of social and communication deficits and repetitive and stereotyped behaviors. The emerging topography of sensorimotor, cognitive, and affective subregions in the cerebellum provides a new framework for interpreting the significance of regional cerebellar findings in ASD and their relationship to broader cerebro-cerebellar circuits. Further, recent research supports the idea that the integrity of cerebro-cerebellar loops might be important for early cortical development; disruptions in specific cerebro-cerebellar loops in ASD might impede the specialization of cortical regions involved in motor control, language, and social interaction, leading to impairments in these domains. Consistent with this concept, structural, and functional differences in sensorimotor regions of the cerebellum and sensorimotor cerebro-cerebellar circuits are associated with deficits in motor control and increased repetitive and stereotyped behaviors in ASD. Further, communication and social impairments are associated with atypical activation and structure in cerebro-cerebellar loops underpinning language and social cognition. Finally, there is converging evidence from structural, functional, and connectivity neuroimaging studies that cerebellar right Crus I/II abnormalities are related to more severe ASD impairments in all domains. We propose that cerebellar abnormalities may disrupt optimization of both structure and function in specific cerebro-cerebellar circuits in ASD.

Cerebellar Hypoplasia and Dysmorphia in Neurofibromatosis Type 1.

Science.gov (United States)

Toelle, Sandra P; Poretti, Andrea; Weber, Peter; Seute, Tatjana; Bromberg, Jacoline E C; Scheer, Ianina; Boltshauser, Eugen

2015-12-01

Unidentified bright objects (UBO) and tumors are well-known cerebellar abnormalities in neurofibromatosis type 1 (NF1). Literature reports on malformative cerebellar anomalies in neurofibromatosis type 1 (NF1), however, are scant. We retrospectively studied the clinical and neuroimaging findings of 5 patients with NF1 (4 females, age 6 to 29 years at last follow-up) and cerebellar anomalies. Cerebellar symptoms on neurological examination were mild or even not evident whereas learning disabilities were more or less pronounced in four patients. Two patients had cerebellar hypoplasia (diffusely enlarged cerebellar interfoliar spaces) and three cerebellar dysmorphias involving mainly one cerebellar hemisphere. In NF1, malformative cerebellar anomalies are rare (estimated prevalence of about 1%), but most likely underestimated and easily overlooked, because physicians tend to focus on more prevalent, obvious, and well-known findings such as optic pathway gliomas, other tumors, and UBO. This kind of cerebellar anomaly in NF1 has most likely a malformative origin, but the exact pathogenesis is unknown. The individual clinical significance is difficult to determine. We suggest that cerebellar anomalies should be systematically evaluated in neuroimaging studies of NF1 patients.

Cerebellar mutism--report of four cases.

Science.gov (United States)

Ozimek, A; Richter, S; Hein-Kropp, C; Schoch, B; Gorissen, B; Kaiser, O; Gizewski, E; Ziegler, W; Timmann, D

2004-08-01

The aim of the present study was to investigate the manifestations of mutism after surgery in children with cerebellar tumors. Speech impairment following cerebellar mutism in children was investigated based on standardized acoustic speech parameters and perceptual criteria. Mutistic and non-mutistic children after cerebellar surgery as well as orthopedic controls were tested pre-and postoperatively. Speech impairment was compared with the localization of cerebellar lesions (i. e. affected lobules and nuclei). Whereas both control groups showed no abnormalities in speech and behavior, the mutistic group could be divided into children with dysarthria in post mutistic phase and children with mainly behavioral disturbances. In the mutistic children involvement of dentate and fastigial nuclei tended to be more frequent and extended than in the nonmutistic cerebellar children. Cerebellar mutism is a complex phenomenon of at least two types. Dysarthric symptoms during resolution of mutism support the anarthria hypothesis, while mainly behavioral changes suggest an explanation independent from speech motor control.

Complex partial seizures: cerebellar metabolism

Energy Technology Data Exchange (ETDEWEB)

Theodore, W.H.; Fishbein, D.; Deitz, M.; Baldwin, P.

1987-07-01

We used positron emission tomography (PET) with (/sup 18/F)2-deoxyglucose to study cerebellar glucose metabolism (LCMRglu) and the effect of phenytoin (PHT) in 42 patients with complex partial seizures (CPS), and 12 normal controls. Mean +/- SD patient LCMRglu was 6.9 +/- 1.8 mg glucose/100 g/min (left = right), significantly lower than control values of 8.5 +/- 1.8 (left, p less than 0.006), and 8.3 +/- 1.6 (right, p less than 0.02). Only four patients had cerebellar atrophy on CT/MRI; cerebellar LCMRglu in these was 5.5 +/- 1.5 (p = 0.054 vs. total patient sample). Patients with unilateral temporal hypometabolism or EEG foci did not have lateralized cerebellar hypometabolism. Patients receiving phenytoin (PHT) at the time of scan and patients with less than 5 years total PHT exposure had lower LCMRglu, but the differences were not significant. There were weak inverse correlations between PHT level and cerebellar LCMRglu in patients receiving PHT (r = -0.36; 0.05 less than p less than 0.1), as well as between length of illness and LCMRglu (r = -0.22; 0.05 less than p less than 0.1). Patients with complex partial seizures have cerebellar hypometabolism that is bilateral and due only in part to the effect of PHT.

Basolateral amygdala inactivation impairs learning-induced long-term potentiation in the cerebellar cortex.

Directory of Open Access Journals (Sweden)

Lan Zhu

Full Text Available Learning to fear dangerous situations requires the participation of basolateral amygdala (BLA. In the present study, we provide evidence that BLA is necessary for the synaptic strengthening occurring during memory formation in the cerebellum in rats. In the cerebellar vermis the parallel fibers (PF to Purkinje cell (PC synapse is potentiated one day following fear learning. Pretraining BLA inactivation impaired such a learning-induced long-term potentiation (LTP. Similarly, cerebellar LTP is affected when BLA is blocked shortly, but not 6 h, after training. The latter result shows that the effects of BLA inactivation on cerebellar plasticity, when present, are specifically related to memory processes and not due to an interference with sensory or motor functions. These data indicate that fear memory induces cerebellar LTP provided that a heterosynaptic input coming from BLA sets the proper local conditions. Therefore, in the cerebellum, learning-induced plasticity is a heterosynaptic phenomenon that requires inputs from other regions. Studies employing the electrically-induced LTP in order to clarify the cellular mechanisms of memory should therefore take into account the inputs arriving from other brain sites, considering them as integrative units. Based on previous and the present findings, we proposed that BLA enables learning-related plasticity to be formed in the cerebellum in order to respond appropriately to new stimuli or situations.

Abnormalities of cerebellar foliation and fissuration: classification, neurogenetics and clinicoradiological correlations

Energy Technology Data Exchange (ETDEWEB)

Demaerel, P. [University Hospital, Department of Radiology, Herestraat 49, 3000 Leuven (Belgium)

2002-08-01

Several genes have been found to influence the different cells involved in the processes of foliation and fissuration in the mouse and rat cerebellum. In the light of these new concepts and on the basis of the imaging findings in 42 patients, a classification is proposed for abnormalities of foliation and fissuration. On the basis of recent genetic and experimental evidence on mechanisms which control the origin of the cerebellum, it is suggested that abnormalities of foliation and fissuration form a single group, with a spectrum of severity. Some patients have only abnormal fissuration of the anterior lobe (type 1a) and others additional dysplasia of the anterior and part of the posterior lobe (type 1b). Extension of abnormalities into the hemispheres is often seen in the latter group. A second group has vermian and hemisphere abnormalities (type 2). In addition to the malformation of the anterior lobe of the vermis, three different hemispheric lesions can be seen in this group: cortical dysgenesis, hypertrophy of the cerebellar cortex, and malorientation of the folia. The mild abnormalities (type 1a) can be considered an incidental observation without clinical relevance. The moderate and severe cerebellar anomalies (type 1b and 2) are always associated with cerebellar symptoms and/or signs. (orig.)

Abnormalities of cerebellar foliation and fissuration: classification, neurogenetics and clinicoradiological correlations

International Nuclear Information System (INIS)

Demaerel, P.

2002-01-01

Several genes have been found to influence the different cells involved in the processes of foliation and fissuration in the mouse and rat cerebellum. In the light of these new concepts and on the basis of the imaging findings in 42 patients, a classification is proposed for abnormalities of foliation and fissuration. On the basis of recent genetic and experimental evidence on mechanisms which control the origin of the cerebellum, it is suggested that abnormalities of foliation and fissuration form a single group, with a spectrum of severity. Some patients have only abnormal fissuration of the anterior lobe (type 1a) and others additional dysplasia of the anterior and part of the posterior lobe (type 1b). Extension of abnormalities into the hemispheres is often seen in the latter group. A second group has vermian and hemisphere abnormalities (type 2). In addition to the malformation of the anterior lobe of the vermis, three different hemispheric lesions can be seen in this group: cortical dysgenesis, hypertrophy of the cerebellar cortex, and malorientation of the folia. The mild abnormalities (type 1a) can be considered an incidental observation without clinical relevance. The moderate and severe cerebellar anomalies (type 1b and 2) are always associated with cerebellar symptoms and/or signs. (orig.)

Uptake and metabolism of L-[3H]glutamate and L-[3H]glutamine in adult rat cerebellar slices

International Nuclear Information System (INIS)

de Barry, J.; Vincendon, G.; Gombos, G.

1983-01-01

Using very low concentrations (1 mumol range) of L-2-3-[ 3 H]glutamate, ( 3 H-Glu) or L-2-3-[ 3 H]glutamine ( 3 H-Gln), the authors have previously shown by autoradiography that these amino acids were preferentially taken up in the molecular layer of the cerebellar cortex. Furthermore, the accumulation of 3 H-Glu was essentially glial in these conditions. Uptake and metabolism of either ( 3 H-Glu) or ( 3 H-Gln) were studied in adult rat cerebellar slices. Both amino acids were rapidly converted into other metabolic compounds: after seven minutes of incubation in the presence of exogenous 3 H-Glu, 70% of the tissue accumulated radioactivity was found to be in compounds other than glutamate. The main metabolites were Gln (42%), alpha-ketoglutarate (25%) and GABA (1,4%). In the presence of exogenous 3 H-Gln the rate of metabolism was slightly slower (50% after seven minutes of incubation) and the metabolites were also Glu (29%), alpha-ketoglutarate (15%) and GABA (5%). Using depolarizing conditions (56 mM KCl) with either exogenous 3 H-Glu or 3 H-Gln, the radioactivity was preferentially accumulated in glutamate compared to control. From these results we conclude: i) there are two cellular compartments for the neurotransmission-glutamate-glutamine cycle; one is glial, the other neuronal; ii) these two cellular compartments contain both Gln and Glu; iii) transmitter glutamate is always in equilibrium with the so-called ''metabolic'' pool of glutamate; iv) the regulation of the glutamate-glutamine cycle occurs at least at two different levels: the uptake of glutamate and the enzymatic activity of the neuronal glutaminase

The Cerebellar-Cerebral Microstructure Is Disrupted at Multiple Sites in Very Preterm Infants with Cerebellar Haemorrhage.

Science.gov (United States)

Neubauer, Vera; Djurdjevic, Tanja; Griesmaier, Elke; Biermayr, Marlene; Gizewski, Elke Ruth; Kiechl-Kohlendorfer, Ursula

2018-01-01

Recent advances in magnetic resonance imaging (MRI) techniques have prompted reconsideration of the anatomical correlates of adverse outcomes in preterm infants. The importance of the contribution made by the cerebellum is now increasingly appreciated. The effect of cerebellar haemorrhage (CBH) on the microstructure of the cerebellar-cerebral circuit is largely unexplored. To investigate the effect of CBH on the microstructure of cerebellar-cerebral connections in preterm infants aged microstructure (fractional anisotropy [FA] and apparent diffusion coefficient) were quantified in 5 vulnerable regions (the centrum semiovale, posterior limb of the internal capsule, corpus callosum, and superior and middle cerebellar peduncles). Group differences between infants with CBH and infants without CBH were assessed. There were 267 infants included in the study. Infants with CBH (isolated and combined) had significantly lower FA values in all regions investigated. Infants with isolated CBH showed lower FA in the middle and superior cerebellar peduncles and in the posterior limb of the internal capsule. This study provides evidence that CBH causes alterations in localised and remote WM pathways in the developing brain. The disruption of the cerebellar-cerebral microstructure at multiple sites adds further support for the concept of developmental diaschisis, which is propagated as an explanation for the consequences of early cerebellar injury on cognitive and affective domains. © 2017 S. Karger AG, Basel.

Characterization of beta-adrenergic receptors in synaptic membranes from rat cerebral cortex and cerebellum

International Nuclear Information System (INIS)

Lautens, L.

1986-01-01

Beta-adrenergic receptor ligand binding sites have been characterized in synaptic membranes from rat cerebral cortex and cerebellum using radioligand binding techniques. The equilibrium and kinetic properties of binding were assessed. The binding sites were non-interacting and exhibited two states of agonist binding which were sensitive to guanyl nucleotide. Synaptic membranes from cerebral cortex contained an equal number of beta 1 - and beta 2 -receptors; membranes from cerebellum possessed more beta 2 -than beta 1 -receptors. Photoaffinity labeling experiments revealed two different beta-adrenergic receptor polypeptides, R 1 and R 2 (and possibly a third, R 3 ) in synaptic membranes. The ratios of incorporation of photoaffinity label into R 1 : 2 were approximately 1:1 (cerebral cortex) and 5:1 (cerebellum). Photoaffinity labeling of R 1 and R 2 was inhibited equally well by both agonist and antagonist in synaptic membranes from cerebellum; whereas agonist was a less potent inhibitor in membranes from cerebral cortex. Both subtypes of beta-adrenergic receptors exhibited the same apparent molecular weight in synaptic membranes from cerebral cortex. The beta-adrenergic receptors in synaptic membranes from cerebral cortex and cerebellum were glycoproteins which exhibited the same apparent molecular weight after exposure to endoglycosidase F. The partial proteolytic digest maps of photoaffinity labeled beta-adrenergic receptors from rat cerebral cortex, cerebellum, lung and heart were compared

[Memory transfer in cerebellar motor learning].

Science.gov (United States)

Nagao, Soichi

2012-01-01

Most of our motor skills are acquired through learning. Experiments of gain adaptation of ocular reflexes have consistently suggested that the memory of adaptation is initially formed in the cerebellar cortex, and is transferred to the cerebellar (vestibular) nuclei for consolidation to long-term memory after repetitions of training. We have recently developed a new system to evaluate the motor learning in human subjects using prism adaptation of hand reaching movement, by referring to the prism adaptation of dart throwing of Martin et al. (1996). In our system, the subject views the small target presented in the touch-panel screen, and touches it with his/her finger without direct visual feedback. After 15-30 trials of touching wearing prisms, an adaptation occurs in healthy subjects: they became able to touch the target correctly. Meanwhile, such an adaptation was impaired in patients of cerebellar disease. We have proposed a model of human prism adaptation that the memory of adaptation is initially encoded in the cerebellar cortex, and is later transferred to the cerebellar nuclei after repetitions of training. The memory in the cerebellar cortex may be formed and extinguished independently of the memory maintained in the cerebellar nuclei, and these two memories work cooperatively.

GABA-B receptor activation and conflict behavior

International Nuclear Information System (INIS)

Ketelaars, C.E.J.; Bollen, E.L.; Rigter, H.; Bruinvels, J.

1988-01-01

Baclofen and oxazepam enhance extinction of conflict behavior in the Geller-Seifter test while baclofen and diazepam release punished behavior in Vogel's conflict test. In order to investigate the possibility that the effect of the selective GABA-B receptor agonist baclofen is mediated indirectly via the GABA-A/benzodiazepine receptor complex, the effect of pretreatment of rats with baclofen on [ 3 H]-diazepam binding to washed and unwashed cortical and cerebellar membranes of rats has been studied. Baclofen pretreatment increase Bmax in washed cerebellar membranes when bicuculline was present in the incubation mixture. No effect was seen in cortical membranes. The present results render it unlikely that the effect of baclofen on extinction of conflict behavior and punished drinking is mediated via the GABA-A/benzodiazepine receptor complex. 50 references, 1 figure, 4 tables

Influence of kaempferol, a flavonoid compound, on membrane-bound ATPases in streptozotocin-induced diabetic rats.

Science.gov (United States)

Al-Numair, Khalid S; Veeramani, Chinnadurai; Alsaif, Mohammed A; Chandramohan, Govindasamy

2015-01-01

Kaempferol is a flavonoid found in many edible plants (e.g. tea, cabbage, beans, tomato, strawberries, and grapes) and in plants or botanical products commonly used in traditional medicine. Numerous preclinical studies have shown that kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, anticancer, cardioprotective, neuroprotective, and antidiabetic activities. The present study investigates the effect of kaempferol on membrane-bound ATPases in erythrocytes and in liver, kidney, and heart of streptozotocin (STZ)-induced diabetic rats. Diabetes was induced into adult male albino rats of the Wistar strain, by intraperitoneal administration of STZ (40 mg/kg body weight (BW)). Kaempferol (100 mg/kg BW) or glibenclamide (600 µg/kg BW) was administered orally once daily for 45 d to normal and STZ-induced diabetic rats. The effects of kaempferol on membrane-bound ATPases (total ATPase, Na(+)/K(+)-ATPase, Ca(2+)-ATPase, and Mg(2+)-ATPase) activity in erythrocytes and in liver, kidney, and heart were determined. In our study, diabetic rats had significantly (p kaempferol (100 mg/kg BW) or glibenclamide (600 µg/kg BW) for a period of 45 d resulted in significant (p kaempferol has the potential to restore deranged activity of membrane-bound ATPases in STZ-induced diabetic rats. Further detailed investigation is necessary to discover kaempferol's action mechanism.

Solubilization of rat kidney plasma membrane proteins associated with 3H-aldosterone

International Nuclear Information System (INIS)

Ozegovic, B.; Dobrovic-Jenik, D.; Milkovic, S.

1988-01-01

The treatment of rat kidney plasma membranes with sodium dodecyl sulphate (SDS) did not essentially affect the ability of the membranes for 3 H-aldosterone binding as compared with the intact plasma membranes (Ozegovic et al., 1977). A gel filtration of 3 H-aldosterone - kidney plasma membranes complex on Sepharose 6B yielded 2 protein and 2 3 H-aldosterone peaks. The proteins which were eluted in the first peak were associated with the first 3 H-aldosterone peak while the second 3 H-aldosterone peak was eluted with Ve corresponding to Ve of free 3 H-aldosterone. Spironolactone, a competitive antagonist of aldosterone, prevented the binding of 3 H-aldosterone to the membrane proteins. The results demonstrated a high affinity of the kidney plasma membranes solubilized with SDS and a specificity of aldosterone binding to the plasma membrane proteins of higher molecular mass. (author)

Vivosorb as a barrier membrane in rat mandibular defects. An evaluation with transversal microradiography.

NARCIS (Netherlands)

Hoogeveen, E.J.; Gielkens, P.F.; Schortinghuis, J.; Ruben, J.L.; Huysmans, M.C.D.N.J.M.; Stegenga, B.

2009-01-01

Vivosorb is a new degradable membrane composed of poly(DL-lactide-epsilon-caprolactone) (PDLLCL). The aim of this study was to appraise its performance in guided bone regeneration procedures. In 192 rats a 5.0 mm defect was drilled in the mandibular angle. The defects were covered with a membrane

Counseling a Patient with the Antenatal Diagnosis of a Cerebellar Abnormality and a Pharyngeal Cyst

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Lissa Francois

2014-11-01

Full Text Available Introduction - Prenatal counseling with regards to the prognosis of a cerebellar abnormality is hindered not only by the diverse clinical presentations but also by the presence of subtle findings. We present a case of a distinct combination of asymmetric cerebellar hypoplasia secondary to an anterior meningoencephalocele through a clival defect that caused a severe airway obstruction in the newborn. Case Description - A 21-year-old gravida 4 para 0 mother with a dichorionic–diamniotic twin pregnancy was referred for a second trimester sonographic survey. An asymmetric cerebellar hypoplasia, mega cisterna magna, and a pharyngeal cystic mass were noted on twin A. Magnetic resonance imaging report confirmed posterior fossa abnormalities and shed no light on the differential diagnosis of the cystic mass. The pregnancy ended by Cesarean delivery at 32 weeksʼ gestation after a preterm premature rupture of the membranes. Twin A had a severe airway obstruction. Postnatal evaluation confirmed a midline anterior meningoencephalocele through a defect in the clivus. The microarray chromosomal analysis demonstrated a 5q15 variant with uncertain clinical significance. Conclusion - Antenatal recognition of the unique combination of a cerebellar hypoplasia with a pharyngeal cyst can impact the prenatal counseling as well as neonatal management.

Clinicopathological features of cerebellar lipidized medulloblastoma: a case report and review of literatures

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LIU Li-yan

2012-06-01

Full Text Available Objective To explore the clinicopathological features of cerebellar lipidized medulloblastoma. Methods The clinical manifestations， neuroimaging, histopathological and immunohistochemical features were analysed in one case of lipidized medulloblastoma in the cerebellar vermis. Related literatures were reviewed. Results A 26-year-old man presented with intermittent headache，accompanied by dizziness, nausea and vomiting. The magnetic resonance imaging (MRI demonstrated a mass located the cerebellar vermis convex to the fourth ventricle. The tumor with well-demarcated boundary was homogeneous hypointense on T1 weighted and heterogeneous hyperintense on T2 weighted images, and enhanced brilliantly and homogenously on contrast. The patient subsequently underwent gross total mass resection. Microscopically，there was diffuse infiltration by high cellularity of tumor cells. The cytoplasm were thin eosinophilic to amphophilic. The neoplastic cells showed round to oval hyperchromatic nuclei with a delicately stippled chromatin and occasional conspicuous nucleoli and numerous mitotic figures were also present. Thin-wall vascular proliferation was detected. Lipid-laden cells were focally distributed in tumor tissue. On immunohistochemical examination, the neoplasm was reactive for CD56 and synaptophysin (Syn, focally positive for neurofilament protein (NF, weakly positive for oligodendrocyte lineage transcription factor 2 (Olig-2, and negtive for nestin, neuronal nuclei (NeuN, S-100 protein (S-100, glial fibrillary acidic protein (GFAP and epithelial membrane antigen (EMA. TP53 protein was over expressed in 10% of tumor cells. Ki-67 antigen labeling index were about 40% . Conclusion Cerebellar lipidized medulloblastoma is rare. Neuroimaging showed space occupying lesion in cerebellar vermis. Histologically, the tumor cells were consisted of monotonous, round cells with focal accumulations of lipidized cells. The differential diagnosis include

Nicotine-like effects of the neonicotinoid insecticides acetamiprid and imidacloprid on cerebellar neurons from neonatal rats.

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Junko Kimura-Kuroda

Full Text Available Acetamiprid (ACE and imidacloprid (IMI belong to a new, widely used class of pesticide, the neonicotinoids. With similar chemical structures to nicotine, neonicotinoids also share agonist activity at nicotinic acetylcholine receptors (nAChRs. Although their toxicities against insects are well established, their precise effects on mammalian nAChRs remain to be elucidated. Because of the importance of nAChRs for mammalian brain function, especially brain development, detailed investigation of the neonicotinoids is needed to protect the health of human children. We aimed to determine the effects of neonicotinoids on the nAChRs of developing mammalian neurons and compare their effects with nicotine, a neurotoxin of brain development.Primary cultures of cerebellar neurons from neonatal rats allow for examinations of the developmental neurotoxicity of chemicals because the various stages of neurodevelopment-including proliferation, migration, differentiation, and morphological and functional maturation-can be observed in vitro. Using these cultures, an excitatory Ca(2+-influx assay was employed as an indicator of neural physiological activity. Significant excitatory Ca(2+ influxes were evoked by ACE, IMI, and nicotine at concentrations greater than 1 µM in small neurons in cerebellar cultures that expressed the mRNA of the α3, α4, and α7 nAChR subunits. The firing patterns, proportion of excited neurons, and peak excitatory Ca(2+ influxes induced by ACE and IMI showed differences from those induced by nicotine. However, ACE and IMI had greater effects on mammalian neurons than those previously reported in binding assay studies. Furthermore, the effects of the neonicotinoids were significantly inhibited by the nAChR antagonists mecamylamine, α-bungarotoxin, and dihydro-β-erythroidine.This study is the first to show that ACE, IMI, and nicotine exert similar excitatory effects on mammalian nAChRs at concentrations greater than 1 µM. Therefore, the

Localization of high affinity [3H]glycine transport sites in the cerebellar cortex

International Nuclear Information System (INIS)

Wilkin, G.P.; Csillag, A.; Balazs, R.; Kingsbury, A.E.; Wilson, J.E.; Johnson, A.L.

1981-01-01

A study was made of [ 3 H ]glycine uptake sites in a preparation greatly enriched in large pieces of the cerebellar glomeruli (glomerulus particles) and in morphologically well preserved slices of rat cerebellum. Electron microscopic autoradiography revealed that of the neurones in the cerebellar cortex only Golgi cells transported [ 3 H]glycine at the low concentration used. Glial cells also took up [ 3 H]glycine but to a lesser extent than the Golgi neurons. It was also confirmed that under comparable conditions Golgi cells transport [ 3 H]GABA. Kinetic studies utilizing the Golgi axon terminal-containing glomerulus particles showed that glycine is a weak non-competitive inhibitor of [ 3 H]GABA uptake (Ksub(i) over 600 μM vs the Ksub(t) of about 20 μM) and that GABA is an even weaker inhibitor of [ 3 H]glycine uptake. (Auth.)

Olopatadine Inhibits Exocytosis in Rat Peritoneal Mast Cells by Counteracting Membrane Surface Deformation

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Asuka Baba

2015-01-01

Full Text Available Backgroud/Aims: Besides its anti-allergic properties as a histamine receptor antagonist, olopatadine stabilizes mast cells by inhibiting the release of chemokines. Since olopatadine bears amphiphilic features and is preferentially partitioned into the lipid bilayers of the plasma membrane, it would induce some morphological changes in mast cells and thus affect the process of exocytosis. Methods: Employing the standard patch-clamp whole-cell recording technique, we examined the effects of olopatadine and other anti-allergic drugs on the membrane capacitance (Cm in rat peritoneal mast cells during exocytosis. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. Results: Low concentrations of olopatadine (1 or 10 µM did not significantly affect the GTP-γ-S-induced increase in the Cm. However, 100 µM and 1 mM olopatadine almost totally suppressed the increase in the Cm. Additionally, these doses completely washed out the trapping of the dye on the cell surface, indicating that olopatadine counteracted the membrane surface deformation induced by exocytosis. As shown by electron microscopy, olopatadine generated inward membrane bending in mast cells. Conclusion: This study provides electrophysiological evidence for the first time that olopatadine dose-dependently inhibits the process of exocytosis in rat peritoneal mast cells. Such mast cell stabilizing properties of olopatadine may be attributed to its counteracting effects on the plasma membrane deformation in degranulating mast cells.

A toolbox to visually explore cerebellar shape changes in cerebellar disease and dysfunction

Science.gov (United States)

Abulnaga, S. Mazdak; Yang, Zhen; Carass, Aaron; Kansal, Kalyani; Jedynak, Bruno M.; Onyike, Chiadi U.; Ying, Sarah H.; Prince, Jerry L.

2016-03-01

The cerebellum plays an important role in motor control and is also involved in cognitive processes. Cerebellar function is specialized by location, although the exact topographic functional relationship is not fully understood. The spinocerebellar ataxias are a group of neurodegenerative diseases that cause regional atrophy in the cerebellum, yielding distinct motor and cognitive problems. The ability to study the region-specific atrophy patterns can provide insight into the problem of relating cerebellar function to location. In an effort to study these structural change patterns, we developed a toolbox in MATLAB to provide researchers a unique way to visually explore the correlation between cerebellar lobule shape changes and function loss, with a rich set of visualization and analysis modules. In this paper, we outline the functions and highlight the utility of the toolbox. The toolbox takes as input landmark shape representations of subjects' cerebellar substructures. A principal component analysis is used for dimension reduction. Following this, a linear discriminant analysis and a regression analysis can be performed to find the discriminant direction associated with a specific disease type, or the regression line of a specific functional measure can be generated. The characteristic structural change pattern of a disease type or of a functional score is visualized by sampling points on the discriminant or regression line. The sampled points are used to reconstruct synthetic cerebellar lobule shapes. We showed a few case studies highlighting the utility of the toolbox and we compare the analysis results with the literature.

A toolbox to visually explore cerebellar shape changes in cerebellar disease and dysfunction.

Science.gov (United States)

Abulnaga, S Mazdak; Yang, Zhen; Carass, Aaron; Kansal, Kalyani; Jedynak, Bruno M; Onyike, Chiadi U; Ying, Sarah H; Prince, Jerry L

2016-02-27

The cerebellum plays an important role in motor control and is also involved in cognitive processes. Cerebellar function is specialized by location, although the exact topographic functional relationship is not fully understood. The spinocerebellar ataxias are a group of neurodegenerative diseases that cause regional atrophy in the cerebellum, yielding distinct motor and cognitive problems. The ability to study the region-specific atrophy patterns can provide insight into the problem of relating cerebellar function to location. In an effort to study these structural change patterns, we developed a toolbox in MATLAB to provide researchers a unique way to visually explore the correlation between cerebellar lobule shape changes and function loss, with a rich set of visualization and analysis modules. In this paper, we outline the functions and highlight the utility of the toolbox. The toolbox takes as input landmark shape representations of subjects' cerebellar substructures. A principal component analysis is used for dimension reduction. Following this, a linear discriminant analysis and a regression analysis can be performed to find the discriminant direction associated with a specific disease type, or the regression line of a specific functional measure can be generated. The characteristic structural change pattern of a disease type or of a functional score is visualized by sampling points on the discriminant or regression line. The sampled points are used to reconstruct synthetic cerebellar lobule shapes. We showed a few case studies highlighting the utility of the toolbox and we compare the analysis results with the literature.

Switch in the expression of mGlu1 and mGlu5 metabotropic glutamate receptors in the cerebellum of mice developing experimental autoimmune encephalomyelitis and in autoptic cerebellar samples from patients with multiple sclerosis

NARCIS (Netherlands)

Fazio, F.; Notartomaso, S.; Aronica, E.; Storto, M.; Battaglia, G.; Vieira, E.; Gatti, S.; Bruno, V.; Biagioni, F.; Gradini, R.; Nicoletti, F.; Di Marco, R.

2008-01-01

Recent evidence suggests that changes in the expression of membrane receptors/ion channels in cerebellar Purkinje cells contribute to the onset of cerebellar motor symptoms in patients with multiple sclerosis (MS). We examined the expression of group-I metabotropic glutamate receptors (mGlu1 and

The bihemispheric posterior inferior cerebellar artery

International Nuclear Information System (INIS)

Cullen, Sean P.; Ozanne, Augustin; Alvarez, Hortensia; Lasjaunias, Pierre

2005-01-01

Rarely, a solitary posterior inferior cerebellar artery (PICA) will supply both cerebellar hemispheres. We report four cases of this variant. We present a retrospective review of clinical information and imaging of patients undergoing angiography at our institution to identify patients with a bihemispheric PICA. There were four patients: three males and one female. One patient presented with a ruptured arteriovenous malformation, and one with a ruptured aneurysm. Two patients had normal angiograms. The bihemispheric PICA was an incidental finding in all cases. The bihemispheric vessel arose from the dominant left vertebral artery, and the contralateral posterior inferior cerebellar artery was absent or hypoplastic. In all cases, contralateral cerebellar supply arose from a continuation of the ipsilateral PICA distal to the choroidal point and which crossed the midline dorsal to the vermis. We conclude that the PICA may supply both cerebellar hemispheres. This rare anatomic variant should be considered when evaluating patients with posterior fossa neurovascular disease. (orig.)

Massive cerebellar infarction: a neurosurgical approach

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Salazar Luis Rafael Moscote

2015-12-01

Full Text Available Cerebellar infarction is a challenge for the neurosurgeon. The rapid recognition will crucial to avoid devastating consequences. The massive cerebellar infarction has pseudotumoral behavior, should affect at least one third of the volume of the cerebellum. The irrigation of the cerebellum presents anatomical diversity, favoring the appearance of atypical infarcts. The neurosurgical management is critical for massive cerebellar infarction. We present a review of the literature.

Cerebellar transcranial static magnetic field stimulation transiently reduces cerebellar brain inhibition.

Science.gov (United States)

Matsugi, Akiyoshi; Okada, Y

The aim of this study was to investigate whether transcranial static magnetic field stimulation (tSMS) delivered using a compact cylindrical NdFeB magnet over the cerebellum modulates the excitability of the cerebellum and contralateral primary motor cortex, as measured using cerebellar brain inhibition (CBI), motor evoked potentials (MEPs), and resting motor threshold (rMT). These parameters were measured before tSMS or sham stimulation and immediately, 5 minutes and 10 minutes after stimulation. There were no significant changes in CBI, MEPs or rMT over time in the sham stimulation condition, and no changes in MEPs or rMT in the tSMS condition. However, CBI was significantly decreased immediately after tSMS as compared to that before and 5 minutes after tSMS. Our results suggest that tSMS delivered to the cerebellar hemisphere transiently reduces cerebellar inhibitory output but does not affect the excitability of the contralateral motor cortex.

Even a Chronic Mild Hyperglycemia Affects Membrane Fluidity and Lipoperoxidation in Placental Mitochondria in Wistar Rats

Science.gov (United States)

Figueroa-García, María del Consuelo; Espinosa-García, María Teresa; Martinez-Montes, Federico; Palomar-Morales, Martín; Mejía-Zepeda, Ricardo

2015-01-01

It is known the deleterious effects of diabetes on embryos, but the effects of diabetes on placenta and its mitochondria are still not well known. In this work we generated a mild hyperglycemia model in female wistar rats by intraperitoneal injection of streptozotocin in 48 hours-old rats. The sexual maturity onset of the female rats was delayed around 6–7 weeks and at 16 weeks-old they were mated, and sacrificed at day 19th of pregnancy. In placental total tissue and isolated mitochondria, the fatty acids composition was analyzed by gas chromatography, and lipoperoxidation was measured by thiobarbituric acid reactive substances. Membrane fluidity in mitochondria was measured with the excimer forming probe dipyrenylpropane and mitochondrial function was measured with a Clark-type electrode. The results show that even a chronic mild hyperglycemia increases lipoperoxidation and decreases mitochondrial function in placenta. Simultaneously, placental fatty acids metabolism in total tissue is modified but in a different way than in placental mitochondria. Whereas the chronic mild hyperglycemia induced a decrease in unsaturated to saturated fatty acids ratio (U/S) in placental total tissue, the ratio increased in placental mitochondria. The measurements of membrane fluidity showed that fluidity of placenta mitochondrial membranes increased with hyperglycemia, showing consistency with the fatty acids composition through the U/S index. The thermotropic characteristics of mitochondrial membranes were changed, showing lower transition temperature and activation energies. All of these data together demonstrate that even a chronic mild hyperglycemia during pregnancy of early reproductive Wistar rats, generates an increment of lipoperoxidation, an increase of placental mitochondrial membrane fluidity apparently derived from changes in fatty acids composition and consequently, mitochondrial malfunction. PMID:26630275

Sleep disorders in cerebellar ataxias

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José L. Pedroso

2011-04-01

Full Text Available Cerebellar ataxias comprise a wide range of etiologies leading to central nervous system-related motor and non-motor symptoms. Recently, a large body of evidence has demonstrated a high frequency of non-motor manifestations in cerebellar ataxias, specially in autosomal dominant spinocerebellar ataxias (SCA. Among these non-motor dysfunctions, sleep disorders have been recognized, although still under or even misdiagnosed. In this review, we highlight the main sleep disorders related to cerebellar ataxias focusing on REM sleep behavior disorder (RBD, restless legs syndrome (RLS, periodic limb movement in sleep (PLMS, excessive daytime sleepiness (EDS, insomnia and sleep apnea.

Acetylcholinesterase potentiates [3H]fluorowillardiine and [3H]AMPA binding to rat cortical membranes

International Nuclear Information System (INIS)

Olivera, S.; Rodriguez-Ithurralde, D.; Henley, J.M.

1999-01-01

In addition to its action at cholinergic synapses acetylcholinesterase (AChE) has been proposed to modulate neuronal activity by mechanisms unrelated to the hydrolysis of acetylcholine. We have investigated the effects of AChE on the binding of the specific AMPA receptor agonists (S)-[ 3 H]5-fluorowillardiine ([ 3 H]FW) and [ 3 H]AMPA to rat cortical membranes. Pretreatment of membranes with AChE causes a dose-dependent increase in the binding of both radiolabelled agonists with a maximal increase to ∼60% above control. This increase is completely blocked by the specific AChE inhibitors propidium, physostigmine, DFP and BW 284C51. AChE pretreatment had no effect on [ 3 H]kainate binding. [ 3 H]FW binding to membranes from young (15-day-old) rats is four orders of magnitude more sensitive to AChE modulation than membranes from adult rats (EC 50 values of 4x10 -5 and 0.1 unit/ml, respectively) although the total percentage increase in binding is similar. Furthermore, the AChE-induced potentiation of [ 3 H]FW binding is Ca 2+ - and temperature-dependent suggesting an enzymatic action for AChE in this system. Saturation binding experiments with [ 3 H]FW to adult membranes reveal high and low affinity binding sites and demonstrate that the main action of AChE is to increase the B max of both sites. These findings suggest that modulation of AMPA receptors could provide a molecular mechanism of action for the previously reported effects of AChE in synapse formation, synaptic plasticity and neurodegeneration. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor

NARCIS (Netherlands)

Buijink, A. W. G.; Broersma, M.; van der Stouwe, A. M. M.; van Wingen, G. A.; Groot, P. F. C.; Speelman, J. D.; Maurits, N. M.; van Rootselaar, A. F.

2015-01-01

Cerebellar circuits are hypothesized to play a central role in the pathogenesis of essential tremor. Rhythmic finger tapping is known to strongly engage the cerebellar motor circuitry. We characterize cerebellar and, more specifically, dentate nucleus function, and neural correlates of cerebellar

Effects of a chitosan membrane coated with polylactic and polyglycolic acid on bone regeneration in a rat calvarial defect

International Nuclear Information System (INIS)

Jung, Ui-Won; Song, Kun-Young; Kim, Chang-Sung; Lee, Yong-Keun; Cho, Kyoo-Sung; Kim, Chong-Kwan; Choi, Seong-Ho

2007-01-01

The purpose of this study was to evaluate the effects of a chitosan membrane coated with polylactic and polyglycolic acid (PLGA) on bone regeneration in a rat calvarial defect. Surgical implantation of chitosan membranes resulted in enhanced local bone formation at both 2 and 8 weeks. In conclusion, the chitosan membrane coated with PLGA had a significant potential to induce bone formation in the rat calvarial defect model. Within the selected PLGA dose range and observation intervals, there appeared to be no meaningful differences in bone formation

Vivosorb (R) as a barrier membrane in rat mandibular defects. An evaluation with transversal microradiography

NARCIS (Netherlands)

Hoogeveen, E. J.; Gielkens, P. F. M.; Schortinghuis, J.; Ruben, J. L.; Huysmans, M-C D. N. J. M.; Stegenga, B.

Vivosorb(R) is a new degradable membrane composed of poly(DL-lactide-epsilon-caprolactone) (PDLLCL). The aim of this study was to appraise its performance in guided bone regeneration procedures. In 192 rats a 5.0 mm defect was drilled in the mandibular angle. The defects were covered with a membrane

Distributed Cerebellar Motor Learning; a Spike-Timing-Dependent Plasticity Model

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Niceto Rafael Luque

2016-03-01

Full Text Available Deep cerebellar nuclei neurons receive both inhibitory (GABAergic synaptic currents from Purkinje cells (within the cerebellar cortex and excitatory (glutamatergic synaptic currents from mossy fibres. Those two deep cerebellar nucleus inputs are thought to be also adaptive, embedding interesting properties in the framework of accurate movements. We show that distributed spike-timing-dependent plasticity mechanisms (STDP located at different cerebellar sites (parallel fibres to Purkinje cells, mossy fibres to deep cerebellar nucleus cells, and Purkinje cells to deep cerebellar nucleus cells in close-loop simulations provide an explanation for the complex learning properties of the cerebellum in motor learning. Concretely, we propose a new mechanistic cerebellar spiking model. In this new model, deep cerebellar nuclei embed a dual functionality: deep cerebellar nuclei acting as a gain adaptation mechanism and as a facilitator for the slow memory consolidation at mossy fibres to deep cerebellar nucleus synapses. Equipping the cerebellum with excitatory (e-STDP and inhibitory (i-STDP mechanisms at deep cerebellar nuclei afferents allows the accommodation of synaptic memories that were formed at parallel fibres to Purkinje cells synapses and then transferred to mossy fibres to deep cerebellar nucleus synapses. These adaptive mechanisms also contribute to modulate the deep-cerebellar-nucleus-output firing rate (output gain modulation towards optimising its working range.

[Peroxide modification of membranes and isomorphic composition of cytochrome P-450 of rat liver microsomes during antioxidant deficiency].

Science.gov (United States)

Gubskiy, Iu I; Paramonova, G I; Boldeskul, A E; Primak, R G; Bogdanova, L A; Zadorina, O V; Litvinova, N V

1992-01-01

Lipid peroxidation (LPO), physico-chemical properties of the membranes and isoformic composition of microsomal cytochrome P-450 from the rat liver were studied under conditions of antioxidant insufficiency (AOI) which was modelled by exclusion of alpha-tocopherol from the animals' ration. An insignificant accumulation of microsomal diene conjugates and schiff bases against a sharp increase of the ability to the prooxidant stimulated LPO in vitro took place. A significant decrease of membrane lipid microviscosity and a change in surface properties of microsomal membranes of rats with AOI was determined. Absence of alpha-tocopherol in the ration was accompanied by a significant change in the content of separate isoforms of cytochrome P-450 exhibited in growth of a polypeptide with m. w. 54 kDa and the lowering of proteins with m. w. 48 and 50 kDa. Less intensive quenching of tryptophan fluorescence by acrylamide was also revealed, which testified to a lower accessibility of the quencher to membrane proteins or their fluorophore sites. Modification of lipid composition and of physicochemical properties of the rat liver membrane microsomes which was observed at AOI was significantly correlated by pretreatment with the antioxidant 4-methyl-2,6-ditretbutylphenol (ionol).

Association of canalicular membrane enzymes with bile acid micelles and lipid aggregates in human and rat bile.

Science.gov (United States)

Accatino, L; Pizarro, M; Solís, N; Koenig, C S

1995-01-18

This study was undertaken to gain insights into the characteristics of the polymolecular association between canalicular membrane enzymes, bile acids, cholesterol and phospholipids in bile and into the celular mechanisms whereby the enzymes are secreted into bile. With this purpose, we studied the distribution of bile acids, cholesterol, phospholipids, proteins and representative canalicular membrane enzymes (alkaline phosphatase, 5'-nucleotidase and gamma-glutamyl transpeptidase), which can be considered specific marker constituents, in bile fractions enriched in phospholipid-cholesterol lamellar structures (multilamellar and unilamellar vesicles) and bile acid-mixed micelles. These fractions were isolated by ultracentrifugation from human hepatic bile, normal rat bile and bile of rats treated with diosgenin, a steroid that induces a marked increase in biliary cholesterol secretion, and were characterized by density, lipid composition and transmission electron microscopy. These studies demonstrate that alkaline phosphatase, 5'-nucleotidase and gamma-glutamyl transpeptidase are secreted into both human and rat bile where they are preferentially associated with bile acid-mixed micelles, suggesting a role for bile acids in both release of these enzymes and lipids from the canalicular membrane and solubilization in bile. In addition, heterogeneous association of these enzymes with nonmicellar, lamellar structures in human and rat bile is consistent with the hypothesis that processes independent of the detergent effects of bile acids might also result in the release of specific intrinsic membrane proteins into bile.

Effects of human low and high density lipoproteins on the binding of rat intermediate density lipoproteins to rat liver membranes

International Nuclear Information System (INIS)

Brissette, L.; Nol, S.P.

1986-01-01

Upon incubation with rat liver membranes, radioiodinated rat intermediate density lipoproteins (IDL) interacted with at least two binding sites having a low and a high affinity as demonstrated by the curvilinear Scatchard plots obtained from the specific binding data. The purpose of our work was to identify the nature of these binding sites. Human low density lipoproteins (LDL), contain apolipoprotein B only, and human high density lipoproteins (HDL3), containing neither apolipoprotein B nor E, were both capable of decreasing the specific binding of rat 125 I-IDL. The Scatchard analysis clearly revealed that only the low affinity component was affected by the addition of these human lipoproteins. In fact, the low affinity binding component gradually decreased as the amount of human LDL or HDL3 increased in the binding assay. At a 200-fold excess of human LDL or HDL3, the low affinity binding was totally masked, and the Scatchard plot of the specific 125 I-IDL binding became linear. Only the high affinity binding component was left, enabling a precise measurement of its binding parameters. In a series of competitive displacement experiments in which the binding assay contained a 200-fold excess of human LDL or HDL3, only unlabeled rat IDL effectively displaced the binding of rat 125 I-IDL. We conclude that the low affinity binding of rat IDL to rat liver membranes is due to weak interactions with unspecified lipoprotein binding sites. The camouflage of these sites by human lipoproteins makes possible the study of IDL binding to the high affinity component which likely represents the combined effect of IDL binding to both the remnant and the LDL receptors

Laminin, a noncollagenous component of epithelial basement membranes synthesized by a rat yolk sac tumor

DEFF Research Database (Denmark)

Wewer, U; Albrechtsen, R; Ruoslahti, E

1981-01-01

Laminin, a glycoprotein antigenically similar or identical to a component of epithelial basement membranes, was identified as a major component of the abundant extracellular matrix synthesized by an experimentally induced rat yolk sac tumor. Immunocytochemical staining revealed laminin in cultured...... polypeptides with molecular weights of approximately 200,000 and 400,000. These comigrated with the polypeptides of mouse laminin isolated previously. The yolk sac tumor tissue grown in vivo contained laminin in the tumor cells and in the extracellular material as evidenced by immunofluorescence...... membranes in rat tissues in a manner indistinguishable from antilaminin. The presence of laminin in rat yolk sac cells, the presumed origin of our yolk sac tumor, was studied in some detail. Laminin was found to be present in normal cells of the visceral as well as the parietal yolk sac layer...

Cerebellar Degeneration

Science.gov (United States)

... FARA) National Ataxia Foundation (NAF) National Multiple Sclerosis Society See all related organizations Publications Degeneración cerebelosa Order NINDS Publications Definition Cerebellar degeneration is a process in which neurons ( ...

Lipoprotein receptors in copper-deficient rats: in vitro binding of high-density lipoprotein subfractions to liver membranes

International Nuclear Information System (INIS)

Hassel, C.A.

1986-01-01

Three studies were conducted to determine whether the elevated plasma and HDL cholesterol levels observed in copper-deficient rats could be explained by the interaction of 125 I-HDL subfractions with liver membrane preparations in vitro. Rats from all studies were randomly divided into two dietary treatments, copper-deficient and adequate (0.7 mg and 8.0 mg Cukg diet, respectively). Total binding data and computer derived estimates (K/sub d/ and B/sub max/) were used to compare differences between treatments. Binding data from all experiments conformed to a one-site model. In all cases, binding was saturable and EDTA and pronase insensitive. Treatment differences were observed in Study I ( 125 I-apo E-free HDL binding to crude liver membranes). Significantly lower total binding and B/sub max/ were observed when lipoproteins and membranes from copper-deficient animals were used in the assay. Competition experiments from Studies II and III demonstrate that the different HDL subfractions competed effectively with one another for binding sites, indicating that apo E is not a determinant in binding of rat 125 I-HDL subfractions to purified liver plasma membranes

Etiology, Localization and Prognosis in Cerebellar Infarctions

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Yavuz Yücel

2006-01-01

Full Text Available Cerebrovasculer disease are the most frequent disease of the brain. Cerebellar infarct remains % 1.5-4.2 of these diseases. Etiological factors, lesion localization, symptoms and findings and relationship with prognosis of our patients with cerebellar infarct were investigated in our study. For this purpose, 32 patients were evaluated who were admitted to the Dicle University Medical School Department of Neurology in 1995-2001 hospitalized with the diagnosis of clinically and radiological confirmed cerebellar infarction.All of patients in the study group, 21 (%65.6 were male and 11 (%34.3 female. Age of overall patients ranged between 40 and 75 years with a mean of 57.8±10.2 years. Atherothrombotic infarct was the most frequent reason at the etiologic clinical classification. The most frequently found localization was the posterior inferior cerebellar artery infarct (%50. The leading two risk factors were hypertension (%78.1 and cigarette smoking (%50. The most common sign and symptoms were vertigo (%93.7, vomiting (%75, headache (%68.7 and cerebellar dysfunction findings (%50. The mean duration of hospitalization was 16.3±7.6 days. Overall mortality rate was found to be % 6.2. Finally, the most remarkable risk factors at cerebellar infarct patients are hypertension and atherosclerosis at etiology. We are considering that, controlling of these factors will reduce the appearance frequency of cerebellar infarcts.

Diode λ830nm laser associated with hydroxyapatite and biological membranes: bone repair in rats

Science.gov (United States)

Carneiro, Vanda S. M.; Limeira, Francisco d. A.; Gerbi, Marleny E. M.; Menezes, Rebeca F. d.; Santos-Neto, Alexandrino P. d.; Araújo, Natália C.

2016-02-01

The aim of the present study was to histologically assess the effect of laser therapy (AsGaAl, 830nm, 40mW, CW, φ ~0,6mm, 16J/cm2 per session, four points of 4J/cm2) on the repair of surgical defects created in the femur of Wistar rats. Background data: Several techniques have been proposed for the correction of bone defects, including the use of grafts and membranes. Despite the increase in the use of laser therapy for the biomodulation of bone repair, very few studies have assessed the associations between laser light and biomaterials. Method: The defects were filled with synthetic micro granular hydroxyapatite (HA) Gen-phos® implants and associated with bovine bone membranes (Gen-derm®). Surgical bone defects were created in 48 rats and divided into four groups: Group IA (control, n=12); Group IB (laser, n=12); Group IIA (HA + membrane, n=12); Group IIB (HA + membrane + laser, n=12). The irradiated groups received the first irradiation immediately after surgery. This radiation was then repeated seven times every 48h. The animals were sacrificed after 15, 21, and 30 days. Results: When comparing the groups irradiated with implants and membranes, it was found that the repair of the defects submitted to laser therapy occurred more quickly, starting 15 and 21 days after surgery. By the 30th day, the level of repair of the defects was similar in the irradiated and the non-irradiated groups. New bone formation was confirmed inside the cavity by the implant's osteoconduction. In the irradiated groups, there was an increment of this new bone formation. Conclusions: In conclusion, the use of laser therapy, particularly when associated with hydroxyapatite and biological membranes, produced a positive biomodulation effect on the healing process of bone defects on the femurs of rats.

Membrane potential of mitochondria from the liver of irradiated rats

International Nuclear Information System (INIS)

Fomenko, B.S.; Kaminin, A.N.; Elfimova, I.A.; Akoev, I.G.

1977-01-01

Measurements of the membrane potential of rat liver mitochondria 1 hour after irradiation with 800 R dose showed a decrease of its value. The potential decreased against the background of the activation of the generating mechanisms (the electron transport chain and ATP-ases). During energization of the membranes by the electron transport chain similar effect has been observed with different oxidation substrates (NAD linked substrates and succinate). It suggests that similar causative factors are at the basis of the changes observed. It is quite possible that the increase in the rate of both mitochondria respiration and ATP hydrolysis after the irradiation of animals was a consequence of the radiation-induced decrease in the potential value. (author)

G-protein activity in Percoll-purified plasma membranes, bulk plasma membranes, and low-density plasma membranes isolated from rat cerebral cortex

Czech Academy of Sciences Publication Activity Database

Bouřová, Lenka; Stöhr, Jiří; Lisý, Václav; Rudajev, Vladimír; Novotný, Jiří; Svoboda, Petr

2009-01-01

Roč. 15, č. 4 (2009), BR111-BR122 ISSN 1234-1010 R&D Projects: GA MŠk(CZ) LC554; GA MŠk(CZ) LC06063; GA ČR(CZ) GA309/06/0121; GA AV ČR(CZ) IAA500110606 Institutional research plan: CEZ:AV0Z50110509 Keywords : rat cerebral cortex * plasma membrane * G-protein activity Subject RIV: CE - Biochemistry Impact factor: 1.543, year: 2009

Maternal Different Degrees of Iodine Deficiency during Pregnant and Lactation Impair the Development of Cerebellar Pinceau in Offspring

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Jing Dong

2017-05-01

Full Text Available Aims: Iodine is critical for synthesis of thyroid hormones (TH. And iodine deficiency (ID is one of the most significant reasons of intellectual disability and motor memory impairment, although the potential mechanisms are still under investigation. Presently, mild ID and marginal ID are largely ignored problems for women of child bearing age. Mild ID is a subtle form of TH deficiency, which shows low levels of free thyroxine (FT4 and relatively normal free triiodothyronine (FT3 or thyroid stimulation hormone (TSH. And marginal ID is a milder form of ID with decreased total T4 (TT4 but relatively normal FT3, FT4, and TSH. Therefore, we investigated the effects of maternal different degrees of ID on the development of pinceau in cerebellar purkinje cells (PCs and studied the expression of pinceau related protein, which is crucial for the development and maturation of pinceau.Methods and Results: Three developmental iodine deficient rat models were created by feeding dam rats with an iodine-deficient diet and deionized water supplemented with potassiumiodide. Our study showed that different degrees of ID inhibited cerebellar pinceau synapse development and maturation on postnatal day (PN 14 and PN21. What's more, mild and severe ID reduced the expression of AnkG, β4-spectrin, neurofascin186 and NrCAM on PN7, PN14, and PN21. However, marginal ID rarely altered expression of these proteins in the offspring.Conclusion: These results suggested that maternal mild and severe ID impaired the development and maturation of cerebellar pinceau, which may be attributed to the decrease of AnkG, β4-spectrin, neurofascin 186, and NrCAM. And the alteration of development and maturation in cerebellar pinceau in the offspring were also observed following maternal marginal ID, which is slighter than that of mild ID.

Dyslexic Children Show Atypical Cerebellar Activation and Cerebro-Cerebellar Functional Connectivity in Orthographic and Phonological Processing.

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Feng, Xiaoxia; Li, Le; Zhang, Manli; Yang, Xiujie; Tian, Mengyu; Xie, Weiyi; Lu, Yao; Liu, Li; Bélanger, Nathalie N; Meng, Xiangzhi; Ding, Guosheng

2017-04-01

Previous neuroimaging studies have found atypical cerebellar activation in individuals with dyslexia in either motor-related tasks or language tasks. However, studies investigating atypical cerebellar activation in individuals with dyslexia have mostly used tasks tapping phonological processing. A question that is yet unanswered is whether the cerebellum in individuals with dyslexia functions properly during orthographic processing of words, as growing evidence shows that the cerebellum is also involved in visual and spatial processing. Here, we investigated cerebellar activation and cerebro-cerebellar functional connectivity during word processing in dyslexic readers and typically developing readers using tasks that tap orthographic and phonological codes. In children with dyslexia, we observed an abnormally higher engagement of the bilateral cerebellum for the orthographic task, which was negatively correlated with literacy measures. The greater the reading impairment was for young dyslexic readers, the stronger the cerebellar activation was. This suggests a compensatory role of the cerebellum in reading for children with dyslexia. In addition, a tendency for higher cerebellar activation in dyslexic readers was found in the phonological task. Moreover, the functional connectivity was stronger for dyslexic readers relative to typically developing readers between the lobule VI of the right cerebellum and the left fusiform gyrus during the orthographic task and between the lobule VI of the left cerebellum and the left supramarginal gyrus during the phonological task. This pattern of results suggests that the cerebellum compensates for reading impairment through the connections with specific brain regions responsible for the ongoing reading task. These findings enhance our understanding of the cerebellum's involvement in reading and reading impairment.

Cerebellar cortical infarct cavities and vertebral artery disease

Energy Technology Data Exchange (ETDEWEB)

Cocker, Laurens J.L. de [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Kliniek Sint-Jan Radiologie, Brussels (Belgium); Compter, A.; Kappelle, L.J.; Worp, H.B. van der [University Medical Center Utrecht, Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, Utrecht (Netherlands); Luijten, P.R.; Hendrikse, J. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands)

2016-09-15

Cerebellar cortical infarct cavities are a newly recognised entity associated with atherothromboembolic cerebrovascular disease and worse physical functioning. We aimed to investigate the relationship of cerebellar cortical infarct cavities with symptomatic vertebrobasilar ischaemia and with vascular risk factors. We evaluated the MR images of 46 patients with a recent vertebrobasilar TIA or stroke and a symptomatic vertebral artery stenosis ≥50 % from the Vertebral Artery Stenting Trial (VAST) for the presence of cerebellar cortical infarct cavities ≤1.5 cm. At inclusion in VAST, data were obtained on age, sex, history of vertebrobasilar TIA or stroke, and vascular risk factors. Adjusted risk ratios were calculated with Poisson regression analyses for the relation between cerebellar cortical infarct cavities and vascular risk factors. Sixteen out of 46 (35 %) patients showed cerebellar cortical infarct cavities on the initial MRI, and only one of these 16 patients was known with a previous vertebrobasilar TIA or stroke. In patients with symptomatic vertebrobasilar ischaemia, risk factor profiles of patients with cerebellar cortical infarct cavities were not different from patients without these cavities. Cerebellar cortical infarct cavities are seen on MRI in as much as one third of patients with recently symptomatic vertebral artery stenosis. Since patients usually have no prior history of vertebrobasilar TIA or stroke, cerebellar cortical infarct cavities should be added to the spectrum of common incidental brain infarcts visible on routine MRI. (orig.)

[Degenerative cerebellar diseases and differential diagnoses].

Science.gov (United States)

Reith, W; Roumia, S; Dietrich, P

2016-11-01

Cerebellar syndromes result in distinct clinical symptoms, such as ataxia, dysarthria, dysmetria, intention tremor and eye movement disorders. In addition to the medical history and clinical examination, imaging is particularly important to differentiate other diseases, such as hydrocephalus and multi-infarct dementia from degenerative cerebellar diseases. Degenerative diseases with cerebellar involvement include Parkinson's disease, multiple system atrophy as well as other diseases including spinocerebellar ataxia. In addition to magnetic resonance imaging (MRI), nuclear medicine imaging investigations are also helpful for the differentiation. Axial fluid-attenuated inversion recovery (FLAIR) and T2-weighted sequences can sometimes show a signal increase in the pons as a sign of degeneration of pontine neurons and transverse fibers in the basilar part of the pons. The imaging is particularly necessary to exclude other diseases, such as normal pressure hydrocephalus (NPH), multi-infarct dementia and cerebellar lesions.

Origin, lineage and function of cerebellar glia.

Science.gov (United States)

Buffo, Annalisa; Rossi, Ferdinando

2013-10-01

The glial cells of the cerebellum, and particularly astrocytes and oligodendrocytes, are characterized by a remarkable phenotypic variety, in which highly peculiar morphological features are associated with specific functional features, unique among the glial cells of the entire CNS. Here, we provide a critical report about the present knowledge of the development of cerebellar glia, including lineage relationships between cerebellar neurons, astrocytes and oligodendrocytes, the origins and the genesis of the repertoire of glial types, and the processes underlying their acquisition of mature morphological and functional traits. In parallel, we describe and discuss some fundamental roles played by specific categories of glial cells during cerebellar development. In particular, we propose that Bergmann glia exerts a crucial scaffolding activity that, together with the organizing function of Purkinje cells, is necessary to achieve the normal pattern of foliation and layering of the cerebellar cortex. Moreover, we discuss some of the functional tasks of cerebellar astrocytes and oligodendrocytes that are distinctive of cerebellar glia throughout the CNS. Notably, we report about the regulation of synaptic signalling in the molecular and granular layer mediated by Bergmann glia and parenchymal astrocytes, and the functional interaction between oligodendrocyte precursor cells and neurons. On the whole, this review provides an extensive overview of the available literature and some novel insights about the origin and differentiation of the variety of cerebellar glial cells and their function in the developing and mature cerebellum. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cellular and Molecular Basis of Cerebellar Development

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Salvador eMartinez

2013-06-01

Full Text Available Historically, the molecular and cellular mechanisms of cerebellar development were investigated through structural descriptions and studying spontaneous mutations in animal models and humans. Advances in experimental embryology, genetic engineering and neuroimaging techniques render today the possibility to approach the analysis of molecular mechanisms underlying histogenesis and morphogenesis of the cerebellum by experimental designs. Several genes and molecules were identified to be involved in the cerebellar plate regionalization, specification and differentiation of cerebellar neurons, as well as the establishment of cellular migratory routes and the subsequent neuronal connectivity. Indeed, pattern formation of the cerebellum requires the adequate orchestration of both key morphogenetic signals, arising from distinct brain regions, and local expression of specific transcription factors. Thus, the present review wants to revisit and discuss these morphogenetic and molecular mechanisms taking place during cerebellar development in order to understand causal processes regulating cerebellar cytoarchitecture, its highly topographically ordered circuitry and its role in brain function.

Sensory Coding by Cerebellar Mossy Fibres through Inhibition-Driven Phase Resetting and Synchronisation

Science.gov (United States)

Holtzman, Tahl; Jörntell, Henrik

2011-01-01

Temporal coding of spike-times using oscillatory mechanisms allied to spike-time dependent plasticity could represent a powerful mechanism for neuronal communication. However, it is unclear how temporal coding is constructed at the single neuronal level. Here we investigate a novel class of highly regular, metronome-like neurones in the rat brainstem which form a major source of cerebellar afferents. Stimulation of sensory inputs evoked brief periods of inhibition that interrupted the regular firing of these cells leading to phase-shifted spike-time advancements and delays. Alongside phase-shifting, metronome cells also behaved as band-pass filters during rhythmic sensory stimulation, with maximal spike-stimulus synchronisation at frequencies close to the idiosyncratic firing frequency of each neurone. Phase-shifting and band-pass filtering serve to temporally align ensembles of metronome cells, leading to sustained volleys of near-coincident spike-times, thereby transmitting synchronised sensory information to downstream targets in the cerebellar cortex. PMID:22046297

Sensory coding by cerebellar mossy fibres through inhibition-driven phase resetting and synchronisation.

Directory of Open Access Journals (Sweden)

Tahl Holtzman

Full Text Available Temporal coding of spike-times using oscillatory mechanisms allied to spike-time dependent plasticity could represent a powerful mechanism for neuronal communication. However, it is unclear how temporal coding is constructed at the single neuronal level. Here we investigate a novel class of highly regular, metronome-like neurones in the rat brainstem which form a major source of cerebellar afferents. Stimulation of sensory inputs evoked brief periods of inhibition that interrupted the regular firing of these cells leading to phase-shifted spike-time advancements and delays. Alongside phase-shifting, metronome cells also behaved as band-pass filters during rhythmic sensory stimulation, with maximal spike-stimulus synchronisation at frequencies close to the idiosyncratic firing frequency of each neurone. Phase-shifting and band-pass filtering serve to temporally align ensembles of metronome cells, leading to sustained volleys of near-coincident spike-times, thereby transmitting synchronised sensory information to downstream targets in the cerebellar cortex.

Mother/offspring co-administration of the traditional herbal remedy yokukansan during the nursing period influences grooming and cerebellar serotonin levels in a rat model of neurodevelopmental disorders.

Science.gov (United States)

Muneoka, Katsumasa; Kuwagata, Makiko; Ogawa, Tetsuo; Shioda, Seiji

2015-04-01

Neurodevelopmental impairment in the serotonergic system may be involved in autism spectrum disorder. Yokukansan is a traditional herbal remedy for restlessness and agitation in children, and mother-infant co-administration (MICA) to both the child and the nursing mother is one of the recommended treatment approaches. Recent studies have revealed the neuropharmacological properties of Yokukansan (YKS), including its 5-HT1A (serotonin) receptor agonistic effects. We investigated the influence of YKS treatment on behavior in a novel environment and on brain monoamine metabolism during the nursing period in an animal model of neurodevelopmental disorders, prenatally BrdU (5-bromo-2'-deoxyuridine)-treated rats (BrdU-rats). YKS treatment did not influence locomotor activity in BrdU-rats but reduced grooming in open-field tests. YKS treatment without MICA disrupted the correlation between locomotor behaviors and rearing and altered levels of serotonin and its metabolite in the cerebellum. These effects were not observed in the group receiving YKS treatment with MICA. These data indicate a direct pharmacological effect of YKS on the development of grooming behavior and profound effects on cerebellar serotonin metabolism, which is thought to be influenced by nursing conditions.

Degenerative cerebellar diseases and differential diagnoses

International Nuclear Information System (INIS)

Reith, W.; Roumia, S.; Dietrich, P.

2016-01-01

Cerebellar syndromes result in distinct clinical symptoms, such as ataxia, dysarthria, dysmetria, intention tremor and eye movement disorders. In addition to the medical history and clinical examination, imaging is particularly important to differentiate other diseases, such as hydrocephalus and multi-infarct dementia from degenerative cerebellar diseases. Degenerative diseases with cerebellar involvement include Parkinson's disease, multiple system atrophy as well as other diseases including spinocerebellar ataxia. In addition to magnetic resonance imaging (MRI), nuclear medicine imaging investigations are also helpful for the differentiation. Axial fluid-attenuated inversion recovery (FLAIR) and T2-weighted sequences can sometimes show a signal increase in the pons as a sign of degeneration of pontine neurons and transverse fibers in the basilar part of the pons. The imaging is particularly necessary to exclude other diseases, such as normal pressure hydrocephalus (NPH), multi-infarct dementia and cerebellar lesions. (orig.) [de

Cerebellar involvement in metabolic disorders: a pattern-recognition approach

International Nuclear Information System (INIS)

Steinlin, M.; Boltshauser, E.; Blaser, S.

1998-01-01

Inborn errors of metabolism can affect the cerebellum during development, maturation and later during life. We have established criteria for pattern recognition of cerebellar abnormalities in metabolic disorders. The abnormalities can be divided into four major groups: cerebellar hypoplasia (CH), hyperplasia, cerebellar atrophy (CA), cerebellar white matter abnormalities (WMA) or swelling, and involvement of the dentate nuclei (DN) or cerebellar cortex. CH can be an isolated typical finding, as in adenylsuccinase deficiency, but is also occasionally seen in many other disorders. Differentiation from CH and CA is often difficult, as in carbohydrate deficient glycoprotein syndrome or 2-l-hydroxyglutaric acidaemia. In cases of atrophy the relationship of cerebellar to cerebral atrophy is important. WMA may be diffuse or patchy, frequently predominantly around the DN. Severe swelling of white matter is present during metabolic crisis in maple syrup urine disease. The DN can be affected by metabolite deposition, necrosis, calcification or demyelination. Involvement of cerebellar cortex is seen in infantile neuroaxonal dystrophy. Changes in DN and cerebellar cortex are rather typical and therefore most helpful; additional features should be sought as they are useful in narrowing down the differential diagnosis. (orig.)

Humor and laughter in patients with cerebellar degeneration.

Science.gov (United States)

Frank, B; Propson, B; Göricke, S; Jacobi, H; Wild, B; Timmann, D

2012-06-01

Humor is a complex behavior which includes cognitive, affective and motor responses. Based on observations of affective changes in patients with cerebellar lesions, the cerebellum may support cerebral and brainstem areas involved in understanding and appreciation of humorous stimuli and expression of laughter. The aim of the present study was to examine if humor appreciation, perception of humorous stimuli, and the succeeding facial reaction differ between patients with cerebellar degeneration and healthy controls. Twenty-three adults with pure cerebellar degeneration were compared with 23 age-, gender-, and education-matched healthy control subjects. No significant difference in humor appreciation and perception of humorous stimuli could be found between groups using the 3 Witz-Dimensionen Test, a validated test asking for funniness and aversiveness of jokes and cartoons. Furthermore, while observing jokes, humorous cartoons, and video sketches, facial expressions of subjects were videotaped and afterwards analysed using the Facial Action Coding System. Using depression as a covariate, the number, and to a lesser degree, the duration of facial expressions during laughter were reduced in cerebellar patients compared to healthy controls. In sum, appreciation of humor appears to be largely preserved in patients with chronic cerebellar degeneration. Cerebellar circuits may contribute to the expression of laughter. Findings add to the literature that non-motor disorders in patients with chronic cerebellar disease are generally mild, but do not exclude that more marked disorders may show up in acute cerebellar disease and/or in more specific tests of humor appreciation.

Bicarbonate sulfate exchange in canalicular rat liver plasma membrane vesicles

International Nuclear Information System (INIS)

Meier, P.J.; Valantinas, J.; Hugentobler, G.; Rahm, I.

1987-01-01

The mechanism(s) and driving forces for biliary excretion of sulfate were investigated in canalicular rat liver plasma membrane vesicles (cLPM). Incubation of cLPM vesicles in the presence of an inside-to-outside (in, out) bicarbonate gradient but not pH or out-to-in sodium gradients, stimulated sulfate uptake 10-fold compared with the absence of bicarbonate and approximately 2-fold above sulfate equilibrium (overshoot). Initial rates of this bicarbonate gradient-driven [ 35 S]-sulfate uptake were saturable with increasing concentrations of sulfate and could be inhibited by probenecid, N-(4-azido-2-nitrophenyl)-2-aminoethylsulfonate, acetazolamide, furosemide, 4-acetamideo-4'-isothiocyanostilbene-2,2'-disulfonic acid, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (IC 50 , ∼40 μM). Cisinhibition of initial bicarbonate gradient-stimulated sulfate uptake and transstimulation of sulfate uptake in the absence of bicarbonate were observed with sulfate, thiosulfate, and oxalate but not with chloride, nitrate, phosphate, acetate, lactate, glutamate, aspartate, cholate, taurocholate, dehydrocholate, taurodehydrocholate, and reduced or oxidized glutathione. These findings indicate the presence of a sulfate (oxalate)-bicarbonate anion exchange system in canalicular rat liver plasma membranes. These findings support the concept that bicarbonate-sensitive transport system might play an important role in bile acid-independent canalicular bile formation

CT and MR imaging of acute cerebellar ataxia

International Nuclear Information System (INIS)

Shoji, H.; Hirai, S.; Ishikawa, K.; Aramaki, M.; Sato, Y.; Abe, T.; Kojima, K.

1991-01-01

An adult female showed mild cerebellar ataxia and CSF pleocytosis following an acute infection of the upper respiratory tract, and was diagnosed as having acute cerebellar ataxia (ACA). CT and MR appearances in the acute stage revealed moderate swelling of the cerebellum and bilaterally increased signal intensity in the cerebellar cortex. (orig.)

Bilateral Cerebellar Cortical Dysplasia without Other Malformations: A Case Report

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Oh, Jung Seok; Ahn Kook Jin; Kim, Jee Young; Lee, Sun Jin; Park, Jeong Mi [Catholic University Yeouido St. Mary' s Hospital, College of Medicine, Seoul (Korea, Republic of)

2010-06-15

Recent advances in MRI have revealed congenital brain malformations and subtle developmental abnormalities of the cerebral and cerebellar cortical architecture. Typical cerebellar cortical dysplasia as a newly categorized cerebellar malformation, has been seen in patients with Fukuyama congenital muscular dystrophy. Cerebellar cortical dysplasia occurs at the embryonic stage and is often observed in healthy newborns. It is also incidentally and initially detected in adults without symptoms. To the best of our knowledge, cerebellar dysplasia without any related disorders is very rare. We describe the MRI findings in one patient with disorganized foliation of both cerebellar hemispheres without a related disorder or syndrome

Cerebellar medulloblastoma presenting with skeletal metastasis

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Barai Sukanta

2004-04-01

Full Text Available Medulloblastomas are highly malignant brain tumours, but only rarely produce skeletal metastases. No case of medulloblastoma has been documented to have produced skeletal metastases prior to craniotomy or shunt surgery. A 21-year-old male presented with pain in the hip and lower back with difficulty in walking of 3 months′ duration. Signs of cerebellar dysfunction were present hence a diagnosis of cerebellar neoplasm or skeletal tuberculosis with cerebellar abscess formation was considered. MRI of brain revealed a lesion in the cerebellum suggestive of medulloblastoma. Bone scan revealed multiple sites of skeletal metastases excluding the lumbar vertebrae. MRI of lumbar spine and hip revealed metastases to all lumbar vertebrae and both hips. Computed tomography-guided biopsy was obtained from the L3 vertebra, which revealed metastatic deposits from medulloblastoma. Cerebrospinal fluid cytology showed the presence of medulloblastoma cells. A final diagnosis of cerebellar medulloblastoma with skeletal metastases was made. He underwent craniotomy and histopathology confirmed medulloblastoma.

Basement membrane heparan sulfate proteoglycan from the L2 rat yolk sac carcinoma

DEFF Research Database (Denmark)

Fenger, M; Wewer, U; Albrechtsen, R

1984-01-01

Heparan sulfate proteoglycan from the L2 rat yolk sac carcinoma has been purified and partially characterized. The proteoglycan has an apparent Mr of 750 000, 35% of which represents the core protein. The core protein seems to be homogeneous, whereas the heparan sulfate chains are heterogeneous...... with an Mr of about 50 000-70 000, with 30% of the glucosamine being N-sulfated. Antibodies raised against the core protein of the heparan sulfate proteoglycan reacted with basement membranes of various rat and human tissue....

Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor.

Science.gov (United States)

Buijink, A W G; Broersma, M; van der Stouwe, A M M; van Wingen, G A; Groot, P F C; Speelman, J D; Maurits, N M; van Rootselaar, A F

2015-04-01

Cerebellar circuits are hypothesized to play a central role in the pathogenesis of essential tremor. Rhythmic finger tapping is known to strongly engage the cerebellar motor circuitry. We characterize cerebellar and, more specifically, dentate nucleus function, and neural correlates of cerebellar output in essential tremor during rhythmic finger tapping employing functional MRI. Thirty-one propranolol-sensitive essential tremor patients with upper limb tremor and 29 healthy controls were measured. T2*-weighted EPI sequences were acquired. The task consisted of alternating rest and finger tapping blocks. A whole-brain and region-of-interest analysis was performed, the latter focusing on the cerebellar cortex, dentate nucleus and inferior olive nucleus. Activations were also related to tremor severity. In patients, dentate activation correlated positively with tremor severity as measured by the tremor rating scale part A. Patients had reduced activation in widespread cerebellar cortical regions, and additionally in the inferior olive nucleus, and parietal and frontal cortex, compared to controls. The increase in dentate activation with tremor severity supports involvement of the dentate nucleus in essential tremor. Cortical and cerebellar changes during a motor timing task in essential tremor might point to widespread changes in cerebellar output in essential tremor. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor

NARCIS (Netherlands)

Buijink, A. W. G.; Broersma, M.; van der Stouwe, A. M. M.; van Wingen, G. A.; Groot, P. F. C.; Speelman, J. D.; Maurits, N. M.; van Rootselaar, A. F.

Introduction: Cerebellar circuits are hypothesized to play a central role in the pathogenesis of essential tremor. Rhythmic finger tapping is known to strongly engage the cerebellar motor circuitry. We characterize cerebellar and, more specifically, dentate nucleus function, and neural correlates of

Effects of methadone hydrochloride on the growth of organotypic cerebellar cultures prepared from methadone-tolerant and control rats.

Science.gov (United States)

Willson, N J; Schneider, J F; Roizin, L; Fleiss, J F; Rivers, W; Demartini, J E

1976-11-01

Male and female Sprague-Dawley rats were given dl-methadone (5 mg/kg) for at least 3 months and then mated. The drug was continued throughout pregnancy and after delivery. The newly born pups were divided into two groups. One group was tested for in vivo methadone tolerance, while the animals in the othergroup were used to prepare organotypic cerebellar cultures. Various amounts of dl-methadone were added to the media of half of these cerebellum cultures. The effect of the drug in the medium was assessed by measuring explant outgrowth. Similar experiments were carried out with control animals. Statistical analysis of the data obtained in the in vivo portion of the experiment indicates that the pups of methadone-treated mothers tolerate methadone better than those of untreated mothers. The culture experiments revealed that the addition of methadone to the medium reduced explant outgrowth size and this was a dose-related effect. Also, there was significantly less outgrowth from explants prepared using pups of methadone-treated mothers as compared to the controls. There was no significant difference in the effect of methadone on the growth of cultures prepared from the methadone-tolerant and control animals.

Computed tomography in alcoholic cerebellar atrophy

Energy Technology Data Exchange (ETDEWEB)

Haubek, A; Lee, K [Hvidovre Hospital Copenhagen (Denmark). Dept. of Radiology; Municipal Hospital, Copenhagen (Denmark). Dept. of Neurology)

1979-01-01

This is a controlled CT evaluation of the infratentorial region in 41 male alcoholics under age 35. Criteria for the presence of atrophy are outlined. Twelve patients had cerebellar atrophy. Vermian atrophy was present in all. Atrophy of the cerebellar hemispheres was demonstrated in eight patients as well. The results are statistically significant when compared to an age-matched group of 40 non-alcoholic males among whom two cases of vermian atrophy were found. There were clinical signs of alcoholic cerebellar atrophy in one patient only. The disparity between the clinical and the radiological data are discussed with reference to previous pneumoencephalographic findings. (orig.) 891 AJ/orig. 892 MKO.

Acute Cerebellar Ataxia Induced by Nivolumab

Science.gov (United States)

Kawamura, Reina; Nagata, Eiichiro; Mukai, Masako; Ohnuki, Yoichi; Matsuzaki, Tomohiko; Ohiwa, Kana; Nakagawa, Tomoki; Kohno, Mitsutomo; Masuda, Ryota; Iwazaki, Masayuki; Takizawa, Shunya

2017-01-01

A 54-year-old woman with adenocarcinoma of the lung and lymph node metastasis experienced nystagmus and cerebellar ataxia 2 weeks after initiating nivolumab therapy. An evaluation for several autoimmune-related antibodies and paraneoplastic syndrome yielded negative results. We eventually diagnosed the patient with nivolumab-induced acute cerebellar ataxia, after excluding other potential conditions. Her ataxic gait and nystagmus resolved shortly after intravenous steroid pulse therapy followed by the administration of decreasing doses of oral steroids. Nivolumab, an immune checkpoint inhibitor, is known to induce various neurological adverse events. However, this is the first report of acute cerebellar ataxia associated with nivolumab treatment. PMID:29249765

Falls and cerebellar ataxia

Directory of Open Access Journals (Sweden)

I. V. Damulin

2015-01-01

Full Text Available The paper considers the main causes of falls. Whatever their cause is, falls may lead to severe maladjustment in everyday life. In nearly 1 out of 10 cases, they are accompanied by severe injuries, including fractures (most commonly those of the proximal femur and humerus, hands, pelvic bones, and vertebrae, subdural hematoma, and severe soft tissue and head injuries. This process is emphasized to be multifactorial. Particular emphasis is laid on the involvement of the cerebellum and its associations, which may be accompanied by falls. This is clinically manifested mainly by gait disorders. Walking is a result of an interaction of three related functions (locomotion, maintenance of balance and adaptive reactions. In addition to synergies related to locomotion and balance maintenance, standing at rest and walking are influenced bythe following factors: postural and environmental information (proprioceptive, vestibular, and visual, the capacity to interpret and integrate this information, the ability of the musculoskeletal system to make movements, and the capability to optimally modulate these movements in view of the specific situation and the ability to choose and adapt synergy in terms of external factors and the capacities and purposes of an individual. The clinical signs of damage to the cerebellum and its associations are considered in detail. These structures are emphasized to be involved not only in movements, but also in cognitive functions. The major symptoms that permit cerebellar dysfunction to be diagnosed are given. Symptoms in cerebellar injuries are generally most pronounced when suddenly changing the direction of movements or attempting to start walking immediately after a dramatic rise. The magnitude of ataxia also increases in a patient who tries to decrease the step size. Falling tendencies or bending to one side (in other symptoms characteristic of cerebellar diseases suggest injury of the corresponding

Photoaffinity labeling of [3H]flunitrazepam- and [3H]Ro15-4513-bound pellets in rat cerebral cortex and cerebellum

International Nuclear Information System (INIS)

Chiu, T.H.; Yu, Onnfoh; Rosenberg, H.C.

1989-01-01

Irreversible incorporation of [ 3 H]flunitrazepam and [ 3 H]Ro15-4513 into GABA/benzodiazepine receptor subunits was studied by UV/irradiation using ligand-bound membrane pellets from rat cerebral cortical and cerebellar synaptic membranes. Specific incorporation for [ 3 H]flunitrazepam was greater in the pellet than in the suspension. The incorporation was identical for [ 3 H]Ro15-4513 in both pellet and suspension. With the ligand-bound pellets, 50% of the available binding sites were photolabeled by both ligands in cortex and cerebellum. SDS polyacrylamide gel electrophoresis and fluorography of [ 3 H]flunitrazepam photo-labeled receptor revealed the same number of major sites in both brain regions. In contrast, [ 3 H]Ro15-4513 appears to label fewer sites in cortex and cerebellum. Photoaffinity labeling with [ 3 H]flunitrazepam in ligand-bound membrane pellet provides a more selective and reliable method for studying the subunit structure of GABA/benzodiazepine receptor complex

Metabolic anatomy of paraneoplastic cerebellar degeneration

International Nuclear Information System (INIS)

Anderson, N.E.; Posner, J.B.; Sidtis, J.J.; Moeller, J.R.; Strother, S.C.; Dhawan, V.; Rottenberg, D.A.

1988-01-01

Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration [PCD]) were evaluated using neuropsychological tests and 18 F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and ataxia. rCMRGlc was reduced in patients with PCD (versus normal control subjects) in all regions except the brainstem. Analysis of patient and control rCMRGlc data using a mathematical model of regional metabolic interactions revealed two metabolic pattern descriptors, SSF1 and SSF2, which distinguished patients with PCD from normal control subjects; SSF2, which described a metabolic coupling between cerebellum, cuneus, and posterior temporal, lateral frontal, and paracentral cortex, correlated with quantitative indices of cerebellar dysfunction. Our inability to document substantial intellectual impairment in 7 of 10 patients with PCD contrasts with the 50% incidence of dementia in PCD reported by previous investigators. Widespread reductions in PCD rCMRGlc may result from the loss of cerebellar efferents to thalamus and forebrain structures, a reverse cerebellar diaschisis

Co-localization of glycine and gaba immunoreactivity in interneurons in Macaca monkey cerebellar cortex.

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Crook, J; Hendrickson, A; Robinson, F R

2006-09-15

Previous work demonstrates that the cerebellum uses glycine as a fast inhibitory neurotransmitter [Ottersen OP, Davanger S, Storm-Mathisen J (1987) Glycine-like immunoreactivity in the cerebellum of rat and Senegalese baboon, Papio papio: a comparison with the distribution of GABA-like immunoreactivity and with [3H]glycine and [3H]GABA uptake. Exp Brain Res 66(1):211-221; Ottersen OP, Storm-Mathisen J, Somogyi P (1988) Colocalization of glycine-like and GABA-like immunoreactivities in Golgi cell terminals in the rat cerebellum: a postembedding light and electron microscopic study. Brain Res 450(1-2):342-353; Dieudonne S (1995) Glycinergic synaptic currents in Golgi cells of the rat cerebellum. Proc Natl Acad Sci U S A 92:1441-1445; Dumoulin A, Triller A, Dieudonne S (2001) IPSC kinetics at identified GABAergic and mixed GABAergic and glycinergic synapses onto cerebellar Golgi cells. J Neurosci 21(16):6045-6057; Dugue GP, Dumoulin A, Triller A, Dieudonne S (2005) Target-dependent use of coreleased inhibitory transmitters at central synapses. J Neurosci 25(28):6490-6498; Zeilhofer HU, Studler B, Arabadzisz D, Schweizer C, Ahmadi S, Layh B, Bosl MR, Fritschy JM (2005) Glycinergic neurons expressing enhanced green fluorescent protein in bacterial artificial chromosome transgenic mice. J Comp Neurol 482(2):123-141]. In the rat cerebellum glycine is not released by itself but is released together with GABA by Lugaro cells onto Golgi cells [Dumoulin A, Triller A, Dieudonne S (2001) IPSC kinetics at identified GABAergic and mixed GABAergic and glycinergic synapses onto cerebellar Golgi cells. J Neurosci 21(16):6045-6057] and by Golgi cells onto unipolar brush and granule cells [Dugue GP, Dumoulin A, Triller A, Dieudonne S (2005) Target-dependent use of coreleased inhibitory transmitters at central synapses. J Neurosci 25(28):6490-6498]. Here we report, from immunolabeling evidence in Macaca cerebellum, that interneurons in the granular cell layer are glycine+ at a density

Contribution of cerebellar sensorimotor adaptation to hippocampal spatial memory.

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Jean-Baptiste Passot

Full Text Available Complementing its primary role in motor control, cerebellar learning has also a bottom-up influence on cognitive functions, where high-level representations build up from elementary sensorimotor memories. In this paper we examine the cerebellar contribution to both procedural and declarative components of spatial cognition. To do so, we model a functional interplay between the cerebellum and the hippocampal formation during goal-oriented navigation. We reinterpret and complete existing genetic behavioural observations by means of quantitative accounts that cross-link synaptic plasticity mechanisms, single cell and population coding properties, and behavioural responses. In contrast to earlier hypotheses positing only a purely procedural impact of cerebellar adaptation deficits, our results suggest a cerebellar involvement in high-level aspects of behaviour. In particular, we propose that cerebellar learning mechanisms may influence hippocampal place fields, by contributing to the path integration process. Our simulations predict differences in place-cell discharge properties between normal mice and L7-PKCI mutant mice lacking long-term depression at cerebellar parallel fibre-Purkinje cell synapses. On the behavioural level, these results suggest that, by influencing the accuracy of hippocampal spatial codes, cerebellar deficits may impact the exploration-exploitation balance during spatial navigation.

Structure of the vitreoretinal border region in spontaneously hypertensive rats (SHR rats)

DEFF Research Database (Denmark)

Heegaard, Steffen

1993-01-01

Øjenpatologi, vitreoretinal border region, inner limiting membrane of the retina, spontaneously hypertensive rats, SHR rats, ultrastructure......Øjenpatologi, vitreoretinal border region, inner limiting membrane of the retina, spontaneously hypertensive rats, SHR rats, ultrastructure...

Membrane phospholipid composition may contribute to exceptional longevity of the naked mole-rat (Heterocephalus glaber): a comparative study using shotgun lipidomics.

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Mitchell, Todd W; Buffenstein, Rochelle; Hulbert, A J

2007-11-01

Phospholipids containing highly polyunsaturated fatty acids are particularly prone to peroxidation and membrane composition may therefore influence longevity. Phospholipid molecules, in particular those containing docosahexaenoic acid (DHA), from the skeletal muscle, heart, liver and liver mitochondria were identified and quantified using mass-spectrometry shotgun lipidomics in two similar-sized rodents that show an approximately 9-fold difference in maximum lifespan. The naked mole rat is the longest-living rodent known with a maximum lifespan of >28 years. Total phospholipid distribution is similar in tissues of both species; DHA is only found in phosphatidylcholines (PC), phosphatidylethanolamines (PE) and phosphatidylserines (PS), and DHA is relatively more concentrated in PE than PC. Naked mole-rats have fewer molecular species of both PC and PE than do mice. DHA-containing phospholipids represent 27-57% of all phospholipids in mice but only 2-6% in naked mole-rats. Furthermore, while mice have small amounts of di-polyunsaturated PC and PE, these are lacking in naked mole-rats. Vinyl ether-linked phospholipids (plasmalogens) are higher in naked mole-rat tissues than in mice. The lower level of DHA-containing phospholipids suggests a lower susceptibility to peroxidative damage in membranes of naked mole-rats compared to mice. Whereas the high level of plasmalogens might enhance membrane antioxidant protection in naked mole-rats compared to mice. Both characteristics possibly contribute to the exceptional longevity of naked mole-rats and may indicate a special role for peroxisomes in this extended longevity.

Synthesis of erythrocyte membrane proteins in dispersed cells from fetal rat liver

International Nuclear Information System (INIS)

Kitagawa, Yasuo; Murakami, Akihiko; Sugimoto, Etsuro

1984-01-01

Protein synthesis in dispersed cells from fetal liver was studied by fluorography of SDS-polyacrylamide gel electrophoresis of a [ 35 S] methionine labeled cell lysate. Synthesis of several proteins with molecular weights ranging from 45,000 to 220,000 was observed during erythropoiesis in fetal liver. Some of these proteins were demonstrated to be erythrocyte membrane proteins because they were immunoprecipitated with antiserum against rat red blood cells and the immunoprecipitation was competitive with non-radioactive proteins solubilized from erythrocyte ghosts. The same antiserum caused agglutination of dispered cells from fetal liver. This supported the possibility that these proteins are translocated onto plasma membranes of the dispersed cells. (author)

Hearing assessment during deep brain stimulation of the central nucleus of the inferior colliculus and dentate cerebellar nucleus in rat

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Jasper V. Smit

2017-10-01

Full Text Available Background Recently it has been shown in animal studies that deep brain stimulation (DBS of auditory structures was able to reduce tinnitus-like behavior. However, the question arises whether hearing might be impaired when interfering in auditory-related network loops with DBS. Methods The auditory brainstem response (ABR was measured in rats during high frequency stimulation (HFS and low frequency stimulation (LFS in the central nucleus of the inferior colliculus (CIC, n = 5 or dentate cerebellar nucleus (DCBN, n = 5. Besides hearing thresholds using ABR, relative measures of latency and amplitude can be extracted from the ABR. In this study ABR thresholds, interpeak latencies (I–III, III–V, I–V and V/I amplitude ratio were measured during off-stimulation state and during LFS and HFS. Results In both the CIC and the CNBN groups, no significant differences were observed for all outcome measures. Discussion DBS in both the CIC and the CNBN did not have adverse effects on hearing measurements. These findings suggest that DBS does not hamper physiological processing in the auditory circuitry.

Cerebellar transcranial direct current stimulation modulates verbal working memory.

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Boehringer, Andreas; Macher, Katja; Dukart, Juergen; Villringer, Arno; Pleger, Burkhard

2013-07-01

Neuroimaging studies show cerebellar activations in a wide range of cognitive tasks and patients with cerebellar lesions often present cognitive deficits suggesting a cerebellar role in higher-order cognition. We used cathodal transcranial direct current stimulation (tDCS), known to inhibit neuronal excitability, over the cerebellum to investigate if cathodal tDCS impairs verbal working memory, an important higher-order cognitive faculty. We tested verbal working memory as measured by forward and backward digit spans in 40 healthy young participants before and after applying cathodal tDCS (2 mA, stimulation duration 25 min) to the right cerebellum using a randomized, sham-controlled, double-blind, cross-over design. In addition, we tested the effect of cerebellar tDCS on word reading, finger tapping and a visually cued sensorimotor task. In line with lower digit spans in patients with cerebellar lesions, cerebellar tDCS reduced forward digit spans and blocked the practice dependent increase in backward digit spans. No effects of tDCS on word reading, finger tapping or the visually cued sensorimotor task were found. Our results support the view that the cerebellum contributes to verbal working memory as measured by forward and backward digit spans. Moreover, the induction of reversible "virtual cerebellar lesions" in healthy individuals by means of tDCS may improve our understanding of the mechanistic basis of verbal working memory deficits in patients with cerebellar lesions. Copyright © 2013 Elsevier Inc. All rights reserved.

Eccentric contractions affect muscle membrane phospholipid fatty acid composition in rats

DEFF Research Database (Denmark)

Helge, Jørn Wulff; Therkildsen, K J; Jørgensen, T B

2001-01-01

This study investigated if prior eccentric contractions, and thus mechanical strain and muscle damage, exert an effect on the muscle membrane phospholipid fatty acid composition in rats, and whether a possible effect could be attenuated by dietary supplements. Twenty-three rats were randomised...... muscle, was excised from both legs. In the muscles stimulated to contract eccentrically, compared to the control muscles, the proportion of arachidonic acid, C20:4,n-6 (17.7 +/- 0.6; 16.4 +/- 0.4% of total fatty acids, respectively) and docosapentanoeic acid, C22:5,n-3 (2.9 +/- 0.1 and 2.7 +/- 0.......1% of total fatty acids, respectively) was uniformly higher across groups (P fatty acids) compared to the control leg (38.2 +/- 0...

Factors associated with the misdiagnosis of cerebellar infarction.

Science.gov (United States)

Masuda, Yoko; Tei, Hideaki; Shimizu, Satoru; Uchiyama, Shinichiro

2013-10-01

Cerebellar infarction is easily misdiagnosed or underdiagnosed. In this study, we investigated factors leading to misdiagnosis of cerebellar infarction in patients with acute ischemic stroke. Data on neurological and radiological findings from 114 consecutive patients with acute cerebellar infarction were analyzed. We investigated factors associated with misdiagnosis from the data on clinical findings. Thirty-two (28%) patients were misdiagnosed on admission. Misdiagnosis was significantly more frequent in patients below 60 years of age and in patients with vertebral artery dissection, and significantly less frequent in patients with dysarthria. It tended to be more frequent in patients with the medial branch of posterior inferior cerebellar artery territory infarction, and infrequent in patients with the medial branch of the superior cerebellar artery territory infarction. Thirty out of 32 (94%) misdiagnosed patients were seen by physicians that were not neurologists at the first visit. Twenty-four of 32 (75%) misdiagnosed patients were screened only by brain CT. However, patients were not checked by brain MRI or follow-up CT until their conditions worsened. Patients below 60 years of age and patients with vertebral artery dissection are more likely to have a cerebellar infarction misdiagnosed by physicians other than neurologists. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Acetylcholinesterase potentiates [{sup 3}H]fluorowillardiine and [{sup 3}H]AMPA binding to rat cortical membranes

Energy Technology Data Exchange (ETDEWEB)

Olivera, S.; Rodriguez-Ithurralde, D. [Department of Anatomy, School of Medical Sciences, University of Bristol, University Walk, Bristol, BS8 1TD (United Kingdom); Henley, J.M. [Molecular Neuroscience Unit, Division Neuromyology, Instituto de Investigaciones Biologicas Clemente Estable, 11600 Montevideo (Uruguay)

1999-04-01

In addition to its action at cholinergic synapses acetylcholinesterase (AChE) has been proposed to modulate neuronal activity by mechanisms unrelated to the hydrolysis of acetylcholine. We have investigated the effects of AChE on the binding of the specific AMPA receptor agonists (S)-[{sup 3}H]5-fluorowillardiine ([{sup 3}H]FW) and [{sup 3}H]AMPA to rat cortical membranes. Pretreatment of membranes with AChE causes a dose-dependent increase in the binding of both radiolabelled agonists with a maximal increase to {approx}60% above control. This increase is completely blocked by the specific AChE inhibitors propidium, physostigmine, DFP and BW 284C51. AChE pretreatment had no effect on [{sup 3}H]kainate binding. [{sup 3}H]FW binding to membranes from young (15-day-old) rats is four orders of magnitude more sensitive to AChE modulation than membranes from adult rats (EC{sub 50} values of 4x10{sup -5} and 0.1 unit/ml, respectively) although the total percentage increase in binding is similar. Furthermore, the AChE-induced potentiation of [{sup 3}H]FW binding is Ca{sup 2+}- and temperature-dependent suggesting an enzymatic action for AChE in this system. Saturation binding experiments with [{sup 3}H]FW to adult membranes reveal high and low affinity binding sites and demonstrate that the main action of AChE is to increase the B{sub max} of both sites. These findings suggest that modulation of AMPA receptors could provide a molecular mechanism of action for the previously reported effects of AChE in synapse formation, synaptic plasticity and neurodegeneration. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

Cerebellar arteriovenous malformations in children

International Nuclear Information System (INIS)

Griffiths, P.D.; Humphreys, R.P.

1998-01-01

We review the presentation, imaging findings and outcome in 18 children with cerebellar arteriovenous malformations (AVM). This group is of particular interest because of the reported poor outcome despite modern imaging and neurosurgical techniques. All children had CT and 15 underwent catheter angiography at presentation. Several of the children in the latter part of the study had MRI. Of the 18 children, 17 presented with a ruptured AVM producing intracranial haemorrhage. The remaining child presented with temporal lobe epilepsy and was shown to have temporal, vermian and cerebellar hemisphere AVM. This child had other stigmata of Osler-Weber-Rendu syndrome. Three other children had pre-existing abnormalities of possible relevance. One had a vascular malformation of the cheek and mandible, one a documented chromosomal abnormality and another a midline cleft upper lip and palate. Six of the 17 children with a ruptured cerebellar AVM died within 7 days of the ictus. Vascular pathology other than an AVM was found in 10 of the 14 children with a ruptured cerebellar AVM who had angiography: 4 intranidal aneurysms, 5 venous aneurysms and 2 cases of venous outflow obstruction (one child having both an aneurysm and obstruction). The severity of clinical presentation was directly related to the size of the acute haematoma, which was a reasonable predictor of outcome. (orig.)

Cerebellar arteriovenous malformations in children

Energy Technology Data Exchange (ETDEWEB)

Griffiths, P.D. [Sheffield Univ. (United Kingdom). Acad. Dept. of Radiol.; Blaser, S.; Armstrong, D.; Chuang, S.; Harwood-Nash, D. [Division of Neuroradiology, The Hospital for Sick Children and University of Toronto, Toronto (Canada); Humphreys, R.P. [Division of Neurosurgery, The Hospital for Sick Children and University of Toronto, Toronto (Canada)

1998-05-01

We review the presentation, imaging findings and outcome in 18 children with cerebellar arteriovenous malformations (AVM). This group is of particular interest because of the reported poor outcome despite modern imaging and neurosurgical techniques. All children had CT and 15 underwent catheter angiography at presentation. Several of the children in the latter part of the study had MRI. Of the 18 children, 17 presented with a ruptured AVM producing intracranial haemorrhage. The remaining child presented with temporal lobe epilepsy and was shown to have temporal, vermian and cerebellar hemisphere AVM. This child had other stigmata of Osler-Weber-Rendu syndrome. Three other children had pre-existing abnormalities of possible relevance. One had a vascular malformation of the cheek and mandible, one a documented chromosomal abnormality and another a midline cleft upper lip and palate. Six of the 17 children with a ruptured cerebellar AVM died within 7 days of the ictus. Vascular pathology other than an AVM was found in 10 of the 14 children with a ruptured cerebellar AVM who had angiography: 4 intranidal aneurysms, 5 venous aneurysms and 2 cases of venous outflow obstruction (one child having both an aneurysm and obstruction). The severity of clinical presentation was directly related to the size of the acute haematoma, which was a reasonable predictor of outcome. (orig.) With 4 figs., 4 tabs., 23 refs.

Contralateral cortico-ponto-cerebellar pathways reconstruction in humans in vivo: implications for reciprocal cerebro-cerebellar structural connectivity in motor and non-motor areas.

Science.gov (United States)

Palesi, Fulvia; De Rinaldis, Andrea; Castellazzi, Gloria; Calamante, Fernando; Muhlert, Nils; Chard, Declan; Tournier, J Donald; Magenes, Giovanni; D'Angelo, Egidio; Gandini Wheeler-Kingshott, Claudia A M

2017-10-09

Cerebellar involvement in cognition, as well as in sensorimotor control, is increasingly recognized and is thought to depend on connections with the cerebral cortex. Anatomical investigations in animals and post-mortem humans have established that cerebro-cerebellar connections are contralateral to each other and include the cerebello-thalamo-cortical (CTC) and cortico-ponto-cerebellar (CPC) pathways. CTC and CPC characterization in humans in vivo is still challenging. Here advanced tractography was combined with quantitative indices to compare CPC to CTC pathways in healthy subjects. Differently to previous studies, our findings reveal that cerebellar cognitive areas are reached by the largest proportion of the reconstructed CPC, supporting the hypothesis that a CTC-CPC loop provides a substrate for cerebro-cerebellar communication during cognitive processing. Amongst the cerebral areas identified using in vivo tractography, in addition to the cerebral motor cortex, major portions of CPC streamlines leave the prefrontal and temporal cortices. These findings are useful since provide MRI-based indications of possible subtending connectivity and, if confirmed, they are going to be a milestone for instructing computational models of brain function. These results, together with further multi-modal investigations, are warranted to provide important cues on how the cerebro-cerebellar loops operate and on how pathologies involving cerebro-cerebellar connectivity are generated.

Modality specificity in the cerebro-cerebellar neurocircuitry during working memory.

Science.gov (United States)

Ng, H B Tommy; Kao, K-L Cathy; Chan, Y C; Chew, Effie; Chuang, K H; Chen, S H Annabel

2016-05-15

Previous studies have suggested cerebro-cerebellar circuitry in working memory. The present fMRI study aims to distinguish differential cerebro-cerebellar activation patterns in verbal and visual working memory, and employs a quantitative analysis to deterimine lateralization of the activation patterns observed. Consistent with Chen and Desmond (2005a,b) predictions, verbal working memory activated a cerebro-cerebellar circuitry that comprised left-lateralized language-related brain regions including the inferior frontal and posterior parietal areas, and subcortically, right-lateralized superior (lobule VI) and inferior cerebellar (lobule VIIIA/VIIB) areas. In contrast, a distributed network of bilateral inferior frontal and inferior temporal areas, and bilateral superior (lobule VI) and inferior (lobule VIIB) cerebellar areas, was recruited during visual working memory. Results of the study verified that a distinct cross cerebro-cerebellar circuitry underlies verbal working memory. However, a neural circuitry involving specialized brain areas in bilateral neocortical and bilateral cerebellar hemispheres subserving visual working memory is observed. Findings are discussed in the light of current models of working memory and data from related neuroimaging studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Cerebellar giant cell glioblastoma multiforme in an adult

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Sudhansu Sekhar Mishra

2014-01-01

Full Text Available Cerebellar glioblastoma multiforme (GBM is a rare tumor that accounts for only 1% of all cases of GBM and its giant cell variant is even much rarely encountered in adults. A case of cerebellar giant cell GBM managed at our institution reporting its clinical presentation, radiological and histological findings, and treatment instituted is described. In conjunction, a literature review, including particular issues, clinical data, advances in imaging studies, pathological characteristics, treatment options, and the behavior of such malignant tumor is presented. It is very important for the neurosurgeon to make the differential diagnosis between the cerebellar GBM, and other diseases such as metastasis, anaplastic astrocytomas, and cerebellar infarct because their treatment modalities, prognosis, and outcome are different.

Biochemical and functional correlates of an increased membrane density of caveolae in hypertrophic rat urinary bladder.

Science.gov (United States)

Shakirova, Yulia; Swärd, Karl; Uvelius, Bengt; Ekman, Mari

2010-12-15

Organ hypertrophy is often found to be associated with changes in the expression of caveolins and altered density of caveolae in the membrane. A plethora of signalling intermediaries are associated with caveolae and loss of caveolae has profound effects on contractility of the urinary bladder. We hypothesized that smooth muscle hypertrophy caused by bladder outflow obstruction (BOO) might lead to an altered caveola density with consequences for contractile regulation. Rat BOO for 6 weeks caused a 2.56-fold increase in the number of smooth muscle caveolae per μm membrane. No changes in the expression of caveolin-1 or cavin-1, normalized to β-actin were seen, but membrane area per unit muscle volume dropped to 0.346. Hypertrophy was associated with altered contraction in response to carbachol. The effect on contraction of cholesterol desorption, which disrupts lipid rafts and caveolae, was however not changed. Contraction in response to bradykinin resisted mβcd in control destrusor, but was inhibited by it after 6 weeks of obstruction. It is concluded that rat detrusor hypertrophy leads to an increased number of caveolae per unit membrane area. This change is due to a reduction of membrane area per volume muscle and it does not play a role for cholinergic activation, but promotes contraction in response to bradykinin after long-term obstruction. Copyright © 2010 Elsevier B.V. All rights reserved.

The protective effect of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes.

Science.gov (United States)

Mohamed, Jamaludin; Shing, Saw Wuan; Idris, Muhd Hanis Md; Budin, Siti Balkis; Zainalabidin, Satirah

2013-10-01

The aim of this study was to investigate the protective effects of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell (RBC) membrane oxidative stress in rats with streptozotocin-induced diabetes. Forty male Sprague-Dawley rats weighing 230-250 g were randomly divided into four groups (n = 10 rats each): control group (N), roselle-treated control group, diabetic group, and roselle-treated diabetic group. Roselle was administered by force-feeding with aqueous extracts of roselle (100 mg/kg body weight) for 28 days. The results demonstrated that the malondialdehyde levels of the red blood cell membranes in the diabetic group were significantly higher than the levels in the roselle-treated control and roselle-treated diabetic groups. The protein carbonyl level was significantly higher in the roselle-treated diabetic group than in the roselle-treated control group but lower than that in the diabetic group. A significant increase in the red blood cell membrane superoxide dismutase enzyme was found in roselle-treated diabetic rats compared with roselle-treated control rats and diabetic rats. The total protein level of the red blood cell membrane, osmotic fragility, and red blood cell morphology were maintained. The present study demonstrates that aqueous extracts of roselle possess a protective effect against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes. These data suggest that roselle can be used as a natural antioxidative supplement in the prevention of oxidative damage in diabetic patients.

Pentoxifylline Ameliorates Glomerular Basement Membrane Ultrastructural Changes Caused by Gentamicin Administration in Rats

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Nenad Stojiljković

2009-08-01

Full Text Available Gentamicin is commonly used for the treatment of severe gram negative bacterial infections but inevi-tably cause renal failure during prolonged use. The aim of our study was to emphasize protective effects of pentoxifylline on glomerular basement membrane (GBM alterations induced by gentamicin in rats. Experiments were done on 40 male Wistar rats divided in three experimental groups. GM-group was treated daily with gentamicin in dose of 100 mg/kg during 8 days. PTX-group was treated daily with pentoxifylline in dose of 45 mg/kg and the same dose of gentamicin as in GM-group during 8 days. The control group received 1 ml/day saline intraperitoneally. Morphometric parameter measured during the analysis was glomerular basement membrane thickness. In GM-group of animals glomeruli were en-larged and GMB was diffusely and unequally thickened with neutrophil cells infiltration. In proximal tu-bules epithelial cells, vacuolization of cytoplasm with coagulation-type necrosis were observed. In PTX-group of animals glomeruli were somewhat enlarged and GBM was thickened only in some segments. Coagulation-type necrosis was not found. Blood urea and serum creatinine concentration in GM-group were significantly elevated in comparison with PTX-group while potassium level was decreased. Our results suggest that PTX has protective effects on GBM and proximal tubules in GM-treated rats.

Perinatal intermittent hypoxia alters γ-aminobutyric acid: a receptor levels in rat cerebellum.

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Pae, Eung-Kwon; Yoon, Audrey J; Ahuja, Bhoomika; Lau, Gary W; Nguyen, Daniel D; Kim, Yong; Harper, Ronald M

2011-12-01

Perinatal hypoxia commonly causes brain injury in infants, but the time course and mechanisms underlying the preferential male injury are unclear. Intermittent hypoxia disturbs cerebellar γ-aminobutyric (GABA)-A receptor profiles during the perinatal period, possibly responding to transient excitatory processes associated with GABA(A) receptors. We examined whether hypoxic insults were particularly damaging to the male rodent cerebellum during a specific developmental time window. We evaluated cerebellar injury and GABA(A) receptor profiles following 5-h intermittent hypoxia (IH: 20.8% and 10.3% ambient oxygen, switched every 240s) or room-air control in groups of male and female rat pups on postnatal d 1-2, wk 1, or wk 3. The cerebella were harvested and compared between groups. The mRNA levels of GABA(A) receptors α6, normalized to a house-keeping gene GAPDH, and assessed using real-time reverse-transcriptase PCR assays were up-regulated by IH at wk 1, more extensively in male rats, with sex influencing the regulatory time-course. In contrast, GABA(A) α6 receptor protein expression levels, assessed using Western blot assays, reached a nadir at wk 1 in both male and female rats, possibly indicating involvement of a post-transcriptional mechanism. The extent of cerebellar damage and level of apoptosis, assessed by DNA fragmentation, were greatest in the wk 3 IH-exposed group. The findings suggest partial protection for female rats against early hypoxic insult in the cerebellum, and that down-regulation of GABA(A) receptors, rather than direct neural injury assessed by DNA fragmentation may modify cerebellar function, with potential later motor and other deficits. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

Aberrant cerebellar connectivity in bipolar disorder with psychosis.

Science.gov (United States)

Shinn, Ann K; Roh, Youkyung S; Ravichandran, Caitlin T; Baker, Justin T; Öngür, Dost; Cohen, Bruce M

2017-07-01

The cerebellum, which modulates affect and cognition in addition to motor functions, may contribute substantially to the pathophysiology of mood and psychotic disorders, such as bipolar disorder. A growing literature points to cerebellar abnormalities in bipolar disorder. However, no studies have investigated the topographic representations of resting state cerebellar networks in bipolar disorder, specifically their functional connectivity to cerebral cortical networks. Using a well-defined cerebral cortical parcellation scheme as functional connectivity seeds, we compared ten cerebellar resting state networks in 49 patients with bipolar disorder and a lifetime history of psychotic features and 55 healthy control participants matched for age, sex, and image signal-to-noise ratio. Patients with psychotic bipolar disorder showed reduced cerebro-cerebellar functional connectivity in somatomotor A, ventral attention, salience, and frontoparietal control A and B networks relative to healthy control participants. These findings were not significantly correlated with current symptoms. Patients with psychotic bipolar disorder showed evidence of cerebro-cerebellar dysconnectivity in selective networks. These disease-related changes were substantial and not explained by medication exposure or substance use. Therefore, they may be mechanistically relevant to the underlying susceptibility to mood dysregulation and psychosis. Cerebellar mechanisms deserve further exploration in psychiatric conditions, and this study's findings may have value in guiding future studies on pathophysiology and treatment of mood and psychotic disorders, in particular.

Cerebellar mutism: review of the literature

DEFF Research Database (Denmark)

Gudrunardottir, Thora; Sehested, Astrid; Juhler, Marianne

2011-01-01

Cerebellar mutism is a common complication of posterior fossa surgery in children. This article reviews current status with respect to incidence, anatomical substrate, pathophysiology, risk factors, surgical considerations, treatment options, prognosis and prevention.......Cerebellar mutism is a common complication of posterior fossa surgery in children. This article reviews current status with respect to incidence, anatomical substrate, pathophysiology, risk factors, surgical considerations, treatment options, prognosis and prevention....

Acute Cerebellar Ataxia Induced by Nivolumab

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Kawamura, Reina; Nagata, Eiichiro; Mukai, Masako; Ohnuki, Yoichi; Matsuzaki, Tomohiko; Ohiwa, Kana; Nakagawa, Tomoki; Kohno, Mitsutomo; Masuda, Ryota; Iwazaki, Masayuki; Takizawa, Shunya

2017-01-01

A 54-year-old woman with adenocarcinoma of the lung and lymph node metastasis experienced nystagmus and cerebellar ataxia 2 weeks after initiating nivolumab therapy. An evaluation for several autoimmune-related antibodies and paraneoplastic syndrome yielded negative results. We eventually diagnosed the patient with nivolumab-induced acute cerebellar ataxia, after excluding other potential conditions. Her ataxic gait and nystagmus resolved shortly after intravenous steroid pulse therapy follow...

Disorganized foliation of unilateral cerebellar hemisphere as cerebellar cortical dysplasia in patients with recurrent seizures: A case report

Energy Technology Data Exchange (ETDEWEB)

Baek, Hye Jin [Dept. of Radiology, Haeundae Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

2013-09-15

We present a rare case of abnormal foliation for one cerebellar hemisphere on MR imaging, showing vertically-oriented folia. Foliation of contralateral cerebellar hemisphere and other structures in the posterior fossa were normal, and the patient has no neurologic deficits. This rare and unique abnormality is considered a kind of developmental error of the cerebellum.

Oxidative Stress Parameters and Erythrocyte Membrane Adenosine Triphosphatase Activities in Streptozotocin-induced Diabetic Rats Administered Aqueous Preparation of Kalanchoe Pinnata Leaves.

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Menon, Nikhil; Sparks, Jean; Omoruyi, Felix O

2016-01-01

Diabetes mellitus is a chronic metabolic disease that according to the World Health Organization affects more than 382 million people. The rise in diabetes mellitus coupled with the lack of an effective treatment has led many to investigate medicinal plants to identify a viable alternative. To evaluate red blood cell (RBC) membrane adenosine triphosphatase (ATPase) activities and antioxidant levels in streptozotocin-induced diabetic rats administered aqueous preparation of Kalanchoe pinnata leaves. Diabetes mellitus was induced in rats by a single administration of streptozotocin (60 mg/kg). Diabetic rats were then treated with aqueous K. pinnata preparation (three mature leaves ~ 9.96 g/70 kg body weight or about 0.14 g/kg body weight/day) for 30 days. Serum glucose, RBC membrane ATPase activities, and antioxidant levels were determined. We noted weight loss and reduced food consumption in the treated diabetic group. Serum glucose levels were reduced in the treated diabetic group compared to the other groups. Superoxide dismutase activity and glutathione levels were not significantly elevated in the treated group compared to the diabetic group. However, serum catalase activity was significantly (P < 0.05) increased in the treated diabetic group compared to the other groups. Serum thiobarbituric acid reactive substances were not significantly altered among the groups. There was a significant (P < 0.05) increase in Mg(2+) ATPase activity and a nonsignificant increase in Na(+)/K(+) ATPase activity in the RBC membrane of the treated diabetic group compared to the diabetic group. The consumption of aqueous preparation of K. pinnata may accrue benefits in the management of diabetes by lowering oxidative stress often associated with the disease and improving the availability of cellular magnesium through an increase in the magnesium ATPase pump in the RBC membrane for increased cellular metabolism of glucose through the glycolytic pathway. We noted weight loss and

Defects in the CAPN1 Gene Result in Alterations in Cerebellar Development and Cerebellar Ataxia in Mice and Humans

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Yubin Wang

2016-06-01

Full Text Available A CAPN1 missense mutation in Parson Russell Terrier dogs is associated with spinocerebellar ataxia. We now report that homozygous or heterozygous CAPN1-null mutations in humans result in cerebellar ataxia and limb spasticity in four independent pedigrees. Calpain-1 knockout (KO mice also exhibit a mild form of ataxia due to abnormal cerebellar development, including enhanced neuronal apoptosis, decreased number of cerebellar granule cells, and altered synaptic transmission. Enhanced apoptosis is due to absence of calpain-1-mediated cleavage of PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1, which results in inhibition of the Akt pro-survival pathway in developing granule cells. Injection of neonatal mice with the indirect Akt activator, bisperoxovanadium, or crossing calpain-1 KO mice with PHLPP1 KO mice prevented increased postnatal cerebellar granule cell apoptosis and restored granule cell density and motor coordination in adult mice. Thus, mutations in CAPN1 are an additional cause of ataxia in mammals, including humans.

Anomalous cerebellar anatomy in Chinese children with dyslexia

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Ying-Hui eYang

2016-03-01

Full Text Available The cerebellar deficit hypothesis for developmental dyslexia (DD claims that cerebellar dysfunction causes the failures in the acquisition of visuomotor skills and automatic reading and writing skills. In people with dyslexia in the alphabetic languages, the abnormal activation and structure of the right or bilateral cerebellar lobes have been identified. Using a typical implicit motor learning task, however, one neuroimaging study demonstrated the left cerebellar dysfunction in Chinese children with dyslexia. In the present study, using voxel-based morphometry, we found decreased gray matter volume in the left cerebellum in Chinese children with dyslexia relative to age-matched controls. The positive correlation between reading performance and regional gray matter volume suggests that the abnormal structure in the left cerebellum is responsible for reading disability in Chinese children with dyslexia.

Network-targeted cerebellar transcranial magnetic stimulation improves attentional control

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Esterman, Michael; Thai, Michelle; Okabe, Hidefusa; DeGutis, Joseph; Saad, Elyana; Laganiere, Simon E.; Halko, Mark A.

2018-01-01

Developing non-invasive brain stimulation interventions to improve attentional control is extremely relevant to a variety of neurologic and psychiatric populations, yet few studies have identified reliable biomarkers that can be readily modified to improve attentional control. One potential biomarker of attention is functional connectivity in the core cortical network supporting attention - the dorsal attention network (DAN). We used a network-targeted cerebellar transcranial magnetic stimulation (TMS) procedure, intended to enhance cortical functional connectivity in the DAN. Specifically, in healthy young adults we administered intermittent theta burst TMS (iTBS) to the midline cerebellar node of the DAN and, as a control, the right cerebellar node of the default mode network (DMN). These cerebellar targets were localized using individual resting-state fMRI scans. Participants completed assessments of both sustained (gradual onset continuous performance task, gradCPT) and transient attentional control (attentional blink) immediately before and after stimulation, in two sessions (cerebellar DAN and DMN). Following cerebellar DAN stimulation, participants had significantly fewer attentional lapses (lower commission error rates) on the gradCPT. In contrast, stimulation to the cerebellar DMN did not affect gradCPT performance. Further, in the DAN condition, individuals with worse baseline gradCPT performance showed the greatest enhancement in gradCPT performance. These results suggest that temporarily increasing functional connectivity in the DAN via network-targeted cerebellar stimulation can enhance sustained attention, particularly in those with poor baseline performance. With regard to transient attention, TMS stimulation improved attentional blink performance across both stimulation sites, suggesting increasing functional connectivity in both networks can enhance this aspect of attention. These findings have important implications for intervention applications

Structural alterations of the DNA in cerebellar neurons after whole-brain irradiation

International Nuclear Information System (INIS)

Wheeler, K.T.; Winstein, R.E.; Kaufman, K.; Ritter, P.

1981-01-01

Male Sprague-Dawley rats weighing 260 to 280 g were whole-brain-irradiated with x-ray doses of 433, 867, 1083, 1300, 1516, and 1713 rad. Over the next 2.25 years rats were killed at various times, and the state of the DNA in their cerebellar neurons was examined by sedimentation through alkaline sucrose gradients in reorienting zonal rotors. The data were analyzed as the percentage of the sedimenting DNA with sedimentation coefficients greater than 300 S, an arbitrarily selected category of no defined molecular significance. The general pattern at all doses consisted first of a slow return to the unirradiated DNA state that was relatively dose dependent. This was followed by an increase in the amount of DNA sedimenting >300 S; both the extent and time course of this increase appeared to be dose dependent. Finally, the DNA degraded at a relatively dose independent rate. There was little change in the neuronal DNA from unirradiated rats during this study. The data suggest that increases in the amount of fast-sedimenting DNA observed 30 to 80 weeks after low to moderate doses of whole-brain irradiation represent a type of DNA damage rather than repair and that this damage ultimately results in degradation of the neuronal DNA and death of the rat

Plasma membrane fatty acid-binding protein and mitochondrial glutamic-oxaloacetic transaminase of rat liver are related

International Nuclear Information System (INIS)

Berk, P.D.; Potter, B.J.; Sorrentino, D.; Zhou, S.L.; Isola, L.M.; Stump, D.; Kiang, C.L.; Thung, S.; Wada, H.; Horio, Y.

1990-01-01

The hepatic plasma membrane fatty acid-binding protein (h-FABP PM ) and the mitochondrial isoenzyme of glutamic-oxaloacetic transaminase (mGOT) of rat liver have similar amino acid compositions and identical amino acid sequences for residues 3-24. Both proteins migrate with an apparent molecular mass of 43 kDa on SDS/polyacrylamide gel electrophoresis, have a similar pattern of basic charge isomers on isoelectric focusing, are eluted similarly from four different high-performance liquid chromatographic columns, have absorption maxima at 435 nm under acid conditions and 354 nm at pH 8.3, and bind oleate. Sinusoidally enriched liver plasma membranes and purified h-FABP PM have GOT enzymatic activity. Monospecific rabbit antiserum against h-FABP PM reacts on Western blotting with mGOT, and vice versa. Antisera against both proteins produce plasma membrane immunofluorescence in rat hepatocytes and selectively inhibit the hepatocellular uptake of [ 3 H]oleate but not that of [ 35 S]sulfobromophthalein or [ 14 C]taurocholate. The inhibition of oleate uptake produced by anti-h-FABP PM can be eliminated by preincubation of the antiserum with mGOT; similarly, the plasma membrane immunofluorescence produced by either antiserum can be eliminated by preincubation with the other antigen. These data suggest that h-FABP PM and mGOT are closely related

Recent Advances in Cerebellar Ischemic Stroke Syndromes Causing Vertigo and Hearing Loss.

Science.gov (United States)

Kim, Hyun-Ah; Yi, Hyon-Ah; Lee, Hyung

2016-12-01

Cerebellar ischemic stroke is one of the common causes of vascular vertigo. It usually accompanies other neurological symptoms or signs, but a small infarct in the cerebellum can present with vertigo without other localizing symptoms. Approximately 11 % of the patients with isolated cerebellar infarction simulated acute peripheral vestibulopathy, and most patients had an infarct in the territory of the medial branch of the posterior inferior cerebellar artery (PICA). A head impulse test can differentiate acute isolated vertigo associated with PICA territory cerebellar infarction from more benign disorders involving the inner ear. Acute hearing loss (AHL) of a vascular cause is mostly associated with cerebellar infarction in the territory of the anterior inferior cerebellar artery (AICA), but PICA territory cerebellar infarction rarely causes AHL. To date, at least eight subgroups of AICA territory infarction have been identified according to the pattern of neurotological presentations, among which the most common pattern of audiovestibular dysfunction is the combined loss of auditory and vestibular functions. Sometimes acute isolated audiovestibular loss can be the initial symptom of impending posterior circulation ischemic stroke (particularly within the territory of the AICA). Audiovestibular loss from cerebellar infarction has a good long-term outcome than previously thought. Approximately half of patients with superior cerebellar artery territory (SCA) cerebellar infarction experienced true vertigo, suggesting that the vertigo and nystagmus in the SCA territory cerebellar infarctions are more common than previously thought. In this article, recent findings on clinical features of vertigo and hearing loss from cerebellar ischemic stroke syndrome are summarized.

The observation of blood-brain barrier of organic mercury poisoned rat

International Nuclear Information System (INIS)

Kuwabara, Takeo; Yuasa, Tatsuhiko; Hidaka, Kazuyuki; Igarashi, Hironaka; Kaneko, Kiyotoshi; Miyatake, Tadashi

1989-01-01

Permeability of the blood-brain barrier (BBB) of methymercury chrolide (MMC) intoxicated rat brain was studied in vivo by gadlinium diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI), measuring the longitudinal relaxation time (T 1 ) and the transverse relaxation time (T 2 ). MMC intoxicated rat brain showed the prolonged T 1 in the cerebral white matter and prolonged T 2 in the cerebellar cortex. After Gd-DTPA administration, T 1 of cerebral and cerebellar white matter shortened from 1.647 to 1.344 sec., and 1.290 to 1.223 sec. respectively. On the contrary, T 2 showed no change after Gd-DTPA injection. It was concluded that, although the shortening of T 1 after Gd-DTPA enhancement was rather little when compared with experimental brain ischemia, the shortening of the relaxation time of the MMC intoxicated rat brain was caused by the increased permeability of BBB. (author)

Stabilization of mitochondrial membrane potential prevents doxorubicin-induced cardiotoxicity in isolated rat heart

International Nuclear Information System (INIS)

Montaigne, David; Marechal, Xavier; Baccouch, Riadh; Modine, Thomas; Preau, Sebastien; Zannis, Konstantinos; Marchetti, Philippe; Lancel, Steve; Neviere, Remi

2010-01-01

The present study was undertaken to examine the effects of doxorubicin on left ventricular function and cellular energy state in intact isolated hearts, and, to test whether inhibition of mitochondrial membrane potential dissipation would prevent doxorubicin-induced mitochondrial and myocardial dysfunction. Myocardial contractile performance and mitochondrial respiration were evaluated by left ventricular tension and its first derivatives and cardiac fiber respirometry, respectively. NADH levels, mitochondrial membrane potential and glucose uptake were monitored non-invasively via epicardial imaging of the left ventricular wall of Langendorff-perfused rat hearts. Heart performance was reduced in a time-dependent manner in isolated rat hearts perfused with Krebs-Henseleit solution containing 1 μM doxorubicin. Compared with controls, doxorubicin induced acute myocardial dysfunction (dF/dt max of 105 ± 8 mN/s in control hearts vs. 49 ± 7 mN/s in doxorubicin-treated hearts; *p < 0.05). In cardiac fibers prepared from perfused hearts, doxorubicin induced depression of mitochondrial respiration (respiratory control ratio of 4.0 ± 0.2 in control hearts vs. 2.2 ± 0.2 in doxorubicin-treated hearts; *p < 0.05) and cytochrome c oxidase kinetic activity (24 ± 1 μM cytochrome c/min/mg in control hearts vs. 14 ± 3 μM cytochrome c/min/mg in doxorubicin-treated hearts; *p < 0.05). Acute cardiotoxicity induced by doxorubicin was accompanied by NADH redox state, mitochondrial membrane potential, and glucose uptake reduction. Inhibition of mitochondrial permeability transition pore opening by cyclosporine A largely prevented mitochondrial membrane potential dissipation, cardiac energy state and dysfunction. These results suggest that in intact hearts an impairment of mitochondrial metabolism is involved in the development of doxorubicin cardiotoxicity.

Learning of Sensory Sequences in Cerebellar Patients

Science.gov (United States)

Frings, Markus; Boenisch, Raoul; Gerwig, Marcus; Diener, Hans-Christoph; Timmann, Dagmar

2004-01-01

A possible role of the cerebellum in detecting and recognizing event sequences has been proposed. The present study sought to determine whether patients with cerebellar lesions are impaired in the acquisition and discrimination of sequences of sensory stimuli of different modalities. A group of 26 cerebellar patients and 26 controls matched for…

The clinical impact of cerebellar grey matter pathology in multiple sclerosis.

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Alfredo Damasceno

Full Text Available BACKGROUND: The cerebellum is an important site for cortical demyelination in multiple sclerosis, but the functional significance of this finding is not fully understood. OBJECTIVE: To evaluate the clinical and cognitive impact of cerebellar grey-matter pathology in multiple sclerosis patients. METHODS: Forty-two relapsing-remitting multiple sclerosis patients and 30 controls underwent clinical assessment including the Multiple Sclerosis Functional Composite, Expanded Disability Status Scale (EDSS and cerebellar functional system (FS score, and cognitive evaluation, including the Paced Auditory Serial Addition Test (PASAT and the Symbol-Digit Modalities Test (SDMT. Magnetic resonance imaging was performed with a 3T scanner and variables of interest were: brain white-matter and cortical lesion load, cerebellar intracortical and leukocortical lesion volumes, and brain cortical and cerebellar white-matter and grey-matter volumes. RESULTS: After multivariate analysis high burden of cerebellar intracortical lesions was the only predictor for the EDSS (p<0.001, cerebellar FS (p = 0.002, arm function (p = 0.049, and for leg function (p<0.001. Patients with high burden of cerebellar leukocortical lesions had lower PASAT scores (p = 0.013, while patients with greater volumes of cerebellar intracortical lesions had worse SDMT scores (p = 0.015. CONCLUSIONS: Cerebellar grey-matter pathology is widely present and contributes to clinical dysfunction in relapsing-remitting multiple sclerosis patients, independently of brain grey-matter damage.

Effect of the Human Amniotic Membrane on Liver Regeneration in Rats

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Mesut Sipahi

2015-01-01

Full Text Available Introduction. Operations are performed for broader liver surgery indications for a better understanding of hepatic anatomy/physiology and developments in operation technology. Surgery can cure some patients with liver metastasis of some tumors. Nevertheless, postoperative liver failure is the most feared complication causing mortality in patients who have undergone excision of a large liver mass. The human amniotic membrane has regenerative effects. Thus, we investigated the effects of the human amniotic membrane on regeneration of the resected liver. Methods. Twenty female Wistar albino rats were divided into control and experimental groups and underwent a 70% hepatectomy. The human amniotic membrane was placed over the residual liver in the experimental group. Relative liver weight, histopathological features, and biochemical parameters were assessed on postoperative day 3. Results. Total protein and albumin levels were significantly lower in the experimental group than in the control group. No difference in relative liver weight was observed between the groups. Hepatocyte mitotic count was significantly higher in the experimental group than in the control group. Hepatic steatosis was detected in the experimental group. Conclusion. Applying the amniotic membrane to residual liver adversely affected liver regeneration. However, mesenchymal stem cell research has the potential to accelerate liver regeneration investigations.

Microvascular anatomy of the cerebellar parafloccular perforating space.

Science.gov (United States)

Sosa, Pablo; Dujovny, Manuel; Onyekachi, Ibe; Sockwell, Noressia; Cremaschi, Fabián; Savastano, Luis E

2016-02-01

The cerebellopontine angle is a common site for tumor growth and vascular pathologies requiring surgical manipulations that jeopardize cranial nerve integrity and cerebellar and brainstem perfusion. To date, a detailed study of vessels perforating the cisternal surface of the middle cerebellar peduncle-namely, the paraflocculus or parafloccular perforating space-has yet to be published. In this report, the perforating vessels of the anterior inferior cerebellar artery (AICA) in the parafloccular space, or on the cisternal surface of the middle cerebellar peduncle, are described to elucidate their relevance pertaining to microsurgery and the different pathologies that occur at the cerebellopontine angle. Fourteen cadaveric cerebellopontine cisterns (CPCs) were studied. Anatomical dissections and analysis of the perforating arteries of the AICA and posterior inferior cerebellar artery at the parafloccular space were recorded using direct visualization by surgical microscope, optical histology, and scanning electron microscope. A comprehensive review of the English-language and Spanish-language literature was also performed, and findings related to anatomy, histology, physiology, neurology, neuroradiology, microsurgery, and endovascular surgery pertaining to the cerebellar flocculus or parafloccular spaces are summarized. A total of 298 perforating arteries were found in the dissected specimens, with a minimum of 15 to a maximum of 26 vessels per parafloccular perforating space. The average outer diameter of the cisternal portion of the perforating arteries was 0.11 ± 0.042 mm (mean ± SD) and the average length was 2.84 ± 1.2 mm. Detailed schematics and the surgical anatomy of the perforating vessels at the CPC and their clinical relevance are reported. The parafloccular space is a key entry point for many perforating vessels toward the middle cerebellar peduncle and lateral brainstem, and it must be respected and protected during surgical approaches to the

The protective effect of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2 against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes

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Jamaludin Mohamed

2013-10-01

Full Text Available OBJECTIVES: The aim of this study was to investigate the protective effects of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2 against red blood cell (RBC membrane oxidative stress in rats with streptozotocin-induced diabetes. METHODS: Forty male Sprague-Dawley rats weighing 230-250 g were randomly divided into four groups (n = 10 rats each: control group (N, roselle-treated control group, diabetic group, and roselle-treated diabetic group. Roselle was administered by force-feeding with aqueous extracts of roselle (100 mg/kg body weight for 28 days. RESULTS: The results demonstrated that the malondialdehyde levels of the red blood cell membranes in the diabetic group were significantly higher than the levels in the roselle-treated control and roselle-treated diabetic groups. The protein carbonyl level was significantly higher in the roselle-treated diabetic group than in the roselle-treated control group but lower than that in the diabetic group. A significant increase in the red blood cell membrane superoxide dismutase enzyme was found in roselle-treated diabetic rats compared with roselle-treated control rats and diabetic rats. The total protein level of the red blood cell membrane, osmotic fragility, and red blood cell morphology were maintained. CONCLUSION: The present study demonstrates that aqueous extracts of roselle possess a protective effect against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes. These data suggest that roselle can be used as a natural antioxidative supplement in the prevention of oxidative damage in diabetic patients.

The protective effect of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes

Science.gov (United States)

Mohamed, Jamaludin; Shing, Saw Wuan; Md Idris, Muhd Hanis; Budin, Siti Balkis; Zainalabidin, Satirah

2013-01-01

OBJECTIVES: The aim of this study was to investigate the protective effects of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell (RBC) membrane oxidative stress in rats with streptozotocin-induced diabetes. METHODS: Forty male Sprague-Dawley rats weighing 230-250 g were randomly divided into four groups (n = 10 rats each): control group (N), roselle-treated control group, diabetic group, and roselle-treated diabetic group. Roselle was administered by force-feeding with aqueous extracts of roselle (100 mg/kg body weight) for 28 days. RESULTS: The results demonstrated that the malondialdehyde levels of the red blood cell membranes in the diabetic group were significantly higher than the levels in the roselle-treated control and roselle-treated diabetic groups. The protein carbonyl level was significantly higher in the roselle-treated diabetic group than in the roselle-treated control group but lower than that in the diabetic group. A significant increase in the red blood cell membrane superoxide dismutase enzyme was found in roselle-treated diabetic rats compared with roselle-treated control rats and diabetic rats. The total protein level of the red blood cell membrane, osmotic fragility, and red blood cell morphology were maintained. CONCLUSION: The present study demonstrates that aqueous extracts of roselle possess a protective effect against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes. These data suggest that roselle can be used as a natural antioxidative supplement in the prevention of oxidative damage in diabetic patients. PMID:24212844

The dynamic relationship between cerebellar Purkinje cell simple spikes and the spikelet number of complex spikes.

Science.gov (United States)

Burroughs, Amelia; Wise, Andrew K; Xiao, Jianqiang; Houghton, Conor; Tang, Tianyu; Suh, Colleen Y; Lang, Eric J; Apps, Richard; Cerminara, Nadia L

2017-01-01

Purkinje cells are the sole output of the cerebellar cortex and fire two distinct types of action potential: simple spikes and complex spikes. Previous studies have mainly considered complex spikes as unitary events, even though the waveform is composed of varying numbers of spikelets. The extent to which differences in spikelet number affect simple spike activity (and vice versa) remains unclear. We found that complex spikes with greater numbers of spikelets are preceded by higher simple spike firing rates but, following the complex spike, simple spikes are reduced in a manner that is graded with spikelet number. This dynamic interaction has important implications for cerebellar information processing, and suggests that complex spike spikelet number may maintain Purkinje cells within their operational range. Purkinje cells are central to cerebellar function because they form the sole output of the cerebellar cortex. They exhibit two distinct types of action potential: simple spikes and complex spikes. It is widely accepted that interaction between these two types of impulse is central to cerebellar cortical information processing. Previous investigations of the interactions between simple spikes and complex spikes have mainly considered complex spikes as unitary events. However, complex spikes are composed of an initial large spike followed by a number of secondary components, termed spikelets. The number of spikelets within individual complex spikes is highly variable and the extent to which differences in complex spike spikelet number affects simple spike activity (and vice versa) remains poorly understood. In anaesthetized adult rats, we have found that Purkinje cells recorded from the posterior lobe vermis and hemisphere have high simple spike firing frequencies that precede complex spikes with greater numbers of spikelets. This finding was also evident in a small sample of Purkinje cells recorded from the posterior lobe hemisphere in awake cats. In addition

Study on the ultrastructure of brain in rats prenatally exposed to tritiated water

International Nuclear Information System (INIS)

Yang Zhiyuan; Guo Yuefen; Lai Chixiang

1993-01-01

At 11th day of gestation, rats were intraperitoneally injected with HTO, the activity of which were 5.55 x 10 6 Bq/mL of body water and 5.55 x 10 5 Bq/mL of body water. In these conditions, the cumulative doses for 1-day-old and 18-day-old young rats were estimated to be 1.6-1.7 Gy and 0.16-0.17 Gy, respectively. Under the above-mentioned conditions, some significant injuries in the ultrastructure of the nucleus of neutron and of the cell apparatuses in the cytoplasm of the cerebral and cerebellar cortexes can be seen on the 1-day-old and 18-day-old young rats. When young rats were 90 days old, these injuries of ultrastructure in brain cells had not be observed but it was observed that the processes of neutroglia cells replenished the crevices in injured neutropilem of the cerebral and cerebellar cortex

New evidence for the cerebellar involvement in personality traits

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Eleonora ePicerni

2013-10-01

Full Text Available Following the recognition of its role in sensory-motor coordination and learning, the cerebellum has been involved in cognitive, emotional and even personality domains. This study investigated the relationships between cerebellar macro- and micro-structural variations and temperamental traits measured by Temperament and Character Inventory (TCI. High resolution T1-weighted and Diffusion Tensor Images of 100 healthy subjects aged 18-59 years were acquired by 3 Tesla Magnetic Resonance scanner. In multiple regression analyses, cerebellar Gray Matter (GM or White Matter (WM volumes, GM Mean Diffusivity (MD, and WM Fractional Anisotropy (FA were used as dependent variables, TCI scores as regressors, gender, age, and education years as covariates. Novelty Seeking scores were associated positively with the cerebellar GM volumes and FA, and negatively with MD. No significant association between Harm Avoidance, Reward Dependence or Persistence scores and cerebellar structural measures was found. The present data put toward a cerebellar involvement in the management of novelty.

Radiation damages to cell membranes of dogs and rats quantitatively estimated by changes in sedimentation behaviour of erythrocytes

International Nuclear Information System (INIS)

Mikhajlov, V.F.; Potemkin, L.A.

1985-01-01

It was shown that injury to plasma membranes leads to a change in the sedimentation behaviour of erythrocytes: the maximum effect is produced when a protein component of the membrane is affected. The same dose dependent character of the change in erythrocyte sedimentation in urografine are observed during the first 24 h after γ-irradiation of rats and dogs

Insulin and adenosine regulate the phosphatidylcholine concentration in isolated rat adipocyte plasma membranes.

Science.gov (United States)

Kiechle, F L; Sykes, E; Artiss, J D

1995-01-01

Blockade of adenosine receptors by 3-isobutyl-1-methylxanthine or degradation of endogenous adenosine with adenosine deaminase increased the phosphatidylcholine concentration in isolated rat adipocyte plasma membranes, an effect which was suppressed by the phosphatidylethanolamine methyltransferase inhibitor, S-adenosyl-L-homocysteine, and reversed by the adenosine analogue, N6-(L-phenylisopropyl)-adenosine. For example, the addition of N6-(L-phenylisopropyl)-adenosine to adenosine deaminase pretreated plasma membranes rapidly lowered the concentration of phosphatidylcholine by 171 nmol/mg at 30 seconds compared to control. Insulin-induced stimulation of phospholipid methylation in membranes treated with 3-isobutyl-1-methylxanthine or adenosine deaminase was achieved only after the addition of N6-(L-phenylisopropyl)-adenosine. These results suggest that adenosine receptor occupancy inhibits phospholipid methylation, is required for insulin stimulation of phospholipid methylation, and may perhaps activate a phosphatidylcholine-specific phospholipase C or phospholipase D.

Rat hair follicle dermal papillae have an extracellular matrix containing basement membrane components

DEFF Research Database (Denmark)

Couchman, J R

1986-01-01

, to be replaced by synthesis of other components including type I and III collagens. It seems likely therefore that the dermal papilla cells in vivo synthesize a basement membrane type of extracellular matrix, although a contribution from epithelial, and in some cases capillary endothelial, cells cannot be ruled......Dermal papillae are small mesenchymally derived zones at the bases of hair follicles which have an important role in hair morphogenesis in the embryo and control of the hair growth cycle in postnatal mammals. The cells of the papilla are enmeshed in a dense extracellular matrix which undergoes...... extensive changes in concert with the hair cycle. Here it is shown that this matrix in anagen pelage follicles of postnatal rats contains an abundance of basement membrane components rather than dermal components such as interstitial collagens. In particular, type IV collagen, laminin, and basement membrane...

Amphipaths Differentially Modulate Membrane Surface Deformation in Rat Peritoneal Mast Cells During Exocytosis

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Itsuro Kazama

2013-04-01

Full Text Available Background/Aims: Salicylate and chlorpromazine exert differential effects on the chemokine release from mast cells. Since these drugs are amphiphilic and preferentially partitioned into the lipid bilayers of the plasma membranes, they would induce some morphological changes in mast cells and thus affect the process of exocytosis. Methods: Employing the standard patch-clamp whole-cell recording technique, we examined the effects of salicylate and chlorpromazine on the membrane capacitance (Cm during exocytosis in rat peritoneal mast cells. Using confocal imaging of a water-soluble fluorescent dye, lucifer yellow, we also examined their effects on plasma membrane deformation of the cells. Results: Salicylate dramatically accelerated the GTP-γ-S-induced increase in the Cm immediately after its application, whereas chlorpromazine significantly suppressed the increase. Treatment with salicylate increased the trapping of the dye on the cell surface, while treatment with chlorpromazine completely washed it out, indicating that both drugs induced membrane surface deformation in mast cells. Conclusion: This study demonstrated for the first time that membrane amphipaths, such as salicylate and chlorpromazine, may oppositely modulate the process of exocytosis in mast cells, as detected by the changes in the Cm. The plasma membrane deformation induced by the drugs was thought to be responsible for their differential effects.

Verbal Memory Impairments in Children after Cerebellar Tumor Resection

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Matthew P. Kirschen

2008-01-01

Full Text Available This study was designed to investigate cerebellar lobular contributions to specific cognitive deficits observed after cerebellar tumor resection. Verbal working memory (VWM tasks were administered to children following surgical resection of cerebellar pilocytic astrocytomas and age-matched controls. Anatomical MRI scans were used to quantify the extent of cerebellar lobular damage from each patient's resection. Patients exhibited significantly reduced digit span for auditory but not visual stimuli, relative to controls, and damage to left hemispheral lobule VIII was significantly correlated with this deficit. Patients also showed reduced effects of articulatory suppression and this was correlated with damage to the vermis and hemispheral lobule IV/V bilaterally. Phonological similarity and recency effects did not differ overall between patients and controls, but outlier patients with abnormal phonological similarity effects to either auditory or visual stimuli were found to have damage to hemispheral lobule VIII/VIIB on the left and right, respectively. We postulate that damage to left hemispheral lobule VIII may interfere with encoding of auditory stimuli into the phonological store. These data corroborate neuroimaging studies showing focal cerebellar activation during VWM paradigms, and thereby allow us to predict with greater accuracy which specific neurocognitive processes will be affected by a cerebellar tumor resection.

Contribution of Somatic and Dendritic SK Channels in the Firing Rate of Deep Cerebellar Nuclei: Implication in Cerebellar Ataxia

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Samira Abbasi

2016-01-01

Discussion: Therefore, inhibition of SK channel in DCN can cause cerebellar ataxia, and SK channel openers can have a therapeutic effect on cerebellar ataxia. In addition, the location of SK channels could be important in therapeutic goals. Dendritic SK channels can be a more effective target compared to somatic SK channels

Endogenous glycosphingolipid acceptor specificity of sialosyltransferase systems in intact golgi membranes, synaptosomes, and synaptic plasma membranes from rat brain

International Nuclear Information System (INIS)

Durrie, R.; Saito, M.; Rosenberg, A.

1988-01-01

Preparations highly enriched in Golgi complex membranes, synaptosomes, and synaptic plasma membranes (SPM) by marker enzyme analysis and electron microscopic morphology were made from the brains of 28-day-old rats. These were incubated with cytidine 5'-monophosphate-N-acetyl[ 14 C]neuraminic acid (CMP-NeuAc) in a physiologic buffer, without detergents. Glycolipid sialosyltransferase activities (SATs) were measured by analyzing incorporation of radiolabeled NeuAc into endogenous membrane gangliosides. Golgi SAT was diversified in producing all the various molecular species of labeled gangliosides. Synaptosomal SAT exhibited a lower activity, but it was highly specific in its labeling pattern, with a marked preference for labeling NeuAcα2 → 8NeuAcα2 → 3Galβ1 → 4Glcβ1 → 1Cer (GD3 ganglioside). SPM prepared from the synaptosomes retained the GD3-related SAT (or SAT-2), and the total specific activity increased, which suggests that the location of the synaptosomal activity is in the SPM. These results indicate that SAT activity in Golgi membranes differs from that in synaptosomes with regard to endogenous acceptor substrate specificity and SAT activity of synaptosomes should be located in the synaptosomal plasma membrane. This SAT could function as an ectoenzyme in concert with ecto-sialidase to modulate the GD3 and other ganglioside population in situ at the SPM of the central nervous system

Differential distribution patterns in cerebellar irrigation. A study with autopsy material

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Hernando Yesid Estupiñan

2018-02-01

Full Text Available Aim: The aim of this investigation was characterize morphologically the cerebellar artery and its branches in a specimen of autopsy material. Methods: This descriptive cross-sectional study evaluated the anatomical characteristics of the cerebellar arteries and their branches in 93 brain stem and cerebellum blocks obtained from fresh cadavers. The specimens were perfused bilaterally channeling the proximal segments of the internal carotid and vertebral arteries with a semi-synthetic resin (Palatal GP40L 85%; styrene 15% impregnated with mineral red dye. We evaluated the distribution patterns of the cerebellar artery and its branches. Results: The calibers of the superior cerebellar artery (SCA, anterior inferior cerebellar artery (AICA and posterior inferior cerebellar artery (PICA were 1.46 ± 0.2 mm, 1.02 ± 0.35 mm and 1.45 ± 0.37 mm, respectively. Agenesis of the SCA was observed in six specimens (3.2%, AICA in 30 (16.1%, and PICA in 14 (7.5% specimens. Usual irrigation was observed in 44 (47.3% cerebellar blocks, whereas 49 (52.7% specimens showed irrigation variants, 23 (46.9% of which appeared bilaterally. The dominant distribution of the cerebellar arteries corresponded to SCA in 9 (12.5% cases, AICA in 46 (63.9% and PICA in 7 (9.7% specimens; shared dominance was found in 10 (13.9% specimens. Conclusion: The high variability of the cerebellar arteries observed in the present study is consistent with previous reports. The diverse anatomic expressions of the cerebellar arteries were typified in relation to their dominance and territories irrigated, useful for the diagnosis and clinical-surgical management of the cerebellum blood supply.

[Molecular organization of glutamate-sensitive chemoexcitatory membranes of nerve cells. Comparative analysis of glutamate-binding membrane proteins from the cerebral cortex of rats and humans].

Science.gov (United States)

Dambinova, S A; Gorodinskiĭ, A I; Lekomtseva, T M; Koreshonkov, O N

1987-10-01

The kinetics of 3H-L-glutamate binding to human brain synaptic membranes revealed the existence of one type of binding sites with Kd and Vmax comparable with those for freshly isolated rat brain membranes. The fraction of glutamate-binding proteins (GBP) was shown to contain three components with Mr of 14, 60 and 280 kD whose stoichiometry is specific for human and rat brain. All fractions were found to bind the radiolabeled neurotransmitter and to dissociate into subunits with Mr of 14 kD after treatment with-potent detergents (with the exception of the 56-60 kD component). Study of association-dissociation of GBP protein subunits by high performance liquid chromatography confirmed the hypothesis on the oligomeric structure of glutamate receptors which are made up of low molecular weight glycoprotein-lipid subunits and which form ionic channels by way of repeated association. Despite the similarity of antigen determinants in the active center of glutamate receptors from human and rat brain, it was assumed that the stoichiometry of structural organization of receptor subunits isolated from different sources is different. The functional role of structural complexity of human brain glutamate receptors is discussed.

Mathematical models of human cerebellar development in the fetal period.

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Dudek, Krzysztof; Nowakowska-Kotas, Marta; Kędzia, Alicja

2018-04-01

The evaluation of cerebellar growth in the fetal period forms a part of a widely used examination to identify any features of abnormalities in early stages of human development. It is well known that the development of anatomical structures, including the cerebellum, does not always follow a linear model of growth. The aim of the study was to analyse a variety of mathematical models of human cerebellar development in fetal life to determine their adequacy. The study comprised 101 fetuses (48 males and 53 females) between the 15th and 28th weeks of fetal life. The cerebellum was exposed and measurements of the vermis and hemispheres were performed, together with statistical analyses. The mathematical model parameters of fetal growth were assessed for crown-rump length (CRL) increases, transverse cerebellar diameter and ventrodorsal dimensions of the cerebellar vermis in the transverse plane, and rostrocaudal dimensions of the cerebellar vermis and hemispheres in the frontal plane. A variety of mathematical models were applied, including linear and non-linear functions. Taking into consideration the variance between models and measurements, as well as correlation parameters, the exponential and Gompertz models proved to be the most suitable for modelling cerebellar growth in the second and third trimesters of pregnancy. However, the linear model gave a satisfactory approximation of cerebellar growth, especially in older fetuses. The proposed models of fetal cerebellar growth constructed on the basis of anatomical examination and objective mathematical calculations could be useful in the estimation of fetal development. © 2018 Anatomical Society.

Diffusion Tensor Imaging of Human Cerebellar Pathways and their Interplay with Cerebral Macrostructure

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Zafer eKeser

2015-04-01

Full Text Available Cerebellar white matter connections to the central nervous system are classified functionally into the spinocerebellar, vestibulocerebellar, and cerebrocerebellar subdivisions. The Spinocerebellar (SC pathways project from spinal cord to cerebellum, whereas the vestibulocerebellar (VC pathways project from vestibular organs of the inner ear. Cerebrocerebellar connections are composed of feed forward and feedback connections between cerebrum and cerebellum including the cortico-ponto-cerebellar (CPC pathways being of cortical origin and the dentate-rubro-thalamo-cortical (DRTC pathway being of cerebellar origin. In this study we systematically quantified the whole cerebellar system connections using diffusion tensor magnetic resonance imaging (DT-MRI. Ten right-handed healthy subjects (7 males and 3 females, age range 20-51 years were studied. DT-MRI data were acquired with a voxel size = 2mm x 2mm x 2 mm at a 3.0 Tesla clinical MRI scanner. The DT-MRI data were prepared and analyzed using anatomically-guided deterministic tractography methods to reconstruct the SC, DRTC, fronto-ponto-cerebellar (FPC, parieto-ponto-cerebellar (PPC, temporo-ponto-cerebellar (TPC and occipito-ponto-cerebellar (OPC. The DTI-attributes or the cerebellar tracts along with their cortical representation (Brodmann areas were presented in standard Montréal Neurological Institute space. All cerebellar tract volumes were quantified and correlated with volumes of cerebral cortical, subcortical gray matter (GM, cerebral white matter (WM and cerebellar GM, and cerebellar WM. On our healthy cohort, the ratio of total cerebellar GM-to-WM was ~ 3.29 ± 0.24, whereas the ratio of cerebral GM-to-WM was approximately 1.10 ± 0.11. The sum of all cerebellar tract volumes is ~ 25.8 ± 7.3 mL, or a percentage of 1.52 ± 0.43 of the total intracranial volume.

GABAB antagonists

DEFF Research Database (Denmark)

Frydenvang, Karla Andrea; Hansen, J J; Krogsgaard-Larsen, P

1994-01-01

chromatographic techniques. The absolute stereochemistry of (-)-(R)-phaclofen was established by X-ray crystallographic analysis. (-)-(R)-Phaclofen was shown to inhibit the binding of [3H]-(R)-baclofen to GABAB receptor sites on rat cerebellar membranes (IC50 = 76 +/- 13 microM), whereas (+)-(S...

Comparative sensitivity of rat cerebellar neurons to dysregulation of divalent cation homeostasis and cytotoxicity caused by methylmercury

International Nuclear Information System (INIS)

Edwards, Joshua R.; Marty, M. Sue; Atchison, William D.

2005-01-01

The objective of the present study was to determine the relative effectiveness of methylmercury (MeHg) to alter divalent cation homeostasis and cause cell death in MeHg-resistant cerebellar Purkinje and MeHg-sensitive granule neurons. Application of 0.5-5 μM MeHg to Purkinje and granule cells grown in culture caused a concentration- and time-dependent biphasic increase in fura-2 fluorescence. At 0.5 and 1 μM MeHg, the elevations of fura-2 fluorescence induced by MeHg were biphasic in both cell types, but significantly delayed in Purkinje as compared to granule cells. Application of the heavy-metal chelator, TPEN, to Purkinje cells caused a precipitous decline in a proportion of the fura-2 fluorescence signal, indicating that MeHg causes release of Ca 2+ and non-Ca 2+ divalent cations. Purkinje cells were also more resistant than granule cells to the neurotoxic effects of MeHg. At 24.5 h after-application of 5 μM MeHg, 97.7% of Purkinje cells were viable. At 3 μM MeHg there was no detectable loss of Purkinje cell viability. In contrast, only 40.6% of cerebellar granule cells were alive 24.5 h after application of 3 μM MeHg. In conclusion, Purkinje neurons in primary cultures appear to be more resistant to MeHg-induced dysregulation of divalent cation homeostasis and subsequent cell death when compared to cerebellar granule cells. There is a significant component of non-Ca 2+ divalent cation released by MeHg in Purkinje neurons

Brainstem and cerebellar changes after cerebrovascular accidents: magnetic resonance imaging

International Nuclear Information System (INIS)

Uchino, A.; Takase, Y.; Nomiyama, K.; Egashira, R.; Kudo, S.

2006-01-01

We illustrate the various types of secondary degeneration in the brainstem and/or cerebellum detected on magnetic resonance (MR) images obtained after cerebrovascular accidents. The changes include: (a) ipsilateral nigral degeneration after striatal infarction; (b) Wallerian degeneration of the pyramidal tract in the brainstem after supratentorial pyramidal tract or motor cortex injury; (c) Wallerian degeneration of the corticopontine tract in the brainstem after frontal lobe infarction; (d) ipsilateral brainstem atrophy and crossed cerebellar atrophy due to an extensive supratentorial lesion; (e) ipsilateral superior cerebellar peduncle atrophy, contralateral rubral degeneration, contralateral inferior olivary degeneration and ipsilateral cerebellar atrophy after dentate nucleus hemorrhage; (f) ipsilateral inferior olivary degeneration after pontine tegmentum hemorrhage; (g) bilateral wallerian degeneration of the pontocerebellar tracts after ventromedial pontine infarction or basis pontis hemorrhage; and (h) ipsilateral cerebellar atrophy after middle cerebellar peduncle hemorrhage. (orig.)

Brainstem and cerebellar changes after cerebrovascular accidents: magnetic resonance imaging

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Uchino, A.; Takase, Y.; Nomiyama, K.; Egashira, R.; Kudo, S. [Saga Medical School, Department of Radiology, Saga (Japan)

2006-03-15

We illustrate the various types of secondary degeneration in the brainstem and/or cerebellum detected on magnetic resonance (MR) images obtained after cerebrovascular accidents. The changes include: (a) ipsilateral nigral degeneration after striatal infarction; (b) Wallerian degeneration of the pyramidal tract in the brainstem after supratentorial pyramidal tract or motor cortex injury; (c) Wallerian degeneration of the corticopontine tract in the brainstem after frontal lobe infarction; (d) ipsilateral brainstem atrophy and crossed cerebellar atrophy due to an extensive supratentorial lesion; (e) ipsilateral superior cerebellar peduncle atrophy, contralateral rubral degeneration, contralateral inferior olivary degeneration and ipsilateral cerebellar atrophy after dentate nucleus hemorrhage; (f) ipsilateral inferior olivary degeneration after pontine tegmentum hemorrhage; (g) bilateral wallerian degeneration of the pontocerebellar tracts after ventromedial pontine infarction or basis pontis hemorrhage; and (h) ipsilateral cerebellar atrophy after middle cerebellar peduncle hemorrhage. (orig.)

Improving cerebellar segmentation with statistical fusion

Science.gov (United States)

Plassard, Andrew J.; Yang, Zhen; Prince, Jerry L.; Claassen, Daniel O.; Landman, Bennett A.

2016-03-01

The cerebellum is a somatotopically organized central component of the central nervous system well known to be involved with motor coordination and increasingly recognized roles in cognition and planning. Recent work in multiatlas labeling has created methods that offer the potential for fully automated 3-D parcellation of the cerebellar lobules and vermis (which are organizationally equivalent to cortical gray matter areas). This work explores the trade offs of using different statistical fusion techniques and post hoc optimizations in two datasets with distinct imaging protocols. We offer a novel fusion technique by extending the ideas of the Selective and Iterative Method for Performance Level Estimation (SIMPLE) to a patch-based performance model. We demonstrate the effectiveness of our algorithm, Non- Local SIMPLE, for segmentation of a mixed population of healthy subjects and patients with severe cerebellar anatomy. Under the first imaging protocol, we show that Non-Local SIMPLE outperforms previous gold-standard segmentation techniques. In the second imaging protocol, we show that Non-Local SIMPLE outperforms previous gold standard techniques but is outperformed by a non-locally weighted vote with the deeper population of atlases available. This work advances the state of the art in open source cerebellar segmentation algorithms and offers the opportunity for routinely including cerebellar segmentation in magnetic resonance imaging studies that acquire whole brain T1-weighted volumes with approximately 1 mm isotropic resolution.

Plasma membrane fatty acid-binding protein and mitochondrial glutamic-oxaloacetic transaminase of rat liver are related

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Berk, P.D.; Potter, B.J.; Sorrentino, D.; Zhou, S.L.; Isola, L.M.; Stump, D.; Kiang, C.L.; Thung, S. (Mount Sinai School of Medicine, New York, NY (USA)); Wada, H.; Horio, Y. (Univ. of Osaka (Japan))

1990-05-01

The hepatic plasma membrane fatty acid-binding protein (h-FABP{sub PM}) and the mitochondrial isoenzyme of glutamic-oxaloacetic transaminase (mGOT) of rat liver have similar amino acid compositions and identical amino acid sequences for residues 3-24. Both proteins migrate with an apparent molecular mass of 43 kDa on SDS/polyacrylamide gel electrophoresis, have a similar pattern of basic charge isomers on isoelectric focusing, are eluted similarly from four different high-performance liquid chromatographic columns, have absorption maxima at 435 nm under acid conditions and 354 nm at pH 8.3, and bind oleate. Sinusoidally enriched liver plasma membranes and purified h-FABP{sub PM} have GOT enzymatic activity. Monospecific rabbit antiserum against h-FABP{sub PM} reacts on Western blotting with mGOT, and vice versa. Antisera against both proteins produce plasma membrane immunofluorescence in rat hepatocytes and selectively inhibit the hepatocellular uptake of ({sup 3}H)oleate but not that of ({sup 35}S)sulfobromophthalein or ({sup 14}C)taurocholate. The inhibition of oleate uptake produced by anti-h-FABP{sub PM} can be eliminated by preincubation of the antiserum with mGOT; similarly, the plasma membrane immunofluorescence produced by either antiserum can be eliminated by preincubation with the other antigen. These data suggest that h-FABP{sub PM} and mGOT are closely related.

Cerebellar blood flow in methylmercury poisoning (Minamata disease)

Energy Technology Data Exchange (ETDEWEB)

Itoh, K.; Korogi, Y.; Tomiguchi, S.; Takahashi, M. [Dept. of Radiology, Kumamoto University School of Medicine (Japan); Okajima, T. [Dept. of Neurology, Johnan Hospital, Maihara, Johnan-mochi (Japan); Sato, H. [Dept. of Neurology, Minamata City General Hospital and Medical Centre (Japan)

2001-04-01

We looked at regional cerebellar blood flow in patients with Minamata disease (MD) using technetium-99 m ethyl cysteinate dimer (99m-Tc-ECD). We carried out single-photon emission computed tomography (SPECT) on 15 patients with MD (eight men, seven women, aged 51-78 years, mean 70.5 years) and 11 control subjects (eight men, three women, aged 62-80 years, mean 72.5 years). Regional blood flow was measured in the superior, middle, and inferior portions of the cerebellar hemispheres, and the frontal, temporal and occipital cerebral lobes. The degree of cerebellar atrophy was assessed on MRI. There were significant differences in regional blood flow in all parts of the cerebellum between patients and control, but no significant decrease was observed in the cerebrum. Blood flow was lower in the inferior cerebellum than in the other parts. Even in patients without cerebellar atrophy, flow was significantly decreased regional blood flow in the inferior part. (orig.)

Cerebellar blood flow in methylmercury poisoning (Minamata disease)

International Nuclear Information System (INIS)

Itoh, K.; Korogi, Y.; Tomiguchi, S.; Takahashi, M.; Okajima, T.; Sato, H.

2001-01-01

We looked at regional cerebellar blood flow in patients with Minamata disease (MD) using technetium-99 m ethyl cysteinate dimer (99m-Tc-ECD). We carried out single-photon emission computed tomography (SPECT) on 15 patients with MD (eight men, seven women, aged 51-78 years, mean 70.5 years) and 11 control subjects (eight men, three women, aged 62-80 years, mean 72.5 years). Regional blood flow was measured in the superior, middle, and inferior portions of the cerebellar hemispheres, and the frontal, temporal and occipital cerebral lobes. The degree of cerebellar atrophy was assessed on MRI. There were significant differences in regional blood flow in all parts of the cerebellum between patients and control, but no significant decrease was observed in the cerebrum. Blood flow was lower in the inferior cerebellum than in the other parts. Even in patients without cerebellar atrophy, flow was significantly decreased regional blood flow in the inferior part. (orig.)

Reduced contralateral hemispheric flow measured by SPECT in cerebellar lesions

International Nuclear Information System (INIS)

Soenmezoglu, K.; Sperling, B.; Lassen, N.A.; Henriksen, T.; Tfelt-Hansen, P.

1993-01-01

Four patients with clinical signs of cerebellar stroke were studied twice by SPECT using 99m Tc-HMPAO as a tracer for cerebral blood flow (CBF). When first scanned 6 to 22 days after onset, all had a region of very low CBF in the symptomatic cerebellar hemisphere, and a mild to moderate CBF reduction (average 10%) in contralateral hemispheric cortex. In all four cases clinical signs of unilateral cerebellar dysfunction were still present when rescanned 1 to 4 months later and the relative CBF decrease in the contralateral cortex of the forebrain also remained. The basal ganglia contralateral to the cerebellar lesion CBF showed variable alterations. A relative CBF decrease was seen in upper part of basal ganglia in all four cases, but it was not a constant phenomenon. A relative CBF increase in both early and late SPECT scans was seen at low levels of neostriatum in two cases. The remote CBF changes in cerebellar stroke seen in the forebrain are probably caused by reduced or abolished cerebellar output. The term ''Crossed Cerebral Diaschisis'' may be used to describe these CBF changes that would appear to reflect both decreased and increased neuronal activity. (au)

Neuroprotective Effect of Total and Sequential Extract of Scrophularia striata Boiss. in Rat Cerebellar Granule Neurons Following Glutamate- Induced Neurotoxicity: An In-vitro Study

Science.gov (United States)

Salavati, Parvin; Ramezani, Mina; Monsef-Esfahani, Hamid R; Hajiagha, Reza; Parsa, Maliheh; Tavajohi, Shoreh; Ostad, Seyed Nasser

2013-01-01

Neuroprotective effect of the extract from aerial parts of Scrophularia striata Boiss (Scrophulariaceae) was investigated against glutamate-induced neurotoxicity on cultured rat pups Cerebellar Granule Neurons (CGNs). CGNs from 8 days old Sprague-Dawley rat were prepared and cultured. The experiments were performed after 8 days in culture. The plant was collected from the northeastern part (Ruin region) of Iran and air-dried at room temperature. The total extract was prepared with maceration of prepared powder in ethanol 80% for three times. Sequential extracts were obtained using dried and powdered aerial parts with increasingly polar solvents: petroleum ether, chloroform, ethyl acetate and methanol 80% solution. Cultured cells were exposed to 125 μM of glutamate for 12 h following a 24 h of incubation with test fractions at concentration of 10 mcg/mL. Morphological assay was performed using invert light microscope after fixation and staining with haematoxylin. Neuronal viability was measured using MTT assay. Statistical analysis was done using SPSS software. One way analysis of variance (ANOVA) was performed by Tukey post-hoc test. Values were considered statistically significant when p-value ≤ 0.05. Results of this study showed a significant neuroprotective activity of high polarity methanolic fraction of aerial parts of Scrophularia striata against glutamate-induced neurotoxicity in a dosedependent manner. Treatment with 10 mcg/mL of the fractions showed the best result. PMID:24250613

Physiological properties of afferents to the rat cerebellum during normal development and after postnatal x irradiation

International Nuclear Information System (INIS)

Puro, D.G.

1975-01-01

The consequences of an altered cerebellar cortical development on afferent transmission and terminal organization were analyzed in adult rats which had received x irradiation to the cerebellum postnatally. Rats, anesthetized with 0.5 percent halothane, were studied in various ages from day 3 to adult. The ascending mossy and climbing fiber systems were activated by electrical stimulation of the limbs with needle electrodes. Stimulation of the motor cortex activated the descending climbing fiber pathways. Extracellular responses from cerebellar Purkinje cells were observed on an oscilloscope as poststimulus time histograms were constructed ''on-line''. Conclusions and assertions include: (1) Synaptogenesis between incoming afferent fibers and target neurons takes place early in cerebellar cortical development. (2) Mossy fiber transmission is mature before the bulk of cerebellar synaptogenesis occurs. (3) The ascending and descending components of the climbing fiber system mature, with respect to latency, in synchrony. (4) The terminal synaptic organization has little effect on the development of transmission characteristics in these afferent systems. (5) One possible mechanism by which an adult neural structure can have an abnormal synaptic organization is to maintain immature synaptic relationships due to the neonatal loss of interneurons

Cerebellar abiotrophy in a family of Border Collie dogs.

Science.gov (United States)

Sandy, J R; Slocombe, R E; Mitten, R W; Jedwab, D

2002-11-01

Cerebellar abiotrophies have a nonsex-linked, autosomal, recessively inherited basis in a number of species, and lesions typically reflect profound and progressive loss of Purkinje cells. In this report, an unusual form of abiotrophy is described for two sibling Border Collies. Extensive loss of the cerebellar granular cell layer was present with relative sparing of Purkinje cells of two female pups. The biochemical basis for this form of cerebellar abiotrophy is unknown, but the lack of disease in other siblings supports an autosomal recessive mode of inheritance.

Blood harmane is correlated with cerebellar metabolism in essential tremor: a pilot study.

Science.gov (United States)

Louis, Elan D; Zheng, Wei; Mao, Xiangling; Shungu, Dikoma C

2007-08-07

On proton magnetic resonance spectroscopic imaging ((1)H MRSI), there is a decrease in cerebellar N-acetylaspartate/total creatine (NAA/tCr) in essential tremor (ET), signifying cerebellar neuronal dysfunction or degeneration. Harmane, which is present in the human diet, is a potent tremor-producing neurotoxin. Blood harmane concentrations seem to be elevated in ET. To assess in patients with ET whether blood harmane concentration is correlated with cerebellar NAA/tCR, a neuroimaging measure of neuronal dysfunction or degeneration. Twelve patients with ET underwent (1)H MRSI. The major neuroanatomic structure of interest was the cerebellar cortex. Secondary regions were the central cerebellar white matter, cerebellar vermis, thalamus, and basal ganglia. Blood concentrations of harmane and another neurotoxin, lead, were also assessed. Mean +/- SD cerebellar NAA/tCR was 1.52 +/- 0.41. In a linear regression model that adjusted for age and gender, log blood harmane concentration was a predictor of cerebellar NAA/tCR (beta = -0.41, p = 0.009); every 1 g(-10)/mL unit increase in log blood harmane concentration was associated with a 0.41 unit decrease in cerebellar NAA/tCR. The association between blood harmane concentration and brain NAA/tCR only occurred in the cerebellar cortex; it was not observed in secondary brain regions of interest. Furthermore, the association was specific to harmane and not another neurotoxin, lead. This study provides additional support for the emerging link between harmane, a neurotoxin, and ET. Further studies are warranted to address whether cerebellar harmane concentrations are associated with cerebellar pathology in postmortem studies of the ET brain.

Anemia of the Belgrade rat: evidence for defective membrane transport of iron

International Nuclear Information System (INIS)

Bowen, B.J.; Morgan, E.H.

1987-01-01

The mechanisms underlying the impaired utilization of transferrin-bound iron by erythroid cells in the anemia of the Belgrade laboratory rat were investigated using reticulocytes from homozygous anemic animals and transferrin labeled with 59 Fe and 125 I. The results were compared with those obtained using reticulocytes from phenylhydrazine-treated rats and iron-deficient rats. Each step in the iron uptake mechanism was investigated, ie, transferrin-receptor interaction, transferrin endocytosis, iron release from transferrin, and transferrin exocytosis. Although there were quantitative differences, no fundamental difference was found in any of the abovementioned aspects of cellular function when the reticulocytes from Belgrade rats were compared with those from iron-deficient animals. The basic defect in the Belgrade reticulocytes must therefore reside in subsequent steps in iron uptake, after it is released from transferrin within endocytotic vesicles, ie, in the mechanism by which it is transferred across the lining membrane of the vesicles into the cell cytosol. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of reticulocyte ghosts extracts demonstrated a prominent protein band of mol wt 69,000 that was absent or present only in low concentration extracts from the other two types of reticulocytes. This may be a result of the genetic defect

Cerebellar malformations alter regional cerebral development.

Science.gov (United States)

Bolduc, Marie-Eve; Du Plessis, Adre J; Evans, Alan; Guizard, Nicolas; Zhang, Xun; Robertson, Richard L; Limperopoulos, Catherine

2011-12-01

The aim of this study was to compare total and regional cerebral volumes in children with isolated cerebellar malformations (CBMs) with those in typically developing children, and to examine the extent to which cerebellar volumetric reductions are associated with total and regional cerebral volumes. This is a case-control study of children diagnosed with isolated CBMs. Each child was matched on age and sex to two typically developing children. Using advanced three-dimensional volumetric magnetic resonance imaging, the cerebrum was segmented into tissue classes and partitioned into eight regions. Analysis of variance was used to compare cerebral volumes between children with CBMs and control children, and linear regressions to examine the impact of cerebellar volume reduction on cerebral volumes. Magnetic resonance imaging was performed at a mean age of 27 months in 20 children (10 males, 10 females) with CBMs and 40 typically developing children. Children with CBMs showed significantly smaller deep grey matter nuclei (p developing children. Greater cerebellar volumetric reduction in children with CBMs was associated with decreased total cerebral volume and deep grey matter nuclei (p = 0.02), subgenual white/grey matter (p = 0.001), midtemporal white (p = 0.02) and grey matter (p = 0.01), and parieto-occipital grey matter (p = 0.004). CBMs are associated with impaired regional cerebral growth, suggesting deactivation of principal cerebello-cerebral pathways. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

[Age-related change in the alpha-tocopherolquinone/alpha-tocopherol ratio in the rat erythrocyte membrane].

Science.gov (United States)

Yanagawa, K; Takeda, H; Matsumiya, T; Takasaki, M

1999-05-01

alpha-Tocopherol (alpha-Toc), a lipophilic phenolic antioxidant that is localized mainly in the biomembrane, protects cells against oxidation-associated cytotoxicity by prevention of membrane lipid peroxidation, maintenance of the redox balance intracellular thiols and stabilization of the membrane structure. We investigated the age-related changes in redox dynamics of alpha-Toc in plasma and erythrocyte membrane of an elderly (66 weeks old) and young group (10 weeks old). Total, alpha-, beta + gamma-, delta-Toc and alpha-tocopherolquinone (alpha-TocQ) in plasma and erythrocyte membrane were determined by high-performance liquid chromatography (HPLC) with a series of multiple coulometric working electrodes (CWE). Rat venous blood sample was divided into plasma and erythrocyte layers by centrifugation, and then erythrocyte membrane sample was prepared according to the method of Dodge et al. under a stream of nitrogen. In plasma, total and alpha-Toc concentrations were increased, and beta + gamma-, delta-Toc and alpha-TocQ concentrations were decreased age-dependently. In the erythrocyte membrane, total, alpha-TocQ concentrations and three fractions of tocopherols decreased age-dependently. Also, a decrease in the alpha-TocQ/alpha-Toc ratio in erythrocyte membrane was observed in the elderly group. These findings suggest that the alpha-Toc uptake in erythrocyte membrane and utilization rate of alpha-Toc in erythrocyte membrane decline age-dependently. This decline may promote membrane lipid peroxidation. alpha-Toc redox dynamics in erythrocyte membrane were useful to investigate the pathophysiology of aging mechanisms related to oxidative stress.

Heat stroke induced cerebellar dysfunction: A “forgotten syndrome”

Science.gov (United States)

Kosgallana, Athula D; Mallik, Shreyashee; Patel, Vishal; Beran, Roy G

2013-01-01

We report a case of heat stroke induced acute cerebellar dysfunction, a rare neurological disease characterized by gross cerebellar dysfunction with no acute radiographic changes, in a 61 years old ship captain presenting with slurred speech and gait ataxia. A systematic review of the literature on heat stroke induced cerebellar dysfunction was performed, with a focus on investigations, treatment and outcomes. After review of the literature and detailed patient investigation it was concluded that this patient suffered heat stroke at a temperature less than that quoted in the literature. PMID:24340279

Crossed cerebellar diaschisis in ischemic stroke

DEFF Research Database (Denmark)

Meneghetti, G; Vorstrup, S; Mickey, B

1984-01-01

Seventy measurements of CBF were performed in 12 stroke patients by 133Xe inhalation and a rapidly rotating single photon emission computerized tomograph. CBF was measured every other day during the acute phase and at 2- and 6-month follow-up visits. A persistent contralateral cerebellar blood flow....... It is concluded from this serial study that crossed cerebellar diaschisis is a common finding in completed stroke. It is probably caused by disconnection of the corticopontine pathways, a disconnection that tends to persist. The phenomenon is in fact less variable than the stroke-related CBF changes...

Cerebellar abnormalities contribute to disability including cognitive impairment in multiple sclerosis.

Directory of Open Access Journals (Sweden)

Katrin Weier

Full Text Available The cerebellum is known to be involved not only in motor but also cognitive and affective processes. Structural changes in the cerebellum in relation to cognitive dysfunction are an emerging topic in the field of neuro-psychiatric disorders. In Multiple Sclerosis (MS cerebellar motor and cognitive dysfunction occur in parallel, early in the onset of the disease, and the cerebellum is one of the predilection sites of atrophy. This study is aimed at determining the relationship between cerebellar volumes, clinical cerebellar signs, cognitive functioning and fatigue in MS. Cerebellar volumetry was conducted using T1-weighted MPRAGE magnetic resonance imaging of 172 MS patients. All patients underwent a clinical and brief neuropsychological assessment (information processing speed, working memory, including fatigue testing. Patients with and without cerebellar signs differed significantly regarding normalized cerebellar total volume (nTCV, normalized brain volume (nBV and whole brain T2 lesion volume (LV. Patients with cerebellar dysfunction likewise performed worse in cognitive tests. A regression analysis indicated that age and nTCV explained 26.3% of the variance in SDMT (symbol digit modalities test performance. However, only age, T2 LV and nBV remained predictors in the full model (r(2 = 0.36. The full model for the prediction of PASAT (Paced Auditory Serial Addition Test scores (r(2 = 0.23 included age, cerebellar and T2 LV. In the case of fatigue, only age and nBV (r(2 = 0.17 emerged as significant predictors. These data support the view that cerebellar abnormalities contribute to disability, including cognitive impairment in MS. However, this contribution does not seem to be independent of, and may even be dominated by wider spread MS pathology as reflected by nBV and T2 LV.

Magnetic resonance imaging of cerebellar Schistosomiasis mansoni

International Nuclear Information System (INIS)

Braga, Bruno Perocco; Costa Junior, Leodante Batista da; Lambertucci, Jose Roberto

2003-01-01

A 15-year-old boy was admitted to hospital with a history of headache, dizziness, vomiting and double vision that started two weeks before. His parents denied any previous disease. During clinical examination he presented diplopia on lateral gaze to the left and horizontal nystagmus. No major neurological dysfunction was detected. He was well built, mentally responsive and perceptive. Laboratory findings revealed a leukocyte count of 10,000/mL, a normal red blood cell count and no eosinophilia. The magnetic resonance images (MRI) of the brain showed a left cerebellar lesion with mass effect compressing the surrounding tissues. Contrast-enhanced images showed a mass like structure and punctate nodules (Figures A and B: axial and coronal contrast-enhanced T1-weighted MR images showed the nodular - yellow arrows - enhancement pattern of a left cerebellar intraxial lesion). The lesion extended to the vermis and brachium pons and compressed the medulla. There was no hydrocephalus. He was taken to the operating room with the presumptive diagnosis of a neuroglial tumor, and submitted to a lateral suboccipital craniectomy. A brown, brittle tumoral mass without a clearly defined margin with the cerebellar tissue was removed. Microscopic examination revealed schistosomal granulomas in the productive phase in the cerebellum (Figure C). After surgery, treatment with praziquantel (50 mg/kg/dia, single dose) and prednisone (1 mg/kg/day) was offered and the patient improved quickly. Thirty days later he was seen again at the outpatient clinic: he was asymptomatic and with no neurological impairment. This is the eighth case of cerebellar involvement in schistosomiasis mansoni and the second report of a tumoral form of cerebellar schistosomiasis documented by magnetic resonance images. (author)

Defective cerebellar control of cortical plasticity in writer’s cramp

Science.gov (United States)

Hubsch, Cecile; Roze, Emmanuel; Popa, Traian; Russo, Margherita; Balachandran, Ammu; Pradeep, Salini; Mueller, Florian; Brochard, Vanessa; Quartarone, Angelo; Degos, Bertrand; Vidailhet, Marie; Kishore, Asha

2013-01-01

A large body of evidence points to a role of basal ganglia dysfunction in the pathophysiology of dystonia, but recent studies indicate that cerebellar dysfunction may also be involved. The cerebellum influences sensorimotor adaptation by modulating sensorimotor plasticity of the primary motor cortex. Motor cortex sensorimotor plasticity is maladaptive in patients with writer’s cramp. Here we examined whether putative cerebellar dysfunction in dystonia is linked to these patients’ maladaptive plasticity. To that end we compared the performances of patients and healthy control subjects in a reaching task involving a visuomotor conflict generated by imposing a random deviation (−40° to 40°) on the direction of movement of the mouse/cursor. Such a task is known to involve the cerebellum. We also compared, between patients and healthy control subjects, how the cerebellum modulates the extent and duration of an ongoing sensorimotor plasticity in the motor cortex. The cerebellar cortex was excited or inhibited by means of repeated transcranial magnetic stimulation before artificial sensorimotor plasticity was induced in the motor cortex by paired associative stimulation. Patients with writer’s cramp were slower than the healthy control subjects to reach the target and, after having repeatedly adapted their trajectories to the deviations, they were less efficient than the healthy control subjects to perform reaching movement without imposed deviation. It was interpreted as impaired washing-out abilities. In healthy subjects, cerebellar cortex excitation prevented the paired associative stimulation to induce a sensorimotor plasticity in the primary motor cortex, whereas cerebellar cortex inhibition led the paired associative stimulation to be more efficient in inducing the plasticity. In patients with writer’s cramp, cerebellar cortex excitation and inhibition were both ineffective in modulating sensorimotor plasticity. In patients with writer’s cramp, but not

Cerebro-cerebellar interactions underlying temporal information processing.

Science.gov (United States)

Aso, Kenji; Hanakawa, Takashi; Aso, Toshihiko; Fukuyama, Hidenao

2010-12-01

The neural basis of temporal information processing remains unclear, but it is proposed that the cerebellum plays an important role through its internal clock or feed-forward computation functions. In this study, fMRI was used to investigate the brain networks engaged in perceptual and motor aspects of subsecond temporal processing without accompanying coprocessing of spatial information. Direct comparison between perceptual and motor aspects of time processing was made with a categorical-design analysis. The right lateral cerebellum (lobule VI) was active during a time discrimination task, whereas the left cerebellar lobule VI was activated during a timed movement generation task. These findings were consistent with the idea that the cerebellum contributed to subsecond time processing in both perceptual and motor aspects. The feed-forward computational theory of the cerebellum predicted increased cerebro-cerebellar interactions during time information processing. In fact, a psychophysiological interaction analysis identified the supplementary motor and dorsal premotor areas, which had a significant functional connectivity with the right cerebellar region during a time discrimination task and with the left lateral cerebellum during a timed movement generation task. The involvement of cerebro-cerebellar interactions may provide supportive evidence that temporal information processing relies on the simulation of timing information through feed-forward computation in the cerebellum.

Activity of adenylate cyclase in plasma membranes of pulmonary tissue remote times following nonlethal gamma-irradiation of rats

International Nuclear Information System (INIS)

Slozhenkina, L.V.; Ruda, V.P.; Ushakova, T.E.; Kuzin, A.M.

1990-01-01

Basal and stimulated activity of adenylate cyclase (cyclizing ATP-pyrophosphate lyase, E.C. 4.6.1.1., AC) in plasma membranes of pumonary tissye was being studied during a year after fractionated irradiation of rats (2 Gyx3). Basal and hormone-stimulated activity of AC was shown to vary significantly from normal 6 and 12 months after irradiation. The exposed membranes responded differently to AC activation by isoproterenol and F -

Visuomotor learning in cerebellar patients.

Science.gov (United States)

Timmann, D; Shimansky, Y; Larson, P S; Wunderlich, D A; Stelmach, G E; Bloedel, J R

1996-11-01

The aim of the present study was to demonstrate that patients with pathology affecting substantial regions of the cerebellum can improve their performance in a series of two-dimensional tracing tasks, thus supporting the view that this type of motor behavior can be acquired even when the integrity of this structure is compromised. Eight patients with chronic, isolated cerebellar lesions and eight age- and sex-matched healthy controls were tested. Three patients had mild, five had moderate upper limb ataxia. The experiment was divided into two parts. In the first, subjects traced an irregularly shaped outline over 20 consecutive trials ('Trace 1' task). Next, subjects were asked to redraw the object without any underlying template as a guide ('Memory 1' task). In the second part of the study, subjects were asked to trace a different, irregularly shaped outline over 20 consecutive trials ('Trace 2' task). Next, they were required to redraw it by memory with its axis rotated 90 degrees ('Memory 2' task). In each of the memory tasks the template was placed over the drawn image after each trial and shown to the subjects. The error of performance was determined by calculating three different measurements, each focused on different aspects of the task. Based on these measurements, the cerebellar patients showed improvement in both memory tasks. In the 'Memory 1' task the calculated error decreased significantly for the patients with mild ataxia. In the 'Memory 2' task all cerebellar patients improved their performance substantially enough to reduce significantly the magnitude of all three error measurements. The experiments demonstrate that patients with cerebellar lesions are capable of improving substantially their performance of a complex motor task involving the recall of memorized shapes and the visuomotor control of a tracing movement.

[Study of cerebellar infarction with isolated vertigo].

Science.gov (United States)

Utsumi, Ai; Enomoto, Hiroyuki; Yamamoto, Kaoru; Kimura, Yu; Koizuka, Izumi; Tsukuda, Mamoru

2010-07-01

Isolated vertigo is generally attributed to labyrinthine disease, but may also signal otherwise asymptomatic cerebellar infarction. Of 309 subjects admitted between April 2004 and March 2009 for the single symptom of acute vertigo initially thought to be labyrinthine, four were found to have cerebellar infarction of the posterior inferior cerebellar artery area (PICA). All were over 60 years old and had risk factors including hypertension, diabetes mellitus, arrhythmia, and/or hyperlipidemia. Two had trunk ataxia, with magnetic resonance imaging (MRI) showing infarction within a few days. The other two could walk without apparent trunk ataxia, however, it took 4 to 7 days to find the infarction, mainly through neurological, neurootological, and MRI findings. Neurologically, astasia, dysbasia or trunk ataxia were important signs. Neurootologically, nystagmus and electronystagmographic testing involving eye tracking, saccade, and optokinetic patttens were useful.

Naloxone-sensitive, haloperidol-sensitive, [3H](+)SKF-10047-binding protein partially purified from rat liver and rat brain membranes: an opioid/sigma receptor?

Science.gov (United States)

Tsao, L I; Su, T P

1997-02-01

A naloxone-sensitive, haloperidol-sensitive, [3H](+)SKF-10047-binding protein was partially purified from rat liver and rat brain membranes in an affinity chromatography originally designed to purify sigma receptors. Detergent-solubilized extracts from membranes were adsorbed to Sephadex G-25 resin containing an affinity ligand for sigma receptors: N-(2- 3,4-dichlorophenyl]ethyl)-N-(6-aminohexyl)-(2-[1-pyrrolidinyl]) ethylamine (DAPE). After eluting the resin with haloperidol, a protein that bound [3H](+)SKF-10047 was detected in the eluates. However, the protein was not the sigma receptor. [3H](+)SKF-10047 binding to the protein was inhibited by the following compounds in the order of decreasing potency: (+)pentazocine > (-) pentazocine > (+/-)cyclazocine > (-)morphine > (-)naloxone > haloperidol > (+)SKF-10047 > DADLE > (-)SKF-10047. Further, the prototypic sigma receptor ligands, such as 1,3-di-o-tolylguanidine (DTG), (+)3-PPP, and progesterone, bound poorly to the protein. Tryptic digestion and heat treatment of the affinity-purified protein abolished radioligand binding. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) of the partially-purified protein from the liver revealed a major diffuse band with a molecular mass of 31 kDa, a polypeptide of 65 kDa, and another polypeptide of > 97 kDa. This study demonstrates the existence of a novel protein in the rat liver and rat brain which binds opioids, benzomorphans, and haloperidol with namomolar affinity. The protein resembles the opioid/sigma receptor originally proposed by Martin et al. [(1976): J. Pharmacol. Exp. Ther., 197:517-532.]. A high degree of purification of this protein has been achieved in the present study.

Prevention of intra-abdominal adhesion by bi-layer electrospun membrane.

Science.gov (United States)

Jiang, Shichao; Wang, Wei; Yan, Hede; Fan, Cunyi

2013-06-04

The aim of this study was to compare the anti-adhesion efficacy of a bi-layer electrospun fibrous membrane consisting of hyaluronic acid-loaded poly(ε-caprolactone) (PCL) fibrous membrane as the inner layer and PCL fibrous membrane as the outer layer with a single-layer PCL electrospun fibrous membrane in a rat cecum abrasion model. The rat model utilized a cecal abrasion and abdominal wall insult surgical protocol. The bi-layer and PCL membranes were applied between the cecum and the abdominal wall, respectively. Control animals did not receive any treatment. After postoperative day 14, a visual semiquantitative grading scale was used to grade the extent of adhesion. Histological analysis was performed to reveal the features of adhesion tissues. Bi-layer membrane treated animals showed significantly lower adhesion scores than control animals (p compared with the PCL membrane. Histological analysis of the bi-layer membrane treated rat rarely demonstrated tissue adhesion while that of the PCL membrane treated rat and control rat showed loose and dense adhesion tissues, respectively. Bi-layer membrane can efficiently prevent adhesion formation in abdominal cavity and showed a significantly decreased adhesion tissue formation compared with the control.

Selective survival of β1-adenergic receptors in rat cerebellum following neonatal X-irradiation

International Nuclear Information System (INIS)

Minneman, K.P.; Pittman, R.N.; Wolfe, B.B.; Molinoff, P.B.

1981-01-01

To investigate the cellular localization of β 1 - and β 2 -adrenergic receptors, the effects of intermittent neonatal X-irradiation focused on the cerebellum were determined on the densities of the two subtypes of β-adrenergic receptor. This treatment destroys the late-maturing cerebellar interneurons including the granule, basket and stellate cells. The total number of β 2 -adrenergic receptors per cerebellum was reduced by 81-83% in 6- and 12-week-old X-irradiated rats. However, the number of β 1 -adrenergic receptors per cerebellum in 6- and 12-week-old X-irradiated rats was not significantly different from that in control animals. The results suggest that β 2 receptors in the rat cerebellum are primarily associated with the small interneurons destroyed by neonatal X-irradiation. The β 1 receptors may be located on a cell population which is unaffected by this treatment, possibly on cerebellar Purkinje cells. (Auth.)

Postural responses to multidirectional stance perturbations in cerebellar ataxia

NARCIS (Netherlands)

Bakker, Maaike; Allum, John H J; Visser, Jasper E; Grüneberg, Christian; van de Warrenburg, Bart P; Kremer, H P H; Bloem, Bastiaan R

2006-01-01

Previous studies of patients with focal cerebellar damage underscored the importance of the cerebellum for balance control. These studies were restricted to postural control in the pitch plane, and focused mainly on leg muscle responses. Here, we examined the effect of degenerative cerebellar

Postural responses to multidirectional stance perturbations in cerebellar ataxia

NARCIS (Netherlands)

Bakker, Maaike; Allum, John H J; Visser, Jasper E; Grüneberg, Christian; van de Warrenburg, Bart P; Kremer, H P H; Bloem, Bastiaan R

Previous studies of patients with focal cerebellar damage underscored the importance of the cerebellum for balance control. These studies were restricted to postural control in the pitch plane, and focused mainly on leg muscle responses. Here, we examined the effect of degenerative cerebellar

Time estimation in Parkinson's disease and degenerative cerebellar disease

NARCIS (Netherlands)

Beudel, Martijin; Galama, Sjoukje; Leenders, Klaus L.; de Jong, Bauke M.

2008-01-01

With functional MRI, we recently identified fronto-cerebellar activations in predicting time to reach a target and basal ganglia activation in velocity estimation, that is, small interval assessment. We now tested these functions in patients with Parkinson's disease (PD) and degenerative cerebellar

Late Onset of Cerebellar Abiotrophy in a Boxer Dog

Directory of Open Access Journals (Sweden)

Sanjeev Gumber

2010-01-01

Full Text Available Cerebellar abiotrophy is a degenerative disorder of the central nervous system and has been reported in humans and animals. This case report documents clinical, histopathological, and immunohistochemical findings of cerebellar abiotrophy in an adult Boxer dog. A 3.5-year-old, female, tan Boxer dog presented with a six-week history of left-sided head tilt. Neurological examination and additional diagnostics during her three subsequent visits over 4.5 months revealed worsening of neurological signs including marked head pressing, severe proprioceptive deficits in all the four limbs, loss of menace response and palpebral reflex in the left eye, and a gradual seizure lasting one hour at her last visit. Based on the immunohistochemical staining for glial fibrillary acidic protein and histopathological examination of cerebellum, cerebellar cortical abiotrophy was diagnosed. This is the first reported case of cerebellar abiotrophy in a Boxer dog to our knowledge.

5'-nucleotidase and protein kinase activity of plasmatic membrane and 5'-nucleotidase activity of liver homogenate in the third and fourth rat generations born in the Chernobyl accident zone

International Nuclear Information System (INIS)

Bezdrobnij, Yu.V.; Serkyiz, Ya.Yi.; Bozhok, O.V.; Yindik, V.M.

1994-01-01

The decrease of plasmatic membrane protein kinase activity of 3 - month rat liver was revealed in animals that have been born and kept in the Chernobyl accident zone during three and four generations. Erythrocyte ghost protein kinase activity from those animals was decreased too. 5'-nucleotidase activity in membranes and in homogenates was increased in the third and decreased in the fourth generation. In 6 month rats of the fourth generation in comparison with 3 month rats of this generation plasmatic membrane protein kinase and 5'-nucleotidase activities did not change but 5'nucleotidase activity of homogenate was increased (to control level). The plasmatic membrane protein kinase activity has been supposed to serve as a bio indicator of ionising irradiation at low dose rate

Cerebellar ataxia of early onset

International Nuclear Information System (INIS)

Yamashita, Sumimasa; Miyake, Shota; Yamada, Michiko; Iwamoto, Hiroko; Yamada, Kazuhiko.

1989-01-01

Eight cases of childhood cerebellar ataxia were reported. All these cases showed chronic cerebellar ataxia with early onset, and the other diseases of cerebellum such as infections, neoplasms and storage diseases were excluded by clinical symptoms and laboratory findings including blood counts, blood chemistry, lactate, pyruvate, ceruloplasmine, urinalysis, serum immunoglobulins, amino acid analysis in blood and urine, CSF analysis, leukocyte lysosomal enzymes, MCV, EMG, EEG and brain X-CT. Two pairs of siblings were included in this study. The clinical diagnosis were cerebellar type (5), spinocerebellar type (1), one Marinesco-Sjoegren syndrome and undetermined type (1). The age of onset was 1 to 5 years. The chief complaint was motor developmental delay in 6 cases; among them 5 patients could walk alone at the ages of 2 to 3 years'. Mental retardation was observed in 7 cases and epilepsy in 2. TRH was effective in 5 cases. The MRI study revealed that the area of medial sagittal slice of the cerebellum was reduced significantly in all cases and also that of pons was reduced in 5 cases. Different from typical adult onset spinocerebellar degenerations, most of the present cases have achieved slow developmental milestones and the clinical course was not progressive. Genetic factors are suspected in the pathogenesis of this disease in some cases. (author)

Distribution of two basement membrane proteoglycans through hair follicle development and the hair growth cycle in the rat

DEFF Research Database (Denmark)

Couchman, J R; King, J L; McCarthy, K J

1990-01-01

The distribution of two distinct populations of basement membrane proteoglycans has been monitored through hair growth development in the rat embryo and subsequent hair growth cycle. An antiserum against a small heparan sulfate proteoglycan uniformly stained the dermal-epidermal junction...... of embryonic rats throughout the period of hair follicle formation. On the other hand, monoclonal antibodies recognizing a basement membrane-specific chondroitin sulfate proteoglycan only weakly stained 16-d embryo dermal-epidermal junction, but strong staining was associated with hair follicle buds...... as they developed. Through the hair growth cycle, it was found that the heparan sulfate proteoglycan persisted around the follicles, while the chondroitin sulfate proteoglycan decreased in amount through catagen until it was undetectable at the base and dermal papilla of the telogen follicle. As anagen commenced...

Does cerebellar neuronal integrity relate to cognitive ability?

International Nuclear Information System (INIS)

Rae, C.; Lee, M.; Dixon, R.M.; Blamire, A.; Thompson, C.; Styles, P.; Radda, G.K.; University of Sydney, NSW; Karmiloff-Smith, A.; Grant, J.

1998-01-01

Full text: Magnetic resonance spectroscopy (MRS) allows the non-invasive measurement of metabolite levels in the brain. One of these is N-acetylaspartate (NA), a molecule found solely in neurones, synthesised there by mitochondria. This compound can be considered as a marker of 1) neuronal density and 2) neuronal mitochondria function. We recently completed a joint MRS and neuropsychological investigation of Williams-Beuren syndrome (WBS), a rare (1/20,000) autosomal dominant disorder caused by a deletion which includes the elastin locus and LIM-kinase. The syndrome has an associated behavioural and cognitive profile which includes hyperactivity, hyperacusis and excessive sociability. Spatial skills are severely affected, while verbal skills are left relatively intact Our investigation showed loss of NA from the cerebellum in WBS compared with normal controls, with the subject population as a whole displaying a continuum of cerebellar NA concentration. Ability at cognitive tests, including the Weschler IQ scale and various verbal and spatial tests, was shown to correlate significantly and positively with the concentration of NA in the cerebellum. This finding can be interpreted in one of two ways: 1. Our sampling of cerebellar metabolite levels represents a 'global' sampling of total brain neuronal density and, as such, is independent of cerebellar integrity. 2. Cerebellar neuronal integrity is associated with performance at cognitive tests. If the latter interpretation is shown to be the case, it will have important implications for our current understanding of cerebellar function. Copyright (1998) Australian Neuroscience Society

Computed tomography in hypertensive cerebellar hemorrhage

Energy Technology Data Exchange (ETDEWEB)

Nose, T; Maki, Y; Ono, Y; Yoshizawa, T; Tsuboi, K [Tsukuba Univ., Sakura, Ibaraki (Japan)

1981-11-01

Fourteen cases of cerebellar hemorrhage were analysed from the point of CT-scan, and the following results were obtained. 1. The number of cases of cerebellar hemorrhage forms 4.4% of that of total intracranial hemorrhage. 2. Most of the cerebellar hematomas extend upward. Downward extension is rare. 3. In acute dead cases hematomas are 5 cm or more in diameter and lie over bilateral hemispheres with the extension to third or fourth ventricles in CT-scans. 4. Slowly progressive cases are detriorated by the secondary hydrocephalus. 5. In mild cases hematomas are 3cm or less in diameter on CT-scans and the hematoma evacuation is not indicated for these cases. 6. The shunt operation alone is sufficient for the life saving of the slowly progressive cases, but the hematoma evacuation is indicated in these cases if the functional prognosis is taken into consideration. 7. Immediate hematoma evacuation together with the ventricular drainage is considered to be effective for the life saving of the acute fulminant cases.

Computed tomography in hypertensive cerebellar hemorrhage

International Nuclear Information System (INIS)

Nose, Tadao; Maki, Yutaka; Ono, Yukio; Yoshizawa, Takashi; Tsuboi, Kohji

1981-01-01

Fourteen cases of cerebellar hemorrhage were analysed from the point of CT-scan, and the following results were obtained. 1. The number of cases of cerebellar hemorrhage forms 4.4% of that of total intracranial hemorrhage. 2. Most of the cerebellar hematomas extend upward. Downward extension is rare. 3. In acute dead cases hematomas are 5 cm or more in diameter and lie over bilateral hemispheres with the extension to third or fourth ventricles in CT-scans. 4. Slowly progressive cases are detriorated by the secondary hydrocephalus. 5. In mild cases hematomas are 3cm or less in diameter on CT-scans and the mematoma evacuation is not indicated for these cases. 6. The shunt operation alone is sufficient for the life saving of the slowly progressive cases, but the hematoma evacuation is indicated in these cases if the functional prognosis is taken into consideration. 7. Immediate hematoma evacuation togather with the ventricular dranage is considered to be effective for the life saving of the acute fulminant cases. (author)

Angiotensin II-induced hypertension increases plasma membrane Na pump activity by enhancing Na entry in rat thick ascending limbs.

Science.gov (United States)

Gonzalez-Vicente, Agustin; Garvin, Jeffrey L

2013-11-01

Thick ascending limbs (TAL) reabsorb 30% of the filtered NaCl load. Na enters the cells via apical Na-K-2Cl cotransporters and Na/H exchangers and exits via basolateral Na pumps. Chronic angiotensin II (ANG II) infusion increases net TAL Na transport and Na apical entry; however, little is known about its effects on the basolateral Na pump. We hypothesized that in rat TALs Na pump activity is enhanced by ANG II-infusion, a model of ANG II-induced hypertension. Rats were infused with 200 ng·kg(-1)·min(-1) ANG II or vehicle for 7 days, and TAL suspensions were obtained. We studied plasma membrane Na pump activity by measuring changes in 1) intracellular Na (Nai) induced by ouabain; and 2) ouabain-sensitive oxygen consumption (QO2). We found that the ouabain-sensitive rise in Nai in TALs from ANG II-infused rats was 12.8 ± 0.4 arbitrary fluorescent units (AFU)·mg(-1)·min(-1) compared with only 9.9 ± 1.1 AFU·mg(-1)·min(-1) in controls (P Na pump expression, the number of Na pumps in the plasma membrane, or the affinity for Na. When furosemide (1.1 mg·kg(-1)·day(-1)) was coinfused with ANG II, no increase in plasma membrane Na pump activity was observed. We concluded that in ANG II-induced hypertension Na pump activity is increased in the plasma membrane of TALs and that this increase is caused by the chronically enhanced Na entry occurring in this model.

Variations au cours de la journée de l'incorporation in vivo de la leucine tritiée dans les protéines du cervelet et du cerveau du jeune rat normal et hypothyroïdien. Daily variations of the in vivo [3H] leucine incorporation into the cerebellar and cerebral proteins of the normal and hypothyroid young rat [(author's transl)].

Science.gov (United States)

Dainat, J; Rebière, A

1978-02-15

In the normal and hypothyroid 6-day-old rat, the specific radioactivity (RSA) and the relative RSA (ratio of the RSA to the [3H] lecine concentration of the acido soluble phase) of the cerebral and cerebellar proteins, changes during the day synchronally. They show a maximum at 15.00 h and a minimum at 0.300 h. At all stages studied, these values are significantly lower in the hyothyroid animals than in normal ones.

[Change in the lipid composition of the inner mitochondrial membranes in rat organs during adaptation to heat].

Science.gov (United States)

Zubareva, E V; Seferova, R I; Denisova, N A

1991-01-01

Under conditions of adaptation to heating lipid composition in mitochondrial membranes of rat inner tissues was altered as follows: an increase in relative concentration of plasmalogenous forms of phospholipids (kidney, heart) and in content of saturated fatty acids (liver tissue), a decrease in the index of fatty acids unsaturation and in the ratio of fatty acids omega-3/omega-6. The alterations observed enabled the membranes to keep sufficient amount of liquidity essential for functional activity of mitochondria in heating.

Effect of chronic psychogenic stress on characteristics of some rat brain synaptic membrane receptors

International Nuclear Information System (INIS)

Nikuradze, V.O.; Kozlovskaya, M.M.; Rozhanets, V.V.; Val'dman, A.V.

1986-01-01

This paper studies characteristics of alpha- and beta-adrenoreceptors, and imipramine and bensodiazepine receptors in brain synaptic membranes of rats after exposure to combined stress for 15 days by a modified Hecht's method. Before the experiment the suspension was thawed and centrifuged. Specific binding of tritium-WB-4101 (30 Ci/mmole), tritium-dihydroalprenolol, tritium-flunitrazepam, and tritium-imipramine was carried out by known methods with certain modifications. The results suggest that pathology of behavior in rats observed in the model may be classed as a depressive-like state rather than a neurosis-like state, and the model itself may be more appropriate for the study of the mechanisms of action of compounds with marked tranquilizing activity

Effect of chronic psychogenic stress on characteristics of some rat brain synaptic membrane receptors

Energy Technology Data Exchange (ETDEWEB)

Nikuradze, V.O.; Kozlovskaya, M.M.; Rozhanets, V.V.; Val' dman, A.V.

1986-02-01

This paper studies characteristics of alpha- and beta-adrenoreceptors, and imipramine and bensodiazepine receptors in brain synaptic membranes of rats after exposure to combined stress for 15 days by a modified Hecht's method. Before the experiment the suspension was thawed and centrifuged. Specific binding of tritium-WB-4101 (30 Ci/mmole), tritium-dihydroalprenolol, tritium-flunitrazepam, and tritium-imipramine was carried out by known methods with certain modifications. The results suggest that pathology of behavior in rats observed in the model may be classed as a depressive-like state rather than a neurosis-like state, and the model itself may be more appropriate for the study of the mechanisms of action of compounds with marked tranquilizing activity.

Cerebellar Volume in Children With Attention-Deficit Hyperactivity Disorder (ADHD).

Science.gov (United States)

Wyciszkiewicz, Aleksandra; Pawlak, Mikolaj A; Krawiec, Krzysztof

2017-02-01

Attention Deficit Hyperactivity Disorder (ADHD) is associated with altered cerebellar volume and cerebellum is associated with cognitive performance. However there are mixed results regarding the cerebellar volume in young patients with ADHD. To clarify the size and direction of this effect, we conducted the analysis on the large public database of brain images. The aim of this study was to confirm that cerebellar volume in ADHD is smaller than in control subjects in currently the largest publicly available cohort of ADHD subjects.We applied cross-sectional case control study design by comparing 286 ADHD patients (61 female) with age and gender matched control subjects. Volumetric measurements of cerebellum were obtained using automated segmentation with FreeSurfer 5.1. Statistical analysis was performed in R-CRAN statistical environment. Patients with ADHD had significantly smaller total cerebellar volumes (134.5±17.11cm 3 vs.138.90±15.32 cm 3 ). The effect was present in both females and males (males 136.9±14.37 cm 3 vs. 141.20±14.75 cm 3 ; females 125.7±12.34 cm 3 vs. 131.20±15.03 cm 3 ). Age was positively and significantly associated with the cerebellar volumes. These results indicate either delayed or disrupted cerebellar development possibly contributing to ADHD pathophysiology.

Location of lesion determines motor vs. cognitive consequences in patients with cerebellar stroke

Directory of Open Access Journals (Sweden)

Catherine J. Stoodley

2016-01-01

Full Text Available Cerebellar lesions can cause motor deficits and/or the cerebellar cognitive affective syndrome (CCAS; Schmahmann's syndrome. We used voxel-based lesion-symptom mapping to test the hypothesis that the cerebellar motor syndrome results from anterior lobe damage whereas lesions in the posterolateral cerebellum produce the CCAS. Eighteen patients with isolated cerebellar stroke (13 males, 5 females; 20–66 years old were evaluated using measures of ataxia and neurocognitive ability. Patients showed a wide range of motor and cognitive performance, from normal to severely impaired; individual deficits varied according to lesion location within the cerebellum. Patients with damage to cerebellar lobules III–VI had worse ataxia scores: as predicted, the cerebellar motor syndrome resulted from lesions involving the anterior cerebellum. Poorer performance on fine motor tasks was associated primarily with strokes affecting the anterior lobe extending into lobule VI, with right-handed finger tapping and peg-placement associated with damage to the right cerebellum, and left-handed finger tapping associated with left cerebellar damage. Patients with the CCAS in the absence of cerebellar motor syndrome had damage to posterior lobe regions, with lesions leading to significantly poorer scores on language (e.g. right Crus I and II extending through IX, spatial (bilateral Crus I, Crus II, and right lobule VIII, and executive function measures (lobules VII–VIII. These data reveal clinically significant functional regions underpinning movement and cognition in the cerebellum, with a broad anterior-posterior distinction. Motor and cognitive outcomes following cerebellar damage appear to reflect the disruption of different cerebro-cerebellar motor and cognitive loops.

Structural properties of lipid reconstructs and lipid composition of normotensive and hypertensive rat vascular smooth muscle cell membranes

Directory of Open Access Journals (Sweden)

T.R. Oliveira

2009-09-01

Full Text Available Multiple cell membrane alterations have been reported to be the cause of various forms of hypertension. The present study focuses on the lipid portion of the membranes, characterizing the microviscosity of membranes reconstituted with lipids extracted from the aorta and mesenteric arteries of spontaneously hypertensive (SHR and normotensive control rat strains (WKY and NWR. Membrane-incorporated phospholipid spin labels were used to monitor the bilayer structure at different depths. The packing of lipids extracted from both aorta and mesenteric arteries of normotensive and hypertensive rats was similar. Lipid extract analysis showed similar phospholipid composition for all membranes. However, cholesterol content was lower in SHR arteries than in normotensive animal arteries. These findings contrast with the fact that the SHR aorta is hyporeactive while the SHR mesenteric artery is hyperreactive to vasopressor agents when compared to the vessels of normotensive animal strains. Hence, factors other than microviscosity of bulk lipids contribute to the vascular smooth muscle reactivity and hypertension of SHR. The excess cholesterol in the arteries of normotensive animal strains apparently is not dissolved in bulk lipids and is not directly related to vascular reactivity since it is present in both the aorta and mesenteric arteries. The lower cholesterol concentrations in SHR arteries may in fact result from metabolic differences due to the hypertensive state or to genes that co-segregate with those that determine hypertension during the process of strain selection.

Fenspiride and membrane transduction signals in rat alveolar macrophages.

Science.gov (United States)

Féray, J C; Mohammadi, K; Taouil, K; Brunet, J; Garay, R P; Hannaert, P

1997-07-15

Fenspiride inhibits the calcium signal evoked by the inflammatory peptide formyl-Met-Leu-Phe (fMLP) in peritoneal macrophages, but at concentrations (approximately 1 mM) far above the therapeutic range (approximately 1 microM). Here, in rat alveolar macrophages, high fenspiride concentrations (1 mM) were required to inhibit the calcium signals evoked by the calcium agonist Bay K8644 or by ionomycin. Moreover, fenspiride (1 mM) was a poor inhibitor of the cell membrane depolarization induced by gramicidine D. By contrast, fenspiride blocked Na+-H+ antiport activation by (i) fMLP with an IC50 = 3.1 +/- 1.9 nM and (ii) PMA (phorbol 12-myristate 13-acetate) with an IC50 = 9.2 +/- 3.1 nM. Finally, protein kinase C (PKC) activity of macrophage homogenate was not significantly modified by 10 or 100 microM fenspiride (at 100 microM: 2.57 +/- 1.60 vs. 2.80 +/- 1.71 pmol/10(6) cells/min). In conclusion, fenspiride inhibits fMLP- and PMA-induced pH signals in rat alveolar macrophages, probably by acting distally on the PKC transduction signal. This pH antagonistic action may be relevant for the antiinflammatory mechanism of fenspiride and requires further investigation.

Non-neoplastic gliotic cerebellar cysts

International Nuclear Information System (INIS)

Weisberg, L.A.

1982-01-01

The clinical and CT findings in 3 patients with non-neoplastic gliotic cerebellar cyst are described. CT does not permit accurate preoperative differentiation of these lesions from neoplastic disorders. (orig.)

Localization of ras antigenicity in rat hepatocyte plasma membrane and rough endoplasmic reticulum fractions

International Nuclear Information System (INIS)

Dominguez, J.M.; Lanoix, J.; Paiement, J.

1991-01-01

We have examined the antigenicity of plasma membrane (PM) and rough microsomal (RM) fractions from rat liver using anti-ras monoclonal antibodies 142-24EO5 and Y13-259 and immunochemistry as well as electron microscope immunocytochemistry. Proteins immunoprecipitated with monoclonal antibody 142-24E05 were separated using single-dimensional gradient-gel electrophoresis. The separated proteins were then blotted onto nitrocellulose sheets and incubated with [alpha-32P]GTP. Radioautograms of blots indicated the presence of specific 21.5- and 22-kDa labeled proteins in the PM fraction. A 23.5-kDa [alpha- 32 P] GTP-binding protein was detected in immunoprecipitates of both PM and RM fractions. Monoclonal antibody Y13-259 reacted only with the 21.5-kDa [alpha- 32 P] GTP-binding protein in the plasma membrane fraction. When anti-ras monoclonal antibody 142-24E05 and the immunogold technique were applied to membrane fractions using a preembedding immunocytochemical method, specific labeling was observed in association with both vesicular structures and membrane sheets in the PM fraction but only with electron-dense vesicular structures in the RM fraction. Thus ras antigenicity is associated with hepatocyte plasma membranes and ras-like antigenicity is probably associated with vesicular (secretory/endocytic) elements in both plasma membrane and rough microsomal preparations

Preparation of rat gastric heavy and light microsomal membranes enriched in (H+-K+)-ATPase using 2H2O and Percoll gradients

International Nuclear Information System (INIS)

Im, W.B.; Davis, J.P.; Blakeman, D.P.

1985-01-01

Gastric heavy microsomal membranes highly enriched in (H + -K + )-ATPase were obtained from cimetidine- or carbachol-treated rats through 2 H 2 O and Percoll gradient centrifugations. Both the resting (cimetidine-treated) and the stimulated (carbachol-treated) heavy membranes which presumably represent the apical membrane of gastric parietal cells were enriched with the polypeptides of 81,000 and 45,000 besides that of 93,000 representing (H + -K + )-ATPase. No apparent differences could be detected between the resting and the stimulated heavy membranes in their polypeptide profiles or their specific activity of (H + -K + )-ATPase. Nevertheless, the level of 86 RbCl uptake was greater in the stimulated than the resting heavy microsomal membrane vesicles. The light gastric microsomes which abound in intracellular tubulovesicles containing reserve (H + -K + )-ATPase as isolated from cimetidine-treated rats were similarly purified with respect to (H + -K + )-ATPase. The purified light gastric membranes were largely devoid of the polypeptides of 81,000 and 45,000 found in the heavy gastric membranes. These observations further support the current hypothesis that secretagogues bring about changes in the environment of (H + -K + )-ATPase and induce KCl permeability in the apical membrane of the parietal cells, although at present the authors have been unable to identify the polypeptide(s) responsible for the KCl pathway

File list: Unc.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Neu.50.AllAg.Cerebellar_granule_neurons mm9 Unclassified Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

File list: His.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Neu.05.AllAg.Cerebellar_granule_neurons mm9 Histone Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.05.AllAg.Cerebellar_granule_neurons.bed ...

File list: His.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Neu.50.AllAg.Cerebellar_granule_neurons mm9 Histone Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

File list: His.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Neu.10.AllAg.Cerebellar_granule_neurons mm9 Histone Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

File list: Unc.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Neu.20.AllAg.Cerebellar_granule_neurons mm9 Unclassified Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.20.AllAg.Cerebellar_granule_neurons.bed ...

File list: Unc.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Neu.10.AllAg.Cerebellar_granule_neurons mm9 Unclassified Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

File list: His.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Neu.20.AllAg.Cerebellar_granule_neurons mm9 Histone Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Neu.20.AllAg.Cerebellar_granule_neurons.bed ...

File list: Pol.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Neu.50.AllAg.Cerebellar_granule_neurons mm9 RNA polymerase Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

File list: Pol.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Neu.20.AllAg.Cerebellar_granule_neurons mm9 RNA polymerase Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.20.AllAg.Cerebellar_granule_neurons.bed ...

File list: Pol.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Neu.10.AllAg.Cerebellar_granule_neurons mm9 RNA polymerase Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

Increased cerebellar PET glucose metabolism corresponds to ataxia in Wernicke-Korsakoff syndrome.

Science.gov (United States)

Fellgiebel, Andreas; Siessmeier, Thomas; Winterer, Georg; Lüddens, Hartmut; Mann, Klaus; Schmidt, Lutz G; Bartenstein, Peter

2004-01-01

To investigate a possible relationship between cerebellar glucose metabolism and recovery from ataxia in the first months of acute Wernicke-Korsakoff syndrome. Two cases of alcoholic Wernicke-Korsakoff syndrome were followed up with the clinical status and cerebral glucose metabolism over a 4- and 9-month period. Initially both patients showed severe ataxia and elevated cerebellar glucose metabolism that decreased corresponding to the restitution of stance and gait. Increased cerebellar glucose metabolism at the onset of the illness may reflect the reorganization process of disturbed motor skills and may indicate cerebellar plasticity.

Congenital Cerebellar Mixed Germ Cell Tumor Presenting with Hemorrhage in a Newborn

International Nuclear Information System (INIS)

Kim, Sung Mok; Kim, Ji Hye; Yoo, So Young; Park, Won Soon; Jang, Yun Sil; Shin, Hyung Jin; Suh, Yeon Lim

2008-01-01

We report here on a neonate with congenital cerebellar mixed germ cell tumor, and this initially presented as cerebellar hemorrhage. Postnatal cranial ultrasonography revealed an echogenic cerebellar mass that exhibited the signal characteristics of hemorrhage rather than tumor on MR images. The short-term follow-up images also suggested a resolving cerebellar hemorrhage. One month later, the neonate developed vomiting. A second set of MR images demonstrated an enlarged mass that exhibited changed signal intensity at the same site, which suggested a neoplasm. Histological examination after the surgical resection revealed a mixed germ cell tumor

Changes in markers of oxidative stress and membrane properties in synaptosomes from rats exposed prenatally to toluene

DEFF Research Database (Denmark)

Edelfors, Sven; Hass, Ulla; Hougaard, Karin S.

2002-01-01

for the experiments, Synaptosomes from rats exposed prenatally to toluene exhibited an increased level of oxidative stress when incubated with toluene in vitro compared to synaptosomes from unexposed offspring. Also the cell membrane was affected, as the calcium leakage was more increased from exposed synaptosomes...

File list: Oth.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Neu.50.AllAg.Cerebellar_granule_neurons mm9 TFs and others Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

File list: Oth.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Neu.20.AllAg.Cerebellar_granule_neurons mm9 TFs and others Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.20.AllAg.Cerebellar_granule_neurons.bed ...

File list: Oth.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Neu.10.AllAg.Cerebellar_granule_neurons mm9 TFs and others Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

File list: Oth.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Neu.05.AllAg.Cerebellar_granule_neurons mm9 TFs and others Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Neu.05.AllAg.Cerebellar_granule_neurons.bed ...

Na+/K+-ATPase inhibition partially mimics the ethanol-induced increase of the Golgi cell-dependent component of the tonic GABAergic current in rat cerebellar granule cells.

Directory of Open Access Journals (Sweden)

Marvin R Diaz

Full Text Available Cerebellar granule cells (CGNs are one of many neurons that express phasic and tonic GABAergic conductances. Although it is well established that Golgi cells (GoCs mediate phasic GABAergic currents in CGNs, their role in mediating tonic currents in CGNs (CGN-I(tonic is controversial. Earlier studies suggested that GoCs mediate a component of CGN-I(tonic that is present only in preparations from immature rodents. However, more recent studies have detected a GoC-dependent component of CGN-I(tonic in preparations of mature rodents. In addition, acute exposure to ethanol was shown to potentiate the GoC component of CGN-I(tonic and to induce a parallel increase in spontaneous inhibitory postsynaptic current frequency at CGNs. Here, we tested the hypothesis that these effects of ethanol on GABAergic transmission in CGNs are mediated by inhibition of the Na(+/K(+-ATPase. We used whole-cell patch-clamp electrophysiology techniques in cerebellar slices of male rats (postnatal day 23-30. Under these conditions, we reliably detected a GoC-dependent component of CGN-I(tonic that could be blocked with tetrodotoxin. Further analysis revealed a positive correlation between basal sIPSC frequency and the magnitude of the GoC-dependent component of CGN-I(tonic. Inhibition of the Na(+/K(+-ATPase with a submaximal concentration of ouabain partially mimicked the ethanol-induced potentiation of both phasic and tonic GABAergic currents in CGNs. Modeling studies suggest that selective inhibition of the Na(+/K(+-ATPase in GoCs can, in part, explain these effects of ethanol. These findings establish a novel mechanism of action of ethanol on GABAergic transmission in the central nervous system.

Cerebellar contribution to feedforward control of locomotion.

Science.gov (United States)

Pisotta, Iolanda; Molinari, Marco

2014-01-01

The cerebellum is an important contributor to feedforward control mechanisms of the central nervous system, and sequencing-the process that allows spatial and temporal relationships between events to be recognized-has been implicated as the fundamental cerebellar mode of operation. By adopting such a mode and because cerebellar activity patterns are sensitive to a variety of sensorimotor-related tasks, the cerebellum is believed to support motor and cognitive functions that are encoded in the frontal and parietal lobes of the cerebral cortex. In this model, the cerebellum is hypothesized to make predictions about the consequences of a motor or cognitive command that originates from the cortex to prepare the entire system to cope with ongoing changes. In this framework, cerebellar predictive mechanisms for locomotion are addressed, focusing on sensorial and motoric sequencing. The hypothesis that sequence recognition is the mechanism by which the cerebellum functions in gait control is presented and discussed.

Thalamic, brainstem, and cerebellar glucose metabolism in the hemiplegic monkey

Energy Technology Data Exchange (ETDEWEB)

Shimoyama, I.; Dauth, G.W.; Gilman, S.; Frey, K.A.; Penney, J.B. Jr.

1988-12-01

Unilateral ablation of cerebral cortical areas 4 and 6 of Brodmann in the macaque monkey results in a contralateral hemiplegia that resolves partially with time. During the phase of dense hemiplegia, local cerebral metabolic rate for glucose (1CMRG1c) is decreased significantly in most of the thalamic nuclei ipsilateral to the ablation, and there are slight contralateral decreases. The lCMRGlc is reduced bilaterally in most of the brainstem nuclei and bilaterally in the deep cerebellar nuclei, but only in the contralateral cerebellar cortex. During the phase of partial motor recovery, lCMRGlc is incompletely restored in many of the thalamic nuclei ipsilateral to the ablation and completely restored in the contralateral nuclei. In the brainstem and deep cerebellar nuclei, poor to moderate recovery occurs bilaterally. Moderate recovery occurs in the contralateral cerebellar cortex. The findings demonstrate that a unilateral cerebral cortical lesion strongly affects lCMRGlc in the thalamus ipsilaterally and in the cerebellar cortex contralaterally, but in the brainstem bilaterally. Partial recovery of lCMRGlc accompanies the progressive motor recovery. The structures affected include those with direct, and also those with indirect, connections to the areas ablated.

Hypoglycemia induced changes in cholinergic receptor expression in the cerebellum of diabetic rats

Directory of Open Access Journals (Sweden)

Anju TR

2010-02-01

Full Text Available Abstract Glucose homeostasis in humans is an important factor for the functioning of nervous system. Hypoglycemia and hyperglycemia is found to be associated with central and peripheral nerve system dysfunction. Changes in acetylcholine receptors have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS. In the present study we showed the effects of insulin induced hypoglycemia and streptozotocin induced diabetes on the cerebellar cholinergic receptors, GLUT3 and muscle cholinergic activity. Results showed enhanced binding parameters and gene expression of Muscarinic M1, M3 receptor subtypes in cerebellum of diabetic (D and hypoglycemic group (D + IIH and C + IIH. α7nAchR gene expression showed a significant upregulation in diabetic group and showed further upregulated expression in both D + IIH and C + IIH group. AchE expression significantly upregulated in hypoglycemic and diabetic group. ChAT showed downregulation and GLUT3 expression showed a significant upregulation in D + IIH and C + IIH and diabetic group. AchE activity enhanced in the muscle of hypoglycemic and diabetic rats. Our studies demonstrated a functional disturbance in the neuronal glucose transporter GLUT3 in the cerebellum during insulin induced hypoglycemia in diabetic rats. Altered expression of muscarinic M1, M3 and α7nAchR and increased muscle AchE activity in hypoglycemic rats in cerebellum is suggested to cause cognitive and motor dysfunction. Hypoglycemia induced changes in ChAT and AchE gene expression is suggested to cause impaired acetycholine metabolism in the cerebellum. Cerebellar dysfunction is associated with seizure generation, motor deficits and memory impairment. The results shows that cerebellar cholinergic neurotransmission is impaired during hyperglycemia and hypoglycemia and the hypoglycemia is causing more prominent imbalance in cholinergic neurotransmission which is suggested to be a cause of cerebellar

File list: DNS.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Neu.50.AllAg.Cerebellar_granule_neurons mm9 DNase-seq Neural Cerebellar granule neurons... SRX685885,SRX685882,SRX685880 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

File list: ALL.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Neu.50.AllAg.Cerebellar_granule_neurons mm9 All antigens Neural Cerebellar granule neurons... SRX685885,SRX685882,SRX685880 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

File list: ALL.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Neu.20.AllAg.Cerebellar_granule_neurons mm9 All antigens Neural Cerebellar granule neurons... SRX685885,SRX685882,SRX685880 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Neu.20.AllAg.Cerebellar_granule_neurons.bed ...

File list: DNS.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Neu.20.AllAg.Cerebellar_granule_neurons mm9 DNase-seq Neural Cerebellar granule neurons... SRX685885,SRX685882,SRX685880 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Neu.20.AllAg.Cerebellar_granule_neurons.bed ...

Metronome Cueing of Walking Reduces Gait Variability after a Cerebellar Stroke

OpenAIRE

Wright, Rachel L.; Bevins, Joseph W.; Pratt, David; Sackley, Catherine M.; Wing, Alan M.

2016-01-01

Cerebellar stroke typically results in increased variability during walking. Previous research has suggested that auditory cueing reduces excessive variability in conditions such as Parkinson's disease and post-stroke hemiparesis. The aim of this case report was to investigate whether the use of a metronome cue during walking could reduce excessive variability in gait parameters after a cerebellar stroke. An elderly female with a history of cerebellar stroke and recurrent falling undertook th...

Cerebellar stroke presenting with isolated dizziness: Brain MRI in 136 patients.

Science.gov (United States)

Perloff, Michael D; Patel, Nimesh S; Kase, Carlos S; Oza, Anuja U; Voetsch, Barbara; Romero, Jose R

2017-11-01

To evaluate occurrence of cerebellar stroke in Emergency Department (ED) presentations of isolated dizziness (dizziness with a normal exam and negative neurological review of systems). A 5-year retrospective study of ED patients presenting with a chief complaint of "dizziness or vertigo", without other symptoms or signs in narrative history or on exam to suggest a central nervous system lesion, and work-up included a brain MRI within 48h. Patients with symptoms commonly peripheral in etiology (nystagmus, tinnitus, gait instability, etc.) were included in the study. Patient demographics, stroke risk factors, and gait assessments were recorded. One hundred and thirty-six patients, who had a brain MRI for isolated dizziness, were included. There was a low correlation of gait assessment between ED physician and Neurologist (49 patients, Spearman's correlation r 2 =0.17). Based on MRI DWI sequence, 3.7% (5/136 patients) had acute cerebellar strokes, limited to or including, the medial posterior inferior cerebellar artery vascular territory. In the 5 cerebellar stroke patients, mean age, body mass index (BMI), hemoglobin A1c, gender distribution, and prevalence of hypertension were similar to the non-cerebellar stroke patient group. Mean LDL/HDL ratio was 3.63±0.80 and smoking prevalence was 80% in the cerebellar stroke group compared to 2.43±0.79 and 22% (respectively, p valuesstroke group. Though there was preselection bias for stroke risk factors, our study suggests an important proportion of cerebellar stroke among ED patients with isolated dizziness, considering how common this complaint is. Copyright © 2017 Elsevier Inc. All rights reserved.

Free radical-mediated stimulation of tyrosine-specific protein kinase in rat liver plasma membrane

International Nuclear Information System (INIS)

Chan, T.M.; Tatoyan, A.; Cheng, E.; Shargill, N.S.; Pleta, M.

1986-01-01

Incorporation of 32 P from (γ- 32 P)-ATP into endogenous proteins of plasma membranes isolated from rat liver was significantly increased by several naphthoquinones including menadione. This apparent stimulation of membrane-associated protein kinase activity by these compounds was most striking (up to 6-7 fold) when the synthetic copolymers containing glutamate and tyrosine residues (4:1) was used as substrate. Since tyrosine residues are the only possible phosphate acceptor in the copolymers, the quinone-stimulated liver membrane protein kinase is most likely tyrosine specific. Although not required for protein kinase activity, dithiothreitol (DTT) was necessary for its stimulation by these quinonoid compounds. Hydrolysis of ATP was not significantly affected by quinones under the experimental conditions. Both menadione and vitamin k 5 increased phosphorylation of plasma membrane proteins of molecular weight 45 and 60 kd. The stimulatory effect of menadione on protein phosphorylation was prevented by the addition of superoxide dismutase. Dihydroxyfumerate, which spontaneously produces various radical species, and H 2 O 2 , also stimulated tyrosine-specific protein phosphorylation. DTT was also required for their full effect. It, therefore, appears that quinonone stimulation of tyrosine-specific protein phosphorylation is mediated by oxygen radicals

The cerebellar Golgi cell and spatiotemporal organization of granular layer activity

Directory of Open Access Journals (Sweden)

Egidio eD‘Angelo

2013-05-01

Full Text Available The cerebellar granular layer has been suggested to perform a complex spatiotemporal reconfiguration of incoming mossy fiber signals. Central to this role is the inhibitory action exerted by Golgi cells over granule cells: Golgi cells inhibit granule cells through double feedforward and feedback inhibitory loops and generate a broad lateral inhibition that extends beyond the afferent synaptic field. This characteristic connectivity has recently been investigated in great detail and been correlated with specific functional properties of the neuron. These include theta-frequency pacemaking, network entrainment into coherent oscillations and phase resetting. Important advances have also been made in terms of determining the membrane and synaptic properties of the neuron, and clarifying the mechanisms of activation by input bursts. Moreover, voltage sensitive dye imaging and multi-electrode array recordings, combined with mathematical simulations based on realistic computational models, have improved our understanding of the impact of Golgi cell activity on granular layer circuit computations. These investigations have highlighted the critical role of Golgi cells in: generating dense clusters of granule cell activity organized in center-surround structures, implementing combinatorial operations on multiple mossy fiber inputs, regulating transmission gain and cut-off frequency, controlling spike timing and burst transmission, and determining the sign, intensity and extension of long-term synaptic plasticity at the mossy fiber-granule cell relay. This review considers recent advances in the field, highlighting the functional implications of Golgi cells for granular layer network computation and indicating new challenges for cerebellar research.

Role of the Na+/K+-ATPase in regulating the membrane potential in rat peritoneal mast cells

DEFF Research Database (Denmark)

Friis, U G; Praetorius, Birger Hans; Knudsen, T

1997-01-01

1. The aim of this study was to investigate the effect of the Na+/K+-ATPase on the membrane potential of peritoneal mast cells isolated from male Sprague-Dawley SPF-rats. 2. Experiments were performed at 22-26 degrees C in the tight-seal whole-cell configuration of the patch-clamp technique by use...

Timing tasks synchronize cerebellar and frontal ramping activity and theta oscillations: Implications for cerebellar stimulation in diseases of impaired cognition

Directory of Open Access Journals (Sweden)

Krystal Lynn Parker

2016-01-01

Full Text Available Timing is a fundamental and highly conserved mammalian capability yet the underlying neural mechanisms are widely debated. Ramping activity of single neurons that gradually increase or decrease activity to encode the passage of time, has been speculated to predict a behaviorally relevant temporal event. Cue-evoked low-frequency activity has also been implicated in temporal processing. Ramping activity and low-frequency oscillations occur throughout the brain and could indicate a network-based approach to timing. Temporal processing requires cognitive mechanisms of working memory, attention, and reasoning which are dysfunctional in neuropsychiatric disease. Therefore, timing tasks could be used to probe cognition in animals with disease phenotypes. The medial frontal cortex and cerebellum are involved in cognition. Cerebellar stimulation has been shown to influence medial frontal activity and improve cognition in schizophrenia. However, the mechanism underlying the efficacy of cerebellar stimulation is unknown. Here we discuss how timing tasks can be used to probe cerebellar interactions with the frontal cortex and the therapeutic potential of cerebellar stimulation. The goal of this theory and hypothesis manuscript is threefold. First, we will summarize evidence indicating that in addition to motor learning, timing tasks involve cognitive processes that are present within both the cerebellum and medial frontal cortex. Second, we propose methodologies to investigate the connections between these areas in patients with Parkinson’s disease, autism, and schizophrenia. We hypothesis that cerebellar transcranial stimulation may rescue medial frontal ramping activity, theta oscillations, and timing abnormalities, thereby restoring executive function in diseases of impaired cognition. These hypotheses could inspire the use of timing tasks as biomarkers for neuronal and cognitive abnormalities in neuropsychiatric disease and promote the therapeutic

Intrauterine Growth Restriction Alters the Postnatal Development of the Rat Cerebellum.

Science.gov (United States)

McDougall, Annie R A; Wiradjaja, Vanny; Azhan, Aminath; Li, Anqi; Hale, Nadia; Wlodek, Mary E; Hooper, Stuart B; Wallace, Megan J; Tolcos, Mary

2017-01-01

Intrauterine growth restriction (IUGR) is a major cause of antenatal brain injury. We aimed to characterize cerebellar deficits following IUGR and to investigate the potential underlying cellular and molecular mechanisms. At embryonic day 18, pregnant rats underwent either sham surgery (controls; n = 23) or bilateral uterine vessel ligation to restrict blood flow to fetuses (IUGR; n = 20). Offspring were collected at postnatal day 2 (P2), P7, and P35. Body weights were reduced at P2, P7, and P35 in IUGR offspring (p < 0.05) compared with controls. At P7, the width of the external granule layer (EGL) was 30% greater in IUGR than control rats (p < 0.05); there was no difference in the width of the proliferative zone or in the density of Ki67-positive cells in the EGL. Bergmann glia were disorganized at P7 and P35 in IUGR pups, and by P35, there was a 10% decrease in Bergmann glial fiber density (p < 0.05) compared with controls. At P7, trophoblast antigen-2 (Trop2) mRNA and protein levels in the cerebellum were decreased by 88 and 40%, respectively, and astrotactin 1 mRNA levels were increased by 20% in the IUGR rats (p < 0.05) compared with controls; there was no difference in ASTN1 protein. The expressions of other factors known to regulate cerebellar development (astrotactin 2, brain-derived neurotrophic factor, erb-b2 receptor tyrosine kinase 4, neuregulin 1, sonic hedgehog and somatostatin) were not different between IUGR and control rats at P7 or P35. These data suggest that damage to the migratory scaffold (Bergmann glial fibers) and alterations in the genes that influence migration (Trop2 and Astn1) may underlie the deficits in postnatal cerebellar development following IUGR. © 2017 S. Karger AG, Basel.

Immobilization of Na,K-ATPase isolated from rat brain synaptic plasma membranes

Directory of Open Access Journals (Sweden)

ANICA HROVAT

2002-12-01

Full Text Available Rat brain Na,K-ATPase partially purified by SDS from synaptic plasma membranes (SPM was immobilized by adsorption on nitrocellulose (NC, polyvinylidene fluoride (PVDF and glass fiber (GF membranes. Partial SDS solubilization increased the enzyme activity by 40 %. With regard to the preservation of the enzyme activity, nitrocellulose was shown to be the optimal support for the immobilization. The enzyme showed the highest percentage activity (14 % after 30 min of SPM adsorption, at 20°C under the vaccum, with 25 mg of proteins per NC disc filter. In addition, adsorption on NC stabilizes the Na,K-ATPase, since the activity was substantial 72 h after adsorption at 20°C. After adsorption, the sensitivity of the enzyme to HgCl2and CdCll2 inhibition was higher. The results show that immobilized Na,K-ATPase SPM can be used as a practical model for the detection of metal ions in different samples.

Imaging of dopamine transporters in rats using high-resolution pinhole single-photon emission tomography

Energy Technology Data Exchange (ETDEWEB)

Booij, Jan; Bruin, Kora de; Habraken, Jan B.A. [Department of Nuclear Medicine, F2N, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam (Netherlands); Voorn, Pieter [Department of Anatomy, Vrije Universiteit Medical Center, Amsterdam (Netherlands)

2002-09-01

To date, the vast majority of investigations on the dopaminergic system in small animals have been in vitro studies. In comparison with in vitro studies, single-photon emission tomography (SPET) or positron emission tomography (PET) imaging of the dopaminergic system in small animals has the advantage of permitting repeated studies within the same group of animals. Dopamine transporter imaging is a valuable non-invasive tool with which to investigate the integrity of dopaminergic neurons. The purpose of this study was to investigate the feasibility of assessing dopamine transporter density semi-quantitatively in rats using a recently developed high-resolution pinhole SPET system. This system was built exclusively for imaging of small animals. In this unique single-pinhole system, the animal rotates instead of the collimated detector. The system has proven to have a high spatial resolution. We performed SPET imaging with [{sup 123}I]FP-CIT to quantify striatal dopamine transporters in rat brain. In all seven studied control rats, symmetrical striatal binding to dopamine transporters was seen 2 h after injection of the radiotracer, with striatal-to-cerebellar binding ratios of approximately 3.5. In addition, test/retest variability of the striatal-to-cerebellar binding ratios was studied and found to be 14.5%. Finally, in unilaterally 6-hydroxydopamine-lesioned rats, striatal binding was only visible on the non-lesioned side. Quantitative analysis revealed that striatal-to-cerebellar SPET ratios were significantly lower on the lesioned (mean binding ratio 2.2{+-}0.2) than on the non-lesioned (mean ratio 3.1{+-}0.4) side. The preliminary results of this study indicate that semi-quantitative assessment of striatal dopamine transporter density using our recently developed high-resolution single-pinhole SPET system is feasible in living rat brain. (orig.)

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Lifescience Database Archive (English)

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File list: ALL.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

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Lifescience Database Archive (English)

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Integrated plasticity at inhibitory and excitatory synapses in the cerebellar circuit

Directory of Open Access Journals (Sweden)

Lisa eMapelli

2015-05-01

Full Text Available The way long-term potentiation (LTP and depression (LTD are integrated within the different synapses of brain neuronal circuits is poorly understood. In order to progress beyond the identification of specific molecular mechanisms, a system in which multiple forms of plasticity can be correlated with large-scale neural processing is required. In this paper we take as an example the cerebellar network , in which extensive investigations have revealed LTP and LTD at several excitatory and inhibitory synapses. Cerebellar LTP and LTD occur in all three main cerebellar subcircuits (granular layer, molecular layer, deep cerebellar nuclei and correspondingly regulate the function of their three main neurons: granule cells (GrCs, Purkinje cells (PCs and deep cerebellar nuclear (DCN cells. All these neurons, in addition to be excited, are reached by feed-forward and feed-back inhibitory connections, in which LTP and LTD may either operate synergistically or homeostatically in order to control information flow through the circuit. Although the investigation of individual synaptic plasticities in vitro is essential to prove their existence and mechanisms, it is insufficient to generate a coherent view of their impact on network functioning in vivo. Recent computational models and cell-specific genetic mutations in mice are shedding light on how plasticity at multiple excitatory and inhibitory synapses might regulate neuronal activities in the cerebellar circuit and contribute to learning and memory and behavioral control.

Integrated plasticity at inhibitory and excitatory synapses in the cerebellar circuit.

Science.gov (United States)

Mapelli, Lisa; Pagani, Martina; Garrido, Jesus A; D'Angelo, Egidio

2015-01-01

The way long-term potentiation (LTP) and depression (LTD) are integrated within the different synapses of brain neuronal circuits is poorly understood. In order to progress beyond the identification of specific molecular mechanisms, a system in which multiple forms of plasticity can be correlated with large-scale neural processing is required. In this paper we take as an example the cerebellar network, in which extensive investigations have revealed LTP and LTD at several excitatory and inhibitory synapses. Cerebellar LTP and LTD occur in all three main cerebellar subcircuits (granular layer, molecular layer, deep cerebellar nuclei) and correspondingly regulate the function of their three main neurons: granule cells (GrCs), Purkinje cells (PCs) and deep cerebellar nuclear (DCN) cells. All these neurons, in addition to be excited, are reached by feed-forward and feed-back inhibitory connections, in which LTP and LTD may either operate synergistically or homeostatically in order to control information flow through the circuit. Although the investigation of individual synaptic plasticities in vitro is essential to prove their existence and mechanisms, it is insufficient to generate a coherent view of their impact on network functioning in vivo. Recent computational models and cell-specific genetic mutations in mice are shedding light on how plasticity at multiple excitatory and inhibitory synapses might regulate neuronal activities in the cerebellar circuit and contribute to learning and memory and behavioral control.

Thyroid hormone modulates the extracellular matrix organization and expression in cerebellar astrocyte: effects on astrocyte adhesion.

Science.gov (United States)

Trentin, Andréa Gonçalves; De Aguiar, Cláudia Beatriz Nedel Mendes; Garcez, Ricardo Castilho; Alvarez-Silva, Marcio

2003-06-01

The effects of thyroid hormone (T(3)) on extracellular matrix (ECM) expression and organization in cerebellar astrocytes were studied. Control astrocytes exhibit laminin immunostaining distributed in a punctate configuration and fibronectin concentrated in focal points at the cell surface. These cells attach to the substratum by membrane points, as shown by scanning microscopy, possibly by focal points stained to fibronectin. In contrast, after T(3) treatment, laminin assumes a fibrillary pattern and fibronectin becomes organized in filaments homogeneously distributed on the cell surface; the cells acquire a very flat and spread morphology. T(3) treatment also modulates astrocyte adhesion. In addition, increased expression of both laminin and fibronectin was detected by Western blot. These alterations in fibronectin and/or laminin production and organization may be involved in the flat and spread morphology and in altered adhesion. We observed that fibroblast growth factor-2 (FGF(2)) added to cultures had similar effects to those described to T(3). Neutralizing antibodies against FGF(2) reversed T(3) effects on fibronectin and laminin distribution. We also observed that cerebellar neurons co-cultured on T(3)-treated astrocytes had an increase in the number of cells and presented longer neurites. Thus, we propose a novel mechanism of the effect of thyroid hormone on cerebellar development mediated by astrocytes: T(3) may induce astrocyte secretion of growth factors, mainly FGF(2), that autocrinally stimulate astrocyte proliferation, reorganization in ECM proteins, and alterations in cell spreading and adhesion. These effects may indirectly influence neuronal development. Copyright 2003 Wiley-Liss, Inc.

Effect of Kaiyu Qingwei Granule (开郁清胃颗粒) on Insulin Receptor in Liver and Skeletal Muscular Cell Membrane in Diabetes Mellitus Rats

Institute of Scientific and Technical Information of China (English)

LIU Hong-fang (柳红芳); TONG Xiao-lin(仝小林); WANG Qing-guo(王庆国); ZUO Ping-ping(左萍萍); GUO An-chen(郭安臣); LIU Hong-xing(刘红星)

2003-01-01

Objective: To investigate the effect of Kaiyu Qingwei granule (KYQWG,开郁清胃颗粒) on the insulin binding capacity of liver and skeletal muscular cell membrane and serum insulin-like growth factor-1 (IGF-1) in streptozotocin-induced diabetic rats. Methods:Rats in four experimental groups were investigated: the control group, the model group, the KYQWG group and the Metformin group. The insulin binding rate (IBR) of liver and skeletal muscular cell membrane was detected by receptor-ligand radiometric method and changes of serum levels of glucose, insulin and IGF-1 were observed before and after 4 weeks of medication. Results: The KYQWG group had a lower blood glucose level and IBR of liver and muscular cell membrane, as compared with those in the model group (P<0.01 or P<0.05), and a higher level of IGF-1 than that in the model group(P<0.01), but had no obvious changes in the serum level of insulin. Conclusion: KYQWG may increase the serum level of IGF-1 in diabetic rats, thus to decrease the insulin resistance at ante-receptor sites and improve the sugar metabolic disturbance in rats with diabetes mellitus.

Cerebellar language mapping and cerebral language dominance in pediatric epilepsy surgery patients

Directory of Open Access Journals (Sweden)

Jennifer N. Gelinas, MD, PhD

2014-01-01

Conclusions: Cerebellar language activation occurs in homologous regions of Crus I/II contralateral to cerebral language activation in patients with both right and left cerebral language dominance. Cerebellar language laterality could contribute to comprehensive pre-operative evaluation of language lateralization in pediatric epilepsy surgery patients. Our data suggest that patients with atypical cerebellar language activation are at risk for having atypical cerebral language organization.

Antioxidant activity of erythrocyte membranes of rats exposed to X-radiation and injected with α-tocopheral acetate

International Nuclear Information System (INIS)

Tsvetkova, T.V.; Tsokur, Eh.V.

1988-01-01

Injection of α-tocopherol acetate to albino mongrel rats potentiates antioxidant activity (AOA) that involves water-soluble factors of the antioxidant system in erythrocyte membranes. The activation of AOA by a α-tocopherol takes place immediately after irradiation and drug injection and persists during the first 24 h following irradiation

Influence of Glucose Deprivation on Membrane Potentials of Plasma Membranes, Mitochondria and Synaptic Vesicles in Rat Brain Synaptosomes.

Science.gov (United States)

Hrynevich, Sviatlana V; Pekun, Tatyana G; Waseem, Tatyana V; Fedorovich, Sergei V

2015-06-01

Hypoglycemia can cause neuronal cell death similar to that of glutamate-induced cell death. In the present paper, we investigated the effect of glucose removal from incubation medium on changes of mitochondrial and plasma membrane potentials in rat brain synaptosomes using the fluorescent dyes DiSC3(5) and JC-1. We also monitored pH gradients in synaptic vesicles and their recycling by the fluorescent dye acridine orange. Glucose deprivation was found to cause an inhibition of K(+)-induced Ca(2+)-dependent exocytosis and a shift of mitochondrial and plasma membrane potentials to more positive values. The sensitivity of these parameters to the energy deficit caused by the removal of glucose showed the following order: mitochondrial membrane potential > plasma membrane potential > pH gradient in synaptic vesicles. The latter was almost unaffected by deprivation compared with the control. The pH-dependent dye acridine orange was used to investigate synaptic vesicle recycling. However, the compound's fluorescence was shown to be enhanced also by the mixture of mitochondrial toxins rotenone (10 µM) and oligomycin (5 µg/mL). This means that acridine orange can presumably be partially distributed in the intermembrane space of mitochondria. Glucose removal from the incubation medium resulted in a 3.7-fold raise of acridine orange response to rotenone + oligomycin suggesting a dramatic increase in the mitochondrial pH gradient. Our results suggest that the biophysical characteristics of neuronal presynaptic endings do not favor excessive non-controlled neurotransmitter release in case of hypoglycemia. The inhibition of exocytosis and the increase of the mitochondrial pH gradient, while preserving the vesicular pH gradient, are proposed as compensatory mechanisms.

Early childhood obesity is associated with compromised cerebellar development.

Science.gov (United States)

Miller, Jennifer L; Couch, Jessica; Schwenk, Krista; Long, Michelle; Towler, Stephen; Theriaque, Douglas W; He, Guojun; Liu, Yijun; Driscoll, Daniel J; Leonard, Christiana M

2009-01-01

As part of a study investigating commonalities between Prader-Willi syndrome (PWS-a genetic imprinting disorder) and early-onset obesity of unknown etiology (EMO) we measured total cerebral and cerebellar volume on volumetric magnetic resonance imaging (MRI) images. Individuals with PWS (N = 16) and EMO (N = 12) had smaller cerebellar volumes than a control group of 15 siblings (p = .02 control vs. EMO; p = .0005 control vs. PWS), although there was no difference among the groups in cerebral volume. Individuals with PWS and EMO also had impaired cognitive function: general intellectual ability (GIA): PWS 65 +/- 25; EMO 81 +/- 19; and Controls 112 +/- 13 (p cognitive development, these results raise the possibility that early childhood obesity retards both cerebellar and cognitive development.

File list: InP.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: InP.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Neu.50.AllAg.Cerebellar_granule_neurons mm9 Input control Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.50.AllAg.Cerebellar_granule_neurons.bed ...

File list: NoD.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

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Full Text Available NoD.Neu.10.AllAg.Cerebellar_granule_neurons mm9 No description Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

File list: InP.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Neu.05.AllAg.Cerebellar_granule_neurons mm9 Input control Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.05.AllAg.Cerebellar_granule_neurons.bed ...

File list: NoD.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Neu.20.AllAg.Cerebellar_granule_neurons mm9 No description Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Neu.20.AllAg.Cerebellar_granule_neurons.bed ...

File list: NoD.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

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File list: InP.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Neu.10.AllAg.Cerebellar_granule_neurons mm9 Input control Neural Cerebellar granule neurons... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Neu.10.AllAg.Cerebellar_granule_neurons.bed ...

Inverse Stochastic Resonance in Cerebellar Purkinje Cells.

Directory of Open Access Journals (Sweden)

Anatoly Buchin

2016-08-01

Full Text Available Purkinje neurons play an important role in cerebellar computation since their axons are the only projection from the cerebellar cortex to deeper cerebellar structures. They have complex internal dynamics, which allow them to fire spontaneously, display bistability, and also to be involved in network phenomena such as high frequency oscillations and travelling waves. Purkinje cells exhibit type II excitability, which can be revealed by a discontinuity in their f-I curves. We show that this excitability mechanism allows Purkinje cells to be efficiently inhibited by noise of a particular variance, a phenomenon known as inverse stochastic resonance (ISR. While ISR has been described in theoretical models of single neurons, here we provide the first experimental evidence for this effect. We find that an adaptive exponential integrate-and-fire model fitted to the basic Purkinje cell characteristics using a modified dynamic IV method displays ISR and bistability between the resting state and a repetitive activity limit cycle. ISR allows the Purkinje cell to operate in different functional regimes: the all-or-none toggle or the linear filter mode, depending on the variance of the synaptic input. We propose that synaptic noise allows Purkinje cells to quickly switch between these functional regimes. Using mutual information analysis, we demonstrate that ISR can lead to a locally optimal information transfer between the input and output spike train of the Purkinje cell. These results provide the first experimental evidence for ISR and suggest a functional role for ISR in cerebellar information processing.

Intracellular and transcellular transport of secretory and membrane proteins in the rat hepatocyte

International Nuclear Information System (INIS)

Sztul, E.S.

1984-01-01

The intra- and transcellular transport of hepatic secretory and membrane proteins was studied in rats in vivo using [ 3 H]fucose and [ 35 S]cyteine as metabolic precursors. Incorporated radioactivity in plasma, bile, and liver subcellular fractions was measured and the labeled proteins of the Golgi complex, bile and plasma were separated by SDS-PAGE and identified by fluorography. 3 H-radioactivity in Golgi fractions peaked at 10 min post injection (p.i.) and then declined concomitantly with the appearance of labeled glycoproteins in plasma. Maximal secretion of secretory fucoproteins from the Golgi complex occurred between 10 and 20 min p.i. In contrast, the clearance of labeled proteins from Golgi membrane subfractions occurred past 30 min p.i., indicating that membrane proteins leave the Golgi complex at least 10 min later than the bulk of content proteins. A major 80K form of Secretory Component (SC) was identified in the bile by precipitation with an anti IgA antibody. A comparative study of kinetics of transport of 35 S-labeled SC and 35 S-labeled albumin showed that albumin peaked in bile at ∼45 min p.i., whereas the SC peak occurred at 80 min p.i., suggesting that the transit time differs for plasma and membrane proteins which are delivered to the bile canaliculus (BC)

Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats

Science.gov (United States)

Calatrava-Ferreras, Lucía; Gonzalo-Gobernado, Rafael; Herranz, Antonio S.; Reimers, Diana; Montero Vega, Teresa; Jiménez-Escrig, Adriano; Richart López, Luis Alberto; Bazán, Eulalia

2012-01-01

Cerebellar ataxias include a heterogeneous group of infrequent diseases characterized by lack of motor coordination caused by disturbances in the cerebellum and its associated circuits. Current therapies are based on the use of drugs that correct some of the molecular processes involved in their pathogenesis. Although these treatments yielded promising results, there is not yet an effective therapy for these diseases. Cell replacement strategies using human umbilical cord blood mononuclear cells (HuUCBMCs) have emerged as a promising approach for restoration of function in neurodegenerative diseases. The aim of this work was to investigate the potential therapeutic activity of HuUCBMCs in the 3-acetylpyridine (3-AP) rat model of cerebellar ataxia. Intravenous administered HuUCBMCs reached the cerebellum and brain stem of 3-AP ataxic rats. Grafted cells reduced 3-AP-induced neuronal loss promoted the activation of microglia in the brain stem, and prevented the overexpression of GFAP elicited by 3-AP in the cerebellum. In addition, HuUCBMCs upregulated the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats. As all these effects were accompanied by a temporal but significant improvement in motor coordination, HuUCBMCs grafts can be considered as an effective cell replacement therapy for cerebellar disorders. PMID:23150735

Radiation inactivation target size of rat adipocyte glucose transporters in the plasma membrane and intracellular pools

International Nuclear Information System (INIS)

Jacobs, D.B.; Berenski, C.J.; Spangler, R.A.; Jung, C.Y.

1987-01-01

The in situ assembly states of the glucose transport carrier protein in the plasma membrane and in the intracellular (microsomal) storage pool of rat adipocytes were assessed by studying radiation-induced inactivation of the D-glucose-sensitive cytochalasin B binding activities. High energy radiation inactivated the glucose-sensitive cytochalasin B binding of each of these membrane preparations by reducing the total number of the binding sites without affecting the dissociation constant. The reduction in total number of binding sites was analyzed as a function of radiation dose based on target theory, from which a radiation-sensitive mass (target size) was calculated. When the plasma membranes of insulin-treated adipocytes were used, a target size of approximately 58,000 daltons was obtained. For adipocyte microsomal membranes, we obtained target sizes of approximately 112,000 and 109,000 daltons prior to and after insulin treatment, respectively. In the case of microsomal membranes, however, inactivation data showed anomalously low radiation sensitivities at low radiation doses, which may be interpreted as indicating the presence of a radiation-sensitive inhibitor. These results suggest that the adipocyte glucose transporter occurs as a monomer in the plasma membrane while existing in the intracellular reserve pool either as a homodimer or as a stoichiometric complex with a protein of an approximately equal size

Proton permeability of membranes of Streptococcus faecalis and submitochondrial particles of rats after irradiation

International Nuclear Information System (INIS)

Fomenko, B.S.; Pinchukova, V.A.

1977-01-01

It has been shown that at a changed, by HCl impulse, pH of Streptococcus faecalis suspension and submitochondrial liver particles (SLP) of rats, H + concentration decreases more rapidly in the irradiated bacteria and SLP than in the controls. The curves of energy dependence of accumulation of the penetrating ions were also displaced toward the alkaline zone depending on pH. These effects are suggested to be connected with an increased proton permeability of irradiated membranes

Cerebellar motor learning: when is cortical plasticity not enough?

Directory of Open Access Journals (Sweden)

John Porrill

2007-10-01

Full Text Available Classical Marr-Albus theories of cerebellar learning employ only cortical sites of plasticity. However, tests of these theories using adaptive calibration of the vestibulo-ocular reflex (VOR have indicated plasticity in both cerebellar cortex and the brainstem. To resolve this long-standing conflict, we attempted to identify the computational role of the brainstem site, by using an adaptive filter version of the cerebellar microcircuit to model VOR calibration for changes in the oculomotor plant. With only cortical plasticity, introducing a realistic delay in the retinal-slip error signal of 100 ms prevented learning at frequencies higher than 2.5 Hz, although the VOR itself is accurate up to at least 25 Hz. However, the introduction of an additional brainstem site of plasticity, driven by the correlation between cerebellar and vestibular inputs, overcame the 2.5 Hz limitation and allowed learning of accurate high-frequency gains. This "cortex-first" learning mechanism is consistent with a wide variety of evidence concerning the role of the flocculus in VOR calibration, and complements rather than replaces the previously proposed "brainstem-first" mechanism that operates when ocular tracking mechanisms are effective. These results (i describe a process whereby information originally learnt in one area of the brain (cerebellar cortex can be transferred and expressed in another (brainstem, and (ii indicate for the first time why a brainstem site of plasticity is actually required by Marr-Albus type models when high-frequency gains must be learned in the presence of error delay.

A Novel Mutation in Isoform 3 of the Plasma Membrane Ca2+ Pump Impairs Cellular Ca2+ Homeostasis in a Patient with Cerebellar Ataxia and Laminin Subunit 1α Mutations.

Science.gov (United States)

Calì, Tito; Lopreiato, Raffaele; Shimony, Joshua; Vineyard, Marisa; Frizzarin, Martina; Zanni, Ginevra; Zanotti, Giuseppe; Brini, Marisa; Shinawi, Marwan; Carafoli, Ernesto

2015-06-26

The particular importance of Ca(2+) signaling to neurons demands its precise regulation within their cytoplasm. Isoform 3 of the plasma membrane Ca(2+) ATPase (the PMCA3 pump), which is highly expressed in brain and cerebellum, plays an important role in the regulation of neuronal Ca(2+). A genetic defect of the PMCA3 pump has been described in one family with X-linked congenital cerebellar ataxia. Here we describe a novel mutation in the ATP2B3 gene in a patient with global developmental delay, generalized hypotonia and cerebellar ataxia. The mutation (a R482H replacement) impairs the Ca(2+) ejection function of the pump. It reduces the ability of the pump expressed in model cells to control Ca(2+) transients generated by cell stimulation and impairs its Ca(2+) extrusion function under conditions of low resting cytosolic Ca(2+) as well. In silico analysis of the structural effect of the mutation suggests a reduced stabilization of the portion of the pump surrounding the mutated residue in the Ca(2+)-bound state. The patient also carries two missense mutations in LAMA1, encoding laminin subunit 1α. On the basis of the family pedigree of the patient, the presence of both PMCA3 and laminin subunit 1α mutations appears to be necessary for the development of the disease. Considering the observed defect in cellular Ca(2+) homeostasis and the previous finding that PMCAs act as digenic modulators in Ca(2+)-linked pathologies, the PMCA3 dysfunction along with LAMA1 mutations could act synergistically to cause the neurological phenotype. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

A Novel Mutation in Isoform 3 of the Plasma Membrane Ca2+ Pump Impairs Cellular Ca2+ Homeostasis in a Patient with Cerebellar Ataxia and Laminin Subunit 1α Mutations*

Science.gov (United States)

Calì, Tito; Lopreiato, Raffaele; Shimony, Joshua; Vineyard, Marisa; Frizzarin, Martina; Zanni, Ginevra; Zanotti, Giuseppe; Brini, Marisa; Shinawi, Marwan; Carafoli, Ernesto

2015-01-01

The particular importance of Ca2+ signaling to neurons demands its precise regulation within their cytoplasm. Isoform 3 of the plasma membrane Ca2+ ATPase (the PMCA3 pump), which is highly expressed in brain and cerebellum, plays an important role in the regulation of neuronal Ca2+. A genetic defect of the PMCA3 pump has been described in one family with X-linked congenital cerebellar ataxia. Here we describe a novel mutation in the ATP2B3 gene in a patient with global developmental delay, generalized hypotonia and cerebellar ataxia. The mutation (a R482H replacement) impairs the Ca2+ ejection function of the pump. It reduces the ability of the pump expressed in model cells to control Ca2+ transients generated by cell stimulation and impairs its Ca2+ extrusion function under conditions of low resting cytosolic Ca2+ as well. In silico analysis of the structural effect of the mutation suggests a reduced stabilization of the portion of the pump surrounding the mutated residue in the Ca2+-bound state. The patient also carries two missense mutations in LAMA1, encoding laminin subunit 1α. On the basis of the family pedigree of the patient, the presence of both PMCA3 and laminin subunit 1α mutations appears to be necessary for the development of the disease. Considering the observed defect in cellular Ca2+ homeostasis and the previous finding that PMCAs act as digenic modulators in Ca2+-linked pathologies, the PMCA3 dysfunction along with LAMA1 mutations could act synergistically to cause the neurological phenotype. PMID:25953895

Cerebellar arteries originating from the internal carotid artery: angiographic evaluation and embryologic explanations

International Nuclear Information System (INIS)

Lee, Jae Young; Han, Moon Hee; Yu, In Gyu; Chang, Ki Hyun; Kim, Eui Jong; Kim, Dae Ho

1997-01-01

To find and describe the cerebellar arteries arising from the internal carotid artery, explain them embryologically, and evaluate their clinical implication. To determine the point in the internal carotid artery from which the cereballar artery arose anomalously, consecutive angiographic studies performed in the last three years were reviewed. The distribution of such anomalous cerebellar arteries, the point in the internal carotid artery from which the anomalous vessels originated, and associated findings were analyzed. Five anomalous origins of cerebellar arteries arising arising directly from the internal carotid artery were found in five patients. Three anterior inferior cerebellar arteries (AICA) and one common trunk of an AICA and a posterior inferior cerebellar artery (PICA) were found to originate from the internal carotid artery at a point close to the origin of the primitive trigeminal artery. A PICA arose from an artery presenting a course similar to the proatlantal intersegmental artery. Intracranial aneurysms in two patients, Moyamoya disease in one, and facial arteriovenous malformation in one. In our series, AICAs supplied from the arteries considered to be persistent trigeminal artery variants were the most common type. A correlation between type of anomalous cerebellar artery and type of carotid-vertebrobasilar anastomosis may exist. Cerebellar arteries originating anomalously from the internal carotid artery seem to occur as a result of the persistence of carotid-vertebrobasilar anastomoses associated with incomplete fusion of the longitudinal neural arteries. An understanding of these anomalous cerebellar arteries may help prevent accidents during therapeutic embolization and surgical treatment, as well as misinterpretation

Biotransformation of endorphins by a synaptosomal plasma membrane preparation of rat brain and by human serum

NARCIS (Netherlands)

Burbach, J.P.H.; Loeber, J.G.; Verhoef, J.; Kloet, E.R. de; Wied, D. de

1979-01-01

β-Endorphin (β-LPH 61–91), γ-endorphin (61–77), des-tyrosine-γ-endorphin (62–77), α-endorphin (61–76), and β-LPH 61–69 either labeled with [125I] at the N-terminal 61-tyrosine residue or unlabeled were incubated with a crude synaptosomal plasma membrane fraction of rat brain or in human serum. At

Biliary atresia and cerebellar hypoplasia in polysplenia syndrome

Energy Technology Data Exchange (ETDEWEB)

Vanderdood, Kurt; Op de Beeck, Bart; Desprechins, Brigitte; Osteaux, Michel [Department of Radiology, Free University Brussels, AZ-VUB, Laarbeeklaan 101, 1090 Brussels (Belgium)

2003-09-01

We report a 3.5-month-old boy with polysplenia syndrome who demonstrated hemiazygos continuation of the inferior vena cava, extrahepatic biliary atresia, multiple splenunculi, bowel malrotation, and the rare finding of brainstem and cerebellar hypoplasia. A possible pathogenesis for cerebellar hypoplasia in this syndrome is suggested after review of the literature. The importance of seeking associated anomalies in biliary atresia, which may be possible indicators of polysplenia syndrome, is stressed since these patients need appropriate management when surgery is considered. (orig.)

Cerebellar modulation of frontal cortex dopamine efflux in mice: relevance to autism and schizophrenia.

Science.gov (United States)

Mittleman, Guy; Goldowitz, Daniel; Heck, Detlef H; Blaha, Charles D

2008-07-01

Cerebellar and frontal cortical pathologies have been commonly reported in schizophrenia, autism, and other developmental disorders. Whether there is a relationship between prefrontal and cerebellar pathologies is unknown. Using fixed potential amperometry, dopamine (DA) efflux evoked by cerebellar or, dentate nucleus electrical stimulation (50 Hz, 200 muA) was recorded in prefrontal cortex of urethane anesthetized lurcher (Lc/+) mice with 100% loss of cerebellar Purkinje cells and wildtype (+/+) control mice. Cerebellar stimulation with 25 and 100 pulses evoked prefrontal cortex DA efflux in +/+ mice that persisted for 12 and 25 s poststimulation, respectively. In contrast, 25 pulse cerebellar stimulation failed to evoke prefrontal cortex DA efflux in Lc/+ mice indicating a dependency on cerebellar Purkinje cell outputs. Dentate nucleus stimulation (25 pulses) evoked a comparable but briefer (baseline recovery within 7 s) increase in prefrontal cortex DA efflux compared to similar cerebellar stimulation in +/+ mice. However, in Lc/+ mice 25 pulse dentate nucleus evoked prefrontal cortex DA efflux was attenuated by 60% with baseline recovery within 4 s suggesting that dentate nucleus outputs to prefrontal cortex remain partially functional. DA reuptake blockade enhanced 100 pulse stimulation evoked prefrontal cortex responses, while serotonin or norepinephrine reuptake blockade were without effect indicating the specificity of the amperometric recordings to DA. Results provide neurochemical evidence that the cerebellum can modulate DA efflux in the prefrontal cortex. Together, these findings may explain why cerebellar and frontal cortical pathologies co-occur, and may provide a mechanism that accounts for the diversity of symptoms common to multiple developmental disorders.

Cerebellar Ataxia from Multiple Potential Causes: Hypothyroidism, Hashimoto's Thyroiditis, Thalamic Stimulation, and Essential Tremor

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Natalya V. Shneyder

2012-04-01

Full Text Available Background: Both hypothyroidism and Hashimoto's thyroiditis (HT can rarely be associated with cerebellar ataxia. Severe essential tremor (ET as well as bilateral thalamic deep brain stimulation (DBS may lead to subtle cerebellar signs. Case Report: We report a 74-year-old male with hypothyroidism and a 20-year history of ET who developed cerebellar ataxia after bilateral thalamic DBS. Extensive workup revealed elevated thyroid stimulating hormone and thyroperoxidase antibody titers confirming the diagnosis of HT. Discussion: Our case demonstrates multiple possible causes of cerebellar ataxia in a patient, including hypothyroidism, HT, chronic ET, and bilateral thalamic DBS. Counseling of patients may be appropriate when multiple risk factors for cerebellar ataxia coexist in one individual.

Use of hyperdry amniotic membrane in operations for cleft palate: a study in rats.

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Tsuno, Hiroaki; Noguchi, Makoto; Okabe, Motonori; Tomihara, Kei; Yoshida, Toshiko; Nikaido, Toshio

2015-04-01

The growth of maxillary bone and the development of dentition are often impaired in patients who have had pushback operations for repair of a cleft palate. There has been considerable discussion about the most suitable technique or material used in such repairs to resolve the problem. Hyperdry amniotic membrane, a new preservable material derived from human amnion, has recently been introduced in several procedures. We have evaluated its use during pushback surgery in animal studies to try to correct the inhibition of growth and development of the maxilla. Mucosal defects were created in 3-week-old rats, and then covered with hyperdry amniotic membrane or not. Healing was assessed by histological and morphological examination at 1 week and 7 weeks postoperatively. In the group treated with hyperdry amniotic membrane, submucosal tissue was reconstructed successfully during the early postoperative period. Lateral palatal growth was not inhibited as much, and medial inclination of the teeth was less, after a period of growth using this material. The results suggest that hyperdry amniotic membrane is a suitable new dressing material for use in the treatment of cleft palate. Copyright © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Local changes in the excitability of the cerebellar cortex produce spatially restricted changes in complex spike synchrony.

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Marshall, Sarah P; Lang, Eric J

2009-11-11

Complex spike (CS) synchrony patterns are modulated by the release of GABA within the inferior olive (IO). The GABAergic projection to most of the IO arises from the cerebellar nuclei, which are themselves subject to strong inhibitory control by Purkinje cells in the overlying cortex. Moreover, the connections between the IO and cerebellum are precisely aligned, raising the possibility that each cortical region controls its own CS synchrony distribution. This possibility was tested using multielectrode recordings of CSs and simple spikes (SSs) in crus 2a of anesthetized rats. Picrotoxin or muscimol was applied to the cerebellar cortex at the borders of the recording array. These drugs induced significant changes in CS synchrony and in CS and SS firing rates and changes in post-CS pauses and modulation of SS activity. The level of CS synchrony was correlated with SS firing rate in control, and application of picrotoxin increased both. In contrast, muscimol decreased CS synchrony. Furthermore, when picrotoxin was applied only at the lateral edge of the array, changes in CS synchrony occurred sequentially across the recording array, with cells located in the lateral half of the array having earlier and larger changes in CS synchrony than cells in the medial half. The results indicate that a double-inhibitory feedback circuit from Purkinje cells to the IO provides a mechanism by which SS activity may regulate CS synchrony. Thus, CS synchrony may be a physiologically controlled parameter of cerebellar activity, with the cerebellum and IO comprising a series of self-updating circuits.

The organization of plasticity in the cerebellar cortex: from synapses to control.

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D'Angelo, Egidio

2014-01-01

The cerebellum is thought to play a critical role in procedural learning, but the relationship between this function and the underlying cellular and synaptic mechanisms remains largely speculative. At present, at least nine forms of long-term synaptic and nonsynaptic plasticity (some of which are bidirectional) have been reported in the cerebellar cortex and deep cerebellar nuclei. These include long-term potentiation (LTP) and long-term depression at the mossy fiber-granule cell synapse, at the synapses formed by parallel fibers, climbing fibers, and molecular layer interneurons on Purkinje cells, and at the synapses formed by mossy fibers and Purkinje cells on deep cerebellar nuclear cells, as well as LTP of intrinsic excitability in granule cells, Purkinje cells, and deep cerebellar nuclear cells. It is suggested that the complex properties of cerebellar learning would emerge from the distribution of plasticity in the network and from its dynamic remodeling during the different phases of learning. Intrinsic and extrinsic factors may hold the key to explain how the different forms of plasticity cooperate to select specific transmission channels and to regulate the signal-to-noise ratio through the cerebellar cortex. These factors include regulation of neuronal excitation by local inhibitory networks, engagement of specific molecular mechanisms by spike bursts and theta-frequency oscillations, and gating by external neuromodulators. Therefore, a new and more complex view of cerebellar plasticity is emerging with respect to that predicted by the original "Motor Learning Theory," opening issues that will require experimental and computational testing. © 2014 Elsevier B.V. All rights reserved.

Regional cerebellar volume and cognitive function from adolescence to late middle age.

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Bernard, Jessica A; Leopold, Daniel R; Calhoun, Vince D; Mittal, Vijay A

2015-03-01

Cerebellar morphology and function have been implicated in a variety of developmental disorders, and in healthy aging. Although recent work has sought to characterize the relationships between volume and age in this structure during adolescence, young, and older adulthood, there have been no investigations of regional cerebellar volume from adolescence through late middle age. Middle age in particular has been largely understudied, and investigating this period of the lifespan may be especially important for our understanding of senescence. Understanding regional patterns of cerebellar volume with respect to age during this portion of the lifespan may provide important insight into healthy aging and cognitive function as well as pathology from adolescence into later life. We investigated regional cerebellar volume using a highly novel lobular segmentation approach in conjunction with a battery of cognitive tasks in a cross-sectional sample of 123 individuals from 12 to 65 years old. Our results indicated that regional cerebellar volumes show different patterns with respect to age. In particular, the more posterior aspect of the neocerebellum follows a quadratic "inverse-U" pattern while the vermis and anterior cerebellum follow logarithmic patterns. In addition, we quantified the relationships between age and a variety of cognitive assessments and found relationships between regional cerebellar volumes and performance. Finally, exploratory analyses of sex differences in the relationships between regional cerebellar volume, age, and cognition were investigated. Taken together, these results provide key insights into the development and aging of the human cerebellum, and its role in cognitive function across the lifespan. © 2014 Wiley Periodicals, Inc.

Olivary degeneration after cerebellar or brain stem haemorrhage: MRI

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Uchino, A. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan) Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Hasuo, K. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan)); Uchida, K. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Matsumoto, S. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan)); Tsukamoto, Y. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Ohno, M. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Masuda, K. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan))

1993-05-01

Magnetic resonance (MR) images of seven patients with olivary degeneration caused by cerebellar or brain stem haemorrhages were reviewed. In four patients with cerebellar haemorrhage, old haematomas were identified as being located in the dentate nucleus; the contralateral inferior olivary nuclei were hyperintense on proton-density- and T2-weighted images. In two patients with pontine haemorrhages, the old haematomas were in the tegmentum and the ipsilateral inferior olivary nuclei, which were hyperintense. In one case of midbrain haemorrhage, the inferior olivary nuclei were hyperintense bilaterally. The briefest interval from the ictus to MRI was 2 months. Hypertrophic olivary nuclei were observed only at least 4 months after the ictus. Olivary degeneration after cerebellar or brain stem haemorrhage should not be confused with ischaemic, neoplastic, or other primary pathological conditions of the medulla. (orig.)

Distinct Critical Cerebellar Subregions for Components of Verbal Working Memory

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Cooper, Freya E.; Grube, Manon; Von Kriegstein, Katharina; Kumar, Sukhbinder; English, Philip; Kelly, Thomas P.; Chinnery, Patrick F.; Griffiths, Timothy D.

2012-01-01

A role for the cerebellum in cognition has been proposed based on studies suggesting a profile of cognitive deficits due to cerebellar stroke. Such studies are limited in the determination of the detailed organisation of cerebellar subregions that are critical for different aspects of cognition. In this study we examined the correlation between…

The Cerebellum and Language: Evidence from Patients with Cerebellar Degeneration

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Stoodley, Catherine J.; Schmahmann, Jeremy D.

2009-01-01

Clinical and imaging studies suggest that the cerebellum is involved in language tasks, but the extent to which slowed language production in cerebellar patients contributes to their poor performance on these tasks is not clear. We explored this relationship in 18 patients with cerebellar degeneration and 16 healthy controls who completed measures…

Direct and indirect spino-cerebellar pathways: shared ideas but different functions in motor control

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Juan eJiang

2015-07-01

Full Text Available The impressive precision of mammalian limb movements relies on internal feedback pathways that convey information about ongoing motor output to cerebellar circuits. The spino-cerebellar tracts (SCT in the cervical, thoracic and lumbar spinal cord have long been considered canonical neural substrates for the conveyance of internal feedback signals. Here we consider the distinct features of an indirect spino-cerebellar route, via the brainstem lateral reticular nucleus (LRN, and the implications of this pre-cerebellar ‘detour’ for the execution and evolution of limb motor control. Both direct and indirect spino-cerebellar pathways signal spinal interneuronal activity to the cerebellum during movements, but evidence suggests that direct SCT neurons are mainly modulated by rhythmic activity, whereas the LRN also receives information from systems active during postural adjustment, reaching and grasping. Thus, while direct and indirect spino-cerebellar circuits can both be regarded as internal copy pathways, it seems likely that the direct system is principally dedicated to rhythmic motor acts like locomotion, while the indirect system also provides a means of pre-cerebellar integration relevant to the execution and coordination of de

Indirect coupling to Na+ of p-aminohippuric acid uptake into rat renal basolateral membrane vesicles

International Nuclear Information System (INIS)

Shimada, H.; Moewes, B.; Burckhardt, G.

1987-01-01

Experiments with basolateral membrane vesicles prepared from rat kidney cortex were performed to study the mechanism by which p-aminohippuric acid (PAH) is taken up across the contraluminal membrane and is concentrated in proximal tubule cells. An inward Na + gradient failed to stimulate [ 3 H]PAH uptake compared with K + or Li + and did not cause intravesicular PAH accumulation above equilibrium distribution. In the absence of Na + , the dicarboxylates glutarate and suberate cis-inhibited and trans-stimulated [ 3 H]PAH uptake, indicating a common transport system. In the presence of Na + , 10 μM glutarate in the incubation medium did not cis-inhibit, but rather stimulated [ 3 H]PAH uptake and caused PAH accumulation above equilibrium distribution (over-shoot). Li + diminished this stimulation, but was without effect on [ 3 H]PAH/PAH- and [ 3 H]PAH/glutarate exchange. The data indicate the coexistence of a Na + -sensitive transport system for dicarboxylates and a Li + -insensitive PAH/dicarboxylate exchanger in the basolateral membrane. The authors propose that dicarboxylates are cotransported with Na + into the cell and subsequently exchange for extracellular PAH at the basolateral membrane. PAH uptake is thereby indirectly coupled to Na + via the Na + /dicarboxylate cotransporter

Ataxias and Cerebellar or Spinocerebellar Degeneration

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... and conducts a broad range of basic and clinical research on cerebellar and spinocerebellar degeneration, including work aimed at finding the cause(s) of ataxias and ways to ... Publications Definition Ataxia ...

Cerebellar contribution to motor and cognitive performance in multiple sclerosis: An MRI sub-regional volumetric analysis.

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D'Ambrosio, Alessandro; Pagani, Elisabetta; Riccitelli, Gianna C; Colombo, Bruno; Rodegher, Mariaemma; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo; Rocca, Maria A

2017-08-01

To investigate the role of cerebellar sub-regions on motor and cognitive performance in multiple sclerosis (MS) patients. Whole and sub-regional cerebellar volumes, brain volumes, T2 hyperintense lesion volumes (LV), and motor performance scores were obtained from 95 relapse-onset MS patients and 32 healthy controls (HC). MS patients also underwent an evaluation of working memory and processing speed functions. Cerebellar anterior and posterior lobes were segmented using the Spatially Unbiased Infratentorial Toolbox (SUIT) from Statistical Parametric Mapping (SPM12). Multivariate linear regression models assessed the relationship between magnetic resonance imaging (MRI) measures and motor/cognitive scores. Compared to HC, only secondary progressive multiple sclerosis (SPMS) patients had lower cerebellar volumes (total and posterior cerebellum). In MS patients, lower anterior cerebellar volume and brain T2 LV predicted worse motor performance, whereas lower posterior cerebellar volume and brain T2 LV predicted poor cognitive performance. Global measures of brain volume and infratentorial T2 LV were not selected by the final multivariate models. Cerebellar volumetric abnormalities are likely to play an important contribution to explain motor and cognitive performance in MS patients. Consistently with functional mapping studies, cerebellar posterior-inferior volume accounted for variance in cognitive measures, whereas anterior cerebellar volume accounted for variance in motor performance, supporting the assessment of cerebellar damage at sub-regional level.

Distal anterior inferior cerebellar artery syndrome after acoustic neuroma surgery.

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Hegarty, Joseph L; Jackler, Robert K; Rigby, Peter L; Pitts, Lawrence H; Cheung, Steven W

2002-07-01

To define a clinicopathologic syndrome associated with persistent cerebellar dysfunction after acoustic neuroma (AN) excision. Case series derived from radiographic and clinical chart review. Tertiary referral center. In 12 patients with AN, persistent cerebellar dysfunction developed after AN removal. Each case demonstrated abnormality in the ipsilateral cerebellar peduncle on postoperative magnetic resonance imaging. Cerebellar function and ambulatory status over the first postoperative year. On magnetic resonance imaging scans, the extent of cerebellar peduncle infarcts was variable. It ranged from focal brain injury (2 cm) spanning the full thickness of the peduncle. Peduncular infarcts were associated with large tumor size (average 3.8 cm, range 2.0-5.5 cm diameter). The long-term functional outcomes (>1 yr) varied. Dysmetria was unchanged or improved in over half of the patients (6 of 11 patients). Gait recovered to normal or to preoperative levels in 5 patients. In the 6 patients with persistent impaired mobility, 2 had mild gait disturbance, 3 required regular use of a cane, and 1 has been dependent on a walker. One patient had sustained mild motor weakness. Three of 11 patients remained dependent on others for activities of daily living. Peduncle injury most likely stems from interruption of distal branches of the anterior inferior cerebellar artery (AICA). These small vessels are intimately related to the capsule of the tumor and may supply both the neoplasm and the brain parenchyma. It has long been recognized that interruption of the proximal segment of the AICA results in severe injury to the pons, with devastating neurologic sequelae. A limited AICA syndrome caused by loss of its distal ramifications seems a more plausible explanation for peduncular infarction than either venous insufficiency or direct surgical trauma.

Reduced contralateral hemispheric flow measured by SPECT in cerebellar lesions

DEFF Research Database (Denmark)

Sönmezoğlu, K; Sperling, B; Henriksen, T

1993-01-01

Four patients with clinical signs of cerebellar stroke were studied twice by SPECT using 99mTc-HMPAO as a tracer for cerebral blood flow (CBF). When first scanned 6 to 22 days after onset, all had a region of very low CBF in the symptomatic cerebellar hemisphere, and a mild to moderate CBF reduct...

Activity of retinene palmitasynthetase and retinene palmitatehydrolase in the small intestine mucosa and membranes of its cells in white rats affected by A-avitaminosis and irradiation

International Nuclear Information System (INIS)

Leutskij, K.M.; Sovtysik, D.D.

1977-01-01

A combined action of A-avitaminosis and ionizing radiation on the activity of retinenepalmitatesynthetase and retinenepalmitatehydrolase in the small intestine mucosa and cell membranes of white rats has been investigated. The activity of retinenepalmitatehydrolase has been shown to decrease in the irradiated animals deficient in vitamin A as compared to the control nonirradiated animals. The activity of retinenepalmitatesynthetase affected by a combination of A-avitaminosis and irradiation increases as compared to the control nonirradiated rats both in the small intestine mucosa and its cell membranes

Parvovirus associated cerebellar hypoplasia and hydrocephalus in day-old broiler chickens

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Cerebellar hypoplasia and hydrocephalus were detected in day-old broiler chickens. Brains of chickens evaluated at necropsy appeared to be abnormal; some were disfigured and cerebellae appeared to be smaller than normal. Histopathologic examination of brains revealed cerebellar folia that were sho...

Dyke–Davidoff–Masson syndrome with crossed cerebellar atrophy

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Sanjay M. Khaladkar

2017-09-01

Full Text Available Dyke–Davidoff–Masson syndrome is a rare condition with classical, clinical and radiological changes – mental retardation, hemiparesis, facial asymmetry, seizures and cerebral hemiatrophy with calvarial changes. Contralateral cerebellar atrophy is rare and occurs if insult occurs after 1 month of age. We report a case of a 6-year-old female child presenting with right-sided hemiparesis, convulsions and left cerebral hemiatrophy with an old infarct in left middle cerebral artery (MCA territory, ipsilateral calvarial thickening and right (crossed cerebellar atrophy.

A PET study of cerebellar metabolism in normal and abnormal states

International Nuclear Information System (INIS)

Kushner, M.; Alavi, A.; Chawluk, J.; Silver, F.; Dann, R.; Rosen, M.; Reivich, M.

1985-01-01

The authors studied cerebellar metabolism under varying conditions of sensory stimulation. Cerebellar glucose consumption was measured by positron emission scanning and 18F-fluorodeoxyglucose in 64 subjects. Cerebellar metabolism relative to the whole brain (CM), and the asymmetry of metabolism between the cerebellar hemispheres (CA) was determined. The lowest CM occurred with maximal sensory deprivation, eyes and ears closed, (CM=96%, n=6). CM increased nonsignificantly with visual stimulation (CM=99%,n=17) and was highest for auditory stimulation (CM=104%,n=10,p<.05). CA was unaffected by sensory input. Under ambient conditions the CM values were 101%, 113% and 135% respectively for young controls (n=9, age=22), old controls (n=8, age=61) and Alzheimer patients (SDAT, n=14, age=69). This difference was significant for SDAT vs young and old controls and was nearly significant for young vs old controls

Glucagon effects on the membrane potential and calcium uptake rate of rat liver mitochondria

International Nuclear Information System (INIS)

Wingrove, D.E.; Amatruda, J.M.; Gunter, T.E.

1984-01-01

It has been widely reported that the in vivo administration of glucagon to rats results in the stimulation of calcium influx in subsequently isolated liver mitochondria. The mechanism of this effect is investigated through simultaneous measurements of calcium uptake rate and mitochondrial membrane potential. This allows the measurement of the calcium uniporter conductance independent of hormonal effects on electron transport or respiration. Two experimental approaches are used. The first involves measuring the uptake of 40-50 nmol of Ca 2+ /mg of mitochondrial protein with the calcium dye antipyrylazo III; the second uses 45 Ca 2+ to follow uptake in the presence of 0.5 to 1.5 μM free calcium, buffered with HEDTA. In both cases a tetraphenyl phosphonium electrode is used to follow membrane potential, and membrane potential is varied using either malonate or butylmalonate in the presence of rotenone. The relative merits of these two approaches are discussed. The conductance of the calcium uniporter is found not to be stimulated by glucagon pretreatment. Also, the relative glucagon stimulation of both calcium influx and membrane potential is found to increase with increasing malonate concentration. These results imply that there is no direct stimulation of calcium uptake into liver mitochondria following glucagon treatment. The results are consistent with a glucagon stimulation of substrate transport, substrate oxidation, or a stimulation of electron transport resulting in an increased membrane potential and secondary stimulation of calcium uptake

Clinical characteristics of patients with cerebellar ataxia associated with anti-GAD antibodies

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Tiago Silva Aguiar

Full Text Available ABSTRACT The enzyme glutamic acid decarboxylase (GAD, present in GABAergic neurons and in pancreatic beta cells, catalyzes the conversion of gamma-aminobutyric acid (GABA. The cerebellum is highly susceptible to immune-mediated mechanisms, with the potentially treatable autoimmune cerebellar ataxia associated with the GAD antibody (CA-GAD-ab being a rare, albeit increasingly detected condition. Few cases of CA-GAD-ab have been described. Methods This retrospective and descriptive study evaluated the clinical characteristics and outcomes of patients with CA-GAD-ab. Result Three patients with cerebellar ataxia, high GAD-ab titers and autoimmune endocrine disease were identified. Patients 1 and 2 had classic stiff person syndrome and insidious-onset cerebellar ataxia, while Patient 3 had pure cerebellar ataxia with subacute onset. Patients received intravenous immunoglobulin therapy with no response in Patients 1 and 3 and partial recovery in Patient 2. Conclusion CA-GAD-ab is rare and its clinical presentation may hamper diagnosis. Clinicians should be able to recognize this potentially treatable autoimmune cerebellar ataxia.

Mutant PrP Suppresses Glutamatergic Neurotransmission in Cerebellar Granule Neurons by Impairing Membrane Delivery of VGCC α2δ-1 Subunit

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Senatore, Assunta; Colleoni, Simona; Verderio, Claudia; Restelli, Elena; Morini, Raffaella; Condliffe, Steven B.; Bertani, Ilaria; Mantovani, Susanna; Canovi, Mara; Micotti, Edoardo; Forloni, Gianluigi; Dolphin, Annette C.; Matteoli, Michela; Gobbi, Marco; Chiesa, Roberto

2012-01-01

Summary How mutant prion protein (PrP) leads to neurological dysfunction in genetic prion diseases is unknown. Tg(PG14) mice synthesize a misfolded mutant PrP which is partially retained in the neuronal endoplasmic reticulum (ER). As these mice age, they develop ataxia and massive degeneration of cerebellar granule neurons (CGNs). Here, we report that motor behavioral deficits in Tg(PG14) mice emerge before neurodegeneration and are associated with defective glutamate exocytosis from granule neurons due to impaired calcium dynamics. We found that mutant PrP interacts with the voltage-gated calcium channel α2δ-1 subunit, which promotes the anterograde trafficking of the channel. Owing to ER retention of mutant PrP, α2δ-1 accumulates intracellularly, impairing delivery of the channel complex to the cell surface. Thus, mutant PrP disrupts cerebellar glutamatergic neurotransmission by reducing the number of functional channels in CGNs. These results link intracellular PrP retention to synaptic dysfunction, indicating new modalities of neurotoxicity and potential therapeutic strategies. PMID:22542184

Gestational Undernourishment Modifies the Composition of Skeletal Muscle Transverse Tubule Membranes and the Mechanical Properties of Muscles in Newborn Rats

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Ricardo Tonathiu Ramírez-Oseguera

2013-10-01

Full Text Available Backgroud/Aims: Skeletal muscle (SM constitutes more than 40% of the body weight in adulthood. Transports dietary glucose mainly through the insulin-dependent glucose transporter (Glut-4 located in the Transverse tubule membrane system (TT. The TT development ends shortly after birth. The TT membrane hosts the proteins involved in excitation-contraction coupling and glucose uptake. Glycaemic regulation through movement is a key function of fully developed skeletal muscle. In this study, we aimed to characterize the effect of gestational undernourishment (GUN in rats GLUT-4 expression and on the protein/lipid content of the TT membranes. We also examined the effect of GUN on the mechanical properties of muscles as an indication of the metabolic condition of the SM at birth. Methods: Isolated TT membrane from SM of GUN rats were used to study lipid/protein content and protein stability by differential scanning calorimetry. The effect of GUN on the SM mechanical properties was determined in isolated Extensor Digitorum Longus (EDL muscle. Results: We demonstrate that compared to control, GUN in the new-born produces; i decreases body weight; ii diminution in SM mass; iii decreases the formation of TT membranes; iv expresses TT membrane proteins with higher thermal stability. The TT membrane expression of GLUT-4 in GUN offspring was twice that of controls. The isolated EDL of GUN offspring was 20% stronger as measured by contractile force and more resistant to fatigue relative to controls. Conclusion; These results provide the first evidence of adaptive changes of the SM in new-borns exposed to severe gestational food restriction. The effects of GUN on muscle at birth are the first step toward detrimental SM metabolic function, contributing to the physiopathology of metabolic diseases in adulthood.

Gestational undernourishment modifies the composition of skeletal muscle transverse tubule membranes and the mechanical properties of muscles in newborn rats.

Science.gov (United States)

Ramírez-Oseguera, Ricardo Tonathiu; Jiménez-Garduño, Aura Matilde; Alvarez, Rocío; Heine, Katharina; Pinzón-Estrada, Enrique; Torres-Saldaña, Ismael; Ortega, Alicia

2013-01-01

[corrected] Skeletal muscle (SM) constitutes more than 40% of the body weight in adulthood. Transports dietary glucose mainly through the insulin-dependent glucose transporter (Glut-4) located in the Transverse tubule membrane system (TT). The TT development ends shortly after birth. The TT membrane hosts the proteins involved in excitation-contraction coupling and glucose uptake. Glycaemic regulation through movement is a key function of fully developed skeletal muscle. In this study, we aimed to characterize the effect of gestational undernourishment (GUN) in rats GLUT-4 expression and on the protein/lipid content of the TT membranes. We also examined the effect of GUN on the mechanical properties of muscles as an indication of the metabolic condition of the SM at birth. Isolated TT membrane from SM of GUN rats were used to study lipid/protein content and protein stability by differential scanning calorimetry. The effect of GUN on the SM mechanical properties was determined in isolated Extensor Digitorum Longus (EDL) muscle. We demonstrate that compared to control, GUN in the new-born produces; i) decreases body weight; ii) diminution in SM mass; iii) decreases the formation of TT membranes; iv) expresses TT membrane proteins with higher thermal stability. The TT membrane expression of GLUT-4 in GUN offspring was twice that of controls. The isolated EDL of GUN offspring was 20% stronger as measured by contractile force and more resistant to fatigue relative to controls. These results provide the first evidence of adaptive changes of the SM in new-borns exposed to severe gestational food restriction. The effects of GUN on muscle at birth are the first step toward detrimental SM metabolic function, contributing to the physiopathology of metabolic diseases in adulthood. © 2013 S. Karger AG, Basel

Cerebellar and pontine tegmental hypermetabolism in miller-fisher syndrome

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Kim, Yu Kyrong; Kim, Ji Soo; Lee, Won Woo; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

2007-07-01

Miller Fisher syndrome (MFS) has been considered as a variant of Guillain-Barre syndrome (GBS), a type of acute immune neuropathies involving peripheral nerve system. Unlike GBS, presence of cerebellar type ataxia and supranuclear ophthalmioplesia in MFS suggests additional involvement of the central nervous system. To determine involvement of the central nervous system in MFS, we investigated the cerebral metabolic abnormalities in patients with MFS using FDG PET. Nine patients who were diagnosed as MFS based on acute ophthalmoplegia, ataxia, and areflexia without other identifiable causes participated in this study. In six patients, serum antibodies possibly related with symptom of MFS (anti- GQ1b or anti-GM1) were detected at the time of the study. With the interval of 25 26 days (range: 3-83 days) from the symptom on set, brain FDG PET were underwent in patients and compared with those from healthy controls. In group analysis comparing with healthy controls, FDG PET of patients revealed increased metabolism in the bilateral cerebellar hemispheres and vermis, and the thalamus. In contrast, the occipital cortex showed decreased metabolism. Individual analyses disclosed hypermetabolism in the cerebellar vermis or hemispheres in 5, and in the pontine tegmentum in 2 of the 9 patients. We also found that the cerebellar vermian hypermetabolism was inversely correlated with the interval between from the symptom on set to PET study. Moreover, follow-up PET of a patient demonstrated that cerebellar hypermetabolism decreased markedly with an improvement of the ophthalmoplegia and ataxia. These findings indicate an involvement of the central nervous system in MFS and suggest an antibody-associated acute inflammatory process as a mechanism of this disorder.

Cerebellar and pontine tegmental hypermetabolism in miller-fisher syndrome

International Nuclear Information System (INIS)

Kim, Yu Kyrong; Kim, Ji Soo; Lee, Won Woo; Kim, Sang Eun

2007-01-01

Miller Fisher syndrome (MFS) has been considered as a variant of Guillain-Barre syndrome (GBS), a type of acute immune neuropathies involving peripheral nerve system. Unlike GBS, presence of cerebellar type ataxia and supranuclear ophthalmioplesia in MFS suggests additional involvement of the central nervous system. To determine involvement of the central nervous system in MFS, we investigated the cerebral metabolic abnormalities in patients with MFS using FDG PET. Nine patients who were diagnosed as MFS based on acute ophthalmoplegia, ataxia, and areflexia without other identifiable causes participated in this study. In six patients, serum antibodies possibly related with symptom of MFS (anti- GQ1b or anti-GM1) were detected at the time of the study. With the interval of 25 26 days (range: 3-83 days) from the symptom on set, brain FDG PET were underwent in patients and compared with those from healthy controls. In group analysis comparing with healthy controls, FDG PET of patients revealed increased metabolism in the bilateral cerebellar hemispheres and vermis, and the thalamus. In contrast, the occipital cortex showed decreased metabolism. Individual analyses disclosed hypermetabolism in the cerebellar vermis or hemispheres in 5, and in the pontine tegmentum in 2 of the 9 patients. We also found that the cerebellar vermian hypermetabolism was inversely correlated with the interval between from the symptom on set to PET study. Moreover, follow-up PET of a patient demonstrated that cerebellar hypermetabolism decreased markedly with an improvement of the ophthalmoplegia and ataxia. These findings indicate an involvement of the central nervous system in MFS and suggest an antibody-associated acute inflammatory process as a mechanism of this disorder

Cerebellar mutism: review of the literature

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Gudrunardottir, Thora; Sehested, Astrid; Juhler, Marianne

2011-01-01

Cerebellar mutism is a common complication of posterior fossa surgery in children. This article reviews current status with respect to incidence, anatomical substrate, pathophysiology, risk factors, surgical considerations, treatment options, prognosis and prevention....

Prenatal MR imaging features of isolated cerebellar haemorrhagic lesions

International Nuclear Information System (INIS)

Martino, Francesca; Malova, Mariya; Ramenghi, Luca A.; Cesaretti, Claudia; Parazzini, Cecilia; Doneda, Chiara; Righini, Andrea; Rossi, Andrea

2016-01-01

Prenatal features of isolated cerebellar haemorrhagic lesions have not been sufficiently characterised. We aimed to better define their MR imaging characteristics, documenting the location, extension, evolution stage and anatomic sequelae, and to better understand cerebellar haemorrhage pathophysiology. We screened our foetal MR imaging database (3200 cases) for reports of haemorrhagic lesions affecting only the cerebellum (without any supratentorial bleeding or other clastic lesions), defined as one of the following: T2-weighted hypointense or mixed hypo-/hyperintense signal; rim of T2-weighted hypointense signal covering the surface of volume-reduced parenchyma; T1-weighted hyperintense signal; increased DWI signal. Seventeen cases corresponded to the selection criteria. All lesions occurred before the 26th week of gestation, with prevalent origin from the peripheral-caudal portion of the hemispheres and equal frequency of unilateral/bilateral involvement. The caudal vermis appeared affected in 2/3 of cases, not in all cases confirmed postnatally. Lesions evolved towards malformed cerebellar foliation. The aetiology and pathophysiology were unknown, although in a subset of cases intra- and extracranial venous engorgement seemed to play a key role. Onset from the peripheral and caudal portion of the hemispheres seems characteristic of prenatal cerebellar haemorrhagic lesions. Elective involvement of the peripheral germinal matrix is hypothesised. (orig.)

4-[[sup 123]I]iodospiperone as a ligand for dopamine DA receptors: in vitro and in vivo experiments in a rat model

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Krogt, J.A. van der; Valkenburg, C F.M. van; Pauwels, E K.J.; Buruma, O J.S. [Rijksuniversiteit Leiden (Netherlands); Reiffers, S [Hospital De Weezenlanden, Zwolle (Netherlands); Doremalen, P.A.P.M. van; Wijnhoven, G [Cygne, Eindhoven (Netherlands)

1992-10-01

Radioiodinated spiperone is of interest for dopamine (DA) receptor studies in the living human brain by single photon emission computed tomography (SPECT). Simulated by data obtained with [[sup 11]C]-N-methyl-spiperone, we synthesized 4-[[sup 123]I]iodospiperone and investigated the in vitro binding characteristics of this ligand to the striatal membrane of the rat and the in vivo distribution over various rat brain regions. The in vitro binding experiments showed that this radioligand displays about 10 times less affinity for the DA receptor than spiperone and specific binding, as shown with [[sup 3]H]spiperone, was not observed. Displacement by butaclamol was not observed. The in vivo studies demonstrated that both 4-[[sup 123]I]iodospiperone and [[sup 3]H]spiperone concentrate in striatal tissue, respectively, 1.9 and 3.5 times as high as in cerebellar tissue. Haloperidol pretreatment largely prevented this accumulation. In view of the obtained target-to-non-target ratios we believe, however, that this accumulation in brain areas rich DA-receptors does not offer prospects for clinical receptor imaging with SPECT. (Author).

Gravity-dependent nystagmus and inner-ear dysfunction suggest anterior and posterior inferior cerebellar artery infarct.

Science.gov (United States)

Shaikh, Aasef G; Miller, Benjamin R; Sundararajan, Sophia; Katirji, Bashar

2014-04-01

Cerebellar lesions may present with gravity-dependent nystagmus, where the direction and velocity of the drifts change with alterations in head position. Two patients had acute onset of hearing loss, vertigo, oscillopsia, nausea, and vomiting. Examination revealed gravity-dependent nystagmus, unilateral hypoactive vestibulo-ocular reflex (VOR), and hearing loss ipsilateral to the VOR hypofunction. Traditionally, the hypoactive VOR and hearing loss suggest inner-ear dysfunction. Vertigo, nausea, vomiting, and nystagmus may suggest peripheral or central vestibulopathy. The gravity-dependent modulation of nystagmus, however, localizes to the posterior cerebellar vermis. Magnetic resonance imaging in our patients revealed acute cerebellar infarct affecting posterior cerebellar vermis, in the vascular distribution of the posterior inferior cerebellar artery (PICA). This lesion explains the gravity-dependent nystagmus, nausea, and vomiting. Acute onset of unilateral hearing loss and VOR hypofunction could be the manifestation of inner-ear ischemic injury secondary to the anterior inferior cerebellar artery (AICA) compromise. In cases of combined AICA and PICA infarction, the symptoms of peripheral vestibulopathy might masquerade the central vestibular syndrome and harbor a cerebellar stroke. However, the gravity-dependent nystagmus allows prompt identification of acute cerebellar infarct. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Detergent-dependent separation of postsynaptic density, membrane rafts and other subsynaptic structures from the synaptic plasma membrane of rat forebrain.

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Zhao, LiYing; Sakagami, Hiroyuki; Suzuki, Tatsuo

2014-10-01

We systematically investigated the purification process of post-synaptic density (PSD) and post-synaptic membrane rafts (PSRs) from the rat forebrain synaptic plasma membranes by examining the components and the structures of the materials obtained after the treatment of synaptic plasma membranes with TX-100, n-octyl β-d-glucoside (OG) or 3-([3-cholamidopropyl]dimethylammonio)-2-hydroxy-1-propanesulfonate (CHAPSO). These three detergents exhibited distinct separation profiles for the synaptic subdomains. Type I and type II PSD proteins displayed mutually exclusive distribution. After TX-100 treatment, type I PSD was recovered in two fractions: a pellet and an insoluble fraction 8, which contained partially broken PSD-PSR complexes. Conventional PSD was suggested to be a mixture of these two PSD pools and did not contain type II PSD. An association of type I PSD with PSRs was identified in the TX-100 treatment, and those with type II PSD in the OG and CHAPSO treatments. An association of GABA receptors with gephyrin was easily dissociated. OG at a high concentration solubilized the type I PSD proteins. CHAPSO treatment resulted in a variety of distinct fractions, which contained certain novel structures. Two different pools of GluA, either PSD or possibly raft-associated, were identified in the OG and CHAPSO treatments. These results are useful in advancing our understanding of the structural organization of synapses at the molecular level. We systematically investigated the purification process of post-synaptic density (PSD) and synaptic membrane rafts by examining the structures obtained after treatment of the SPMs with TX-100, n-octyl β-d-glucoside or CHAPSO. Differential distribution of type I and type II PSD, synaptic membrane rafts, and other novel subdomains in the SPM give clues to understand the structural organization of synapses at the molecular level. © 2014 International Society for Neurochemistry.

Language Impairment in Cerebellar Ataxia

NARCIS (Netherlands)

van Gaalen, Judith; de Swart, Bert J. M.; Oostveen, Judith; Knuijt, Simone; van de Warrenburg, Bart P. C.; Kremer, Berry (H. ) P. H.

Background: Several studies have suggested that language impairment can be observed in patients with cerebellar pathology. The aim of this study was to investigate language performance in patients with spinocerebellar ataxia type 6 (SCA6). Methods: We assessed speech and language in 29 SCA6 patients

Cerebellar patients demonstrate preserved implicit knowledge of association strengths in musical sequences.

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Tillmann, Barbara; Justus, Timothy; Bigand, Emmanuel

2008-03-01

Recent findings suggest the involvement of the cerebellum in perceptual and cognitive tasks. Our study investigated whether cerebellar patients show musical priming based on implicit knowledge of tonal-harmonic music. Participants performed speeded phoneme identification on sung target chords, which were either related or less-related to prime contexts in terms of the tonal-harmonic system. As groups, both cerebellar patients and age-matched controls showed facilitated processing for related targets, as previously observed for healthy young adults. The outcome suggests that an intact cerebellum is not mandatory for accessing implicit knowledge stored in long-term memory and for its influence on perception. One patient showed facilitated processing for less-related targets (suggesting sensory priming). The findings suggest directions for future research on auditory perception in cerebellar patients to further our understanding of cerebellar functions.

Dicer Is Required for Normal Cerebellar Development and to Restrain Medulloblastoma Formation.

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Frederique Zindy

Full Text Available Dicer, a ribonuclease III enzyme, is required for the maturation of microRNAs. To assess its role in cerebellar and medulloblastoma development, we genetically deleted Dicer in Nestin-positive neural progenitors and in mice lacking one copy for the Sonic Hedgehog receptor, Patched 1. We found that conditional loss of Dicer in mouse neural progenitors induced massive Trp53-independent apoptosis in all proliferative zones of the brain and decreased proliferation of cerebellar granule progenitors at embryonic day 15.5 leading to abnormal cerebellar development and perinatal lethality. Loss of one copy of Dicer significantly accelerated the formation of mouse medulloblastoma of the Sonic Hedgehog subgroup in Patched1-heterozygous mice. We conclude that Dicer is required for proper cerebellar development, and to restrain medulloblastoma formation.

Cerebellar cytokine expression in a rat model for fetal asphyctic preconditioning and perinatal asphyxia

DEFF Research Database (Denmark)

Vlassaks, Evi; Brudek, Tomasz; Pakkenberg, Bente

2014-01-01

the effects of perinatal asphyxia and fetal asphyctic preconditioning on the inflammatory cytokine response in the cerebellum. Fetal asphyxia was induced at embryonic day 17 by clamping the uterine vasculature for 30 min. At term birth, global perinatal asphyxia was induced by placing the uterine horns...... was decreased 96 h postfetal asphyxia. When applied as preconditioning stimulus, fetal asphyxia attenuates the cerebellar cytokine response. These results indicate that sublethal fetal asphyxia may protect the cerebellum from perinatal asphyxia-induced damage via inhibition of inflammation.......Asphyctic brain injury is a major cause of neuronal inflammation in the perinatal period. Fetal asphyctic preconditioning has been shown to modulate the cerebral inflammatory cytokine response, hereby protecting the brain against asphyctic injury at birth. This study was designated to examine...

Changes in cerebro-cerebellar interaction during response inhibition after performance improvement.

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Hirose, Satoshi; Jimura, Koji; Kunimatsu, Akira; Abe, Osamu; Ohtomo, Kuni; Miyashita, Yasushi; Konishi, Seiki

2014-10-01

It has been demonstrated that motor learning is supported by the cerebellum and the cerebro-cerebellar interaction. Response inhibition involves motor responses and the higher-order inhibition that controls the motor responses. In this functional MRI study, we measured the cerebro-cerebellar interaction during response inhibition in two separate days of task performance, and detected the changes in the interaction following performance improvement. Behaviorally, performance improved in the second day, compared to the first day. The psycho-physiological interaction (PPI) analysis revealed the interaction decrease from the right inferior frontal cortex (rIFC) to the cerebellum (lobule VII or VI). It was also revealed that the interaction increased from the same cerebellar region to the primary motor area. These results suggest the involvement of the cerebellum in response inhibition, and raise the possibility that the performance improvement was supported by the changes in the cerebro-cerebellar interaction. Copyright © 2014 Elsevier Inc. All rights reserved.

Long term clinical and neurophysiological effects of cerebellar transcranial direct current stimulation in patients with neurodegenerative ataxia.

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Benussi, Alberto; Dell'Era, Valentina; Cotelli, Maria Sofia; Turla, Marinella; Casali, Carlo; Padovani, Alessandro; Borroni, Barbara

Neurodegenerative cerebellar ataxias represent a group of disabling disorders for which we currently lack effective therapies. Cerebellar transcranial direct current stimulation (tDCS) is a non-invasive technique, which has been demonstrated to modulate cerebellar excitability and improve symptoms in patients with cerebellar ataxias. The present study investigated whether a two-weeks' treatment with cerebellar anodal tDCS could improve symptoms in patients with neurodegenerative cerebellar ataxia and could modulate cerebello-motor connectivity, at short and long term. We performed a double-blind, randomized, sham controlled trial with cerebellar tDCS (5 days/week for 2 weeks) in twenty patients with ataxia. Each patient underwent a clinical evaluation pre- and post-anodal tDCS or sham stimulation. A follow-up evaluation was performed at one and three months. Cerebello-motor connectivity was evaluated using transcranial magnetic stimulation (TMS) at baseline and at follow-up. Patients who underwent anodal tDCS showed a significant improvement in all performance scores (scale for the assessment and rating of ataxia, international cooperative ataxia rating scale, 9-hole peg test, 8-m walking time) and in cerebellar brain inhibition compared to patients who underwent sham stimulation. A two-weeks' treatment with anodal cerebellar tDCS improves symptoms in patients with ataxia and restores physiological cerebellar brain inhibition pathways. Cerebellar tDCS might represent a promising future therapeutic and rehabilitative approach in patients with neurodegenerative ataxia. Copyright © 2016 Elsevier Inc. All rights reserved.

Speech Prosody in Cerebellar Ataxia

Science.gov (United States)

Casper, Maureen A.; Raphael, Lawrence J.; Harris, Katherine S.; Geibel, Jennifer M.

2007-01-01

Persons with cerebellar ataxia exhibit changes in physical coordination and speech and voice production. Previously, these alterations of speech and voice production were described primarily via perceptual coordinates. In this study, the spatial-temporal properties of syllable production were examined in 12 speakers, six of whom were healthy…

3. Impact of altered gravity on CNS development and behavior in male and female rats

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Sajdel-Sulkowska, E. M.; Nguon, K.; Ladd, B.; Sulkowski, V. A.; Sulkowski, Z. L.; Baxter, M. G.

The present study examined the effect of altered gravity on CNS development. Specifically, we compared neurodevelopment, behavior, cerebellar structure and protein expression in rat neonates exposed perinatally to hypergravity. Pregnant Sprague-Dawley rats were exposed to 1.5G-1.75G hypergravity on a 24-ft centrifuge starting on gestational day (G) 10, through giving birth on G22/G23, and nursing their offspring through postnatal day (P) 21. Cerebellar mass on P6 was decreased in 1.75G-exposed male pups by 27.5 percent; in 1.75G-exposed female pups it was decreased by 22.5 percent. The observed cerebellar changes were associated with alterations in neurodevelopment and motor behavior. Exposure to hypergravity impaired performance on the following neurocognitive tests: (1) righting time on P3 was more than doubled in 1.75G-exposed rats and the effect appeared more pronounced in female pups, (2) startle response on P10 was delayed in both male and female HG pups; HG pups were one-fifth as likely to respond to a clapping noise as SC pups, and (3) performance on a rotorod on P21 was decreased in HG pups; the duration of the stay on rotorod recorded for HG pups of both sexes was one tenth of the SC pups. Furthermore, Western blot analysis of selected cerebellar proteins suggested gender-specific changes in glial and neuronal proteins. On P6, GFAP expression was decreased by 59.2 percent in HG males, while no significant decrease was observed in female cerebella. Synaptophysin expression was decreased in HG male neonates by 29.9 percent and in HG female neonates by 20.7 percent as compared to its expression in SC cerebella. The results of this experiment suggest that perinatal exposure to hypergravity affects cerebellar development and behavior differently in male and female neonates. If one accepts that hypergravity is a good paradigm to study the effect of microgravity on the CNS, and since males and females were shown to respond differently to hypergravity, it can be

Cocaine promotes oxidative stress and microglial-macrophage activation in rat cerebellum

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Rosa M López-Pedrajas

2015-07-01

Full Text Available Different mechanisms have been suggested for cocaine neurotoxicity, including oxidative stress alterations. Nuclear factor kappa B (NF-κB, considered a sensor of oxidative stress and inflammation, is involved in drug toxicity and addiction. NF-κB is a key mediator for immune responses that induces microglial/macrophage activation under inflammatory processes and neuronal injury/degeneration. Although cerebellum is commonly associated to motor control, muscular tone and balance. Its relation with addiction is getting relevance, being associated to compulsive and perseverative behaviors. Some reports indicate that cerebellar microglial activation induced by cannabis or ethanol, promote cerebellar alterations and these alterations could be associated to addictive-related behaviors. After considering the effects of some drugs on cerebellum, the aim of the present work analyzes pro-inflammatory changes after cocaine exposure. Rats received daily 15 mg/kg cocaine i.p. for 18 days. Reduced and oxidized forms of glutathione (GSH and GSSG, glutathione peroxidase (GPx activity and glutamate were determined in cerebellar homogenates. NF-κB activity, CD68 and GFAP expression were determined.Cerebellar GPx activity and GSH/GSSG ratio are significantly decreased after cocaine exposure. A significant increase of glutamate concentration is also observed. Interestingly, increased NF-κB activity is also accompanied by an increased expression of the lysosomal mononuclear phagocytic marker ED1 without GFAP alterations.Current trends in addiction biology are focusing on the role of cerebellum on addictive behaviors. Cocaine-induced cerebellar changes described herein fit with previosus data showing cerebellar alterations on addict subjects and support the proposed role of cerebelum in addiction.

Role of Lactobacillus plantarum MTCC1325 in membrane-bound transport ATPases system in Alzheimer’s disease-induced rat brain

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Nimgampalle Mallikarjuna

2016-12-01

Results: Chronic injection of D-Galactose caused lipid peroxidation, oxidative stress, and mitochondrial dysfunction leading to the damage of neurons in the brain, finally bringing a significant decrease (-20% in the brain total membrane bound ATPases over the controls. Contrary to this, treatment of AD-induced rats with L. plantarum MTCC1325 reverted all the constituents of ATPase enzymes to near normal levels within 30 days. Conclusion: Lactobacillus plantarum MTCC1325 exerted a beneficial action on the entire ATPases system in AD-induced rat brain by delaying neurodegeneration.

Abnormality in cerebellar blood flow in solo vertigo patients

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Nagahori, Takeshi [Shakaihoken Takaoka Hospital, Toyama (Japan); Nishijima, Michiharu; Endo, Shunro; Takaku, Akira

1997-03-01

Little is known about the blood flow of the vertebrobasilar system as a cause of vertigo and dizziness. We used Xe-CT to study cerebellar blood flow in 53 patients who ranged in age from 35 to 85 years. The patients were divided into two groups. One of them was the vertigo group that comprised 28 patients with rotatory sensation, and the other, the non-vertigo group of 25 patients with a sensation other than rotation. At the stage of severe symptoms, there was decreased cerebellar blood flow in all patients of both, the vertigo and the non-vertigo groups, and a decrease in the bilateral cerebellar hemisphere was observed in five patients and in a unilateral hemisphere in three patients of the vertigo group. By comparison, in the non-vertigo group, unilateral decrease of cerebellar blood flow was observed in only one patient, and a bilateral decrease in five. At the stage of severe symptoms, the mean regional cerebellar blood flow was 40.5{+-}8.0 ml/100 g/min (n=16 sides) in the vertigo group and 45.3{+-}9.5 ml/100 g/min (n=12 sides) in the non-vertigo group. At the stage of moderate symptoms, blood flow image was normal in four of 14 vertigo patients and in seven of 12 non-vertigo patients. The mean regional blood flow was 47.8{+-}8.6 ml/100 g/min (n=28 sides) in the vertigo group and 47.1{+-}5.1 ml/100 g/min (n=24 sides) in the non-vertigo group. At the asymptomatic stage, a high proportion of normal blood flow images (nine of 16 vertigo patients and 10 of 10 non-vertigo patients) was observed. The mean regional cerebellar blood flow was 51.6{+-}10.7 ml/100 g/min (n=32 sides) in the vertigo group and 52.8{+-}8.5 ml/100 g/min (n=20 sides) in the non-vertigo group. This study demonstrates that a unilateral or bilateral decrease in blood flow of the vertebrobasilar system may cause vertigo and dizziness. It also shows that Xe-CT of the cerebellum may be a valuable examination modality for the diagnosis and treatment of vertigo and dizziness. (author)

Abnormality in cerebellar blood flow in solo vertigo patients

International Nuclear Information System (INIS)

Nagahori, Takeshi; Nishijima, Michiharu; Endo, Shunro; Takaku, Akira

1997-01-01

Little is known about the blood flow of the vertebrobasilar system as a cause of vertigo and dizziness. We used Xe-CT to study cerebellar blood flow in 53 patients who ranged in age from 35 to 85 years. The patients were divided into two groups. One of them was the vertigo group that comprised 28 patients with rotatory sensation, and the other, the non-vertigo group of 25 patients with a sensation other than rotation. At the stage of severe symptoms, there was decreased cerebellar blood flow in all patients of both, the vertigo and the non-vertigo groups, and a decrease in the bilateral cerebellar hemisphere was observed in five patients and in a unilateral hemisphere in three patients of the vertigo group. By comparison, in the non-vertigo group, unilateral decrease of cerebellar blood flow was observed in only one patient, and a bilateral decrease in five. At the stage of severe symptoms, the mean regional cerebellar blood flow was 40.5±8.0 ml/100 g/min (n=16 sides) in the vertigo group and 45.3±9.5 ml/100 g/min (n=12 sides) in the non-vertigo group. At the stage of moderate symptoms, blood flow image was normal in four of 14 vertigo patients and in seven of 12 non-vertigo patients. The mean regional blood flow was 47.8±8.6 ml/100 g/min (n=28 sides) in the vertigo group and 47.1±5.1 ml/100 g/min (n=24 sides) in the non-vertigo group. At the asymptomatic stage, a high proportion of normal blood flow images (nine of 16 vertigo patients and 10 of 10 non-vertigo patients) was observed. The mean regional cerebellar blood flow was 51.6±10.7 ml/100 g/min (n=32 sides) in the vertigo group and 52.8±8.5 ml/100 g/min (n=20 sides) in the non-vertigo group. This study demonstrates that a unilateral or bilateral decrease in blood flow of the vertebrobasilar system may cause vertigo and dizziness. It also shows that Xe-CT of the cerebellum may be a valuable examination modality for the diagnosis and treatment of vertigo and dizziness. (author)

Cerebellar Shaping of Motor Cortical Firing Is Correlated with Timing of Motor Actions

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Abdulraheem Nashef

2018-05-01

Full Text Available Summary: In higher mammals, motor timing is considered to be dictated by cerebellar control of motor cortical activity, relayed through the cerebellar-thalamo-cortical (CTC system. Nonetheless, the way cerebellar information is integrated with motor cortical commands and affects their temporal properties remains unclear. To address this issue, we activated the CTC system in primates and found that it efficiently recruits motor cortical cells; however, the cortical response was dominated by prolonged inhibition that imposed a directional activation across the motor cortex. During task performance, cortical cells that integrated CTC information fired synchronous bursts at movement onset. These cells expressed a stronger correlation with reaction time than non-CTC cells. Thus, the excitation-inhibition interplay triggered by the CTC system facilitates transient recruitment of a cortical subnetwork at movement onset. The CTC system may shape neural firing to produce the required profile to initiate movements and thus plays a pivotal role in timing motor actions. : Nashef et al. identified a motor cortical subnetwork recruited by cerebellar volley that was transiently synchronized at movement onset. Cerebellar control of cortical firing was dominated by inhibition that shaped task-related firing of neurons and may dictate motor timing. Keywords: motor control, primates, cerebellar-thalamo-cortical, synchrony, noise correlation, reaction time

Cerebellar atrophy is frequently associated with non-paraneoplastic sensory neuronopathy

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Alfredo Damasceno

2011-08-01

Full Text Available Sensory neuronopathies (SN are peripheral nervous system disorders associated with degeneration of dorsal root ganglion neurons. Despite the evidence of a defective proprioceptive sensory input in SN,the prominent gait and truncal ataxia raises the question of a concomitant involvement of the cerebellum. OBJECTIVE: To evaluate cerebellar atrophy in SN. METHOD: We analyzed MRI-based volumetry of anterior lobe (paleocerebellum and total cerebellum in patients with non-paraneoplastic chronic SN and compared to age- and gender-matched controls. RESULTS: Cerebellum and anterior lobe MRI volumetry were performed in 20 patients and nine controls. Mean anterior lobe and cerebellar volume were not statistically different. Three patients (15%, however, had an abnormal anterior lobe and cerebellar volume index (values outside 2.5 standard deviations. One of them also had a specific atrophy of the anterior lobe. All these patients had infectious or dysimmune associated SN. CONCLUSION: Cerebellar atrophy is infrequently associated with SN, but can be found in some patients with SN related to infectious or immune mediated conditions. It can be more prominent in the anterior lobe and may contribute to the ataxia seen in these patients.

Neuroprotective effects of thymoquinone against cerebellar ...

African Journals Online (AJOL)

cerebellum mainly functions to coordinate motor functions and control ... development of the brain and life-long cognitive function [2]. ... and serial equidistant sections of the right cerebellar ... Cells outside of the left vertical and bottom bars ...

Post-traumatic cerebellar infarction due to vertebral artery foramina fracture: case report

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Moscote-Salazar Luis Rafael

2016-03-01

Full Text Available Posttraumatic cerebral infarction is an uncommon cause of morbidity and mortality and many studies have highlighted that trauma needs to considered as causative factor for cerebellar infarction. We present a case of cerebellar infarction in a 35 year old young patient secondary to vertebral fracture involving the vertebral foramen and vertebral artery injury. CT scan cervical spine showed C2-3 fracture on left side with fracture extending into the left vertebral foramen. A CT scan angiogram could not be performed because of poor neurological status. Possibly the infarction was due to left vertebral artery injury. Without surgical intervention prognosis of these patients remain poor. Prognosis of patients with traumatic cerebellar infarction depends on the neurological status of the patient, intrinsic parenchymal damage and more importantly extrinsic compression of the brainstem by the edematous cerebellar hemispheres.

Supplementation of T3 Recovers Hypothyroid Rat Liver Cells from Oxidatively Damaged Inner Mitochondrial Membrane Leading to Apoptosis

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Sutapa Mukherjee

2014-01-01

Full Text Available Hypothyroidism is a growing medical concern. There are conflicting reports regarding the mechanism of oxidative stress in hypothyroidism. Mitochondrial oxidative stress is pivotal to thyroid dysfunction. The present study aimed to delineate the effects of hepatic inner mitochondrial membrane dysfunction as a consequence of 6-n-propyl-2-thiouracil-induced hypothyroidism in rats. Increased oxidative stress predominance in the submitochondrial particles (SMP and altered antioxidant defenses in the mitochondrial matrix fraction correlated with hepatocyte apoptosis. In order to check whether the effects caused by hypothyroidism are reversed by T3, the above parameters were evaluated in a subset of T3-treated hypothyroid rats. Complex I activity was inhibited in hypothyroid SMP, whereas T3 supplementation upregulated electron transport chain complexes. Higher mitochondrial H2O2 levels in hypothyroidism due to reduced matrix GPx activity culminated in severe oxidative damage to membrane lipids. SMP and matrix proteins were stabilised in hypothyroidism but exhibited increased carbonylation after T3 administration. Glutathione content was higher in both. Hepatocyte apoptosis was evident in hypothyroid liver sections; T3 administration, on the other hand, exerted antiapoptotic and proproliferative effects. Hence, thyroid hormone level critically regulates functional integrity of hepatic mitochondria; hypothyroidism injures mitochondrial membrane lipids leading to hepatocyte apoptosis, which is substantially recovered upon T3 supplementation.

Comparative neuronal morphology of the cerebellar cortex in afrotherians, carnivores, cetartiodactyls, and primates

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Bob eJacobs

2014-04-01

Full Text Available Although the basic morphological characteristics of neurons in the cerebellar cortex have been documented in several species, virtually nothing is known about the quantitative morphological characteristics of these neurons across different taxa. To that end, the present study investigated cerebellar neuronal morphology among eight different, large-brained mammalian species comprising a broad phylogenetic range: afrotherians (African elephant, Florida manatee, carnivores (Siberian tiger, clouded leopard, cetartiodactyls (humpback whale, giraffe and primates (human, common chimpanzee. Specifically, several neuron types (e.g., stellate, basket, Lugaro, Golgi, and granule neurons; N = 317 of the cerebellar cortex were stained with a modified rapid Golgi technique and quantified on a computer-assisted microscopy system. There was a 64-fold variation in brain mass across species in our sample (from clouded leopard to the elephant and a 103-fold variation in cerebellar volume. Most dendritic measures tended to increase with cerebellar volume. The cerebellar cortex in these species exhibited the trilaminate pattern common to all mammals. Morphologically, neuron types in the cerebellar cortex were generally consistent with those described in primates (Fox et al., 1967 and rodents (Palay and Chan-Palay, 1974, although there was substantial quantitative variation across species. In particular, Lugaro neurons in the elephant appeared to be disproportionately larger than those in other species. To explore potential quantitative differences in dendritic measures across species, MARSplines analyses were used to evaluate whether species could be differentiated from each other based on dendritic characteristics alone. Results of these analyses indicated that there were significant differences among all species in dendritic measures.

Psychosocial stress affects the acquisition of cerebellar-dependent sensorimotor adaptation.

Science.gov (United States)

Gheorghe, Delia A; Panouillères, Muriel T N; Walsh, Nicholas D

2018-03-27

Despite being overlooked in theoretical models of stress-related disorders, differences in cerebellar structure and function are consistently reported in studies of individuals exposed to current and early-life stressors. However, the mediating processes through which stress impacts upon cerebellar function are currently unknown. The aim of the current experiment was to test the effects of experimentally-induced acute stress on cerebellar functioning, using a classic, forward saccadic adaptation paradigm in healthy, young men and women. Stress induction was achieved by employing the Montreal Imaging Stress Task (MIST), a task employing mental arithmetic and negative social feedback to generate significant physiological and endocrine stress responses. Saccadic adaptation was elicited using the double-step target paradigm. In the experiment, 48 participants matched for gender and age were exposed to either a stress (n = 25) or a control (n = 23) condition. Saliva for cortisol analysis was collected before, immediately after, and 10, and 30 min after the MIST. Saccadic adaptation was assessed approximately 10 min after stress induction, when cortisol levels peaked. Participants in the stress group reported significantly more stress symptoms and exhibited greater total cortisol output compared to controls. The stress manipulation was associated with slower learning rates in the stress group, while control participants acquired adaptation faster. Learning rates were negatively associated with cortisol output and mood disturbance. Results suggest that experimentally-induced stress slowed acquisition of cerebellar-dependent saccadic adaptation, related to increases in cortisol output. These 'proof-of-principle' data demonstrate that stress modulates cerebellar-related functions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cerebellar leukoencephalopathy: most likely histiocytosis-related

NARCIS (Netherlands)

van der Knaap, M.S.; Arts, W.F.M.; Garbern, J.Y.; Hedlund, G.; Winkler, F.; Barbosa, C.; King, M.D.; Bjornstad, A.; Hussain, N.; Beyer, M.K.; Gomez, C.; Patterson, M.C.; Grattan-Smith, P.; Timmons, M.; van der Valk, P.

2008-01-01

Background: Histiocytosis, both Langerhans and non-Langerhans cell type, can be associated with cerebellar white matter abnormalities, thought to be paraneoplastic. The associated clinical picture consists of ataxia, spasticity, and cognitive decline. Hormonal dysfunction is frequent. MRI shows

Systemic inflammation combined with neonatal cerebellar haemorrhage aggravates long-term structural and functional outcomes in a mouse model.

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Tremblay, Sophie; Pai, Alex; Richter, Lindsay; Vafaei, Rod; Potluri, Praneetha; Ellegood, Jacob; Lerch, Jason P; Goldowitz, Daniel

2017-11-01

Despite the increased recognition of cerebellar injury in survivors of preterm birth, the neurodevelopmental consequences of isolated cerebellar injury have been largely unexplored and our current understanding of the functional deficits requires further attention in order to translate knowledge to best practices. Preterm infants are exposed to multiple stressors during their postnatal development including perinatal cerebellar haemorrhage (CBH) and postnatal infection, two major risk factors for neurodevelopmental impairments. We developed a translational mouse model of CBH and/or inflammation to measure the short- and long-term outcomes in cerebellar structure and function. Mice exposed to early combined insults of CBH and early inflammatory state (EIS) have a delay in grasping acquisition, neonatal motor deficits and deficient long-term memory. CBH combined with late inflammatory state (LIS) does not induce neonatal motor problems but leads to poor fine motor function and long-term memory deficits at adulthood. Early combined insults result in poor cerebellar growth from postnatal day 15 until adulthood shown by MRI, which are reflected in diminished volumes of cerebellar structures. There are also decreases in volumes of gray matter and hippocampus. Cerebellar microgliosis appears 24h after the combined insults and persists until postnatal day 15 in the cerebellar molecular layer and cerebellar nuclei in association with a disrupted patterning of myelin deposition, a delay of oligodendrocyte maturation and reduced white matter cerebellar volume. Together, these findings reveal poor outcomes in developing brains exposed to combined cerebellar perinatal insults in association with cerebellar hypoplasia, persistence of microgliosis and alterations of cerebellar white matter maturation and growth. Copyright © 2017 Elsevier Inc. All rights reserved.

Cerebellar interaction with the acoustic reflex.

Science.gov (United States)

Jastreboff, P J

1981-01-01

The involvement of the cerebellar vermis in the acoustic reflex was analyzed in 12 cats, decerebrated or in pentobarbital anesthesia. Anatomical data suggested the existence of a connection of lobules VIII with the ventral cochlear nucleus. Single cell recording and evoked potential techniques demonstrated the existence of the acoustic projection to lobulus VIII. Electrical stimulation of this area changed the tension of the middle ear muscle and caused evoked potential responses in the caudal part of the ventral cochlear nucleus. Electrical stimulation of the motor nucleus of the facial nerve evoked a slow wave in the recording taken from the surrounding of the cochlear round window. A hypothesis is proposed which postulates the involvement of the acoustic reflex in space localization of acoustic stimuli and the action of cerebellar vermis in order to assure the stability and plasticity of the acoustic reflex arc.

Surgical approach to posterior inferior cerebellar artery aneurysms.

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La Pira, Biagia; Sturiale, Carmelo Lucio; Della Pepa, Giuseppe Maria; Albanese, Alessio

2018-02-01

The far-lateral is a standardised approach to clip aneurysms of the posterior inferior cerebellar artery (PICA). Different variants can be adopted to manage aneurysms that differ in morphology, topography, ruptured status, cerebellar swelling and surgeon preference. We distinguished five paradigmatic approaches aimed to manage aneurysms that are: proximal unruptured; proximal ruptured requiring posterior fossa decompression (PFD); proximal ruptured not requiring PFD; distal unruptured; distal ruptured. Preoperative planning in the setting of PICA aneurysm surgery is of paramount importance to perform an effective and safe procedure, to ensure an adequate PFD and optimal proximal control before aneurysm manipulation.

Exercise increases the plasma membrane content of the Na+ -K+ pump and its mRNA in rat skeletal muscles.

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Tsakiridis, T; Wong, P P; Liu, Z; Rodgers, C D; Vranic, M; Klip, A

1996-02-01

Muscle fibers adapt to ionic challenges of exercise by increasing the plasma membrane Na+-K+ pump activity. Chronic exercise training has been shown to increase the total amount of Na+-K+ pumps present in skeletal muscle. However, the mechanism of adaptation of the Na+-K+ pump to an acute bout of exercise has not been determined, and it is not known whether it involves alterations in the content of plasma membrane pump subunits. Here we examine the effect of 1 h of treadmill running (20 m/min, 10% grade) on the subcellular distribution and expression of Na+-K+ pump subunits in rat skeletal muscles. Red type I and IIa (red-I/IIa) and white type IIa and IIb (white-IIa/IIb) hindlimb muscles from resting and exercised female Sprague-Dawley rats were removed for subcellular fractionation. By homogenization and gradient centrifugation, crude membranes and purified plasma membranes were isolated and subjected to gel electrophoresis and immunoblotting by using pump subunit-specific antibodies. Furthermore, mRNA was isolated from specific red type I (red-I) and white type IIb (white-IIb) muscles and subjected to Northern blotting by using subunit-specific probes. In both red-I/IIa and white-IIa/IIb muscles, exercise significantly raised the plasma membrane content of the alpha1-subunit of the pump by 64 +/- 24 and 55 +/- 22%, respectively (P < 0.05), and elevated the alpha2-polypeptide by 43 +/- 22 and 94 +/- 39%, respectively (P < 0.05). No significant effect of exercise could be detected on the amount of these subunits in an internal membrane fraction or in total membranes. In addition, exercise significantly increased the alpha1-subunit mRNA in red-I muscle (by 50 +/- 7%; P < 0.05) and the beta2-subunit mRNA in white-IIb muscles (by 64 +/- 19%; P < 0.01), but the alpha2- and beta1-mRNA levels were unaffected in this time period. We conclude that increased presence of alpha1- and alpha2-polypeptides at the plasma membrane and subsequent elevation of the alpha1- and beta2

In vivo and in vitro effect of imipramine and fluoxetine on Na+,K+-ATPase activity in synaptic plasma membranes from the cerebral cortex of rats

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L.M. Zanatta

2001-10-01

Full Text Available The effects of in vivo chronic treatment and in vitro addition of imipramine, a tricyclic antidepressant, or fluoxetine, a selective serotonin reuptake inhibitor, on the cortical membrane-bound Na+,K+-ATPase activity were studied. Adult Wistar rats received daily intraperitoneal injections of 10 mg/kg of imipramine or fluoxetine for 14 days. Twelve hours after the last injection rats were decapitated and synaptic plasma membranes (SPM from cerebral cortex were prepared to determine Na+,K+-ATPase activity. There was a significant decrease (10% in enzyme activity after imipramine but fluoxetine treatment caused a significant increase (27% in Na+,K+-ATPase activity compared to control (P<0.05, ANOVA; N = 7 for each group. When assayed in vitro, the addition of both drugs to SPM of naive rats caused a dose-dependent decrease in enzyme activity, with the maximal inhibition (60-80% occurring at 0.5 mM. We suggest that a imipramine might decrease Na+,K+-ATPase activity by altering membrane fluidity, as previously proposed, and b stimulation of this enzyme might contribute to the therapeutic efficacy of fluoxetine, since brain Na+,K+-ATPase activity is decreased in bipolar patients.

Acute ethanol exposure inhibits silencing of cerebellar Golgi cell firing induced by granule cell axon input

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Paolo eBotta

2014-02-01

Full Text Available Golgi cells (GoCs are specialized interneurons that provide inhibitory input to granule cells in the cerebellar cortex. GoCs are pacemaker neurons that spontaneously fire action potentials, triggering spontaneous inhibitory postsynaptic currents in granule cells and also contributing to the generation tonic GABAA receptor-mediated currents in granule cells. In turn, granule cell axons provide feedback glutamatergic input to GoCs. It has been shown that high frequency stimulation of granule cell axons induces a transient pause in GoC firing in a type 2-metabotropic glutamate receptor (mGluR2-dependent manner. Here, we investigated the effect ethanol on the pause of GoC firing induced by high frequency stimulation of granule cell axons. GoC electrophysiological recordings were performed in parasagittal cerebellar vermis slices from postnatal day 23 to 26 rats. Loose-patch cell-attached recordings revealed that ethanol (40 mM reversibly decreases the pause duration. An antagonist of mGluR2 reduced the pause duration but did not affect the effect of ethanol. Whole-cell voltage-clamp recordings showed that currents evoked by an mGluR2 agonist were not significantly affected by ethanol. Perforated-patch experiments in which hyperpolarizing and depolarizing currents were injected into GoCs demonstrated that there is an inverse relationship between spontaneous firing and pause duration. Slight inhibition of the Na+/K+ pump mimicked the effect of ethanol on pause duration. In conclusion, ethanol reduces the granule cell axon-mediated feedback mechanism by reducing the input responsiveness of GoCs. This would result in a transient increase of GABAA receptor-mediated inhibition of granule cells, limiting information flow at the input stage of the cerebellar cortex.

Effect of long-term propranolol administration on specific binding of 3H-WB-4101 with rat mesenteric vascular membranes

International Nuclear Information System (INIS)

Ismailov, S.I.; Rozhanets, V.V.; Val'dman, A.V.

1985-01-01

The aim of this investigation was, first, to study the affinity of certain beta-adrenoblockers for specific binding sites of 3 H-WB-4101 (identifiable as alpha-adrenoreceptors) of brain membranes and, second, to study the characteristics of these same receptors in membranes of mesenteric vessels of rats during long-term administration of propranolol. Isotherms of specific binding, because of the limited quantity of vascular membranes, were determined by the use of three concentrations of 3 H-WB-4101: 0.1, 0.5, and 1.0 nM. It is shown that some beta-adrenoblockers have weak affinity for alpha-adrenoreceptors of brain synaptic membranes exhibited only when these compounds are present in relatively high concentrations. It is also shown that administration of propranolol for 15 days led to a significant decrease in affinity of the alpha-adrenorecptors for their specific antagonist WB-4101

A Multiple-Plasticity Spiking Neural Network Embedded in a Closed-Loop Control System to Model Cerebellar Pathologies.

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Geminiani, Alice; Casellato, Claudia; Antonietti, Alberto; D'Angelo, Egidio; Pedrocchi, Alessandra

2018-06-01

The cerebellum plays a crucial role in sensorimotor control and cerebellar disorders compromise adaptation and learning of motor responses. However, the link between alterations at network level and cerebellar dysfunction is still unclear. In principle, this understanding would benefit of the development of an artificial system embedding the salient neuronal and plastic properties of the cerebellum and operating in closed-loop. To this aim, we have exploited a realistic spiking computational model of the cerebellum to analyze the network correlates of cerebellar impairment. The model was modified to reproduce three different damages of the cerebellar cortex: (i) a loss of the main output neurons (Purkinje Cells), (ii) a lesion to the main cerebellar afferents (Mossy Fibers), and (iii) a damage to a major mechanism of synaptic plasticity (Long Term Depression). The modified network models were challenged with an Eye-Blink Classical Conditioning test, a standard learning paradigm used to evaluate cerebellar impairment, in which the outcome was compared to reference results obtained in human or animal experiments. In all cases, the model reproduced the partial and delayed conditioning typical of the pathologies, indicating that an intact cerebellar cortex functionality is required to accelerate learning by transferring acquired information to the cerebellar nuclei. Interestingly, depending on the type of lesion, the redistribution of synaptic plasticity and response timing varied greatly generating specific adaptation patterns. Thus, not only the present work extends the generalization capabilities of the cerebellar spiking model to pathological cases, but also predicts how changes at the neuronal level are distributed across the network, making it usable to infer cerebellar circuit alterations occurring in cerebellar pathologies.

Functional reorganization of motor and limbic circuits after exercise training in a rat model of bilateral parkinsonism.

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Zhuo Wang

Full Text Available Exercise training is widely used for neurorehabilitation of Parkinson's disease (PD. However, little is known about the functional reorganization of the injured brain after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise in a rat model of dopaminergic deafferentation (bilateral, dorsal striatal 6-hydroxydopamine lesions. One week after training, cerebral perfusion was mapped during treadmill walking or at rest using [(14C]-iodoantipyrine autoradiography. Regional cerebral blood flow-related tissue radioactivity (rCBF was analyzed in three-dimensionally reconstructed brains by statistical parametric mapping. In non-exercised rats, lesions resulted in persistent motor deficits. Compared to sham-lesioned rats, lesioned rats showed altered functional brain activation during walking, including: 1. hypoactivation of the striatum and motor cortex; 2. hyperactivation of non-lesioned areas in the basal ganglia-thalamocortical circuit; 3. functional recruitment of the red nucleus, superior colliculus and somatosensory cortex; 4. hyperactivation of the ventrolateral thalamus, cerebellar vermis and deep nuclei, suggesting recruitment of the cerebellar-thalamocortical circuit; 5. hyperactivation of limbic areas (amygdala, hippocampus, ventral striatum, septum, raphe, insula. These findings show remarkable similarities to imaging findings reported in PD patients. Exercise progressively improved motor deficits in lesioned rats, while increasing activation in dorsal striatum and rostral secondary motor cortex, attenuating a hyperemia of the zona incerta and eliciting a functional reorganization of regions participating in the cerebellar-thalamocortical circuit. Both lesions and exercise increased activation in mesolimbic areas (amygdala, hippocampus, ventral striatum, laterodorsal tegmental n., ventral pallidum, as well as in related paralimbic regions (septum, raphe, insula. Exercise, but not lesioning, resulted

Functional Reorganization of Motor and Limbic Circuits after Exercise Training in a Rat Model of Bilateral Parkinsonism

Science.gov (United States)

Wang, Zhuo; Myers, Kalisa G.; Guo, Yumei; Ocampo, Marco A.; Pang, Raina D.; Jakowec, Michael W.; Holschneider, Daniel P.

2013-01-01

Exercise training is widely used for neurorehabilitation of Parkinson’s disease (PD). However, little is known about the functional reorganization of the injured brain after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise in a rat model of dopaminergic deafferentation (bilateral, dorsal striatal 6-hydroxydopamine lesions). One week after training, cerebral perfusion was mapped during treadmill walking or at rest using [14C]-iodoantipyrine autoradiography. Regional cerebral blood flow-related tissue radioactivity (rCBF) was analyzed in three-dimensionally reconstructed brains by statistical parametric mapping. In non-exercised rats, lesions resulted in persistent motor deficits. Compared to sham-lesioned rats, lesioned rats showed altered functional brain activation during walking, including: 1. hypoactivation of the striatum and motor cortex; 2. hyperactivation of non-lesioned areas in the basal ganglia-thalamocortical circuit; 3. functional recruitment of the red nucleus, superior colliculus and somatosensory cortex; 4. hyperactivation of the ventrolateral thalamus, cerebellar vermis and deep nuclei, suggesting recruitment of the cerebellar-thalamocortical circuit; 5. hyperactivation of limbic areas (amygdala, hippocampus, ventral striatum, septum, raphe, insula). These findings show remarkable similarities to imaging findings reported in PD patients. Exercise progressively improved motor deficits in lesioned rats, while increasing activation in dorsal striatum and rostral secondary motor cortex, attenuating a hyperemia of the zona incerta and eliciting a functional reorganization of regions participating in the cerebellar-thalamocortical circuit. Both lesions and exercise increased activation in mesolimbic areas (amygdala, hippocampus, ventral striatum, laterodorsal tegmental n., ventral pallidum), as well as in related paralimbic regions (septum, raphe, insula). Exercise, but not lesioning, resulted in decreases

Microangiographic study of the normal anatomy of the cerebral venous system in rats

International Nuclear Information System (INIS)

Schumacher, M.

1984-01-01

Microangiographic serial cuts were performed in 20 Sprague-Dawley rats for a systematic study of the normal anatomy of the cerebral veins. The draining pathways of the cerebral and cerebellar cortex, basal ganglia, hypothalamus, hippocampus and the midbrain are described and discussed with regard to their different functions. (orig.)

Bilateral, Mirror-imaged, Postero-inferior Cerebellar Artery Aneurysms: Report of a Rare Case

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G R Sharma

2011-06-01

Full Text Available A 60-year-old right-handed lady presented with the features of subarachnoid haemorrhage. The CT angiogram showed a pair of very rare bilateral, mirror-imaged distal postero-inferior cerebellar artery aneurysms. Both aneurysms were clipped via the midline posterior fossa craniectomy under general anaesthesia. The literatures is reviewed on the incidence, presentation, management and outcome of bilateral distal posterior-inferior cerebellar artery aneurysms. Keywords: bilateral mirror image, distal postero-inferior cerebellar artery aneurysms, posterior fossa craniectomy, microsurgical clipping

Biochemical and functional correlates of an increased membrane density of caveolae in hypertrophic rat urinary bladder.

OpenAIRE

Shakirova, Yulia; Swärd, Karl; Uvelius, Bengt; Ekman, Mari

2010-01-01

Organ hypertrophy is often found to be associated with changes in the expression of caveolins and altered density of caveolae in the membrane. A plethora of signalling intermediaries are associated with caveolae and loss of caveolae has profound effects on contractility of the urinary bladder. We hypothesized that smooth muscle hypertrophy caused by bladder outflow obstruction (BOO) might lead to an altered caveola density with consequences for contractile regulation. Rat BOO for 6weeks cause...

Enhancing the Temporal Complexity of Distributed Brain Networks with Patterned Cerebellar Stimulation

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Farzan, Faranak; Pascual-Leone, Alvaro; Schmahmann, Jeremy D.; Halko, Mark

2016-01-01

Growing evidence suggests that sensory, motor, cognitive and affective processes map onto specific, distributed neural networks. Cerebellar subregions are part of these networks, but how the cerebellum is involved in this wide range of brain functions remains poorly understood. It is postulated that the cerebellum contributes a basic role in brain functions, helping to shape the complexity of brain temporal dynamics. We therefore hypothesized that stimulating cerebellar nodes integrated in different networks should have the same impact on the temporal complexity of cortical signals. In healthy humans, we applied intermittent theta burst stimulation (iTBS) to the vermis lobule VII or right lateral cerebellar Crus I/II, subregions that prominently couple to the dorsal-attention/fronto-parietal and default-mode networks, respectively. Cerebellar iTBS increased the complexity of brain signals across multiple time scales in a network-specific manner identified through electroencephalography (EEG). We also demonstrated a region-specific shift in power of cortical oscillations towards higher frequencies consistent with the natural frequencies of targeted cortical areas. Our findings provide a novel mechanism and evidence by which the cerebellum contributes to multiple brain functions: specific cerebellar subregions control the temporal dynamics of the networks they are engaged in. PMID:27009405

Humor, laughter, and the cerebellum: insights from patients with acute cerebellar stroke.

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Frank, B; Andrzejewski, K; Göricke, S; Wondzinski, E; Siebler, M; Wild, B; Timmann, D

2013-12-01

Extent of cerebellar involvement in cognition and emotion is still a topic of ongoing research. In particular, the cerebellar role in humor processing and control of laughter is not well known. A hypermetric dysregulation of affective behavior has been assumed in cerebellar damage. Thus, we aimed at investigating humor comprehension and appreciation as well as the expression of laughter in 21 patients in the acute or subacute state after stroke restricted to the cerebellum, and in the same number of matched healthy control subjects. Patients with acute and subacute cerebellar damage showed preserved comprehension and appreciation of humor using a validated humor test evaluating comprehension, funniness and aversiveness of cartoons ("3WD Humor Test"). Additionally, there was no difference when compared to healthy controls in the number and intensity of facial reactions and laughter while observing jokes, humorous cartoons, or video sketches measured by the Facial Action Coding System. However, as depression scores were significantly increased in patients with cerebellar stroke, a concealing effect of accompanying depression cannot be excluded. Current findings add to descriptions in the literature that cognitive or affective disorders in patients with lesions restricted to the cerebellum, even in the acute state after damage, are frequently mild and might only be present in more sensitive or specific tests.

Isolated rhomboencephalosynapsis – a rare cerebellar anomaly

International Nuclear Information System (INIS)

Paprocka, Justyna; Jamroz, Ewa; Ścieszka, Ewa; Kluczewska, Ewa

2012-01-01

Rhomboencephalosynapsis (RES, RS) is a unique entity usually recognized in infancy based on neuroimaging. Cerebellar fusion and absence of cerebellar vermis is often associated with supratentorial findings. Since now there are about 50 cases described worldwide, with approximately 36 patients diagnosed by MRI. The authors present the first in Poland case of this uncommon malformation and review the literature. The authors describe a 28-month-old-girl with microcephaly and proper psychomotor development. The family history was unrelevant. Based on MRI the congenital malformation of posterior fossa-rhombencephalosynapsis was confirmed Presented patient is a typical example of MRI usefulness especially in patients with RES. RES symptoms are mild and that is why the diagnosis is usually made only in adulthood

Adaptive filters and internal models: multilevel description of cerebellar function.

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Porrill, John; Dean, Paul; Anderson, Sean R

2013-11-01

Cerebellar function is increasingly discussed in terms of engineering schemes for motor control and signal processing that involve internal models. To address the relation between the cerebellum and internal models, we adopt the chip metaphor that has been used to represent the combination of a homogeneous cerebellar cortical microcircuit with individual microzones having unique external connections. This metaphor indicates that identifying the function of a particular cerebellar chip requires knowledge of both the general microcircuit algorithm and the chip's individual connections. Here we use a popular candidate algorithm as embodied in the adaptive filter, which learns to decorrelate its inputs from a reference ('teaching', 'error') signal. This algorithm is computationally powerful enough to be used in a very wide variety of engineering applications. However, the crucial issue is whether the external connectivity required by such applications can be implemented biologically. We argue that some applications appear to be in principle biologically implausible: these include the Smith predictor and Kalman filter (for state estimation), and the feedback-error-learning scheme for adaptive inverse control. However, even for plausible schemes, such as forward models for noise cancellation and novelty-detection, and the recurrent architecture for adaptive inverse control, there is unlikely to be a simple mapping between microzone function and internal model structure. This initial analysis suggests that cerebellar involvement in particular behaviours is therefore unlikely to have a neat classification into categories such as 'forward model'. It is more likely that cerebellar microzones learn a task-specific adaptive-filter operation which combines a number of signal-processing roles. Copyright © 2012 Elsevier Ltd. All rights reserved.

Adams Oliver syndrome: Description of a new phenotype with cerebellar abnormalities in a family

International Nuclear Information System (INIS)

D’Amico, Alessandra; Melis, Daniela; D’Arco, Felice; Di Paolo, Nilde; Carotenuto, Barbara; D’Anna, Gennaro; Russo, Carmela; Boemio, Pasquale; Brunetti, Arturo

2013-01-01

To describe cerebellar abnormalities in a family composed by a father and two affected sibs with Adams Oliver syndrome (AOS) (OMIM 100300). Brain MRI and MR angiography were performed at 1.5T. The siblings presented cerebellar cortex dysplasia characterized by the presence of cysts. Abnormalities of CNS are an unusual manifestation of AOS. To our knowledge, this is the first report of cerebellar cortical dysplasia in a family with AOS

Cerebellar Ataxia from Multiple Potential Causes: Hypothyroidism, Hashimoto's Thyroiditis, Thalamic Stimulation, and Essential Tremor

OpenAIRE

Shneyder, Natalya; Lyons, Mark K.; Driver-dunckley, Erika; Evidente, Virgilio Gerald H.

2012-01-01

Background: Both hypothyroidism and Hashimoto's thyroiditis (HT) can rarely be associated with cerebellar ataxia. Severe essential tremor (ET) as well as bilateral thalamic deep brain stimulation (DBS) may lead to subtle cerebellar signs. Case Report: We report a 74-year-old male with hypothyroidism and a 20-year history of ET who developed cerebellar ataxia after bilateral thalamic DBS. Extensive workup revealed elevated thyroid stimulating hormone and thyroperoxidase antibody titers c...

Biochemical characterization of domain-specific glycoproteins of the rat hepatocyte plasma membrane

International Nuclear Information System (INIS)

Bartles, J.R.; Braiterman, L.T.; Hubbard, A.L.

1985-01-01

Seven integral proteins (CE 9, HA 21, HA 116, HA 16, HA 4, HA 201, and HA 301) were isolated from rat hepatocyte plasma membranes by immunoaffinity chromatography on monoclonal antibody-Sepharose. Six of the proteins (all but HA 16) exhibit domain-specific localizations (either bile canalicular or sinusoidal/lateral) about the hepatocyte surface. The authors identified three of these protein antigens as leucine aminopeptidase (HA 201), dipeptidyl peptidase IV (HA 301), and the asialoglycoprotein receptor (HA 116). They also developed 125 I-lectin blotting procedures that, when used in conjunction with chemical and glycosidase treatments, permitted a comparison of the types of oligosaccharides present on the seven proteins. All seven are sialoglycoproteins, based upon the effects of prior neuraminidase and periodate-aniline-cyanoborohydride treatments of blots on labeling by 125 I-wheat germ agglutinin. Depending upon the protein, they estimated the presence of 2-26 N-linked oligosaccharides/polypeptide chain from the Mr reductions accompanying chemical or enzymatic deglycosylation. Three of these mature plasma membrane proteins (HA 21, HA 116, and HA 4) have both high mannose-type and complex-type oligosaccharides on every copy of their polypeptide chains

Protective Effect of Edaravone in Primary Cerebellar Granule Neurons against Iodoacetic Acid-Induced Cell Injury

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Xinhua Zhou

2015-01-01

Full Text Available Edaravone (EDA is clinically used for treatment of acute ischemic stroke in Japan and China due to its potent free radical-scavenging effect. However, it has yet to be determined whether EDA can attenuate iodoacetic acid- (IAA- induced neuronal death in vitro. In the present study, we investigated the effect of EDA on damage of IAA-induced primary cerebellar granule neurons (CGNs and its possible underlying mechanisms. We found that EDA attenuated IAA-induced cell injury in CGNs. Moreover, EDA significantly reduced intracellular reactive oxidative stress production, loss of mitochondrial membrane potential, and caspase 3 activity induced by IAA. Taken together, EDA protected CGNs against IAA-induced neuronal damage, which may be attributed to its antiapoptotic and antioxidative activities.

Sporadic Creutzfeldt–Jakob disease with cerebellar ataxia at onset in the UK

Science.gov (United States)

Cooper, S A; Murray, K L; Heath, C A; Will, R G; Knight, R S G

2006-01-01

Objective To determine the frequency, in the UK, of sporadic Creutzfeldt–Jakob Disease (sCJD) with a cerebellar ataxic onset, and to describe the clinical features of the syndrome. Methods A retrospective review of autopsy‐proved cases of sCJD cases in the UK, 1990–2005, identifying those presenting with cerebellar features without early cognitive decline. Results 29 of 618 (5%) patients with sCJD had an isolated cerebellar onset. Mean illness duration was 9 months. Subsequently, 21 (72%) developed myoclonus and 23 (79%) developed pyramidal features. Magnetic resonance imaging showed high signal in the basal ganglia in 11 of 14 (79%) patients. 7 of 15 (47%) patients were valine homozygotic at prion protein gene (PRNP)‐129. Only 8 (28%) cases were referred to the surveillance unit after death. Conclusion A better definition of sCJD presenting with an isolated cerebellar syndrome might improve future case recognition and contribute to the determination of its cause. PMID:16835290

Transient cerebellopontine demyelinisation revealed by MRI in acute cerebellar ataxia

International Nuclear Information System (INIS)

Aufricht, C.A.; Tenner, W.; Rosenmayr, F.; Stiglbauer, R.

1990-01-01

An eight year old boy was admitted to our ward with a history of abrupt onset of rapidly progressive gait disorder, nausea, vertigo and vomiting. The clinical as well as the laboratory findings suggested the diagnosis of acute cerebellar ataxia. Magnetic resonance imaging (MRI), however, showed marked demyelinisation in the cerebellar region and visual evoked potentials were pathologic. After immunosuppression the patient promptly improved clinically and the lesions depicted by MRI disappeared almost completely. (orig.)

Radiation-induced cerebellar chondrosarcoma. Case report

International Nuclear Information System (INIS)

Bernstein, M.; Perrin, R.G.; Platts, M.E.; Simpson, W.J.

1984-01-01

The authors report a case of chondrosarcoma arising in the cerebellum 16 years after treatment of a cerebellar malignant astrocytoma by subtotal resection and irradiation. It is thought that the chondrosarcoma arising within the intracranial cavity was a probable consequence of previous ionizing radiation

Cerebellar Plasticity in Health and Disease

NARCIS (Netherlands)

M.P.H. Coesmans (Michiel)

2004-01-01

textabstractThe cerebellum helps fine-tuning movements by evaluating disparities between intention and action, in order to adjust the execution of movements ‘online’, and to keep movements calibrated in the long term. The cerebellar capacity to store information, which provides the ‘memory’ needed

In vivo turnover of the basement membrane and other heparan sulfate proteoglycans of rat glomerulus

DEFF Research Database (Denmark)

Beavan, L A; Davies, M; Couchman, J R

1989-01-01

The metabolic turnover of rat glomerular proteoglycans in vivo was investigated. Newly synthesized proteoglycans were labeled during a 7-h period after injecting sodium [35S]sulfate intraperitoneally. At the end of the labeling period a chase dose of sodium sulfate was given. Subsequently......-propanesulfonate-4 M guanidine hydrochloride, a procedure which solubilized greater than 95% of the 35S-labeled macromolecules. Of these 11-13% was immunoprecipitated by an antiserum against heparan sulfate proteoglycan which, in immunolocalization experiments, showed specificity for staining the basement membrane...

Membrane-associated IL 1-like activity on rat dendritic cells

International Nuclear Information System (INIS)

Nagelkerken, L.M.; van Breda Vriesman, P.J.C.

1986-01-01

The secretion of interleukin 1 (IL 1) by rat dendritic cells (DC) was studied in relation to their ability to induce the production interleukin 2 (IL 2 ) and to induce IL 2 responsiveness. IL 1 (or IL 1-like activity) was measured by its capacity to enhance IL 2 production by EL4 cells. In contrast to peritoneal exudate cells (PEC) or splenic adherent cells, DC from thoracic duct lymph (TD-DC) or from spleen did not secrete detectable amounts of IL 1 on stimulation with LPS/Silica. However, TD-DC and splenic DC were able to enhance IL 2 production by EL4 cells directly, and were only two times less effective than PEC. By preventing cell-to-cell contact between stimulator cells and EL4 cells, it was demonstrated that most of the IL 2-inducing activity of TD-DC and PEC was associated with the cell membrane. Treatment with 1% paraformaldehyde (PFA) to abolish metabolic activity resulted in a 50% decrease (or inactivation) of IL 2-inducing activity of TD-DC in the EL4 assay. Moreover, UVB-irradiation (300 mJ/cm 2 ) of TD-DC, which has been described to inhibit the release of IL 1 by macrophages, caused a 70% decrease in IL 2-inducing activity. These results suggest that membrane-associated structures, that are identical to or mimic Il 1, are involved in the activation of T cells by DC

Uptake of oleate by isolated rat adipocytes is mediated by a 40-kDa plasma membrane fatty acid binding protein closely related to that in liver and gut

International Nuclear Information System (INIS)

Schwieterman, W.; Sorrentino, D.; Potter, B.J.; Rand, J.; Kiang, C.L.; Stump, D.; Berk, P.D.

1988-01-01

A portion of the hepatocellular uptake of nonesterified long-chain fatty acids is mediated by a specific 40-kDa plasma membrane fatty acid binding protein, which has also been isolated from the gut. To investigate whether a similar transport process exists in other tissues with high transmembrane fatty acid fluxes, initial rates (V/sub O/) of [ 3 H]-oleate uptake into isolated rat adipocytes were studied as a function of the concentration of unbound [ 3 H]oleate in the medium. V/sub O/ reached a maximum as the concentration of unbound oleate was increased and was significantly inhibited both by phloretin and by prior incubation of the cells with Pronase. A rabbit antibody to the rat liver plasma membrane fatty acid binding protein inhibited adipocyte fatty acid uptake by up to 63% in dose-dependent fashion. Inhibition was noncompetitive; at an immunoglobulin concentration of 250 μg/ml V/sub max/ was reduced from 2480 /plus minus/ 160 to 1870 /plus minus/ 80 pmol/min per 5 /times/ 10 4 adipocytes, with no change in K/sub m/. A basic kDa adipocyte plasma membrane fatty acid binding protein, isolated from crude adipocyte plasma membrane fractions, reacted strongly in both agar gel diffusion and electrophoretic blots with the antibody raised against the corresponding hepatic plasma membrane protein. These data indicate that the uptake of oleate by rat adipocytes is mediated by a 40-kDa plasma membrane fatty acid binding protein closely related to that in liver and gut

Continuous theta burst stimulation (cTBS on left cerebellar hemisphere affects mental rotation tasks during music listening.

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Silvia Picazio

Full Text Available Converging evidence suggests an association between spatial and music domains. A cerebellar role in music-related information processing as well as in spatial-temporal tasks has been documented. Here, we investigated the cerebellar role in the association between spatial and musical domains, by testing performances in embodied (EMR or abstract (AMR mental rotation tasks of subjects listening Mozart Sonata K.448, which is reported to improve spatial-temporal reasoning, in the presence or in the absence of continuous theta burst stimulation (cTBS of the left cerebellar hemisphere. In the absence of cerebellar cTBS, music listening did not influence either MR task, thus not revealing a "Mozart Effect". Cerebellar cTBS applied before musical listening made subjects faster (P = 0.005 and less accurate (P = 0.005 in performing the EMR but not the AMR task. Thus, cerebellar inhibition by TBS unmasked the effect of musical listening on motor imagery. These data support a coupling between music listening and sensory-motor integration in cerebellar networks for embodied representations.

Stars and Stripes in the Cerebellar Cortex: A Voltage Sensitive Dye Study

Science.gov (United States)

Rokni, Dan; Llinas, Rodolfo; Yarom, Yosef

2007-01-01

The lattice-like structure of the cerebellar cortex and its anatomical organization in two perpendicular axes provided the foundations for many theories of cerebellar function. However, the functional organization does not always match the anatomical organization. Thus direct measurement of the functional organization is central to our understanding of cerebellar processing. Here we use voltage sensitive dye imaging in the isolated cerebellar preparation to characterize the spatio-temporal organization of the climbing and mossy fiber (MF) inputs to the cerebellar cortex. Spatial and temporal parameters were used to develop reliable criteria to distinguish climbing fiber (CF) responses from MF responses. CF activation excited postsynaptic neurons along a parasagittal cortical band. These responses were composed of slow (∼25 ms), monophasic depolarizing signals. Neither the duration nor the spatial distribution of CF responses were affected by inhibition. Activation of MF generated responses that were organized in radial patches, and were composed of a fast (∼5 ms) depolarizing phase followed by a prolonged (∼100 ms) negative wave. Application of a GABAA blocker eliminated the hyperpolarizing phase and prolonged the depolarizing phase, but did not affect the spatial distribution of the response, thus suggesting that it is not the inhibitory system that is responsible for the inability of the MF input to generate beams of activity that propagate along the parallel fiber system. PMID:18958242

Stars and stripes in the cerebellar cortex: a voltage sensitive dye study

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Dan Rokni

2007-08-01

Full Text Available The lattice-like structure of the cerebellar cortex and its anatomical organization in two perpendicular axes provided the foundations for many theories of cerebellar function. However, the functional organization does not always match the anatomical organization. Thus direct measurement of the functional organization is central to our understanding of cerebellar processing. Here we use voltage sensitive dye imaging in the isolated cerebellar preparation to characterize the spatio-temporal organization of the climbing and mossy fiber (MF inputs to the cerebellar cortex. Spatial and temporal parameters were used to develop reliable criteria to distinguish climbing fiber (CF responses from MF responses. CF activation excited postsynaptic neurons along a parasagittal cortical band. These responses were composed of slow (~25 ms, monophasic depolarizing signals. Neither the duration nor the spatial distribution of CF responses were affected by inhibition. Activation of MF generated responses that were organized in radial patches, and were composed of a fast (~5 ms depolarizing phase followed by a prolonged (~100 ms negative wave. Application of a GABAA blocker eliminated the hyperpolarizing phase and prolonged the depolarizing phase, but did not affect the spatial distribution of the response, thus suggesting that it is not the inhibitory system that is responsible for the inability of the MF input to generate beams of activity that propagate along the parallel fiber system.

Adaptive robotic control driven by a versatile spiking cerebellar network.

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Claudia Casellato

Full Text Available The cerebellum is involved in a large number of different neural processes, especially in associative learning and in fine motor control. To develop a comprehensive theory of sensorimotor learning and control, it is crucial to determine the neural basis of coding and plasticity embedded into the cerebellar neural circuit and how they are translated into behavioral outcomes in learning paradigms. Learning has to be inferred from the interaction of an embodied system with its real environment, and the same cerebellar principles derived from cell physiology have to be able to drive a variety of tasks of different nature, calling for complex timing and movement patterns. We have coupled a realistic cerebellar spiking neural network (SNN with a real robot and challenged it in multiple diverse sensorimotor tasks. Encoding and decoding strategies based on neuronal firing rates were applied. Adaptive motor control protocols with acquisition and extinction phases have been designed and tested, including an associative Pavlovian task (Eye blinking classical conditioning, a vestibulo-ocular task and a perturbed arm reaching task operating in closed-loop. The SNN processed in real-time mossy fiber inputs as arbitrary contextual signals, irrespective of whether they conveyed a tone, a vestibular stimulus or the position of a limb. A bidirectional long-term plasticity rule implemented at parallel fibers-Purkinje cell synapses modulated the output activity in the deep cerebellar nuclei. In all tasks, the neurorobot learned to adjust timing and gain of the motor responses by tuning its output discharge. It succeeded in reproducing how human biological systems acquire, extinguish and express knowledge of a noisy and changing world. By varying stimuli and perturbations patterns, real-time control robustness and generalizability were validated. The implicit spiking dynamics of the cerebellar model fulfill timing, prediction and learning functions.

Adaptive robotic control driven by a versatile spiking cerebellar network.

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Casellato, Claudia; Antonietti, Alberto; Garrido, Jesus A; Carrillo, Richard R; Luque, Niceto R; Ros, Eduardo; Pedrocchi, Alessandra; D'Angelo, Egidio

2014-01-01

The cerebellum is involved in a large number of different neural processes, especially in associative learning and in fine motor control. To develop a comprehensive theory of sensorimotor learning and control, it is crucial to determine the neural basis of coding and plasticity embedded into the cerebellar neural circuit and how they are translated into behavioral outcomes in learning paradigms. Learning has to be inferred from the interaction of an embodied system with its real environment, and the same cerebellar principles derived from cell physiology have to be able to drive a variety of tasks of different nature, calling for complex timing and movement patterns. We have coupled a realistic cerebellar spiking neural network (SNN) with a real robot and challenged it in multiple diverse sensorimotor tasks. Encoding and decoding strategies based on neuronal firing rates were applied. Adaptive motor control protocols with acquisition and extinction phases have been designed and tested, including an associative Pavlovian task (Eye blinking classical conditioning), a vestibulo-ocular task and a perturbed arm reaching task operating in closed-loop. The SNN processed in real-time mossy fiber inputs as arbitrary contextual signals, irrespective of whether they conveyed a tone, a vestibular stimulus or the position of a limb. A bidirectional long-term plasticity rule implemented at parallel fibers-Purkinje cell synapses modulated the output activity in the deep cerebellar nuclei. In all tasks, the neurorobot learned to adjust timing and gain of the motor responses by tuning its output discharge. It succeeded in reproducing how human biological systems acquire, extinguish and express knowledge of a noisy and changing world. By varying stimuli and perturbations patterns, real-time control robustness and generalizability were validated. The implicit spiking dynamics of the cerebellar model fulfill timing, prediction and learning functions.

Properties of the luminal membrane of isolated perfused rat pancreatic ducts. Effect of cyclic AMP and blockers of chloride transport

DEFF Research Database (Denmark)

Novak, I; Greger, R

1988-01-01

- and interlobular ducts of rat pancreas was used. Responses of the epithelium to inhibitors and agonists were monitored by electrophysiological techniques. Addition of HCO-3/CO2 to the bath side of nonstimulated ducts depolarized the PD across the basolateral membrane (PDbl) by about 9 mV, as also observed...

Ataxia-telangiectasia: the pattern of cerebellar atrophy on MRI

International Nuclear Information System (INIS)

Tavani, F.; Zimmerman, R.A.; Gatti, R.; Bingham, P.; Berry, G.T.; Sullivan, K.

2003-01-01

We describe MRI of the brain in 19 patients with ataxia-telangiectasia (AT) and correlate the appearances with the degree of neurologic deficit. We examined 10 male and nine female patients; 17 were aged between 2 and 12 years (mean 8 years) but a woman and her brother were 35 and 38 years old, and had a variant of AT. Ataxia was the first recognized sign of the disease in every patient. We detected the following patterns of cerebellar atrophy: in the youngest patient, aged 2 years, the study was normal; in the five next youngest patients 3-7 years of age, the lateral cerebellum and superior vermis showed the earliest changes of atrophy; and all but one of the other patients had moderate to marked diffuse atrophy of vermis and cerebellar hemispheres. There were 12 patients aged 9 years and above; one, who was normal, was 9 years old. The five patients who at the time of examination were unable to walk all had diffuse atrophy involving both vermis and cerebellar hemispheres. (orig.)

The genesis of cerebellar GABAergic neurons: fate potential and specification mechanisms

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Ketty eLeto

2012-02-01

Full Text Available The variety of neuronal phenotypes that populate the cerebellum derives from progenitors that proliferate in two germinal neuroepithelia: the ventricular zone generates GABAergic neurons, whereas the rhombic lip is the origin of glutamatergic types. Progenitors of the ventricular zone produce GABAergic projection neurons (Purkinje cells and nucleo-olivary neurons at the onset of cerebellar neurogenesis. Later on, however, these progenitors migrate into the prospective white matter, where they continue to divide up to postnatal development and generate different categories of inhibitory interneurons, according to precise spatio-temporal schedules. Projection neurons derive from discrete progenitor pools located in distinct microdomains of the ventricular zone, whereas interneurons originate from a single population of precursors, distinguished by the expression of the transcription factor Pax-2. Heterotopic/heterochronic transplantation experiments indicate that interneuron progenitors maintain full developmental potentialities up to the end of cerebellar development and acquire mature phenotypes under the influence of environmental cues present in the prospective white matter. Furthermore, the final fate choice occurs in postmitotic cells, rather than dividing progenitors. Extracerebellar cells grafted to the postnatal cerebellum are not responsive to local neurogenic cues and fail to adopt clear cerebellar identities. On the other hand, cerebellar cells grafted to extracerebellar regions retain typical phenotypes of cerebellar GABAergic interneurons, but acquire specific traits under the influence of local cues. These findings indicate that interneuron progenitors are multipotent and sensitive to spatio-temporally patterned environmental signals that regulate the genesis of different categories of interneurons, in precise quantities and at defined times and places.

The Cerebellar Deficit Hypothesis and Dyslexic Tendencies in a Non-Clinical Sample

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Brookes, Rebecca L.; Stirling, John

2005-01-01

In order to assess the relationship between cerebellar deficits and dyslexic tendencies in a non-clinical sample, 27 primary school children aged 8-9 completed a cerebellar soft signs battery and were additionally assessed for reading age, sequential memory, picture arrangement and knowledge of common sequences. An average measure of the soft…

The protective effect of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes

OpenAIRE

Mohamed, Jamaludin; Shing, Saw Wuan; Idris, Muhd Hanis Md; Budin, Siti Balkis; Zainalabidin, Satirah

2013-01-01

OBJECTIVES: The aim of this study was to investigate the protective effects of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell (RBC) membrane oxidative stress in rats with streptozotocin-induced diabetes. METHODS: Forty male Sprague-Dawley rats weighing 230-250 g were randomly divided into four groups (n = 10 rats each): control group (N), roselle-treated control group, diabetic group, and roselle-treated diabetic group. Roselle was administered by force-f...

Basement membrane-specific chondroitin sulfate proteoglycan is abnormally associated with the glomerular capillary basement membrane of diabetic rats

DEFF Research Database (Denmark)

McCarthy, K J; Abrahamson, D R; Bynum, K R

1994-01-01

exception being the normal glomerular capillary basement membrane (GBM), where it is absent. In the present study of mature kidneys we examined the distribution of BM-CSPG in streptozocin-induced diabetes mellitus in rats. We found BM-CSPG atypically associated with the GBM of diabetic animals as early as 1...... month after induction of diabetes mellitus. Immunoelectron microscopy (IEM) of affected capillary loops showed BM-CSPG present in the subendothelial matrix in areas of GBM thickening and absent in areas where the GBM appears to be of normal thickness. Moreover, the association of BM-CSPG with regions...... of the pericapillary GBM affects the morphology of the capillary endothelial cells within these areas, directly displacing the cell body from the GBM proper and causing loss of fenestrae. These new data on BM-CSPG distribution reflect abnormal glomerular extracellular matrix protein biosynthesis/turnover in diabetes...

Differential effects of benzodiazepines on phospholipid methylation in hippocampus and cerebellum of rats

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Tacconi, M.T.; Salmona, M.

1988-01-01

To elucidate the relationship between the occupancy of BDZ binding sites and phospholipid methylation in brain, the authors examined phosphatidylethanolamine-N-methyltransferase (PEMT) activity in synaptosomes of rat hippocampi and cerebella in the presence of BDZ ligands with different modes of action. We found that Ro 5-4864, a specific ligand for peripheral type receptors, increased PL methylation in hippocampal and cerebellar synaptosomes. This effect was directly related to receptor occupancy, since the specific antagonist PK11195 inhibited the rise in PEMT activity induced by Ro 5-4864. Clonazepam, on the other hand, tended to reduce PL production in cerebellum and hippocampus except for hiccocampal (/sup 3/H)-phosphatidyl-N-monomethylethanolamine which was elevated by 40 to 70% at doses ranging from 10/sup -9/ to 10/sup -6/M. When equimolar concentrations of the antagonist Ro 15-1788 were given in association the clonazepam-induced phosphatidyl-N-monomethylethanolamine increase was reduced by 70%. These data support the involvement of structural and functional membrane alterations in the action of BDZ. 20 references, 2 figures, 2 tables.

Epidemiology of Cerebellar Ataxia on the Etiological Basis: A Cross Sectional Study

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Simindokht Hosseini Seyede

2009-12-01

Full Text Available Cerebellar ataxias are a heterogenous group of disorders, clinically and etiologically, that result in considerable health burden. Finding out about the various etiologies, and their relative prevalences in the population suffering from cerebellar ataxia helps the clinician to perform a better management, in treatment process. This is a cross sectional study designed to estimate the relative prevalence of each etiologic factor. One-hundred and thirty-five patients ,in the range of 6 to 73 years from march 1993 to march1999, were classified in different groups on the basis of etiological findings. Relative prevalence of each of the etiological factors , common accompanying disorders besides ataxia in the patients,CT and MRI changes,and CSF alterations are studied and recorded. A widely spread age group, and the extended number of the cases under study, are the advantages of the current study over the previously reported case series. Among the etiologic groups, multiple sclerosis, cerebrovascular accidents and hereditary cerebellar ataxia, were the most common etiologic factors associated with cerebellar ataxia respectively.

Structure–function relationships in the developing cerebellum: evidence from early-life cerebellar injury and neurodevelopmental disorders

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Stoodley, Catherine J.; Limperopoulos, Catherine

2016-01-01

SUMMARY The increasing appreciation of the role of the cerebellum in motor and non-motor functions is crucial to understanding the outcomes of acquired cerebellar injury and developmental lesions in high-risk fetal and neonatal populations, children with cerebellar damage (e.g. posterior fossa tumors), and neurodevelopmental disorders (e.g. autism). We review available data regarding the relationship between the topography of cerebellar injury or abnormality and functional outcomes. We report emerging structure–function relationships with specific symptoms: cerebellar regions that interconnect with sensorimotor cortices are associated with motor impairments when damaged; disruption to posterolateral cerebellar regions that form circuits with association cortices impact long-term cognitive outcomes; and midline posterior vermal damage is associated with behavioral dysregulation and an autism-like phenotype. We also explore the impact of age and the potential role for critical periods on cerebellar structure and child function. These findings suggest that the cerebellum plays a critical role in motor, cognitive, and social–behavioral development, possibly via modulatory effects on the developing cerebral cortex. PMID:27184461

Surgical Treatment of A Dissecting Aneurysm of the Superior Cerebellar Artery: Case Report

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Stefanescu Florin

2014-10-01

Full Text Available Dissecting aneurysm located in the peripheral region of the superior cerebellar artery is very rare. There is little experience regarding their surgical or endovascular treatment. We present the case of a peripheral dissecting superior cerebellar artery aneurysm treated by surgical clipping.

Anti-glomerular basement membrane autoantibodies in the Brown Norway rat: detection by a solid-phase radioimmunoassay

International Nuclear Information System (INIS)

Bowman, C.; Peters, D.K.; Lockwood, C.M.

1983-01-01

A solid-phase radioimmunoassay (RIA) is described for the detection of IgG autoantibodies to glomerular basement membrane (GBM) induced in the Brown Norway rat by mercuric chloride. The assay involves the adsorption of a collagenase digest of GBM to plastic microtitre plates and detection of bound antibody with affinity purified radiolabelled rabbit anti-rat IgG. Comparison with existing immunofluorescence methods for detection of anti-GBM antibody showed that the solid-phase RIA is highly sensitive, allowing detection of antibody in solutions with as low as 0.5 ng protein/ml. The assay is suitable for detection of anti-GBM antibody both in serum and in eluates from nephritic kidneys. The assay proved to be specific in competitive studies of inhibition brought about by GBM, keyhole limpet antigen and ovalbumin. This solid-phase RIA is reproducible, robust and easy to perform. (Auth.)

Modality Specific Cerebro-Cerebellar Activations in Verbal Working Memory: An fMRI Study

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Matthew P. Kirschen

2010-01-01

Full Text Available Verbal working memory (VWM engages frontal and temporal/parietal circuits subserving the phonological loop, as well as, superior and inferior cerebellar regions which have projections from these neocortical areas. Different cerebro-cerebellar circuits may be engaged for integrating aurally- and visually-presented information for VWM. The present fMRI study investigated load (2, 4, or 6 letters and modality (auditory and visual dependent cerebro-cerebellar VWM activation using a Sternberg task. FMRI revealed modality-independent activations in left frontal (BA 6/9/44, insular, cingulate (BA 32, and bilateral inferior parietal/supramarginal (BA 40 regions, as well as in bilateral superior (HVI and right inferior (HVIII cerebellar regions. Visual presentation evoked prominent activations in right superior (HVI/CrusI cerebellum, bilateral occipital (BA19 and left parietal (BA7/40 cortex while auditory presentation showed robust activations predominately in bilateral temporal regions (BA21/22. In the cerebellum, we noted a visual to auditory emphasis of function progressing from superior to inferior and from lateral to medial regions. These results extend our previous findings of fMRI activation in cerebro-cerebellar networks during VWM, and demonstrate both modality dependent commonalities and differences in activations with increasing memory load.

Modality Specific Cerebro-Cerebellar Activations in Verbal Working Memory: An fMRI Study

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Kirschen, Matthew P.; Chen, S. H. Annabel; Desmond, John E.

2010-01-01

Verbal working memory (VWM) engages frontal and temporal/parietal circuits subserving the phonological loop, as well as, superior and inferior cerebellar regions which have projections from these neocortical areas. Different cerebro-cerebellar circuits may be engaged for integrating aurally- and visually-presented information for VWM. The present fMRI study investigated load (2, 4, or 6 letters) and modality (auditory and visual) dependent cerebro-cerebellar VWM activation using a Sternberg task. FMRI revealed modality-independent activations in left frontal (BA 6/9/44), insular, cingulate (BA 32), and bilateral inferior parietal/supramarginal (BA 40) regions, as well as in bilateral superior (HVI) and right inferior (HVIII) cerebellar regions. Visual presentation evoked prominent activations in right superior (HVI/CrusI) cerebellum, bilateral occipital (BA19) and left parietal (BA7/40) cortex while auditory presentation showed robust activations predominately in bilateral temporal regions (BA21/22). In the cerebellum, we noted a visual to auditory emphasis of function progressing from superior to inferior and from lateral to medial regions. These results extend our previous findings of fMRI activation in cerebro-cerebellar networks during VWM, and demonstrate both modality dependent commonalities and differences in activations with increasing memory load. PMID:20714061

Activity-Dependent Plasticity of Spike Pauses in Cerebellar Purkinje Cells

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Giorgio Grasselli

2016-03-01

Full Text Available The plasticity of intrinsic excitability has been described in several types of neurons, but the significance of non-synaptic mechanisms in brain plasticity and learning remains elusive. Cerebellar Purkinje cells are inhibitory neurons that spontaneously fire action potentials at high frequencies and regulate activity in their target cells in the cerebellar nuclei by generating a characteristic spike burst-pause sequence upon synaptic activation. Using patch-clamp recordings from mouse Purkinje cells, we find that depolarization-triggered intrinsic plasticity enhances spike firing and shortens the duration of spike pauses. Pause plasticity is absent from mice lacking SK2-type potassium channels (SK2−/− mice and in occlusion experiments using the SK channel blocker apamin, while apamin wash-in mimics pause reduction. Our findings demonstrate that spike pauses can be regulated through an activity-dependent, exclusively non-synaptic, SK2 channel-dependent mechanism and suggest that pause plasticity—by altering the Purkinje cell output—may be crucial to cerebellar information storage and learning.

Electrophysiological mapping of novel prefrontal - cerebellar pathways

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Thomas C Watson

2009-08-01

Full Text Available Whilst the cerebellum is predominantly considered a sensorimotor control structure, accumulating evidence suggests that it may also subserve non motor functions during cognition. However, this possibility is not universally accepted, not least because the nature and pattern of links between higher cortical structures and the cerebellum are poorly characterized. We have therefore used in vivo electrophysiological methods in anaesthetized rats to directly investigate connectivity between the medial prefrontal cortex (prelimbic subdivision, PrL and the cerebellum. Stimulation of deep layers of PrL evoked distinct field potentials in the cerebellar cortex with a mean latency to peak of approximately 35ms. These responses showed a well-defined topography, and were maximal in lobule VII of the contralateral vermis (a known oculomotor centre; they were not attenuated by local anesthesia of the overlying M2 motor cortex, though M2 stimulation did evoke field potentials in lobule VII with a shorter latency. Single-unit recordings showed that prelimbic cortical stimulation elicits complex spikes in lobule VII Purkinje cells, indicating transmission via a previously undescribed cerebro-olivocerebellar pathway. Our results therefore establish a physiological basis for communication between PrL and the cerebellum. The role(s of this pathway remain to be resolved, but presumably relate to control of eye movements and/or distributed networks associated with integrated prefrontal cortical functions.

Morphological Constraints on Cerebellar Granule Cell Combinatorial Diversity.

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Gilmer, Jesse I; Person, Abigail L

2017-12-13

Combinatorial expansion by the cerebellar granule cell layer (GCL) is fundamental to theories of cerebellar contributions to motor control and learning. Granule cells (GrCs) sample approximately four mossy fiber inputs and are thought to form a combinatorial code useful for pattern separation and learning. We constructed a spatially realistic model of the cerebellar GCL and examined how GCL architecture contributes to GrC combinatorial diversity. We found that GrC combinatorial diversity saturates quickly as mossy fiber input diversity increases, and that this saturation is in part a consequence of short dendrites, which limit access to diverse inputs and favor dense sampling of local inputs. This local sampling also produced GrCs that were combinatorially redundant, even when input diversity was extremely high. In addition, we found that mossy fiber clustering, which is a common anatomical pattern, also led to increased redundancy of GrC input combinations. We related this redundancy to hypothesized roles of temporal expansion of GrC information encoding in service of learned timing, and we show that GCL architecture produces GrC populations that support both temporal and combinatorial expansion. Finally, we used novel anatomical measurements from mice of either sex to inform modeling of sparse and filopodia-bearing mossy fibers, finding that these circuit features uniquely contribute to enhancing GrC diversification and redundancy. Our results complement information theoretic studies of granule layer structure and provide insight into the contributions of granule layer anatomical features to afferent mixing. SIGNIFICANCE STATEMENT Cerebellar granule cells are among the simplest neurons, with tiny somata and, on average, just four dendrites. These characteristics, along with their dense organization, inspired influential theoretical work on the granule cell layer as a combinatorial expander, where each granule cell represents a unique combination of inputs

Cerebellar infarct patterns: The SMART-Medea study

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Laurens J.L. De Cocker, MD

2015-01-01

Conclusions: Small cerebellar infarcts proved to be much more common than larger infarcts, and preferentially involved the cortex. Small cortical infarcts predominantly involved the posterior lobes, showed sparing of subcortical white matter and occurred in characteristic topographic patterns.

Polyethylenimine-mediated impairment of mitochondrial membrane potential, respiration and membrane integrity

DEFF Research Database (Denmark)

Larsen, Anna Karina; Malinska, Dominika; Koszela-Piotrowska, Izabela

2012-01-01

The 25 kDa branched polyethylenimine (PEI) is a highly efficient synthetic polycation used in transfection protocols, but also triggers mitochondrial-mediated apoptotic cell death processes where the mechanistic issues are poorly understood. We now demonstrate that PEI in a concentration- and time......-dependent manner can affect functions (membrane potential, swelling and respiration) and ultrastructural integrity of freshly isolated rat liver mitochondria. The threshold concentration for detection of PEI-mediated impairment of rat liver mitochondrial functions is 3 µg/mL, however, lower PEI levels still exert...... some effects on mitochondrial morphology and respiration, and these may be related to the inherent membrane perturbing properties of this polycation. The PEI-mediated mitochondrial swelling phase is biphasic, with a fast decaying initial period (most prominent from 4 µg/mL PEI) followed by a slower...

Zinc oxide nanoparticles decrease the expression and activity of plasma membrane calcium ATPase, disrupt the intracellular calcium homeostasis in rat retinal ganglion cells.

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Guo, Dadong; Bi, Hongsheng; Wang, Daoguang; Wu, Qiuxin

2013-08-01

Zinc oxide nanoparticle is one of the most important materials with diverse applications. However, it has been reported that zinc oxide nanoparticles are toxic to organisms, and that oxidative stress is often hypothesized to be an important factor in cytotoxicity mediated by zinc oxide nanoparticles. Nevertheless, the mechanism of toxicity of zinc oxide nanoparticles has not been completely understood. In this study, we investigated the cytotoxic effect of zinc oxide nanoparticles and the possible molecular mechanism involved in calcium homeostasis mediated by plasma membrane calcium ATPase in rat retinal ganglion cells. Real-time cell electronic sensing assay showed that zinc oxide nanoparticles could exert cytotoxic effect on rat retinal ganglion cells in a concentration-dependent manner; flow cytometric analysis indicated that zinc oxide nanoparticles could lead to cell damage by inducing the overproduction of reactive oxygen species. Furthermore, zinc oxide nanoparticles could also apparently decrease the expression level and their activity of plasma membrane calcium ATPase, which finally disrupt the intracellular calcium homeostasis and result in cell death. Taken together, zinc oxide nanoparticles could apparently decrease the plasma membrane calcium ATPase expression, inhibit their activity, cause the elevated intracellular calcium ion level and disrupt the intracellular calcium homeostasis. Further, the disrupted calcium homeostasis will trigger mitochondrial dysfunction, generate excessive reactive oxygen species, and finally initiate cell death. Thus, the disrupted calcium homeostasis is involved in the zinc oxide nanoparticle-induced rat retinal ganglion cell death. Copyright © 2013 Elsevier Ltd. All rights reserved.

Identification of the glucose transporter in mammalian cell membranes using an 125(I)-forskolin photoaffinity label

International Nuclear Information System (INIS)

Ruoho, A.; Wadzinski, B.; Shanahan, M.

1987-01-01

The glucose transporter has been identified in a variety of mammlian cell membranes using a carrier-free photoactivatable radioiodinated derivative of forskolin, 3-iodo-4-azidophenethylamido-7-0-succinyldeacetyl-forskolin, [I-125]IAPS-Fsk, at 1-10 nM. The membranes which have been photolabeled with [I-125]IAPS-Fsk are: rat cardiac sarcolemmal membranes, rat cortex and cerebellum synaptic membranes, human placental membranes, and wild type S49 lymphoma cell membranes. The glucose transporter in rat cardiac sarcolemmal membranes and rat cortex and cerebellum synaptic membranes was determined to be 45 kDa by SDS-PAGE. Photolysis of human placental membranes and S49 lymphoma membranes with [I-125]IAPS-Fsk followed by SDS-PAGE indicated specific derivatization of a broad band (45-55 kDa) in placental membranes and a narrower band (45 kDa) in the S49 lymphoma membranes. Digestion of the [I-125]IPAS-Fsk labelled placental and S49 lymphoma membranes with endo-B-galactosidase showed a reduction in the apparent molecular weight of the radiolabelled band to 40 kDa. Trypsinization of labelled placental and lymphoma membranes produced an 18 kDa radiolabelled proteolytic fragment. [I-125]IAPS-Fsk is a highly effective probe for identifying low levels of glucose transporters in mammalian tissues

Cerebellar hemangioblastomas with computed tomographic, angiographic, and positron-emission tomographic evaluations

International Nuclear Information System (INIS)

Kikuchi, Kenji; Sakamoto, Tetsuya; Kowada, Masayoshi; Tamakawa, Yoshiharu; Uemura, Kazuo.

1986-01-01

Ten patients with cerebellar hemangioblastomas were reviewed, and evaluations were made by computed tomography (CT), vertebral angiography, and positron-emission tomography (PET). Cerebellar hemangioblastomas were classified into three types on the basis of their CT appearances: Type I: a cystic tumor without a demonstrable mural nodule; Type II: a cystic tumor with a mural nodule, and Type III: a solid tumor without any cyst formation. All of the cystic tumors classified here as Types I and II were associated with a shift and deformity of the fourth ventricule and an enlarged lateral ventricle, and yet no low-density area in the adjacent cerebellar tissue indicating perifocal edema was demonstrated. By contrast, in the solid hemangioblastomas designated as Type III, finger-shaped, low-density areas were visualized around the enhancing mass lesion, extending to the white matter of the entire affected cerebellar hemisphere. The vertebral angiographic classification of cerebellar hemangioblastomas was also attempted as follows: Type I: an avascular tumor without a demonstrable mural nodule; Type II: an avascular tumor with a mural nodule, and Type III: a solid vascular tumor with enlarged feeding arteries and distinct draining veins. In Type II, a relatively small mural nodule was visualized, fed mostly by a single feeding artery, and the tumor stain was at its peak at the arterial phase. No draining vein was opacified in most cases. In contrast, solid tumors classified as Type III were demonstrated to be hypervascular tumors with a multiplicity of feeding arteries and draining veins. The vascular mass remained to be opacified through the venous phase with delayed blood circulation. PET was performed on a 31-year-old male with a solid hemangioblastoma. (J.P.N)

Metronome cueing of walking reduces gait variability after a cerebellar stroke

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Rachel Lindsey Wright

2016-06-01

Full Text Available Cerebellar stroke typically results in increased variability during walking. Previous research has suggested that auditory-cueing reduces excessive variability in conditions such as Parkinson’s disease and post-stroke hemiparesis. The aim of this case report was to investigate whether the use of a metronome cue during walking could reduce excessive variability in gait parameters after a cerebellar stroke. An elderly female with a history of cerebellar stroke and recurrent falling undertook 3 standard gait trials and 3 gait trials with an auditory metronome. A Vicon system was used to collect 3-D marker trajectory data. The coefficient of variation was calculated for temporal and spatial gait parameters. Standard deviations of the joint angles were calculated and used to give a measure of joint kinematic variability. Step time, stance time and double support time variability were reduced with metronome cueing. Variability in the sagittal hip, knee and ankle angles were reduced to normal values when walking to the metronome. In summary, metronome cueing resulted in a decrease in variability for step, stance and double support times and joint kinematics. Further research is needed to establish whether a metronome may be useful in gait rehabilitation after cerebellar stroke, and whether this leads to a decreased risk of falling.

Metronome Cueing of Walking Reduces Gait Variability after a Cerebellar Stroke.

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Wright, Rachel L; Bevins, Joseph W; Pratt, David; Sackley, Catherine M; Wing, Alan M

2016-01-01

Cerebellar stroke typically results in increased variability during walking. Previous research has suggested that auditory cueing reduces excessive variability in conditions such as Parkinson's disease and post-stroke hemiparesis. The aim of this case report was to investigate whether the use of a metronome cue during walking could reduce excessive variability in gait parameters after a cerebellar stroke. An elderly female with a history of cerebellar stroke and recurrent falling undertook three standard gait trials and three gait trials with an auditory metronome. A Vicon system was used to collect 3-D marker trajectory data. The coefficient of variation was calculated for temporal and spatial gait parameters. SDs of the joint angles were calculated and used to give a measure of joint kinematic variability. Step time, stance time, and double support time variability were reduced with metronome cueing. Variability in the sagittal hip, knee, and ankle angles were reduced to normal values when walking to the metronome. In summary, metronome cueing resulted in a decrease in variability for step, stance, and double support times and joint kinematics. Further research is needed to establish whether a metronome may be useful in gait rehabilitation after cerebellar stroke and whether this leads to a decreased risk of falling.

The protective effect of DNA on the rat cell membrane damage induced by ultraviolet radiation

International Nuclear Information System (INIS)

Ma Shouxiang; Zhong Jinyan

1988-01-01

The protective effect of DNA on the cell membrane damage induced by ultra-violet radiation was studied. Rat erythrocytes were used as experimental materials. Blood samples were taken from the rat, and centrifuged to separate the plasma. The cells were washed twice with isotonic saline, resuspended in normal saline solution and then irradiated by ultra-violet radiation. The DNA was added before or after irradiation. THe cell suspensions were kept at 5 deg C for 20 hours after irradiation, and then centrifuged. The supernatants were used for hemoglobin determination. The main results obtained may summarized as follows: the cell suspension of erythrocytes were irradiated for 5, 10 and 20 min. The amount of hemolysis induced by irradiation dosage revealed a direct proportional relationship. If DNA (20-40μg/ml) was applied before irradiation, the amount of hemolysis induced apparently decreased. The differences between the control and DNA treated were statistically significant, P<0.01, but insignificant for DNA added after irradiation

GDF15 regulates Kv2.1-mediated outward K+ current through the Akt/mTOR signalling pathway in rat cerebellar granule cells.

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Wang, Chang-Ying; Huang, An-Qi; Zhou, Meng-Hua; Mei, Yan-Ai

2014-05-15

GDF15 (growth/differentiation factor 15), a novel member of the TGFβ (transforming growth factor β) superfamily, plays critical roles in the central and peripheral nervous systems, but the signal transduction pathways and receptor subtypes involved are not well understood. In the present paper, we report that GDF15 specifically increases the IK (delayed-rectifier outward K+ current) in rat CGNs (cerebellar granule neurons) in time- and concentration-dependent manners. The GDF15-induced amplification of the IK is mediated by the increased expression and reduced lysosome-dependent degradation of the Kv2.1 protein, the main α-subunit of the IK channel. Exposure of CGNs to GDF15 markedly induced the phosphorylation of ERK (extracellular-signal-regulated kinase), Akt and mTOR (mammalian target of rapamycin), but the GDF15-induced IK densities and increased expression of Kv2.1 were attenuated only by Akt and mTOR, and not ERK, inhibitors. Pharmacological inhibition of the Src-mediated phosphorylation of TGFβR2 (TGFβ receptor 2), not TGFβR1, abrogated the effect of GDF15 on IK amplification and Kv2.1 induction. Immunoprecipitation assays showed that GDF15 increased the tyrosine phosphorylation of TGFβRII in the CGN lysate. The results of the present study reveal a novel regulation of Kv2.1 by GDF15 mediated through the TGFβRII-activated Akt/mTOR pathway, which is a previously uncharacterized Smad-independent mechanism of GDF15 signalling.

Aldosterone induction of electrogenic sodium transport in the apical membrane vesicles of rat distal colon

International Nuclear Information System (INIS)

Rajendran, V.M.; Kashgarian, M.; Binder, H.J.

1989-01-01

Na-H exchange is present in apical membrane vesicles (AMV) isolated from distal colon of normal rats. Because in intact tissue aldosterone both induces amiloride-sensitive electrogenic sodium transport and inhibits electroneutral sodium absorption, these studies with AMV were designed to establish the effect of aldosterone on sodium transport. An outward-directed proton gradient stimulated 22Na uptake in AMV isolated from distal colon of normal and dietary sodium depleted (with elevated aldosterone levels) experimental rats. Unlike normal AMV, proton gradient-dependent 22Na uptake in experimental AMV was inhibited when uptake was measured under voltage-clamped conditions. 10 microM amiloride inhibited the initial rate of proton gradient-dependent 22Na uptake in AMV of normal and experimental rats by 30 and 75%, respectively. In contrast, 1 mM amiloride produced comparable inhibition (90 and 80%) of 22Na uptake in normal and experimental AMV. Intravesicular-negative potential stimulated 22Na uptake in experimental but not in normal AMV. This increase was inhibited by 90% by 10 microM amiloride. An analogue of amiloride, 5-(N-ethylisopropyl) amiloride (1 microM), a potent inhibitor of electroneutral Na-H exchange in AMV of normal rat distal colon, did not alter potassium diffusion potential-dependent 22Na uptake. Increasing sodium concentration saturated proton gradient-dependent 22Na uptake in normal AMV. However, in experimental AMV, 22Na uptake stimulated by both proton gradient and potassium diffusion potential did not saturate as a function of increasing sodium concentration. We conclude from these results that an electrically sensitive conductive channel, not electroneutral Na-H exchange, mediates 22Na uptake in AMV isolated from the distal colon of aldosterone rats

Crossed cerebellar atrophy in children: a neurologic sequela of extreme prematurity

International Nuclear Information System (INIS)

Rollins, N.K.; Wen, T.S.; Dominguez, R.

1995-01-01

We retrospectively identified eight children, aged 8 months to 13 years, in whom cerebellar atrophy associated with cerebral injury was diagnosed on MR or CT, and reviewed their past medical history, neurologic findings, and neuroimaging studies. Seven patients were born extremely premature, EGA 25-28 weeks, and had severe perinatal intracranial hemorrhage. Neurologic problems include severe developmental delay in seven, spastic paresis in six, and seizures in five. Neuroimaging showed severe unilaterial holohemispheric atrophy in four, bilateral asymmetric holohemispheric atrophy in two, and left temporoparietal atrophy in one. Cerebellar atrophy was unilateral in five and bilateral but asymmetric in two. Gliosis of the atrophic cerebellum occurred in one patient. Sequential neuroimaging in one patient showed evolution of crossed cerebellar atrophy at 8 months of age. The final patient, a term infant, had an idiopathic perinatal left cerebral infarct. (orig./MG)

Structural and Functional Magnetic Resonance Imaging of the Cerebellum: Considerations for Assessing Cerebellar Ataxias.

Science.gov (United States)

Deistung, Andreas; Stefanescu, Maria R; Ernst, Thomas M; Schlamann, Marc; Ladd, Mark E; Reichenbach, Jürgen R; Timmann, Dagmar

2016-02-01

Magnetic resonance imaging (MRI) of the brain is of high interest for diagnosing and understanding degenerative ataxias. Here, we present state-of-the-art MRI methods to characterize structural alterations of the cerebellum and introduce initial experiments to show abnormalities in the cerebellar nuclei. Clinically, T1-weighted MR images are used to assess atrophy of the cerebellar cortex, the brainstem, and the spinal cord, whereas T2-weighted and PD-weighted images are typically employed to depict potential white matter lesions that may be associated with certain types of ataxias. More recently, attention has also focused on the characterization of the cerebellar nuclei, which are discernible on spatially highly resolved iron-sensitive MR images due to their relatively high iron content, including T2 (*)-weighted images, susceptibility-weighted images (SWI), effective transverse relaxation rate (R2 (*)) maps, and quantitative susceptibility maps (QSM). Among these iron-sensitive techniques, QSM reveals the best contrast between cerebellar nuclei and their surroundings. In particular, the gyrification of the dentate nuclei is prominently depicted, even at the clinically widely available field strength of 3 T. The linear relationship between magnetic susceptibility and local iron content allows for determination of iron deposition in cerebellar nuclei non-invasively. The increased signal-to-noise ratio of ultrahigh-field MRI (B0 ≥ 7 T) and advances in spatial normalization methods enable functional MRI (fMRI) at the level of the cerebellar cortex and cerebellar nuclei. Data from initial fMRI studies are presented in three common forms of hereditary ataxias (Friedreich's ataxia, spinocerebellar ataxia type 3, and spinocerebellar ataxia type 6). Characteristic changes in the fMRI signal are discussed in the light of histopathological data and current knowledge of the underlying physiology of the fMRI signal in the cerebellum.

Ultrasonically detectable cerebellar haemorrhage in preterm infants.

LENUS (Irish Health Repository)

McCarthy, Lisa Kenyon

2011-07-01

To determine the frequency and pattern of cerebellar haemorrhage (CBH) on routine cranial ultrasound (cUS) imaging in infants of ≤32 weeks gestation, and to investigate how extremely preterm infants with CBH differ from those with severe intraventricular haemorrhage (IVH).

Synaptic glutamate spillover increases NMDA receptor reliability at the cerebellar glomerulus

OpenAIRE

Mitchell, Cassie S.; Lee, Robert H.

2011-01-01

Glutamate spillover in the mossy fiber to granule cell cerebellar glomeruli has been hypothesized to increase neurotransmission reliability. In this study, we evaluate this hypothesis using an experimentally-based quantitative model of glutamate spillover on the N-methyl-d-aspartate receptors (NMDA-Rs) at the cerebellar glomerulus. The transient and steady-state responses of NMDA-Rs were examined over a physiological range of firing rates. Examined cases included direct glutamate release acti...

Studies on interaction of insulin and insulin receptor in rat liver cell membranes

Energy Technology Data Exchange (ETDEWEB)

Sakai, Y; Hara, H; Kawate, R; Kawasaki, T [Hiroshima Univ. (Japan). School of Medicine

1975-07-01

Rat liver was homogenized with a Polytron PT 20 ST and fractionated by differential centrifugation. Prepared plasma membranes (100 ..mu..g protein) were incubated with enzymatically iodinated /sup 125/I-insulin (0.3 ng, specific activity 107 ..mu..Ci/..mu..g) in 25 mM Tris-HCl buffer, pH 7.5, containing 0.9% NaCl and 1% bovine serum albumin. The 12,000xg- and 17,000xg-sediments obtained after subfractionation of liver homogenates showed almost equally high specific binding activity with /sup 125/I-insulin and less activity was detected in the 600 g-, 5,000 g- and 40,000 g- sediments and the 40,000 g- supernatant. Specific binding of insulin with the membrane fraction was time-, temperature- and ionic strength-dependent. The highest binding was obtained under conditions in which the membrane fraction was incubated with insulin for 24 hours at 4/sup 0/C in the buffer containing 1 M NaCl. Under these conditions, specific binding of /sup 125/I-insulin was 26.8% of the total radioactivity. The effect of native insulin on the binding of /sup 125/I-insulin with the membrane fraction was studied in the range of 0--6.4 x 10/sup 5/ ..mu..U/ml of unlabeled insulin and a distinct competitive displacement of /sup 125/I-insulin with native insulin was observed between 10 and 10/sup 4/ ..mu..U/ml. Kinetic studies by Scatchard plot analysis of the above results revealed heterogeneity in insulin receptors or receptor sites, one with a high affinity of 10/sup 9/ M/sup -1/ order and the other with a low affinity of 10/sup 8/ M/sup -1/ order. Both affinities were also affected by temperature and ionic strength.

Stereotactic biopsy of cerebellar lesions: straight versus oblique frame positioning.

Science.gov (United States)

Quick-Weller, Johanna; Brawanski, Nina; Dinc, Nazife; Behmanesh, Bedjahn; Kammerer, Sara; Dubinski, Daniel; Seifert, Volker; Marquardt, Gerhard; Weise, Lutz

2017-10-26

Biospies of brain lesions with unknown entity are an everyday procedure among many neurosurgical departments. Biopsies can be performed frame-guided or frameless. However, cerebellar lesions are a special entity with a more complex approach. All biopsies in this study were performed stereotactically frame guided. Therefore, only biopsies of cerebellar lesions were included in this study. We compared whether the frame was attached straight versus oblique and we focused on diagnostic yield and complication rate. We evaluated 20 patients who underwent the procedure between 2009 and 2017. Median age was 56.5 years. 12 (60%) Patients showed a left sided lesion, 6 (30%) showed a lesion in the right cerebellum and 2 (10%) patients showed a midline lesion. The stereotactic frame was mounted oblique in 12 (60%) patients and straight in 8 (40%) patients. Postoperative CT scan showed small, clinically silent blood collection in two (10%) of the patients, one (5%) patient showed haemorrhage, which caused a hydrocephalus. He received an external ventricular drain. In both patients with small haemorrhage the frame was positioned straight, while in the patient who showed a larger haemorrhage the frame was mounted oblique. In all patients a final histopathological diagnosis was established. Cerebellar lesions of unknown entity can be accessed transcerebellar either with the stereotactic frame mounted straight or oblique. Also for cerebellar lesions the procedure shows a high diagnostic yield with a low rate of severe complications, which need further treatment.

Genetic regulation by amino acids of specific membrane protein biosynthesis in isolated rat hepatocytes

International Nuclear Information System (INIS)

Chiles, T.C.; Handlogten, M.E.; Kilberg, M.S.

1986-01-01

Rat Hepatocytes in primary culture were incubated in amino acid-free (AAF) medium or amino acid-supplemented (AAS) medium for 2-6 hr. The effect of amino acid starvation on the synthesis of specific membrane proteins was monitored by including 3 H-leucine during the incubation. A crude plasma membrane fraction was prepared and then analyzed by 2-D gel electrophoresis followed by fluorography. Amino acid deprivation caused an induction of the synthesis of 5 of the 30 proteins studied. The ratio (AAF/-AAS) of cpm incorporated into the remaining 25 proteins was 0.8 +/- 0.2, whereas the ratio for the 5 proteins that showed amino acid-dependent synthesis ranged from 1.5 to 2.5. The presence of 4 μM actinomycin in the AAF medium completely blocked the starvation-induced synthesis of the 5 proteins tested, but did not alter significantly the ratio of cpm incorporated into the other 25 proteins. Binding studies involving ConA suggested a plasma membrane location for the 5 proteins. The molecular weight values of the starvation-induced proteins are 70, 66, 66, 67, and 45kD. Surface-labelling of intact cells and preparation of antibodies against the 5 proteins will be used to establish the subcellular location and to describe the amino acid-dependent synthesis of each in more detail

β-Catenin is critical for cerebellar foliation and lamination.

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Jing Wen

Full Text Available The cerebellum has a conserved foliation pattern and a well-organized layered structure. The process of foliation and lamination begins around birth. β-catenin is a downstream molecule of Wnt signaling pathway, which plays a critical role in tissue organization. Lack of β-catenin at early embryonic stages leads to either prenatal or neonatal death, therefore it has been difficult to resolve its role in cerebellar foliation and lamination. Here we used GFAP-Cre to ablate β-catenin in neuronal cells of the cerebellum after embryonic day 12.5, and found an unexpected role of β-catenin in determination of the foliation pattern. In the mutant mice, the positions of fissure formation were changed, and the meninges were improperly incorporated into fissures. At later stages, some lobules were formed by Purkinje cells remaining in deep regions of the cerebellum and the laminar structure was dramatically altered. Our results suggest that β-catenin is critical for cerebellar foliation and lamination. We also found a non cell-autonomous role of β-catenin in some developmental properties of major cerebellar cell types during specific stages.

Bilateral cerebellar activation in unilaterally challenged essential tremor

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Marja Broersma

2016-01-01

Conclusions: Our results expand on previous findings of bilateral cerebellar involvement in ET. We have identified specific areas in the bilateral somatomotor regions of the cerebellum: lobules V, VI and VIII.

Magnetic resonance imaging findings in patients presenting with (sub)acute cerebellar ataxia

Energy Technology Data Exchange (ETDEWEB)

Schneider, Tanja [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Neuroradiology, Hamburg (Germany); The Johns Hopkins Hospital School of Medicine, Russell H. Morgan Department of Radiology and Radiological Sciences, Division of Neuroradiology, Baltimore, MD (United States); Thomalla, Goetz [University Medical Center Hamburg-Eppendorf, Department of Neurology, Hamburg (Germany); Goebell, Einar [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Neuroradiology, Hamburg (Germany); Piotrowski, Anna [The Johns Hopkins University School of Medicine, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD (United States); Yousem, David Mark [The Johns Hopkins Hospital School of Medicine, Russell H. Morgan Department of Radiology and Radiological Sciences, Division of Neuroradiology, Baltimore, MD (United States)

2015-02-17

Acute or subacute cerebellar inflammation is mainly caused by postinfectious, toxic, neoplastic, vascular, or idiopathic processes and can result in cerebellar ataxia. Previous magnetic resonance (MR) studies in single patients who developed acute or subacute ataxia showed varying imaging features. Eighteen patients presenting with acute and subacute onset of ataxia were included in this study. Cases of chronic-progressive/hereditary and noncerebellar causes (ischemia, multiple sclerosis lesions, metastasis, bleedings) were excluded. MR imaging findings were then matched with the clinical history of the patient. An underlying etiology for ataxic symptoms were found in 14/18 patients (postinfectious/infectious, paraneoplastic, autoimmune, drug-induced). In two of five patients without MR imaging findings and three of eight patients with minimal imaging features (cerebellar atrophy, slight signal alterations, and small areas of restricted diffusion), adverse clinical outcomes were documented. Of the five patients with prominent MR findings (cerebellar swelling, contrast enhancement, or broad signal abnormalities), two were lost to follow-up and two showed long-term sequelae. No correlation was found between the presence of initial MRI findings in subacute or acute ataxia patients and their long-term clinical outcome. MR imaging was more flagrantly positive in cases due to encephalitis. (orig.)

Magnetic resonance imaging findings in patients presenting with (sub)acute cerebellar ataxia.

Science.gov (United States)

Schneider, Tanja; Thomalla, Götz; Goebell, Einar; Piotrowski, Anna; Yousem, David Mark

2015-06-01

Acute or subacute cerebellar inflammation is mainly caused by postinfectious, toxic, neoplastic, vascular, or idiopathic processes and can result in cerebellar ataxia. Previous magnetic resonance (MR) studies in single patients who developed acute or subacute ataxia showed varying imaging features. Eighteen patients presenting with acute and subacute onset of ataxia were included in this study. Cases of chronic-progressive/hereditary and noncerebellar causes (ischemia, multiple sclerosis lesions, metastasis, bleedings) were excluded. MR imaging findings were then matched with the clinical history of the patient. An underlying etiology for ataxic symptoms were found in 14/18 patients (postinfectious/infectious, paraneoplastic, autoimmune, drug-induced). In two of five patients without MR imaging findings and three of eight patients with minimal imaging features (cerebellar atrophy, slight signal alterations, and small areas of restricted diffusion), adverse clinical outcomes were documented. Of the five patients with prominent MR findings (cerebellar swelling, contrast enhancement, or broad signal abnormalities), two were lost to follow-up and two showed long-term sequelae. No correlation was found between the presence of initial MRI findings in subacute or acute ataxia patients and their long-term clinical outcome. MR imaging was more flagrantly positive in cases due to encephalitis.

Cerebellar stem cells do not produce neurons and astrocytes in adult mouse

International Nuclear Information System (INIS)

Su, Xin; Guan, Wuqiang; Yu, Yong-Chun; Fu, Yinghui

2014-01-01

Highlights: • No new neurons and astrocytes are generated in adult mouse cerebellum. • Very few mash1 + or nestin + stem cells exist, and most of them are quiescent. • Cell proliferation rate is diversified among cerebellar regions and decreases over time. - Abstract: Although previous studies implied that cerebellar stem cells exist in some adult mammals, little is known about whether these stem cells can produce new neurons and astrocytes. In this study by bromodeoxyuridine (BrdU) intraperitoneal (i.p.) injection, we found that there are abundant BrdU + cells in adult mouse cerebellum, and their quantity and density decreases significantly over time. We also found cell proliferation rate is diversified in different cerebellar regions. Among these BrdU + cells, very few are mash1 + or nestin + stem cells, and the vast majority of cerebellar stem cells are quiescent. Data obtained by in vivo retrovirus injection indicate that stem cells do not produce neurons and astrocytes in adult mouse cerebellum. Instead, some cells labeled by retrovirus are Iba1 + microglia. These results indicate that very few stem cells exist in adult mouse cerebellum, and none of these stem cells contribute to neurogenesis and astrogenesis under physiological condition

In vivo turnover of the basement membrane and other heparan sulfate proteoglycans of rat glomerulus

International Nuclear Information System (INIS)

Beavan, L.A.; Davies, M.; Couchman, J.R.; Williams, M.A.; Mason, R.M.

1989-01-01

The metabolic turnover of rat glomerular proteoglycans in vivo was investigated. Newly synthesized proteoglycans were labeled during a 7-h period after injecting sodium [35S]sulfate intraperitoneally. At the end of the labeling period a chase dose of sodium sulfate was given. Subsequently at defined times (0-163 h) the kidneys were perfused in situ with 0.01% cetylpyridinium chloride in phosphate-buffered saline to maximize the recovery of 35S-proteoglycans. Glomeruli were isolated from the renal cortex and analyzed for 35S-proteoglycans by autoradiographic, biochemical, and immunochemical methods. Grain counting of autoradiographs revealed a complex turnover pattern of 35S-labeled macromolecules, commencing with a rapid phase followed by a slower phase. Biochemical analysis confirmed the biphasic pattern and showed that the total population of [35S]heparan sulfate proteoglycans had a metabolic half-life (t1/2) of 20 and 60 h in the early and late phases, respectively. Heparan sulfate proteoglycans accounted for 80% of total 35S-proteoglycans, the remainder being chondroitin/dermatan sulfate proteoglycans. Whole glomeruli were extracted with 4% 3-[(cholamidopropyl)dimethy-lammonio]-1-propanesulfonate-4 M guanidine hydrochloride, a procedure which solubilized greater than 95% of the 35S-labeled macromolecules. Of these 11-13% was immunoprecipitated by an antiserum against heparan sulfate proteoglycan which, in immunolocalization experiments, showed specificity for staining the basement membrane of rat glomeruli. Autoradiographic analysis showed that 18% of total radioactivity present at the end of the labeling period was associated with the glomerular basement membrane

Fluorodeoxyglucose positron emission tomography/computed tomography findings in a patient with cerebellar mutism after operation in posterior fossa

Directory of Open Access Journals (Sweden)

Gonca Kara Gedik

2017-03-01

Full Text Available Cerebellar mutism is a transient period of speechlessness that evolves after posterior fossa surgery in children. Although direct cerebellar and brain stem injury and supratentorial dysfunction have been implicated in the mediation of mutism, the pathophysiological mechanisms involved in the evolution of this kind of mutism remain unclear. Magnetic resonance imaging revealed dentatothalamocortical tract injuries and single photon emission computed tomography showed cerebellar and cerebral hypoperfusion in patients with cerebellar mutism. However, findings with 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT in this group of patients have not been documented previously. In this clinical case, we report a patient who experienced cerebellar mutism after undergoing a posterior fossa surgery. Right cerebellar and left frontal lobe hypometabolism was shown using FDG PET/CT. The FDG metabolism of both the cerebellum and the frontal lobe returned to normal levels after the resolution of the mutism symptoms.

Statistical characteristics of climbing fiber spikes necessary for efficient cerebellar learning.

Science.gov (United States)

Kuroda, S; Yamamoto, K; Miyamoto, H; Doya, K; Kawat, M

2001-03-01

Mean firing rates (MFRs), with analogue values, have thus far been used as information carriers of neurons in most brain theories of learning. However, the neurons transmit the signal by spikes, which are discrete events. The climbing fibers (CFs), which are known to be essential for cerebellar motor learning, fire at the ultra-low firing rates (around 1 Hz), and it is not yet understood theoretically how high-frequency information can be conveyed and how learning of smooth and fast movements can be achieved. Here we address whether cerebellar learning can be achieved by CF spikes instead of conventional MFR in an eye movement task, such as the ocular following response (OFR), and an arm movement task. There are two major afferents into cerebellar Purkinje cells: parallel fiber (PF) and CF, and the synaptic weights between PFs and Purkinje cells have been shown to be modulated by the stimulation of both types of fiber. The modulation of the synaptic weights is regulated by the cerebellar synaptic plasticity. In this study we simulated cerebellar learning using CF signals as spikes instead of conventional MFR. To generate the spikes we used the following four spike generation models: (1) a Poisson model in which the spike interval probability follows a Poisson distribution, (2) a gamma model in which the spike interval probability follows the gamma distribution, (3) a max model in which a spike is generated when a synaptic input reaches maximum, and (4) a threshold model in which a spike is generated when the input crosses a certain small threshold. We found that, in an OFR task with a constant visual velocity, learning was successful with stochastic models, such as Poisson and gamma models, but not in the deterministic models, such as max and threshold models. In an OFR with a stepwise velocity change and an arm movement task, learning could be achieved only in the Poisson model. In addition, for efficient cerebellar learning, the distribution of CF spike

Low-grade intraventricular hemorrhage disrupts cerebellar white matter in preterm infants: evidence from diffusion tensor imaging

Energy Technology Data Exchange (ETDEWEB)

Morita, Takashi; Morimoto, Masafumi; Hasegawa, Tatsuji; Morioka, Shigemi; Kidowaki, Satoshi; Moroto, Masaharu; Yamashita, Satoshi; Maeda, Hiroshi; Chiyonobu, Tomohiro; Tokuda, Sachiko; Hosoi, Hajime [Kyoto Prefectural University of Medicine, Department of Pediatrics, Graduate School of Medical Science, Kyoto (Japan); Yamada, Kei [Kyoto Prefectural University of Medicine, Department of Radiology, Graduate School of Medical Science, Kyoto (Japan)

2015-05-01

Recent diffusion tensor imaging (DTI) studies have demonstrated that leakage of hemosiderin into cerebrospinal fluid (CSF), which is caused by high-grade intraventricular hemorrhage (IVH), can affect cerebellar development in preterm born infants. However, a direct effect of low-grade IVH on cerebellar development is unknown. Thus, we evaluated the cerebellar and cerebral white matter (WM) of preterm infants with low-grade IVH. Using DTI tractography performed at term-equivalent age, we analyzed 42 infants who were born less than 30 weeks gestational age (GA) at birth (22 with low-grade IVH, 20 without). These infants were divided into two birth groups depending on GA, and we then compared the presence and absence of IVH which was diagnosed by cerebral ultrasound (CUS) within 10 days after birth or conventional magnetic resonance imaging (MRI) at term-equivalent age in each group. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) at the superior cerebellar peduncle (SCP), middle cerebellar peduncle (MCP), motor tract, and sensory tract were measured. In the SCP, preterm born infants with IVH had lower FA values compared with infants without IVH. In particular, younger preterm birth with IVH had lower FA values in the SCP and motor tract and higher ADC values in the MCP. Low-grade IVH impaired cerebellar and cerebral WM, especially in the SCP. Moreover, younger preterm infants exhibited greater disruptions to cerebellar WM and the motor tract than infants of older preterm birth. (orig.)

Transcranial cerebellar direct current stimulation and transcutaneous spinal cord direct current stimulation as innovative tools for neuroscientists

Science.gov (United States)

Priori, Alberto; Ciocca, Matteo; Parazzini, Marta; Vergari, Maurizio; Ferrucci, Roberta

2014-01-01

Two neuromodulatory techniques based on applying direct current (DC) non-invasively through the skin, transcranial cerebellar direct current stimulation (tDCS) and transcutaneous spinal DCS, can induce prolonged functional changes consistent with a direct influence on the human cerebellum and spinal cord. In this article we review the major experimental works on cerebellar tDCS and on spinal tDCS, and their preliminary clinical applications. Cerebellar tDCS modulates cerebellar motor cortical inhibition, gait adaptation, motor behaviour, and cognition (learning, language, memory, attention). Spinal tDCS influences the ascending and descending spinal pathways, and spinal reflex excitability. In the anaesthetised mouse, DC stimulation applied under the skin along the entire spinal cord may affect GABAergic and glutamatergic systems. Preliminary clinical studies in patients with cerebellar disorders, and in animals and patients with spinal cord injuries, have reported beneficial effects. Overall the available data show that cerebellar tDCS and spinal tDCS are two novel approaches for inducing prolonged functional changes and neuroplasticity in the human cerebellum and spinal cord, and both are new tools for experimental and clinical neuroscientists. PMID:24907311

Marked increase in rat red blood cell membrane protein glycosylation by one-month treatment with a cafeteria diet

Directory of Open Access Journals (Sweden)

Laia Oliva

2015-07-01

Full Text Available Background and Objectives. Glucose, an aldose, spontaneously reacts with protein amino acids yielding glycosylated proteins. The compounds may reorganize to produce advanced glycosylation products, which regulatory importance is increasingly being recognized. Protein glycosylation is produced without the direct intervention of enzymes and results in the loss of function. Glycosylated plasma albumin, and glycosylated haemoglobin are currently used as index of mean plasma glucose levels, since higher glucose availability results in higher glycosylation rates. In this study we intended to detect the early changes in blood protein glycosylation elicited by an obesogenic diet.Experimental Design. Since albumin is in constant direct contact with plasma glucose, as are the red blood cell (RBC membranes, we analyzed their degree or glycosylation in female and male rats, either fed a standard diet or subjected to a hyper-energetic self-selected cafeteria diet for 30 days. This model produces a small increase in basal glycaemia and a significant increase in body fat, leaving the animals in the initial stages of development of metabolic syndrome. We also measured the degree of glycosylation of hemoglobin, and the concentration of glucose in contact with this protein, that within the RBC. Glycosylation was measured by colorimetric estimation of the hydroxymethylfurfural liberated from glycosyl residues by incubation with oxalate.Results. Plasma glucose was higher in cafeteria diet and in male rats, both independent effects. However, there were no significant differences induced by sex or diet in either hemoglobin or plasma proteins. Purified RBC membranes showed a marked effect of diet: higher glycosylation in cafeteria rats, which was more marked in females (not in controls. In any case, the number of glycosyl residues per molecule were higher in hemoglobin than in plasma proteins (after correction for molecular weight. The detected levels of glucose in

The coevolution of play and the cortico-cerebellar system in primates.

Science.gov (United States)

Kerney, Max; Smaers, Jeroen B; Schoenemann, P Thomas; Dunn, Jacob C

2017-10-01

Primates are some of the most playful animals in the natural world, yet the reason for this remains unclear. One hypothesis posits that primates are so playful because playful activity functions to help develop the sophisticated cognitive and behavioural abilities that they are also renowned for. If this hypothesis were true, then play might be expected to have coevolved with the neural substrates underlying these abilities in primates. Here, we tested this prediction by conducting phylogenetic comparative analyses to determine whether play has coevolved with the cortico-cerebellar system, a neural system known to be involved in complex cognition and the production of complex behaviour. We used phylogenetic generalised least squares analyses to compare the relative volume of the largest constituent parts of the primate cortico-cerebellar system (prefrontal cortex, non-prefrontal heteromodal cortical association areas, and posterior cerebellar hemispheres) to the mean percentage of time budget spent in play by a sample of primate species. Using a second categorical data set on play, we also used phylogenetic analysis of covariance to test for significant differences in the volume of the components of the cortico-cerebellar system among primate species exhibiting one of three different levels of adult-adult social play. Our results suggest that, in general, a positive association exists between the amount of play exhibited and the relative size of the main components of the cortico-cerebellar system in our sample of primate species. Although the explanatory power of this study is limited by the correlational nature of its analyses and by the quantity and quality of the data currently available, this finding nevertheless lends support to the hypothesis that play functions to aid the development of cognitive and behavioural abilities in primates.

Relationship between ultrasound estimated fetal gestational age and cerebellar appearance in healthy pregnant Nigerian women.

Science.gov (United States)

Adeyekun, Ademola A; Orji, Michael O

2015-01-01

Fetal biometry by ultrasound provides reliable and important information about fetal growth and wellbeing. Evaluation of the fetal posterior fossa is useful in the assessment of neural tube-defects. Studies on normal ultrasound fetal cerebellar appearance and diameter across gestational age (GA) are scanty in the Nigerian medical literature. This study was carried out to study normal fetal cerebellar appearance and diameter at various GAs among healthy pregnant Nigerian Africans. This was a prospective study of 450 healthy singleton pregnant women between 13 and 42 weeks gestation. A curvilinear probe with a 3.5 MHz transducer of a SonoAce X6 (Medison Inc., Korea 2010) scanner was used to assess fetal transcerebellar diameter (TCD) and appearance. GA was also determined using fetal biometric parameters such as the biparietal diameter, femur length, and abdominal circumference. Fetal cerebellar appearance was correlated against GA. The cerebellar appearance was graded into: Grade I: 164 fetuses (36.4%), Grade II; 102 fetuses (22.7%) and Grade III: 184 fetuses (40.9%). Mean GA and TCD was 21 weeks and 21.2 mm for Grade I; 28 weeks and 32.6 mm for Grade II; and 35 weeks and 47.1 mm for Grade III. There was significance difference among the cerebellar grades at the GA groups and transverse cerebellar diameter (P < 0.000). There is a gradual and steady change in ultrasonographic appearance of the fetal cerebellar and diameter appearance with advancing gestation. The changes ranged from anechoic, "pair of eye glass" appearance at second trimester to relatively echogenic, "dumb-bell" appearance at early third trimester, and solid, "fan-shape" in late third trimester.

Diffusion tensor imaging parameters' changes of cerebellar hemispheres in Parkinson's disease

Energy Technology Data Exchange (ETDEWEB)

Mormina, Enricomaria; Arrigo, Alessandro; Granata, Francesca; Anastasi, Giuseppe P.; Gaeta, Michele [University of Messina, Department of Biomedical Science and Morphological and Functional Images, Messina (Italy); Calamuneri, Alessandro; Quartarone, Angelo [University of Messina, Department of Neurosciences, Messina (Italy); Ghilardi, Maria F.; Inglese, Matilde; Di Rocco, Alessandro [Mount Sinai Hospital, New York, NY (United States); Milardi, Demetrio [University of Messina, Department of Biomedical Science and Morphological and Functional Images, Messina (Italy); IRCCS Centro Neurolesi Bonino Pulejo, Messina (Italy)

2015-03-01

Studies with diffusion tensor imaging (DTI) analysis have produced conflicting information about the involvement of the cerebellar hemispheres in Parkinson's disease (PD). We, thus, used a new approach for the analysis of DTI parameters in order to ascertain the involvement of the cerebellum in PD. We performed a fiber tract-based analysis of cerebellar peduncles and cerebellar hemispheres in 16 healthy subjects and in 16 PD patients with more than 5 years duration of disease, using a 3T MRI scanner and a constrained spherical deconvolution (CSD) approach for tractographic reconstructions. In addition, we performed statistical analysis of DTI parameters and fractional anisotropy (FA) XYZ direction samplings. We found a statistically significant decrement of FA values in PD patients compared to controls (p < 0.05). In addition, extrapolating and analyzing FA XYZ direction samplings for each patient and each control, we found that this result was due to a stronger decrement of FA values along the Y axis (antero-posterior direction) (p < 0.01); FA changes along X and Z axes were not statistically significant (p > 0.05). We confirmed also no statistically significant differences of FA and apparent diffusion coefficient (ADC) for cerebellar peduncles in PD patients compared to healthy controls. The DTI-based cerebellar abnormalities in PD could constitute an advance in the knowledge of this disease. We demonstrated a statistically significant reduction of FA in cerebellar hemispheres of PD patients compared to healthy controls. Our work also demonstrated that the use of more sophisticated approaches in the DTI parameter analysis could potentially have a clinical relevance. (orig.)

Diffusion tensor imaging parameters' changes of cerebellar hemispheres in Parkinson's disease

International Nuclear Information System (INIS)

Mormina, Enricomaria; Arrigo, Alessandro; Granata, Francesca; Anastasi, Giuseppe P.; Gaeta, Michele; Calamuneri, Alessandro; Quartarone, Angelo; Ghilardi, Maria F.; Inglese, Matilde; Di Rocco, Alessandro; Milardi, Demetrio

2015-01-01

Studies with diffusion tensor imaging (DTI) analysis have produced conflicting information about the involvement of the cerebellar hemispheres in Parkinson's disease (PD). We, thus, used a new approach for the analysis of DTI parameters in order to ascertain the involvement of the cerebellum in PD. We performed a fiber tract-based analysis of cerebellar peduncles and cerebellar hemispheres in 16 healthy subjects and in 16 PD patients with more than 5 years duration of disease, using a 3T MRI scanner and a constrained spherical deconvolution (CSD) approach for tractographic reconstructions. In addition, we performed statistical analysis of DTI parameters and fractional anisotropy (FA) XYZ direction samplings. We found a statistically significant decrement of FA values in PD patients compared to controls (p < 0.05). In addition, extrapolating and analyzing FA XYZ direction samplings for each patient and each control, we found that this result was due to a stronger decrement of FA values along the Y axis (antero-posterior direction) (p < 0.01); FA changes along X and Z axes were not statistically significant (p > 0.05). We confirmed also no statistically significant differences of FA and apparent diffusion coefficient (ADC) for cerebellar peduncles in PD patients compared to healthy controls. The DTI-based cerebellar abnormalities in PD could constitute an advance in the knowledge of this disease. We demonstrated a statistically significant reduction of FA in cerebellar hemispheres of PD patients compared to healthy controls. Our work also demonstrated that the use of more sophisticated approaches in the DTI parameter analysis could potentially have a clinical relevance. (orig.)

Crossed cerebellar atrophy in cases with cerebrovascular disease

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Yagishita, Toshiyuki; Kojima, Shigeyuki; Hirayama, Keizo; Iwabuchi, Sadamu.

1989-01-01

Crossed cerebellar atrophy (CCA) was investigated by X-ray CT to establish the incidence, mechanism, and the relation to cerebral lesions in 130 cases of unilateral supratentorial cerebrovascular diseases. The 130 cases consisted of 83 males and 47 females with cerebral infarction (65 cases) and cerebral hemorrhage (65 cases). The patients' average age was 57.6 years. Crossed cerebellar atrophy was demonstrated in 8 cases (6.2%), 6 of whom had massive cerebral infarction in the middle cerebral artery area (9.2% of the 65 cases of cerebral infarction. The six cases of CCA caused by cerebral infarction had lesions in the frontal and temporal lobes. Two had a cerebral hemorrhage in the putamen and in the thalamus, respectively, accounting for 3.1% of the 65 cases of cerebral hemorrhage. Of the 2 cases, one had putaminal hemorrhage, and the other had thalamic hemorrhage. Cerebrovascular stroke had occured in these patients with CCA more than 2 months previously. In 5 of the 8 cases of CCA, atrophy was present in the basis pedunculi and the basis pontis on the side of the cerebral lesion. However, neither dilation nor deformity of the fourth ventricle was present in any of the patients, suggesting that none of the CCA patients had atrophy of the dentate nucleus. The CCA patients had massive cerebral lesion in the frontal and temporal lobes or atrophy of the basis pedunculi and basis pontis, suggesting the presence of the transsynaptic degeneration of the cortico-ponto-cerebellar pathway. In the case of the thalamic hemorrhage, who had not hemorrhagic lesion in the frontal and temporal lobes, atrophy of the basis peduncli and basis pontis was not observed. Though dilation or deformity of the fourth ventricle is not observed in this case, presence of the degeneration of the dentate-rubro-thalamic pathway cannot be denied. CCA seems to be caused by both the transsynaptic degeneration of the cortico-ponto-cerebellar pathway and the dentate-rubro-thalamic pathway. (J.P.N.)

Impaired Cerebellar Maturation, Growth Restriction, and Circulating Insulin-Like Growth Factor 1 in Preterm Rabbit Pups

Science.gov (United States)

Sveinsdóttir, Kristbjörg; Länsberg, John-Kalle; Sveinsdóttir, Snjólaug; Garwicz, Martin; Ohlsson, Lennart; Hellström, Ann; Smith, Lois; Gram, Magnus; Ley, David

2018-01-01

Cerebellar growth is impeded following very preterm birth in human infants and the observed reduction in cerebellar volume is associated with neurodevelopmental impairment. Decreased levels of circulating insulin-like growth factor 1 (IGF-1) are associated with decreased cerebellar volume. The relationship between preterm birth, circulating IGF-1, and key cell populations supporting cerebellar proliferation is unknown. The aim of this study was to evaluate the effect of preterm birth on postnatal growth, circulating IGF-1, and cerebellar maturation in a preterm rabbit pup model. Preterm rabbit pups (PT) were delivered by cesarean section at day 29 of gestation, cared for in closed incubators with humidified air, and gavage fed with formula. Control term pups (T) delivered by spontaneous vaginal delivery at day 32 of gestation were housed and fed by their lactating doe. In vivo perfusion-fixation for immunohistochemical evaluation of cerebellar proliferation, cell maturation, and apoptosis was performed at repeated time points in PT and T pups. Results show that the mean weight of the pups and circulating IGF-1 protein levels were lower in the PT group at all time points (p staining at P0 (p = 0.003), P2 (p = 0.004), and P5 (p = 0.04) in the PT group compared to in the T group. Staining for sonic hedgehog was positive in neuronal EGL progenitors and Purkinje cells at early time points but was restricted to a well-defined Purkinje cell monolayer at later time points. Preterm birth in rabbit pups is associated with lower circulating levels of IGF-1, decreased postnatal growth, and decreased cerebellar EGL proliferation and Purkinje cell maturation. The preterm rabbit pup model exhibits important characteristics of human preterm birth, and may thus be suitable for the evaluation of interventions aiming to modify growth and cerebellar development in the preterm population. PMID:28972955

Morphometric magnetic resonance imaging and genetic testing in cerebellar abiotrophy in Arabian horses

Science.gov (United States)

2013-01-01

Background Cerebellar abiotrophy (CA) is a rare but significant disease in Arabian horses caused by progressive death of the Purkinje cells resulting in cerebellar ataxia characterized by a typical head tremor, jerky head movements and lack of menace response. The specific role of magnetic resonance imaging (MRI) to support clinical diagnosis has been discussed. However, as yet MR imaging has only been described in one equine CA case. The role of MR morphometry in this regard is currently unknown. Due to the hereditary nature of the disease, genetic testing can support the diagnosis of CA. Therefore, the objective of this study was to perform MR morphometric analysis and genetic testing in four CA-affected Arabian horses and one German Riding Pony with purebred Arabian bloodlines in the third generation. Results CA was diagnosed pathohistologically in the five affected horses (2 months - 3 years) supported by clinical signs, necropsy, and genetic testing which confirmed the TOE1:g.2171G>A SNP genotype A/A in all CA-affected horses. On MR images morphometric analysis of the relative cerebellar size and relative cerebellar cerebrospinal fluid (CSF) space were compared to control images of 15 unaffected horses. It was demonstrated that in MR morphometric analyses, CA affected horses displayed a relatively smaller cerebellum compared to the entire brain mass than control animals (P = 0.0088). The relative cerebellar CSF space was larger in affected horses (P = 0.0017). Using a cut off value of 11.0% for relative cerebellar CSF space, the parameter differentiated between CA-affected horses and controls with a sensitivity of 100% and a specificity of 93.3%. Conclusions In conclusion, morphometric MRI and genetic analysis could be helpful to support the diagnosis of CA in vivo. PMID:23702154

Quantitative changes in adipocyte plasma membrane in response to nutritional manipulations

International Nuclear Information System (INIS)

Lewis, D.S.; Masoro, E.J.; Yu, B.P.

1981-01-01

The effects of changes in adipocyte size and the effects of nutritional manipulations on the quantity of plasma membrane per adipocyte were investigated. A method for estimating the quantity of plasma membrane was developed based on the specific labeling of adipocyte plasma membrane protein with the nonpermeable labeling agent 125I-labeled diazotized diiodosulfanilic acid. By studying rats (ranging in age from 50 to 125 days) fed a standard laboratory chow or a low fat diet or a high fat diet, a wide range of mean fat cell sizes was obtained. It was found that as the volume of the fat cell increased, the amount of plasma membrane increased in a linear fashion and that this linear relationship had the same slope whether the size of the adipocyte increased slowly with age or rapidly in response to a high fat diet. In contrast, fasting for up to 3 days caused a marked decrease in the mean volume of the adipocytes, but either no change or much less change in the amount of plasma membrane per cell than would have been predicted from the linear relationship between adipocytes, but either no change or much less change in the amount of plasma membrane per cell than would have been predicted form the linear relationship between adipocyte volume and amount of plasma membrane per cell obtained with fed rats, i.e., adipocytes from fasted rats contain more plasma membrane per cell than do fat cells of the same size from fed rats. Neither feeding a high fat diet nor fasting caused detectable changes in the protein and lipid composition of the adipocyte plasma membrane

GAD Antibody-Associated Late-Onset Cerebellar Ataxia in Two Female Siblings

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Joseph Kuchling

2014-11-01

Full Text Available Background: Anti-glutamic acid decarboxylase antibody (GAD-ab-associated cerebellar ataxia is a rare neurological disorder characterized by cerebellar symptoms concomitant with high GAD-ab levels in serum and cerebrospinal fluid (CSF. Case Report: We report on 2 female siblings (aged 74 and 76 years presenting with gradual progression of rotational vertigo, gait ataxia and vertical diplopia, continuously progressing for 6 months and 6 years, respectively. Autoimmune laboratory examinations showed remarkably increased serum and CSF GAD-ab levels. Their medical histories revealed late-onset type 1 diabetes mellitus (T1DM and other concomitant autoimmune disorders (Grave's disease, Hashimoto's thyroiditis. Cerebral MRI and laboratory examinations were unremarkable. The diagnosis of GAD-ab-associated cerebellar ataxia with particular brainstem involvement was established in both women. After the exclusion of an underlying malignancy, immunosuppressive therapy has been initiated in both patients, which resulted in stabilization in one and in clinical improvement in the other patient. Discussion: The unique association of autoantibody-mediated cerebellar ataxia and late-onset T1DM in 2 siblings with similar clinical and paraclinical phenotypes strengthens the concept that hereditary factors might play a relevant role also in autoimmune diseases so far considered to be sporadic. Moreover, the occurrence of continuous vertical diplopia broadens the clinical spectrum of GAD-ab-associated neurological syndromes.

Cerebellar damage impairs the self-rating of regret feeling in a gambling task

Science.gov (United States)

Clausi, Silvia; Coricelli, Giorgio; Pisotta, Iolanda; Pavone, Enea Francesco; Lauriola, Marco; Molinari, Marco; Leggio, Maria

2015-01-01

Anatomical, clinical, and neuroimaging evidence implicates the cerebellum in processing emotions and feelings. Moreover recent studies showed a cerebellar involvement in pathologies such as autism, schizophrenia and alexithymia, in which emotional processing have been found altered. However, cerebellar function in the modulation of emotional responses remains debated. In this study, emotions that are involved directly in decision-making were examined in 15 patients (six males; age range 17–60 years) affected by cerebellar damage and 15 well matched healthy controls. We used a gambling task, in which subjects’ choices and evaluation of outcomes with regard to their anticipated and actual emotional impact were analyzed. Emotions, such as regret and relief, were elicited, based on the outcome of the unselected gamble. Interestingly, despite their ability to avoid regret in subsequent choices, patients affected by cerebellar lesions were significantly impaired in evaluating the feeling of regret subjectively. These results demonstrate that the cerebellum is involved in conscious recognizing of negative feelings caused by the sense of self-responsibility for an incorrect decision. PMID:25999829

Immunohistochemical localization of chondroitin sulfate, chondroitin sulfate proteoglycan, heparan sulfate proteoglycan, entactin, and laminin in basement membranes of postnatal developing and adult rat lungs

DEFF Research Database (Denmark)

Sannes, P L; Burch, K K; Khosla, J

1993-01-01

Histologic preparations of lungs from 1-, 5-, 10-, 18-, and 25-day-old postnatal and adult rats were examined immunohistochemically with antibodies specific against chondroitin sulfate (CS), basement membrane chondroitin sulfate proteoglycan (BM-CSPG), heparan sulfate proteoglycan (HSPG), entactin...

Human iPSC-Derived Cerebellar Neurons from a Patient with Ataxia-Telangiectasia Reveal Disrupted Gene Regulatory Networks

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Sam P. Nayler

2017-10-01

Full Text Available Ataxia-telangiectasia (A-T is a rare genetic disorder caused by loss of function of the ataxia-telangiectasia-mutated kinase and is characterized by a predisposition to cancer, pulmonary disease, immune deficiency and progressive degeneration of the cerebellum. As animal models do not faithfully recapitulate the neurological aspects, it remains unclear whether cerebellar degeneration is a neurodevelopmental or neurodegenerative phenotype. To address the necessity for a human model, we first assessed a previously published protocol for the ability to generate cerebellar neuronal cells, finding it gave rise to a population of precursors highly enriched for markers of the early hindbrain such as EN1 and GBX2, and later more mature cerebellar markers including PTF1α, MATH1, HOXB4, ZIC3, PAX6, and TUJ1. RNA sequencing was used to classify differentiated cerebellar neurons generated from integration-free A-T and control induced pluripotent stem cells. Comparison of RNA sequencing data with datasets from the Allen Brain Atlas reveals in vitro-derived cerebellar neurons are transcriptionally similar to discrete regions of the human cerebellum, and most closely resemble the cerebellum at 22 weeks post-conception. We show that patient-derived cerebellar neurons exhibit disrupted gene regulatory networks associated with synaptic vesicle dynamics and oxidative stress, offering the first molecular insights into early cerebellar pathogenesis of ataxia-telangiectasia.

Degenerative cerebellar diseases and differential diagnoses; Degenerative Kleinhirnerkrankungen und Differenzialdiagnosen

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Reith, W.; Roumia, S.; Dietrich, P. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany)

2016-11-15

Cerebellar syndromes result in distinct clinical symptoms, such as ataxia, dysarthria, dysmetria, intention tremor and eye movement disorders. In addition to the medical history and clinical examination, imaging is particularly important to differentiate other diseases, such as hydrocephalus and multi-infarct dementia from degenerative cerebellar diseases. Degenerative diseases with cerebellar involvement include Parkinson's disease, multiple system atrophy as well as other diseases including spinocerebellar ataxia. In addition to magnetic resonance imaging (MRI), nuclear medicine imaging investigations are also helpful for the differentiation. Axial fluid-attenuated inversion recovery (FLAIR) and T2-weighted sequences can sometimes show a signal increase in the pons as a sign of degeneration of pontine neurons and transverse fibers in the basilar part of the pons. The imaging is particularly necessary to exclude other diseases, such as normal pressure hydrocephalus (NPH), multi-infarct dementia and cerebellar lesions. (orig.) [German] Klinisch imponieren Kleinhirnsyndrome durch Ataxie, Dysarthrie, Dysmetrie, Intentionstremor und Augenbewegungsstoerungen. Neben der Anamnese und klinischen Untersuchung ist die Bildgebung v. a. wichtig um andere Erkrankungen wie Hydrozephalus und Multiinfarktdemenz von degenerativen Kleinhirnerkrankungen zu differenzieren. Zu den degenerativen Erkrankungen mit Kleinhirnbeteiligung gehoeren der Morbus Parkinson, die Multisystematrophie sowie weitere Erkrankungen einschliesslich der spinozerebellaeren Ataxien. Neben der MRT sind auch nuklearmedizinische Untersuchungen zur Differenzierung hilfreich. Axiale Fluid-attenuated-inversion-recovery(FLAIR)- und T2-gewichtete Sequenzen koennen mitunter eine Signalsteigerung im Pons als Ausdruck einer Degeneration der pontinen Neuronen und transversalen Bahnen im Brueckenfuss zeigen. Die Bildgebung ist aber v. a. notwendig, um andere Erkrankungen wie Normaldruckhydrozephalus

CT evaluation of cerebellar atrophy with aging in healthy persons

International Nuclear Information System (INIS)

Nishimiya, Jin

1988-01-01

In a retrospective analysis of CT scans available from 2,102 neurologically normal persons, dilatations of the cerebellar vermis fissures (CVF), cerebellar hemispheric fissures (CHF), subarachnoid space (SAS) around the cerebellum and the fourth ventricle (FV) were examined according the age groups of persons younger than one year, one to four, five to nine, 10 to 19, 20 to 29, 30 to 39, 40 to 49, 50 to 59, 60 to 69, and 70 years and older. An dilatation of both the CVF and CHF was associated with aging, with statistically significant differences among age groups of persons older than 20 years. This was especially noted in age groups of 60 years or older. There was a significant enlargement in the SAS around the cerebellum in age groups 60 years or more compared with age groups less than 60 years. For age groups of persons 20 years or older, both the FV transverse width and the radio of the FV transverse width to the inside diameter of the posterior fossa (PF) increased with aging. This was significant in age groups 60 years or older. For age groups younger than 10 years, however, there was inverse correlation between the ratio of the FV transverse width to the PF inside diameter and aging. Plotted curve of the ratio of the FV to the PF was U-shaped with smallest value in persons in their twenties. Since changes in the FV might reflect the volume of the cerebellar medullary substance, the cerebellar medullary substance should increase up to the age of 20. (Namekawa, K.)

PDE9A, PDE10A, and PDE11A expression in rat trigeminovascular pain signalling system

DEFF Research Database (Denmark)

Kruse, Lars S; Møller, Morten; Tibaek, Maiken

2009-01-01

as neocortex and cerebellar cortex. Real-time PCR and Western blotting showed that PDE9A, PDE10A and PDE11A are expressed in components of the rat trigeminovascular pain signalling system including middle cerebral artery, basilar artery, meninges, trigeminal ganglion and spinal trigeminal nucleus. Aorta...... and mesenteric artery as well as cerebral neocortex and cerebellar cortex also showed expression of PDE9A, PDE10A and PDE11A. Immunohistochemistry revealed that PDE9A, PDE10A and PDE11A are localised in the cytosol of nerve cell bodies of the trigeminal ganglion. We here present, for the first time...

MR diagnosis of cerebellar infarction due to vertebral artery dissection in children

International Nuclear Information System (INIS)

Cheon, J.E.; Kim, I.O.; Kim, W.S.; Yeon, K.M.; Hwang, Y.S.; Wang, K.C.