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Sample records for cerebellum

  1. Cerebellum and nonmotor function.

    Science.gov (United States)

    Strick, Peter L; Dum, Richard P; Fiez, Julie A

    2009-01-01

    Does the cerebellum influence nonmotor behavior? Recent anatomical studies demonstrate that the output of the cerebellum targets multiple nonmotor areas in the prefrontal and posterior parietal cortex, as well as the cortical motor areas. The projections to different cortical areas originate from distinct output channels within the cerebellar nuclei. The cerebral cortical area that is the main target of each output channel is a major source of input to the channel. Thus, a closed-loop circuit represents the major architectural unit of cerebro-cerebellar interactions. The outputs of these loops provide the cerebellum with the anatomical substrate to influence the control of movement and cognition. Neuroimaging and neuropsychological data supply compelling support for this view. The range of tasks associated with cerebellar activation is remarkable and includes tasks designed to assess attention, executive control, language, working memory, learning, pain, emotion, and addiction. These data, along with the revelations about cerebro-cerebellar circuitry, provide a new framework for exploring the contribution of the cerebellum to diverse aspects of behavior. PMID:19555291

  2. The cerebellum and psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Joseph ePhillips

    2015-05-01

    Full Text Available The cerebellum has been considered for a long time to play a role solely in motor coordination. However, studies over the past two decades have shown that the cerebellum also plays a key role in many motor, cognitive, and emotional processes. In addition, studies have also shown that the cerebellum is implicated in many psychiatric disorders including attention deficit hyperactivity disorder, autism spectrum disorders, schizophrenia, bipolar disorder, major depressive disorder and anxiety disorders. In this review, we discuss existing studies reporting cerebellar dysfunction in various psychiatric disorders. We will also discuss future directions for studies linking the cerebellum to psychiatric disorders.

  3. Regional functionality of the cerebellum.

    Science.gov (United States)

    Witter, Laurens; De Zeeuw, Chris I

    2015-08-01

    Over the recent years, advances in brain imaging, optogenetics and viral tracing have greatly advanced our understanding of the cerebellum and its connectivity. It has become clear that the cerebellum can be divided into functional units, each connected with particular brain areas involved in specific tasks, allowing afferent and efferent pathways to process task-specific information. The activity patterns in these pathways can be widely different among cerebellar areas. Therefore, it is expected that each cerebellar module is tailored to interpret inputs with a specific activity profile. In this paper we will review the evidence for region-specific inputs, region-specific connectivity with the rest of the brain, and region-specific processing within the cerebellum. PMID:25884963

  4. Cerebellum and Ocular Motor Control

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    Amir eKheradmand

    2011-09-01

    Full Text Available An intact cerebellum is a prerequisite for optimal ocular motor performance. The cerebellum fine-tunes each of the subtypes of eye movements so they work together to bring and maintain images of objects of interest on the fovea. Here we review the major aspects of the contribution of the cerebellum to ocular motor control. The approach will be based on structural-functional correlation, combining the effects of lesions and the results from physiologic studies, with the emphasis on the cerebellar regions known to be most closely related to ocular motor function: 1 the flocculus/paraflocculus for high-frequency (brief vestibular responses, sustained pursuit eye movements and gaze-holding, 2 the nodulus/ventral uvula for low-frequency (sustained vestibular responses, and 3 the dorsal oculomotor vermis and its target in the posterior portion of the fastigial nucleus (the fastigial oculomotor region for saccades and pursuit initiation.

  5. The Cerebellum and Neurodevelopmental Disorders.

    Science.gov (United States)

    Stoodley, Catherine J

    2016-02-01

    Cerebellar dysfunction is evident in several developmental disorders, including autism, attention deficit-hyperactivity disorder (ADHD), and developmental dyslexia, and damage to the cerebellum early in development can have long-term effects on movement, cognition, and affective regulation. Early cerebellar damage is often associated with poorer outcomes than cerebellar damage in adulthood, suggesting that the cerebellum is particularly important during development. Differences in cerebellar development and/or early cerebellar damage could impact a wide range of behaviors via the closed-loop circuits connecting the cerebellum with multiple cerebral cortical regions. Based on these anatomical circuits, behavioral outcomes should depend on which cerebro-cerebellar circuits are affected. Here, we briefly review cerebellar structural and functional differences in autism, ADHD, and developmental dyslexia, and discuss clinical outcomes following pediatric cerebellar damage. These data confirm the prediction that abnormalities in different cerebellar subregions produce behavioral symptoms related to the functional disruption of specific cerebro-cerebellar circuits. These circuits might also be crucial to structural brain development, as peri-natal cerebellar lesions have been associated with impaired growth of the contralateral cerebral cortex. The specific contribution of the cerebellum to typical development may therefore involve the optimization of both the structure and function of cerebro-cerebellar circuits underlying skill acquisition in multiple domains; when this process is disrupted, particularly in early development, there could be long-term alterations of these neural circuits, with significant impacts on behavior. PMID:26298473

  6. The Cerebellum as a Novel Tinnitus Generator

    OpenAIRE

    Bauer, Carol A.; Wisner, Kurt; Sybert, Lauren T.; Brozoski, Thomas J.

    2013-01-01

    The role of the cerebellum in auditory processing is largely unknown. Recently it was shown that rats with psychophysical evidence of tinnitus had significantly elevated neural activity in the paraflocculus of the cerebellum (PFL), as indicated by functional imaging. It was further shown that PFL activity was not elevated in normal rats listening to a tinnitus-like sound. This suggests that plastic changes in the PFL may underpin chronic tinnitus, i.e., it may serve as a tinnitus generator. U...

  7. The basal ganglia communicate with the cerebellum.

    Science.gov (United States)

    Bostan, Andreea C; Dum, Richard P; Strick, Peter L

    2010-05-01

    The basal ganglia and cerebellum are major subcortical structures that influence not only movement, but putatively also cognition and affect. Both structures receive input from and send output to the cerebral cortex. Thus, the basal ganglia and cerebellum form multisynaptic loops with the cerebral cortex. Basal ganglia and cerebellar loops have been assumed to be anatomically separate and to perform distinct functional operations. We investigated whether there is any direct route for basal ganglia output to influence cerebellar function that is independent of the cerebral cortex. We injected rabies virus (RV) into selected regions of the cerebellar cortex in cebus monkeys and used retrograde transneuronal transport of the virus to determine the origin of multisynaptic inputs to the injection sites. We found that the subthalamic nucleus of the basal ganglia has a substantial disynaptic projection to the cerebellar cortex. This pathway provides a means for both normal and abnormal signals from the basal ganglia to influence cerebellar function. We previously showed that the dentate nucleus of the cerebellum has a disynaptic projection to an input stage of basal ganglia processing, the striatum. Taken together these results provide the anatomical substrate for substantial two-way communication between the basal ganglia and cerebellum. Thus, the two subcortical structures may be linked together to form an integrated functional network. PMID:20404184

  8. Psychiatry, Neurology, and the Role of the Cerebellum

    OpenAIRE

    Gillig, Paulette Marie; Sanders, Richard D.

    2010-01-01

    The cerebellum has long been considered quite separate from the neocortex, and accordingly the understanding of its role has been limited. Recent work has revealed that the cerebellum interacts regularly with the forebrain and it is involved in mood and cognition. In this article, the authors discuss an extensive system of neural circuits connecting the prefrontal, temporal, posterior parietal, and limbic cortices with the cerebellum. Language functions of the cerebellum are described, as wel...

  9. The neurochemical maturation of the rabbit cerebellum.

    OpenAIRE

    Lossi, L; Ghidella, S; Marroni, P.; Merighi, A

    1995-01-01

    The immunocytochemical distribution of several neuronal and glial antigens was investigated in the cerebellum of the developing and adult rabbit. Neurofilament positive neurons appeared at embryonic day (E) 25. Purkinje cells transiently expressed neurofilament polypeptides from postnatal day (P) 0 to 15. At later postnatal ages, staining was localised to the parallel fibres, the axonal arbors of the basket cells and fibres of the white matter. Neuron specific enolase (NSE) immunoreactivity w...

  10. The cerebellum as a novel tinnitus generator.

    Science.gov (United States)

    Bauer, Carol A; Kurt, Wisner; Sybert, Lauren T; Brozoski, Thomas J

    2013-01-01

    The role of the cerebellum in auditory processing is largely unknown. Recently it was shown that rats with psychophysical evidence of tinnitus had significantly elevated neural activity in the paraflocculus of the cerebellum (PFL), as indicated by functional imaging. It was further shown that PFL activity was not elevated in normal rats listening to a tinnitus-like sound. This suggests that plastic changes in the PFL may underpin chronic tinnitus, i.e., it may serve as a tinnitus generator. Using a rat model of acoustic trauma-induced tinnitus, the role of the cerebellum was further examined in a series of experiments:The PFL was surgically ablated in animals with established tinnitus; the PFL was surgically ablated in animals before induction of tinnitus; the PFL was reversibly inactivated by chronic lidocaine infusion into the subarcuate fossa of animals with established tinnitus. It was found that PFL ablation eliminated established tinnitus without altering auditory discrimination. Similar to the ablation results, PFL inactivation with lidocaine reversibly eliminated existing tinnitus. In contrast however, PFL ablation before tinnitus induction attenuated, but did not completely eliminate, tinnitus. In a rat model of noise-induced chronic tinnitus, the cerebellar PFL may serve as a sufficient but non-obligatory generator of tinnitus. PMID:23418634

  11. Quantitative examination of the bottlenose dolphin cerebellum.

    Science.gov (United States)

    Hanson, Alicia; Grisham, William; Sheh, Colleen; Annese, Jacopo; Ridgway, Sam

    2013-08-01

    Neuroanatomical research into the brain of the bottlenose dolphin (Tursiops truncatus) has revealed striking similarities with the human brain in terms of size and complexity. However, the dolphin brain also contains unique allometric relationships. When compared to the human brain, the dolphin cerebellum is noticeably larger. Upon closer examination, the lobule composition of the cerebellum is distinct between the two species. In this study, we used magnetic resonance imaging to analyze cerebellar anatomy in the bottlenose dolphin and measure the volume of the separate cerebellar lobules in the bottlenose dolphin and human. Lobule identification was assisted by three-dimensional modeling. We find that lobules VI, VIIb, VIII, and IX are the largest lobules of the bottlenose dolphin cerebellum, while the anterior lobe (I-V), crus I, crus II, and the flocculonodular lobe are smaller. Different lobule sizes may have functional implications. Auditory-associated lobules VIIb, VIII, IX are likely large in the bottlenose dolphin due to echolocation abilities. Our study provides quantitative information on cerebellar anatomy that substantiates previous reports based on gross observation and subjective analysis. This study is part of a continuing effort toward providing explicit descriptions of cetacean neuroanatomy to support the interpretation of behavioral studies on cetacean cognition. PMID:23775830

  12. Pilomyxoid astrocytoma in the adult cerebellum.

    Science.gov (United States)

    Chen, Annie S; Paldor, Iddo; Tsui, Alpha E; Yuen, Tanya I

    2016-05-01

    Pilomyxoid astrocytoma (PMA) is a recently recognised World Health Organization (WHO) Grade II tumour that was previously characterised as a subtype of the WHO Grade I pilocytic astrocytoma (PA). PMA has a histological appearance distinct from PA and a poorer prognosis due to its greater propensity for local recurrence and cerebrospinal dissemination. Although originally considered a paediatric tumour involving mainly the hypothalamic and chiasmatic region, reports of the lesion occurring in the adult population and other areas of the neuroaxis are emerging. We review the literature on PMA within the adult population and present the first case of PMA in the cerebellum of an adult female. PMID:26777083

  13. New roles for the cerebellum in health and disease

    OpenAIRE

    Reeber, Stacey L.; Otis, Tom S.; Sillitoe, Roy V.

    2013-01-01

    The cerebellum has a well-established role in maintaining motor coordination and studies of cerebellar learning suggest that it does this by recognizing neural patterns, which it uses to predict optimal movements. Serious damage to the cerebellum impairs this learning and results in a set of motor disturbances called ataxia. However, recent work implicates the cerebellum in cognition and emotion, and it has been argued that cerebellar dysfunction contributes to non-motor conditions such as au...

  14. Encoding of Sensory Prediction Errors in the Human Cerebellum

    OpenAIRE

    Schlerf, John; Richard B. Ivry; Diedrichsen, Jörn

    2012-01-01

    A central tenet of motor neuroscience is that the cerebellum learns from sensory prediction errors. Surprisingly, neuroimaging studies have not revealed definitive signatures of error processing in the cerebellum. Furthermore, neurophysiologic studies suggest an asymmetry, such that the cerebellum may encode errors arising from unexpected sensory events, but not errors reflecting the omission of expected stimuli. We conducted an imaging study to compare the cerebellar response to these two ty...

  15. The Cerebellum and Premenstrual Dysphoric Disorder

    Directory of Open Access Journals (Sweden)

    Andrea J. Rapkin

    2014-07-01

    Full Text Available The cerebellum constitutes ten percent of brain volume and contains the majority of brain neurons. Although it was historically viewed primarily as processing motoric computations, current evidence supports a more comprehensive role, where cerebro-cerebellar feedback loops also modulate various forms of cognitive and affective processing. Here we present evidence for a role of the cerebellum in premenstrual dysphoric disorder (PMDD, which is characterized by severe negative mood symptoms during the luteal phase of the menstrual cycle. Although a link between menstruation and cyclical dysphoria has long been recognized, neuroscientific investigations of this common disorder have only recently been explored. This article reviews functional and structural brain imaging studies of PMDD and the similar but less well defined condition of premenstrual syndrome (PMS. The most consistent findings are that women with premenstrual dysphoria exhibit greater relative activity than other women in the dorsolateral prefrontal cortex and posterior lobules VI and VII of the neocerebellum. Since both brain areas have been implicated in emotional processing and mood disorders, working memory and executive functions, this greater activity probably represents coactivation within a cerebro-cerebellar feedback loop regulating emotional and cognitive processing. Some of the evidence suggests that increased activity within this circuit may preserve cerebellar structure during aging, and possible mechanisms and implications of this finding are discussed.

  16. How the cerebellum may monitor sensory information for spatial representation

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    Laure eRondi-Reig

    2014-11-01

    Full Text Available The cerebellum has already been shown to participate in the navigation function. We propose here that this structure is involved in maintaining a sense of direction and location during self-motion by monitoring sensory information and interacting with navigation circuits to update the mental representation of space.To better understand the processing performed by the cerebellum in the navigation function, we have reviewed: the anatomical pathways that convey self-motion information to the cerebellum; the computational algorithm(s thought to be performed by the cerebellum from these multi-source inputs; the cerebellar outputs directed toward navigation circuits and the influence of self-motion information on space-modulated cells receiving cerebellar outputs. This review highlights that the cerebellum is adequately wired to combine the diversity of sensory signals to be monitored during self-motion and fuel the navigation circuits. The direct anatomical projections of the cerebellum toward the head-direction cell system and the parietal cortex make those structures possible relays of the cerebellum influence on the hippocampal spatial map. We describe computational models of the cerebellar function showing that the cerebellum can filter out the components of the sensory signals that are predictable, and provides a novelty output. We finally speculate that this novelty output is taken into account by the navigation structures, which implement an update over time of position and stabilize perception during navigation.

  17. Functional Anatomy Of The Intermediate Cerebellum In The Rat

    NARCIS (Netherlands)

    W.C.T.M. Pijpers (Angelique)

    2007-01-01

    textabstractThe cerebellum is situated in the posterior part of the scull, dorsal to the brainstem and pontine nuclei (Fig.1). Despite the fact that it is called “little brain” it harbors about half of the total number of neurons within the central nervous system (Kandel, 2003). The cerebellum is di

  18. The cerebellum: a neuronal learning machine?

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    Raymond, J. L.; Lisberger, S. G.; Mauk, M. D.

    1996-01-01

    Comparison of two seemingly quite different behaviors yields a surprisingly consistent picture of the role of the cerebellum in motor learning. Behavioral and physiological data about classical conditioning of the eyelid response and motor learning in the vestibulo-ocular reflex suggests that (i) plasticity is distributed between the cerebellar cortex and the deep cerebellar nuclei; (ii) the cerebellar cortex plays a special role in learning the timing of movement; and (iii) the cerebellar cortex guides learning in the deep nuclei, which may allow learning to be transferred from the cortex to the deep nuclei. Because many of the similarities in the data from the two systems typify general features of cerebellar organization, the cerebellar mechanisms of learning in these two systems may represent principles that apply to many motor systems.

  19. The cerebellum for jocks and nerds alike

    Directory of Open Access Journals (Sweden)

    Timothy J Ebner

    2014-06-01

    Full Text Available Historically the cerebellum has been implicated in the control of movement. However, the cerebellum’s role in non-motor functions, including cognitive and emotional processes, has also received increasing attention. Starting from the premise that the uniform architecture of the cerebellum underlies a common mode of information processing, this review examines recent electrophysiological findings on the motor signals encoded in the cerebellar cortex and then relates these signals to observations in the non-motor domain. Simple spike firing of individual Purkinje cells encodes performance errors, both predicting upcoming errors as well as providing feedback about those errors. Further, this dual temporal encoding of prediction and feedback involves a change in the sign of the simple spike modulation. Therefore, Purkinje cell simple spike firing both predicts and responds to feedback about a specific parameter, consistent with computing sensory prediction errors in which the predictions about the consequences of a motor command are compared with the feedback resulting from the motor command execution. These new findings are in contrast with the historical view that complex spikes encode errors. Evaluation of the kinematic coding in the simple spike discharge shows the same dual temporal encoding, suggesting this is a common mode of signal processing in the cerebellar cortex. Decoding analyses show the considerable accuracy of the predictions provided by Purkinje cells across a range of times. Further, individual Purkinje cells encode linearly and independently a multitude of signals, both kinematic and performance errors. Therefore, the cerebellar cortex’s capacity to make associations across different sensory, motor and non-motor signals is large. The results from studying how Purkinje cells encode movement signals suggest that the cerebellar cortex circuitry can support associative learning, sequencing, working memory, and forward internal

  20. Linking Essential Tremor to the Cerebellum: Neurochemical Evidence.

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    Marin-Lahoz, Juan; Gironell, Alexandre

    2016-06-01

    The pathophysiology and the exact anatomy of essential tremor (ET) is not well known. One of the pillars that support the cerebellum as the main anatomical locus in ET is neurochemistry. This review examines the link between neurochemical abnormalities found in ET and cerebellum. The review is based on published data about neurochemical abnormalities described in ET both in human and in animal studies. We try to link those findings with cerebellum. γ-aminobutyric acid (GABA) is the main neurotransmitter involved in the pathophysiology of ET. There are several studies about GABA that clearly points to a main role of the cerebellum. There are few data about other neurochemical abnormalities in ET. These include studies with noradrenaline, glutamate, adenosine, proteins, and T-type calcium channels. One single study reveals high levels of noradrenaline in the cerebellar cortex. Another study about serotonin neurotransmitter results negative for cerebellum involvement. Finally, studies on T-type calcium channels yield positive results linking the rhythmicity of ET and cerebellum. Neurochemistry supports the cerebellum as the main anatomical locus in ET. The main neurotransmitter involved is GABA, and the GABA hypothesis remains the most robust pathophysiological theory of ET to date. However, this hypothesis does not rule out other mechanisms and may be seen as the main scaffold to support findings in other systems. We clearly need to perform more studies about neurochemistry in ET to better understand the relations among the diverse systems implied in ET. This is mandatory to develop more effective pharmacological therapies. PMID:26498765

  1. Trace element distribution in the rat cerebellum

    International Nuclear Information System (INIS)

    Spatial distributions and concentrations of trace elements (TE) in the brain are important because TE perform catalytic structural functions in enzymes which regulate brain function and development. We have investigated the distributions of TE in rat cerebellum. Structures were sectioned and analyzed by the Synchrotron Radiation Induced X-ray Emission (SRIXE) method using the NSLS X-26 white-light microprobe facility. Advantages important for TE analysis of biological specimens with x-ray microscopy include short time of measurement, high brightness and flux, good spatial resolution, multielemental detection, good sensitivity, and non-destructive irradiation. Trace elements were measured in thin rat brain sections of 20-micrometers thickness. The analyses were performed on sample volumes as small as 0.2 nl with Minimum Detectable Limits (MDL) of 50 ppb wet weight for Fe, 100 ppb wet weight for Cu, and Zn, and 1 ppM wet weight for Pb. The distribution of TE in the molecular cell layer, granule cell layer and fiber tract of rat cerebella was investigated. Both point analyses and two-dimensional semi-quantitative mapping of the TE distribution in a section were used

  2. Ectopic anterior cerebellum (ala lobule centralis).

    Science.gov (United States)

    Algin, Oktay; Ozmen, Evrim

    2015-06-01

    In this case report we present an adolescent girl who was referred to our radiology department for assessment with advanced magnetic resonance (MR) imaging on suspicion of low-grade quadrigeminal cistern neoplasm on 1.5 Tesla MR examination. We were able to evaluate detailed cerebellar anatomy more clearly, and detected that the lesion was compatible with ectopic cerebellar tissue (a very rare developmental variation) on submillimetric 3-dimensional (3D) images from a 3 Tesla MR unit which has a 32-channel head coil. Our findings were further supported by diffusion tensor imaging which clearly indicated that the lesion was a part of the cerebellum. Furthermore, MR spectroscopic metabolite ratios were in accordance with the characteristics of normal neuronal tissue. As far we know there is no published report that contains similar findings to those of our patient. In conclusion, cranial MR images, if possible in 3D format (with very small isotropic voxels) should be obtained for the precise diagnosis of the lesions located in this region; in addition, the differential diagnostic list should be well known and advanced imaging techniques should be used when necessary. PMID:26246096

  3. Reciprocal evolution of the cerebellum and neocortex in fossil humans

    OpenAIRE

    Weaver, Anne H.

    2005-01-01

    Human brain evolution involved both neurological reorganization and an increase in overall brain volume relative to body mass. It is generally difficult to draw functional inferences about the timing and nature of brain reorganization, given that superficial brain morphology recorded on fossil endocasts is functionally ambiguous. However, the cerebellum, housed in the clearly delineated posterior cranial fossa, is functionally and ontologically discrete. The cerebellum is reciprocally connect...

  4. Temporal learning in the cerebellum: The microcircuit model

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    Miles, Coe F.; Rogers, David

    1990-01-01

    The cerebellum is that part of the brain which coordinates motor reflex behavior. To perform effectively, it must learn to generate specific motor commands at the proper times. We propose a fundamental circuit, called the MicroCircuit, which is the minimal ensemble of neurons both necessary and sufficient to learn timing. We describe how learning takes place in the MicroCircuit, which then explains the global behavior of the cerebellum as coordinated MicroCircuit behavior.

  5. Autism Spectrum Disorders and Neuropathology of the Cerebellum

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    David R Hampson

    2015-11-01

    Full Text Available The cerebellum contains the largest number of neurons and synapses of any structure in the central nervous system. The concept that the cerebellum is solely involved in fine motor function has become outdated; substantial evidence has accumulated linking the cerebellum with higher cognitive functions including language. Cerebellar deficits have been implicated in autism for more than two decades. The computational power of the cerebellum is essential for many, if not most of the processes that are perturbed in autism including language and communication, social interactions, stereotyped behavior, motor activity and motor coordination, and higher cognitive functions. The link between autism and cerebellar dysfunction should not be surprising to those who study its cellular, physiological, and functional properties. Postmortem studies have revealed neuropathological abnormalities in cerebellar cellular architecture while studies on mouse lines with cell loss or mutations in single genes restricted to cerebellar Purkinje cells have also strongly implicated this brain structure in contributing to the autistic phenotype. This connection has been further substantiated by studies investigating brain damage in humans restricted to the cerebellum. In this review, we summarize advances in research on idiopathic autism and three genetic forms of autism that highlight the key roles that the cerebellum plays in this spectrum of neurodevelopmental disorders.

  6. Anomalous extracellular diffusion in rat cerebellum.

    Science.gov (United States)

    Xiao, Fanrong; Hrabe, Jan; Hrabetova, Sabina

    2015-05-01

    Extracellular space (ECS) is a major channel transporting biologically active molecules and drugs in the brain. Diffusion-mediated transport of these substances is hindered by the ECS structure but the microscopic basis of this hindrance is not fully understood. One hypothesis proposes that the hindrance originates in large part from the presence of dead-space (DS) microdomains that can transiently retain diffusing molecules. Because previous theoretical and modeling work reported an initial period of anomalous diffusion in similar environments, we expected that brain regions densely populated by DS microdomains would exhibit anomalous extracellular diffusion. Specifically, we targeted granular layers (GL) of rat and turtle cerebella that are populated with large and geometrically complex glomeruli. The integrative optical imaging (IOI) method was employed to evaluate diffusion of fluorophore-labeled dextran (MW 3000) in GL, and the IOI data analysis was adapted to quantify the anomalous diffusion exponent dw from the IOI records. Diffusion was significantly anomalous in rat GL, where dw reached 4.8. In the geometrically simpler turtle GL, dw was elevated but not robustly anomalous (dw = 2.6). The experimental work was complemented by numerical Monte Carlo simulations of anomalous ECS diffusion in several three-dimensional tissue models containing glomeruli-like structures. It demonstrated that both the duration of transiently anomalous diffusion and the anomalous exponent depend on the size of model glomeruli and the degree of their wrapping. In conclusion, we have found anomalous extracellular diffusion in the GL of rat cerebellum. This finding lends support to the DS microdomain hypothesis. Transiently anomalous diffusion also has a profound effect on the spatiotemporal distribution of molecules released into the ECS, especially at diffusion distances on the order of a few cell diameters, speeding up short-range diffusion-mediated signals in less permeable

  7. PECULIARITIES OF THE CEREBELLUM NUCLEI IN AGED PERSONS.

    Science.gov (United States)

    Shyian, D; Galata, D; Potapov, S; Gargin, V

    2016-04-01

    The study of the clinical anatomy and functional features of the cortex, subcortical and conductive pathways of the cerebellum is necessary for clinicians for elaboration rational surgical approaches to these formations, for determination the localization of pathological processes associated with these formations. Cerebellar nucleus neurons are crucial to the olivo-cerebellar circuit as they provide the sole output of the entire cerebellum. The relationship between mobility and cognition in aging is well established, but the relationship between mobility and the structure and function of the aging brain is relatively unknown. In connection with the above, the purpose of our study was detection of the morphological characteristics of the cerebellum nuclei in aged persons. Study was performed on 48 specimens of the cerebellum from people (24 male and 24 female), who died at the age from 75 to 99 years due to diseases, which were not related to the central nervous system damaging. Formalin-fixed human hemispheres were dissected with the Ludwig and Klingler fiber dissection technique under x6 to x40 magnifications of binocular microscope Olympus BX41 (Japan). The morphological features of the human cerebellar nuclei were established. Namely, on the series of sections of the cerebellum in the horizontal, frontal and sagittal planes, as well as on the macro-microscopic preparations of the cerebellar nuclei location, their relative position, shape, linear dimensions, weight and volume were described. The features of macro-microscopic and histological structure of the nuclei of the cerebellum were made own classification of the gyri and teeth of the dentate nucleus of the cerebellum was offered. Macro-microscopic dissection of persons died after 75 years old show no significant variability of linear dimensions of cerebellar nuclei with their specific location and options. Simultaneously, reliable reducing of cellular density was detected for Purkinje, granule and basket

  8. PATTERN FORMATION DURING DEVELOPMENT OF THE EMBRYONIC CEREBELLUM

    OpenAIRE

    Richard Hawkes

    2012-01-01

    The patterning of the embryonic cerebellum is vital to establish the elaborate zone and stripe architecture of the adult. This review considers early stages in cerebellar Purkinje cell patterning, from the organization of the ventricular zone to the development of Purkinje cell clusters – the precursors of the adult stripes.

  9. Autism and the Cerebellum: Evidence from Tuberous Sclerosis.

    Science.gov (United States)

    Weber, Anna M.; Egelhoff, John C.; McKellop, J. Mark; Franz, David Neal

    2000-01-01

    A study examined the relationship between neuroimaging findings and the behavioral characteristics of 29 patients with tuberous sclerosis. Findings indicate a positive linear relationship between a patient's total number of tubers and degree of intellectual impairment. The number of tubers in the cerebellum was associated with more autistic…

  10. New roles for the cerebellum in health and disease

    Directory of Open Access Journals (Sweden)

    Stacey L Reeber

    2013-11-01

    Full Text Available The cerebellum has a well-established role in maintaining motor coordination and studies of cerebellar learning suggest that it does this by recognizing neural patterns, which it uses to predict optimal movements. Serious damage to the cerebellum impairs this learning and results in a set of motor disturbances called ataxia. However, recent work implicates the cerebellum in cognition and emotion, and it has been argued that cerebellar dysfunction contributes to non-motor conditions such as autism spectrum disorders. Based on human and animal model studies, two major questions arise. Does the cerebellum contribute to non-motor as well as motor diseases, and if so, how does altering its function contribute to such diverse symptoms? The architecture and connectivity of cerebellar circuits may hold the answers to these questions. An emerging view is that cerebellar defects can trigger motor and non-motor neurological conditions by globally influencing brain function. Furthermore, during development cerebellar circuits may play a role in wiring events necessary for higher cognitive functions such as social behavior and language. We discuss genetic, electrophysiological, and behavioral evidence that implicates Purkinje cell dysfunction as a major culprit in several diseases and offer a hypothesis as to how canonical cerebellar functions might be at fault in non-motor as well as motor diseases.

  11. Comparative morphology of the avian cerebellum: I. Degree of foliation.

    Science.gov (United States)

    Iwaniuk, Andrew N; Hurd, Peter L; Wylie, Douglas R W

    2006-01-01

    Despite the conservative circuitry of the cerebellum, there is considerable variation in the shape of the cerebellum among vertebrates. One aspect of cerebellar morphology that is of particular interest is the degree of folding, or foliation, of the cerebellum and its functional significance. Here, we present the first comprehensive analysis of variation in cerebellar foliation in birds with the aim of determining the effects that allometry, phylogeny and development have on species differences in the degree of cerebellar foliation. Using both conventional and phylogenetically based statistics, we assess the effects of these variables on cerebellar foliation among 91 species of birds. Overall, our results indicate that allometry exerts the strongest effect and accounts for more than half of the interspecific variation in cerebellar foliation. In addition, we detected a significant phylogenetic effect. A comparison among orders revealed that several groups, corvids, parrots and seabirds, have significantly more foliated cerebella than other groups, after accounting for allometric effects. Lastly, developmental mode was weakly correlated with relative cerebellar foliation, but incubation period and fledging age were not. From our analyses, we conclude that allometric and phylogenetic effects exert the strongest effects and developmental mode a weak effect on avian cerebellar foliation. The phylogenetic distribution of highly foliated cerebella also suggests that cognitive and/or behavioral differences play a role in the evolution of the cerebellum. PMID:16717442

  12. Linking Essential Tremor to the Cerebellum: Clinical Evidence.

    Science.gov (United States)

    Benito-León, Julián; Labiano-Fontcuberta, Andrés

    2016-06-01

    Essential tremor (ET) might be a family of diseases unified by the presence of kinetic tremor, but also showing etiological, pathological, and clinical heterogeneity. In this review, we will describe the most significant clinical evidence, which suggests that ET is linked to the cerebellum. Data for this review were identified by searching PUBMED (January 1966 to May 2015) crossing the terms "essential tremor" (ET) and "cerebellum," which yielded 201 entries, 11 of which included the term "cerebellum" in the article title. This was supplemented by articles in the author's files that pertained to this topic. The wide spectrum of clinical features of ET that suggest that it originates as a cerebellar or cerebellar outflow problem include the presence of intentional tremor, gait and balance abnormalities, subtle features of dysarthria, and oculomotor abnormalities, as well as deficits in eye-hand coordination, motor learning deficits, incoordination during spiral drawing task, abnormalities in motor timing and visual reaction time, impairment of social abilities, improvement in tremor after cerebellar stroke, efficacy of deep brain stimulation (which blocks cerebellar outflow), and cognitive dysfunction. It is unlikely, however, that cerebellar dysfunction, per se, fully explains ET-associated dementia, because the cognitive deficits that have been described in patients with cerebellar lesions are generally mild. Overall, a variety of clinical findings suggest that in at least a sizable proportion of patients with ET, there is an underlying abnormality of the cerebellum and/or its pathways. PMID:26521074

  13. Pattern formation during development of the embryonic cerebellum

    OpenAIRE

    Dastjerdi, F. V.; Consalez, G G; Hawkes, R

    2012-01-01

    The patterning of the embryonic cerebellum is vital to establish the elaborate zone and stripe architecture of the adult. This review considers early stages in cerebellar Purkinje cell patterning, from the organization of the ventricular zone to the development of Purkinje cell clusters—the precursors of the adult stripes.

  14. Oscillations, Timing, Plasticity, and Learning in the Cerebellum.

    Science.gov (United States)

    Cheron, G; Márquez-Ruiz, J; Dan, B

    2016-04-01

    The highly stereotyped, crystal-like architecture of the cerebellum has long served as a basis for hypotheses with regard to the function(s) that it subserves. Historically, most clinical observations and experimental work have focused on the involvement of the cerebellum in motor control, with particular emphasis on coordination and learning. Two main models have been suggested to account for cerebellar functioning. According to Llinás's theory, the cerebellum acts as a control machine that uses the rhythmic activity of the inferior olive to synchronize Purkinje cell populations for fine-tuning of coordination. In contrast, the Ito-Marr-Albus theory views the cerebellum as a motor learning machine that heuristically refines synaptic weights of the Purkinje cell based on error signals coming from the inferior olive. Here, we review the role of timing of neuronal events, oscillatory behavior, and synaptic and non-synaptic influences in functional plasticity that can be recorded in awake animals in various physiological and pathological models in a perspective that also includes non-motor aspects of cerebellar function. We discuss organizational levels from genes through intracellular signaling, synaptic network to system and behavior, as well as processes from signal production and processing to memory, delegation, and actual learning. We suggest an integrative concept for control and learning based on articulated oscillation templates. PMID:25808751

  15. Multiple sclerosis impairs regional functional connectivity in the cerebellum

    DEFF Research Database (Denmark)

    Dogonowski, Anne-Marie; Andersen, Kasper Winther; Madsen, Kristoffer Hougaard;

    2013-01-01

    . Patients with MS showed a decrease in regional homogeneity in the upper left cerebellar hemisphere in lobules V and VI relative to healthy controls. Similar trend changes in regional homogeneity were present in the right cerebellar hemisphere. The results indicate a disintegration of regional processing in...... the cerebellum in MS. This might be caused by a functional disruption of cortico-ponto-cerebellar and spino-cerebellar inputs, since patients with higher lesion load in the left cerebellar peduncles showed a stronger reduction in cerebellar homogeneity. In patients, two clusters in the left posterior...... cerebellum expressed a reduction in regional homogeneity with increasing global disability as reflected by the Expanded Disability Status Scale (EDSS) score or higher ataxia scores. The two clusters were mainly located in Crus I and extended into Crus II and the dentate nucleus but with little spatial...

  16. Electrophysiological Representation of Scratching CPG Activity in the Cerebellum

    OpenAIRE

    Martínez-Silva, Lourdes; Manjarrez, Elias; Gutiérrez-Ospina, Gabriel; Quevedo, Jorge N.

    2014-01-01

    We analyzed the electrical activity of neuronal populations in the cerebellum and the lumbar spinal cord during fictive scratching in adult decerebrate cats before and after selective sections of the Spino-Reticulo Cerebellar Pathway (SRCP) and the Ventral-Spino Cerebellar Tract (VSCT). During fictive scratching, we found a conspicuous sinusoidal electrical activity, called Sinusoidal Cerebellar Potentials (SCPs), in the cerebellar vermis, which exhibited smaller amplitude in the paravermal a...

  17. The Cerebellum in Emotional Processing: Evidence from Human and Non-Human Animals

    Directory of Open Access Journals (Sweden)

    Wanda M. Snow

    2014-06-01

    Full Text Available The notion that the cerebellum is a central regulator of motor function is undisputed. There exists, however, considerable literature to document a similarly vital role for the cerebellum in the regulation of various non-motor domains, including emotion. Research from numerous avenues of investigation (i.e., neurophysiological, behavioural, electrophysiological, imagining, lesion, and clinical studies have documented the importance of the cerebellum, in particular, the vermis, in affective processing that appears preserved across species. The cerebellum possesses a distinct laminar arrangement and highly organized neuronal circuitry. Moreover, the cerebellum forms reciprocal connections with several brain regions implicated in diverse functional domains, including motor, sensory, and emotional processing. It has been argued that these unique neuroanatomical features afford the cerebellum with the capacity to integrate information about an organism, its environment, and its place within the environment such that it can respond in an appropriate, coordinated fashion, with such theories extending to the regulation of emotion. This review puts our current understanding of the cerebellum and its role in behaviour in historical perspective, presents an overview of the neuroanatomical and functional organization of the cerebellum, and reviews the literature describing the involvement of the cerebellum in emotional regulation in both humans and non-human animals. In summary, this review discusses the importance of the functional connectivity of the cerebellum with various brain regions in the ability of the cerebellum to effectively regulate emotional behaviour.

  18. Cell population-specific expression analysis of human cerebellum

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    Kuhn Alexandre

    2012-11-01

    Full Text Available Abstract Background Interpreting gene expression profiles obtained from heterogeneous samples can be difficult because bulk gene expression measures are not resolved to individual cell populations. We have recently devised Population-Specific Expression Analysis (PSEA, a statistical method that identifies individual cell types expressing genes of interest and achieves quantitative estimates of cell type-specific expression levels. This procedure makes use of marker gene expression and circumvents the need for additional experimental information like tissue composition. Results To systematically assess the performance of statistical deconvolution, we applied PSEA to gene expression profiles from cerebellum tissue samples and compared with parallel, experimental separation methods. Owing to the particular histological organization of the cerebellum, we could obtain cellular expression data from in situ hybridization and laser-capture microdissection experiments and successfully validated computational predictions made with PSEA. Upon statistical deconvolution of whole tissue samples, we identified a set of transcripts showing age-related expression changes in the astrocyte population. Conclusions PSEA can predict cell-type specific expression levels from tissues homogenates on a genome-wide scale. It thus represents a computational alternative to experimental separation methods and allowed us to identify age-related expression changes in the astrocytes of the cerebellum. These molecular changes might underlie important physiological modifications previously observed in the aging brain.

  19. Effect of Maternal Diabetes on Cerebellum Histomorphometry in Neonatal Rats

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    Z Khaksar

    2010-04-01

    Full Text Available Introduction: In pregnant mothers, maternal diabetes occurs when pancreas can't produce enough insulin resulting in increased blood glucose levels in the mother and subsequently in the fetus. This investigation was conducted to evaluate the effects of maternal diabetes on cerebellum of offspring of diabetic mothers (ODM, which was carried out at the veterinary faculty of Shiraz University in 2007-2008. Methods: This was an experimental study that included sixteen normal adult female rats divided in two groups. Diabetes was induced in one group by Alloxan agent. Both groups became pregnant by natural mating . At 7, 14, 21 and 28 days after birth, the cerebellum of all offsprings were collected and the weight of neonates was also measured. After producing histological slides, Olympus BX51 microscope and ‍‍‍‍‍‍‍ Olysia softwarwere used. Various histological parameters used included gray and white matters thicknesses (µ, the number of cells in gray and white matter separately per unit and the ratio of gray matter to white matter. Results: Cerebellar parameters decreased in ODM as compared to the control group. The body weight of ODM was significantly more than that of the control group (p< 0.05. Conclusions: Maternal hyperglycaemia exhibited deleterious effects on cerebellum during fetal life, which remained persistent during postneonatal period. Maternal diabetes also resulted in reduction of number of cells and thicknesses of both gray and white matter.

  20. STUDY ON THE GROWTH OF CEREBELLUM IN NEWBORN INFANTS

    Institute of Scientific and Technical Information of China (English)

    张伟利; 钟美萍; 吴圣楣; 罗敏洁

    2000-01-01

    Objective To know the growth of the cerebellum in newborn infants. Methods The central vermian area (CVA) of the cerebellum was measured by head ultrasonography in 90 newborns including 65full- terms, 14 preterms and 11 small for gestational age infants (SGA). Results The average age of the newborn infants were 4.7d (3~7d). The mean CVA in full- terms was 5.8±0.8cm2, which was significantly greater than that in preterms (3.7±1.0cm2), and SGA (5.1±0.8cm2), respectively. However, when corrected for birth weight (BW), the ratio of CVA/BW in term SGA was 2.07, being significantly higher than the ratio of 1.72 in normal full-term newborns. There was no difference between male and female infants. Statistically significant relationships were found between CVA and BW (r=0.8129, P<0.01) and between CVA and gestational age (r=0.7450, P<0.01). Conclusion The study provide some understanding on the growth of the cerebellum, and the cerebellar measurement by cranial ultrasound is helpful for the assessment of neurological maturation in newborn infants.

  1. Chronic hyperammonemia induces tonic activation of NMDA receptors in cerebellum.

    Science.gov (United States)

    ElMlili, Nisrin; Boix, Jordi; Ahabrach, Hanan; Rodrigo, Regina; Errami, Mohammed; Felipo, Vicente

    2010-02-01

    Reduced function of the glutamate--nitric oxide (NO)--cGMP pathway is responsible for some cognitive alterations in rats with hyperammonemia and hepatic encephalopathy. Hyperammonemia impairs the pathway in cerebellum by increasing neuronal nitric oxide synthase (nNOS) phosphorylation in Ser847 by calcium-calmodulin-dependent protein kinase II (CaMKII), reducing nNOS activity, and by reducing nNOS amount in synaptic membranes, which reduces its activation following NMDA receptors activation. The reason for increased CaMKII activity in hyperammonemia remains unknown. We hypothesized that it would be as a result of increased tonic activation of NMDA receptors. The aims of this work were to assess: (i) whether tonic NMDA activation receptors is increased in cerebellum in chronic hyperammonemia in vivo; and (ii) whether this tonic activation is responsible for increased CaMKII activity and reduced activity of nNOS and of the glutamate--NO--cGMP pathway. Blocking NMDA receptors with MK-801 increases cGMP and NO metabolites in cerebellum in vivo and in slices from hyperammonemic rats. This is because of reduced phosphorylation and activity of CaMKII, leading to normalization of nNOS phosphorylation and activity. MK-801 also increases nNOS in synaptic membranes and reduces it in cytosol. This indicates that hyperammonemia increases tonic activation of NMDA receptors leading to reduced activity of nNOS and of the glutamate--NO--cGMP pathway. PMID:20002515

  2. Encoding of action by the Purkinje cells of the cerebellum.

    Science.gov (United States)

    Herzfeld, David J; Kojima, Yoshiko; Soetedjo, Robijanto; Shadmehr, Reza

    2015-10-15

    Execution of accurate eye movements depends critically on the cerebellum, suggesting that the major output neurons of the cerebellum, Purkinje cells, may predict motion of the eye. However, this encoding of action for rapid eye movements (saccades) has remained unclear: Purkinje cells show little consistent modulation with respect to saccade amplitude or direction, and critically, their discharge lasts longer than the duration of a saccade. Here we analysed Purkinje-cell discharge in the oculomotor vermis of behaving rhesus monkeys (Macaca mulatta) and found neurons that increased or decreased their activity during saccades. We estimated the combined effect of these two populations via their projections to the caudal fastigial nucleus, and uncovered a simple-spike population response that precisely predicted the real-time motion of the eye. When we organized the Purkinje cells according to each cell's complex-spike directional tuning, the simple-spike population response predicted both the real-time speed and direction of saccade multiplicatively via a gain field. This suggests that the cerebellum predicts the real-time motion of the eye during saccades via the combined inputs of Purkinje cells onto individual nucleus neurons. A gain-field encoding of simple spikes emerges if the Purkinje cells that project onto a nucleus neuron are not selected at random but share a common complex-spike property. PMID:26469054

  3. The therapeutic potential of the cerebellum in schizophrenia

    Directory of Open Access Journals (Sweden)

    Krystal Lynn Parker

    2014-09-01

    Full Text Available The cognitive role of the cerebellum is critically tied to its distributed connections throughout the brain. Accumulating evidence from anatomical, structural and functional imaging, and lesion studies advocate a cognitive network involving indirect connections between the cerebellum and non-motor areas in the prefrontal cortex. Cerebellar stimulation dynamically influences activity in several regions of the frontal cortex and effectively improves cognition in schizophrenia. In this manuscript, we summarize current literature on the cingulocerebellar circuit and we introduce a method to interrogate this circuit combining opotogenetics, neuropharmacology, and electrophysiology in awake-behaving animals while minimizing incidental stimulation of neighboring cerebellar nuclei. We propose the novel hypothesis that optogenetic cerebellar stimulation can restore aberrant frontal activity and rescue impaired cognition in schizophrenia. We focus on how a known cognitive region in the frontal cortex, the anterior cingulate, is influenced by the cerebellum. This circuit is of particular interest because it has been confirmed using tracing studies, neuroimaging reveals its role in cognitive tasks, it is conserved from rodents to humans, and diseases such as schizophrenia and autism appear in its aberrancy. Novel tract tracing results presented here provide support for how these two areas communicate. The primary pathway involves a disynaptic connection between the cerebellar dentate nuclei and the anterior cingulate cortex. Secondarily, the pathway from cerebellar fastigial nuclei to the ventral tegmental area, which supplies dopamine to the prefrontal cortex, may play a role as schizophrenia characteristically involves dopamine deficiencies. We hope that the hypothesis described here will inspire new therapeutic strategies targeting currently untreatable cognitive impairments in schizophrenia.

  4. MRI Study of the Cerebellum in Young Bipolar Patients

    OpenAIRE

    Monkul, E. Serap; Hatch, John P; Sassi, Roberto B.; Axelson, David; Brambilla, Paolo; Nicoletti, Mark A.; Keshavan, Matcheri S.; Ryan, Neal D.; Birmaher, Boris; Soares, Jair C.

    2007-01-01

    Prior studies demonstrate structural abnormalities of cerebellar vermis in adult bipolar patients. Cerebella of 16 young bipolar patients (mean age ± S.D. = 15.5 ± 3.4) and 21 healthy controls (mean age ± S.D. = 16.9 ± 3.8) were examined using magnetic resonance imaging. The volumes of right, left and total cerebellum, vermis, and areas of vermal regions V1 (lobules I–V), V2 (lobules VI–VII), and V3 (lobules VIII–X) were measured. Analysis of covariance, with age, gender, and intra-cranial br...

  5. The human cerebellum: a review of physiologic neuroanatomy.

    Science.gov (United States)

    Roostaei, Tina; Nazeri, Arash; Sahraian, Mohammad Ali; Minagar, Alireza

    2014-11-01

    The cerebellum resides in the posterior cranial fossa dorsal to the brainstem and has diverse connections to the cerebrum, brain stem, and spinal cord. It is anatomically and physiologically divided into distinct functional compartments and is composed of highly regular arrays of neuronal units, each sharing the same basic cerebellar microcircuitry. Its circuitry is critically involved in motor control and motor learning, and its role in nonmotor cognitive and affective functions is becoming increasingly recognized. This article describes the cerebellar gross and histologic neuroanatomy in relation to its function, and the relevance of cerebellar circuitry and firing patterns to motor learning. PMID:25439284

  6. Encoding of action by the Purkinje cells of the cerebellum

    OpenAIRE

    Herzfeld, David J.; Kojima, Yoshiko; Soetedjo, Robijanto; Shadmehr, Reza

    2015-01-01

    Summary Execution of accurate eye movements depends critically on the cerebellum 1,2,3 , suggesting that Purkinje cells (P-cells) may predict motion of the eye. Yet, this encoding has remained a long-standing puzzle: P-cells show little consistent modulation with respect to saccade amplitude 4,5 or direction 4 , and critically, their discharge lasts longer than duration of a saccade 6,7 . Here, we analyzed P-cell discharge in the oculomotor vermis of behaving monkeys 8,9 and found neurons tha...

  7. Linking Essential Tremor to the Cerebellum-Neuroimaging Evidence.

    Science.gov (United States)

    Cerasa, Antonio; Quattrone, Aldo

    2016-06-01

    Essential tremor (ET) is the most common pathological tremor disorder in the world, and post-mortem evidence has shown that the cerebellum is the most consistent area of pathology in ET. In the last few years, advanced neuroimaging has tried to confirm this evidence. The aim of the present review is to discuss to what extent the evidence provided by this field of study may be generalised. We performed a systematic literature search combining the terms ET with the following keywords: MRI, VBM, MRS, DTI, fMRI, PET and SPECT. We summarised and discussed each study and placed the results in the context of existing knowledge regarding the cerebellar involvement in ET. A total of 51 neuroimaging studies met our search criteria, roughly divided into 19 structural and 32 functional studies. Despite clinical and methodological differences, both functional and structural imaging studies showed similar findings but without defining a clear topography of neurodegeneration. Indeed, the vast majority of studies found functional and structural abnormalities in several parts of the anterior and posterior cerebellar lobules, but it remains to be established to what degree these neural changes contribute to clinical symptoms of ET. Currently, advanced neuroimaging has confirmed the involvement of the cerebellum in pathophysiological processes of ET, although a high variability in results persists. For this reason, the translation of this knowledge into daily clinical practice is again partially limited, although new advanced multivariate neuroimaging approaches (machine-learning) are proving interesting changes of perspective. PMID:26626626

  8. The cerebellum: a new key structure in the navigation system

    Directory of Open Access Journals (Sweden)

    Laure Rondi-Reig

    2013-03-01

    Full Text Available Early investigations of cerebellar function focused on motor learning, in particular on eyeblink conditioning and adaptation of the vestibulo-ocular reflex, and led to the general view that cerebellar Long Term Depression (LTD at parallel fiber-Purkinje cell synapses is the neural correlate of cerebellar motor learning. Thereafter, while the full complexity of cerebellar plasticities was being unraveled, cerebellar involvement in more cognitive tasks - including spatial navigation - was further investigated. However, cerebellar implication in spatial navigation remains a matter of debate because motor deficits frequently associated with cerebellar damage often prevent the dissociation between its role in spatial cognition from its implication in motor function. Here, we review recent findings from behavioral and electrophysiological analyses of cerebellar mutant mouse models, which show that the cerebellum might participate in the construction of hippocampal spatial representation map (i.e. place cells and thereby in goal-directed navigation. These recent advances in cerebellar research point toward a model in which computation from the cerebellum could be required for spatial representation and would involve the integration of multi-source self-motion information to: 1 transform the reference frame of vestibular signals and 2 distinguish between self- and externally-generated vestibular signals. We eventually present herein anatomical and functional connectivity data supporting a cerebello-hippocampal interaction. Whilst a direct cerebello-hippocampal projection has been suggested, recent investigations rather favor a multi-synaptic pathway involving posterior parietal and retrosplenial cortices, two regions critically involved in spatial navigation.

  9. Cerebellum: from Fundamentals to Translational Approaches. The Seventh International Symposium of the Society for Research on the Cerebellum.

    Science.gov (United States)

    Manto, Mario; Mariën, Peter

    2016-02-01

    In terms of cerebellar research and ataxiology, a most fascinating period is currently going on. Numerous academic groups are now focusing their innovative research on the so-called little brain, hidden at the bottom of our brain. Indeed, its unique anatomical features make the cerebellum a wonderful window to address major questions about the central nervous system. The seventh international symposium of the SRC was held in Brussels at the Palace of Academies from May 8 to 10, 2015. The main goal of this dense symposium was to gather in a 2-day meeting senior researchers of exceptional scientific quality and talented junior scientists from all over the world working in the multidisciplinary field of cerebellar research. Fundamental and clinical researchers shared the latest knowledge and developments in this rapidly growing field. New ideas, addressed in a variety of inspiring talks, provoked a vivid debate. Advances in genetics, development, electrophysiology, neuroimaging, neurocognition and affect, as well as in the cerebellar ataxias and the controversies on the roles and functions of the cerebellum were presented. The Ferdinando Rossi lecture and the key-note lecture were delivered by Jan Voogd and Chris De Zeeuw, respectively. Contacts between researchers of different neuroscientific disciplines established a robust basis for novel trends and promising new cooperations between researchers and their centers spread all over the world. PMID:26744149

  10. Cerebellum and psychiatric disorders O cerebelo e os transtornos psiquiátricos

    OpenAIRE

    Leonardo Baldaçara; João Guilherme Fiorani Borgio; Acioly Luiz Tavares Lacerda; Andrea Parolin Jackowski

    2008-01-01

    OBJECTIVE: The objective of this update article is to report structural and functional neuroimaging studies exploring the potential role of cerebellum in the pathophysiology of psychiatric disorders. METHOD: A non-systematic literature review was conducted by means of Medline using the following terms as a parameter: "cerebellum", "cerebellar vermis", "schizophrenia", "bipolar disorder", "depression", "anxiety disorders", "dementia" and "attention deficit hyperactivity disorder". The electron...

  11. Interactions between Prefrontal Cortex and Cerebellum Revealed by Trace Eyelid Conditioning

    Science.gov (United States)

    Kalmbach, Brian E.; Ohyama, Tatsuya; Kreider, Joy C.; Riusech, Frank; Mauk, Michael D.

    2009-01-01

    Eyelid conditioning has proven useful for analysis of learning and computation in the cerebellum. Two variants, delay and trace conditioning, differ only by the relative timing of the training stimuli. Despite the subtlety of this difference, trace eyelid conditioning is prevented by lesions of the cerebellum, hippocampus, or medial prefrontal…

  12. High frequency repetitive transcranial magnetic stimulation to the cerebellum and implicit processing of happy facial expressions

    NARCIS (Netherlands)

    Schutter, D.J.L.G.; Enter, D.; Hoppenbrouwers, S.S.

    2009-01-01

    Background Previous research has demonstrated that the cerebellum is involved in emotive and cognitive processes. Furthermore, recent findings suggest high-frequency repetitive transcranial magnetic stimulation (rTMS) to the cerebellum has mood-improving properties. We sought to further explore the

  13. Wavelet analysis of MR functional data from the cerebellum

    Energy Technology Data Exchange (ETDEWEB)

    Karen, Romero Sánchez, E-mail: alphacentauri-hp@hotmail.com, E-mail: marcos-vaquezr@hotmail.com, E-mail: isabeldgg@hotmail.com; Vásquez Reyes Marcos, A., E-mail: alphacentauri-hp@hotmail.com, E-mail: marcos-vaquezr@hotmail.com, E-mail: isabeldgg@hotmail.com; González Gómez Dulce, I., E-mail: alphacentauri-hp@hotmail.com, E-mail: marcos-vaquezr@hotmail.com, E-mail: isabeldgg@hotmail.com; Hernández López, Javier M., E-mail: javierh@fcfm.buap.mx [Faculty of Physics and Mathematics, BUAP, Puebla, Pue (Mexico); Silvia, Hidalgo Tobón, E-mail: shidbon@gmail.com [Infant Hospital of Mexico, Federico Gómez, Mexico DF. Mexico and Physics Department, Universidad Autónoma Metropolitana. Iztapalapa, Mexico DF. (Mexico); Pilar, Dies Suarez, E-mail: pilydies@yahoo.com, E-mail: neurodoc@prodigy.net.mx; Eduardo, Barragán Pérez, E-mail: pilydies@yahoo.com, E-mail: neurodoc@prodigy.net.mx [Infant Hospital of Mexico, Federico Gómez, Mexico DF. (Mexico); Benito, De Celis Alonso, E-mail: benileon@yahoo.com [Faculty of Physics and Mathematics, BUAP, Puebla, Pue. Mexico and Foundation for Development Carlos Sigüenza. Puebla, Pue. (Mexico)

    2014-11-07

    The main goal of this project was to create a computer algorithm based on wavelet analysis of BOLD signals, which automatically diagnosed ADHD using information from resting state MR experiments. Male right handed volunteers (infants with ages between 7 and 11 years old) were studied and compared with age matched controls. Wavelet analysis, which is a mathematical tool used to decompose time series into elementary constituents and detect hidden information, was applied here to the BOLD signal obtained from the cerebellum 8 region of all our volunteers. Statistical differences between the values of the a parameters of wavelet analysis was found and showed significant differences (p<0.02) between groups. This difference might help in the future to distinguish healthy from ADHD patients and therefore diagnose ADHD.

  14. Wavelet analysis of MR functional data from the cerebellum

    International Nuclear Information System (INIS)

    The main goal of this project was to create a computer algorithm based on wavelet analysis of BOLD signals, which automatically diagnosed ADHD using information from resting state MR experiments. Male right handed volunteers (infants with ages between 7 and 11 years old) were studied and compared with age matched controls. Wavelet analysis, which is a mathematical tool used to decompose time series into elementary constituents and detect hidden information, was applied here to the BOLD signal obtained from the cerebellum 8 region of all our volunteers. Statistical differences between the values of the a parameters of wavelet analysis was found and showed significant differences (p<0.02) between groups. This difference might help in the future to distinguish healthy from ADHD patients and therefore diagnose ADHD

  15. CEREBELLUM: LINKS BETWEEN DEVELOPMENT, DEVELOPMENTAL DISORDERS AND MOTOR LEARNING

    Directory of Open Access Journals (Sweden)

    Mario U Manto

    2012-01-01

    Full Text Available The study of the links and interactions between development and motor learning has noticeable implications for the understanding and management of neurodevelopmental disorders. This is particularly relevant for the cerebellum which is critical for sensorimotor learning. The olivocerebellar pathway is a key pathway contributing to learning of motor skills. Its developmental maturation and remodelling are being unravelled. Advances in genetics have led to major improvements in our appraisal of the genes involved in cerebellar development, especially studies in mutant mice. Cerebellar neurogenesis is compartmentalized in relationship with neurotransmitter fate. The Engrailed-2 gene is a major actor of the specification of cerebellar cell types and late embryogenic morphogenesis. Math1, expressed by the rhombic lip (RL, is required for the genesis of glutamatergic neurons. Mutants deficient for the transcription factor Ptf1a display a lack of Purkinje cells and gabaergic interneurons. Rora gene contributes to the developmental signalling between granule cells and Purkinje neurons. The expression profile of SHH (Sonic hedgehog in postnatal stages determines the final size/shape of the cerebellum. Genes affecting the development impact upon the physiological properties of the cerebellar circuits. For instance, receptors are developmentally regulated and their action interferes directly with developmental processes. Another field of research which is expanding relates to very preterm neonates. They are at risk for cerebellar lesions, which may themselves impair the developmental events. Very preterm neonates often show sensori-motor deficits, highlighting another major link between impaired development and learning deficiencies. Pathways playing a critical role in cerebellar development are likely to become therapeutical targets for several neurodevelopmental disorders.

  16. The Effect of Spaceflight on the Ultrastructure of the Cerebellum

    Science.gov (United States)

    Holstein, Gay R.; Martinelli, Giorgio P.

    2003-01-01

    In weightlessness, astronauts and cosmonauts may experience postural illusions as well as motion sickness symptoms known as the space adaptation syndrome. Upon return to Earth, they have irregularities in posture and balance. The adaptation to microgravity and subsequent re-adaptation to Earth occurs over several days. At the cellular level, a process called neuronal plasticity may mediate this adaptation. The term plasticity refers to the flexibility and modifiability in the architecture and functions of the nervous system. In fact, plastic changes are thought to underlie not just behavioral adaptation, but also the more generalized phenomena of learning and memory. The goal of this experiment was to identify some of the structural alterations that occur in the rat brain during the sensory and motor adaptation to microgravity. One brain region where plasticity has been studied extensively is the cerebellar cortex-a structure thought to be critical for motor control, coordination, the timing of movements, and, most relevant to the present experiment, motor learning. Also, there are direct as well as indirect connections between projections from the gravity-sensing otolith organs and several subregions of the cerebellum. We tested the hypothesis that alterations in the ultrastructural (the structure within the cell) architecture of rat cerebellar cortex occur during the early period of adaptation to microgravity, as the cerebellum adapts to the absence of the usual gravitational inputs. The results show ultrastructural evidence for neuronal plasticity in the central nervous system of adult rats after 24 hours of spaceflight. Qualitative studies conducted on tissue from the cerebellar cortex (specifically, the nodulus of the cerebellum) indicate that ultrastructural signs of plasticity are present in the cerebellar zones that receive input from the gravity-sensing organs in the inner ear (the otoliths). These changes are not observed in this region in cagematched

  17. Emotion and Theory of Mind in Schizophrenia-Investigating the Role of the Cerebellum.

    Science.gov (United States)

    Mothersill, Omar; Knee-Zaska, Charlotte; Donohoe, Gary

    2016-06-01

    Social cognitive dysfunction, including deficits in facial emotion recognition and theory of mind, is a core feature of schizophrenia and more strongly predicts functional outcome than neurocognition alone. Although traditionally considered to play an important role in motor coordination, the cerebellum has been suggested to play a role in emotion processing and theory of mind, and also shows structural and functional abnormalities in schizophrenia. The aim of this systematic review was to investigate the specific role of the cerebellum in emotion and theory of mind deficits in schizophrenia using previously published functional neuroimaging studies. PubMed and PsycINFO were used to search for all functional neuroimaging studies reporting altered cerebellum activity in schizophrenia patients during emotion processing or theory of mind tasks, published until December 2014. Overall, 14 functional neuroimaging studies were retrieved. Most emotion studies reported lower cerebellum activity in schizophrenia patients relative to healthy controls. In contrast, the theory of mind studies reported mixed findings. Altered activity was observed across several posterior cerebellar regions involved in emotion and cognition. Weaker cerebellum activity in schizophrenia patients relative to healthy controls during emotion processing may contribute to blunted affect and reduced ability to recognise emotion in others. This research could be expanded by examining the relationship between cerebellum function, symptomatology and behaviour, and examining cerebellum functional connectivity in patients during emotion and theory of mind tasks. PMID:26155761

  18. [Synapse elimination and functional neural circuit formation in the cerebellum].

    Science.gov (United States)

    Kano, Masanobu

    2013-06-01

    Neuronal connections are initially redundant, but unnecessary connections are eliminated subsequently during postnatal development. This process, known as 'synapse elimination', is thought to be crucial for establishing functionally mature neural circuits. The climbing fiber (CF) to the Purkinje cell (PC) synapse in the cerebellum is a representative model of synapse elimination. We disclose that one-to-one connection from CF to PC is established through four distinct phases: (1) strengthening of a single CF among multiple CFs in each PC at P3-P7, (2) translocation of a single strengthened CF to PC dendrites from around P9, and (3) early phase (P7 to around P11) and (4) late phase (around P12 to P17) of elimination of weak CF synapses from PC somata. Mice with PC-selective deletion of P/Q-type voltage-dependent Ca2+ channel (VDCC) exhibit severe defects in strengthening of single CFs, dendritic translocation of single CFs and CF elimination from P7. In contrast, mice with a mutation of a single allele for the GABA-synthesizing enzyme GAD67 have a selective impairment of CF elimination from P10 due to reduced inhibition and elevated Ca2+ influx to PC somata. Thus, regulation of Ca2+ influx to PCs is crucial for the four phases of CF synapse elimination. PMID:25069248

  19. Ethanol Neurotoxicity in the Developing Cerebellum: Underlying Mechanisms and Implications

    Directory of Open Access Journals (Sweden)

    Ambrish Kumar

    2013-06-01

    Full Text Available Ethanol is the main constituent of alcoholic beverages that exerts toxicity to neuronal development. Ethanol affects synaptogenesis and prevents proper brain development. In humans, synaptogenesis takes place during the third trimester of pregnancy, and in rodents this period corresponds to the initial few weeks of postnatal development. In this period neuronal maturation and differentiation begin and neuronal cells start migrating to their ultimate destinations. Although the neuronal development of all areas of the brain is affected, the cerebellum and cerebellar neurons are more susceptible to the damaging effects of ethanol. Ethanol’s harmful effects include neuronal cell death, impaired differentiation, reduction of neuronal numbers, and weakening of neuronal plasticity. Neuronal development requires many hormones and growth factors such as retinoic acid, nerve growth factors, and cytokines. These factors regulate development and differentiation of neurons by acting through various receptors and their signaling pathways. Ethanol exposure during development impairs neuronal signaling mechanisms mediated by the N-methyl-d-aspartate (NMDA receptors, the retinoic acid receptors, and by growth factors such as brain-derived neurotrophic factor (BDNF, insulin-like growth factor 1 (IGF-I, and basic fibroblast growth factor (bFGF. In combination, these ethanol effects disrupt cellular homeostasis, reduce the survival and migration of neurons, and lead to various developmental defects in the brain. Here we review the signaling mechanisms that are required for proper neuronal development, and how these processes are impaired by ethanol resulting in harmful consequences to brain development.

  20. [Ultrastructural changes in the cerebellum of experimental hypothyroidism (cretinism)].

    Science.gov (United States)

    Deshimaru, M; Miyakawa, T; Kuramoto, M

    1983-08-01

    We examined the cerebellum of the rats being the experimental hypothyroidism (cretinism) on the 20th day, 35th day and 60th day by the light and electron microscope. The remarkable findings were observed to the experimental group on the 20th day. The maturational states of this group correspond to that of the 16th day of the control group. On the other hand, the remarkable pathological findings were not observed on the 35th and 60th day of the experimental group. According to the findings of the experimental rats on the 20th day, the changes of the cells were the retention of the external granule cells and the maturational changes of the internal granule cells. We recognized the retardation of the maturational timing and a disagreement of the maturational rate of the internal granule cells. The lamellar bodies being the disturbance of the mitochondrial cristae were observed. About the white matter, the myelinated nerve fibers were a small quantity in number, and the deficiency of the myelin synthesis, the maturational disturbance of oligoglia were seen. In the several axons, the lamellar bodies and the honeycomb like structures were seen. It is concluded that the maturational disturbance of the internal granule cells are due to the disturbance of the secondary protein synthesis by the hypothyroid state and the degeneration of the mitocondria. The deficiency of the myelin synthesis is related to the maturational disturbance of oligoglia. PMID:6639807

  1. Sudden death due to a cystic lesion in the cerebellum.

    Science.gov (United States)

    Igari, Yui; Hosoya, Tadashi; Hayashizaki, Yoshie; Usui, Akihito; Kawasumi, Yusuke; Usui, Kiyotaka; Funayama, Masato

    2014-12-01

    A middle-aged female patient with a depressive disorder presented to a mental hospital because of a 2-month worsening history of headache, dizziness, and nausea. The next morning, she was observed to be sleeping, but was then found dead 1h later. Postmortem computed tomography and autopsy revealed a large cyst in the right cerebellar hemisphere, hydrocephalus, and transforaminal herniation. Careful observation revealed an approximately 0.4cm×0.8cm slightly grayish discoloration in the cyst wall that was diagnosed as hemangioblastoma based on its histological features. Finally, we concluded that the cause of death in this case was attributable to the brain stem compression, which was caused by obstructive hydrocephalus secondary to the cystic hemangioblastoma in the cerebellum. The symptoms for 2 months before her death had most likely resulted from increased intracranial pressure. Hemangioblastomas usually appear as nodules in the wall of the cyst, but the tumor in our case looked like just a slightly grayish discoloration. Therefore, cystic lesions in the CNS need to be carefully examined. PMID:25459277

  2. A functional MRI study of somatotopic representation of somatosensory stimulation in the cerebellum

    Energy Technology Data Exchange (ETDEWEB)

    Takanashi, M.; Abe, K.; Yanagihara, T.; Sakoda, S. [Dept. of Neurology D4, Osaka Univ. Graduate School of Medicine, Suita City, Osaka (Japan); Tanaka, H.; Hirabuki, N.; Nakamura, H.; Fujita, N. [Dept. of Radiology, Osaka Univ. Graduate School of Medicine, Suita City, Osaka (Japan)

    2003-03-01

    Somatotopic representation in the cerebral cortex of somatosensory stimulation has been widely reported, but that in the cerebellum has not. We investigated the latter in the human cerebellum by functional MRI (fMRI). Using a 1.5 tesla imager, we obtained multislice blood oxygen level-dependent fMRI with single-shot gradient-echo echoplanar imaging in seven right-handed volunteers during electrical stimulation of the left index finger and big toe. In the anterior and posterior cerebellum, activated pixels for the index finger were separate from those for the toe. This suggests that somatosensory stimulation of different parts of the body may involve distinct areas of in the cerebellum as well as the cerebral cortex. (orig.)

  3. A functional MRI study of somatotopic representation of somatosensory stimulation in the cerebellum

    International Nuclear Information System (INIS)

    Somatotopic representation in the cerebral cortex of somatosensory stimulation has been widely reported, but that in the cerebellum has not. We investigated the latter in the human cerebellum by functional MRI (fMRI). Using a 1.5 tesla imager, we obtained multislice blood oxygen level-dependent fMRI with single-shot gradient-echo echoplanar imaging in seven right-handed volunteers during electrical stimulation of the left index finger and big toe. In the anterior and posterior cerebellum, activated pixels for the index finger were separate from those for the toe. This suggests that somatosensory stimulation of different parts of the body may involve distinct areas of in the cerebellum as well as the cerebral cortex. (orig.)

  4. Familial Vulnerability to ADHD Affects Activity in the Cerebellum in Addition to the Prefrontal Systems

    Science.gov (United States)

    Mulder, Martijn J.; Baeyens, Dieter; Davidson, Matthew C.; Casey, B. J.; Van Den Ban, Els; Van Engeland, Herman; Durston, Sarah

    2008-01-01

    The study examines whether cerebellar systems are sensitive to familial risk for ADHD in addition to frontostriatal circuitry. The results conclude that familial vulnerability to ADHD affects activity in both the prefrontal cortex and cerebellum.

  5. Remote Hemorrhage in the Cerebellum and Temporal Lobe after Lumbar Spine Surgery

    OpenAIRE

    Shotaro Watanabe; Seiji Ohtori; Sumihisa Orita; Kazuyo Yamauchi; Yawara Eguchi; Yasuchika Aoki; Junichi Nakamura; Masayuki Miyagi; Miyako Suzuki; Gou Kubota; Kazuhide Inage; Takeshi Sainoh; Jun Sato; Yasuhiro Shiga; Koki Abe

    2015-01-01

    Cerebellar hemorrhage remote from the site of surgery can complicate neurosurgical procedures. However, this complication after lumbar surgery is rare. Furthermore, hemorrhage in both the cerebellum and the temporal lobe after spine surgery is rarer still. Herein we present a case of remote hemorrhage in both the cerebellum and the temporal lobe after lumbar spine surgery. A 79-year-old woman with a Schwannoma at the L4 level presented with low back and bilateral leg pain refractory to conser...

  6. Contributions of the cerebellum and the motor cortex to acquisition and retention of motor memories

    OpenAIRE

    Herzfeld, David J.; Pastor, Damien; Haith, Adrian M.; Rossetti, Yves; Shadmehr, Reza; O’Shea, Jacinta

    2014-01-01

    We investigated the contributions of the cerebellum and the motor cortex (M1) to acquisition and retention of human motor memories in a force field reaching task. We found that anodal transcranial direct current stimulation (tDCS) of the cerebellum, a technique that is thought to increase neuronal excitability, increased the ability to learn from error and form an internal model of the field, while cathodal cerebellar stimulation reduced this error-dependent learning. In addition, cathodal ce...

  7. Sexual dimorphism and asymmetry in human cerebellum: an MRI-based morphometric study.

    Science.gov (United States)

    Fan, Lingzhong; Tang, Yuchun; Sun, Bo; Gong, Gaolang; Chen, Zhang J; Lin, Xiangtao; Yu, Taifei; Li, Zhenping; Evans, Alan C; Liu, Shuwei

    2010-09-24

    Structural sexual dimorphism and asymmetry in human cerebellum have been described in previous research, but results remain inconclusive or even conflicting. In this study, gender differences and hemispheric asymmetries in global and regional human cerebellum gray matter (GM) were estimated in an age-matched sample (n=112) of young Chinese adults. An optimized voxel-based morphometry (VBM) in spatial unbiased infratentorial template (SUIT) space together with an automated atlas-based volumetric approach were performed for mapping regional gray matter (GM) gender-related differences across the entire cerebellum. The two methods provided consistent findings on gender differences. The cerebellar GM volume was significantly larger in the anterior and middle posterior lobes of male group. In addition, a trend of greater GM volume in lateral posterior lobe of female group was observed. With the created symmetric cerebellar template, the asymmetric properties of cerebellar hemisphere were also assessed by VBM analysis, showing rightward asymmetry distributed in most cerebellar lobules and leftwards asymmetry distributed in the lobules around the medial posterior lobe. Gender differences in males showed higher leftward asymmetry sparsely within a few lobules and lower rightward asymmetry mainly within lobule Crus II, as compared with females. The acquired detailed morphologic knowledge of normal human cerebellum could establish a baseline for comparison with pathologic changes in the cerebellum. Moreover, our results might help to address controversies in thestudy of sexual dimorphisms and asymmetric patterns in human cerebellum. PMID:20647004

  8. Realtime cerebellum: a large-scale spiking network model of the cerebellum that runs in realtime using a graphics processing unit.

    Science.gov (United States)

    Yamazaki, Tadashi; Igarashi, Jun

    2013-11-01

    The cerebellum plays an essential role in adaptive motor control. Once we are able to build a cerebellar model that runs in realtime, which means that a computer simulation of 1 s in the simulated world completes within 1 s in the real world, the cerebellar model could be used as a realtime adaptive neural controller for physical hardware such as humanoid robots. In this paper, we introduce "Realtime Cerebellum (RC)", a new implementation of our large-scale spiking network model of the cerebellum, which was originally built to study cerebellar mechanisms for simultaneous gain and timing control and acted as a general-purpose supervised learning machine of spatiotemporal information known as reservoir computing, on a graphics processing unit (GPU). Owing to the massive parallel computing capability of a GPU, RC runs in realtime, while reproducing qualitatively the same simulation results of the Pavlovian delay eyeblink conditioning with the previous version. RC is adopted as a realtime adaptive controller of a humanoid robot, which is instructed to learn a proper timing to swing a bat to hit a flying ball online. These results suggest that RC provides a means to apply the computational power of the cerebellum as a versatile supervised learning machine towards engineering applications. PMID:23434303

  9. The Intracellular Signaling Molecule Darpp-32 Is a Marker for Principal Neurons in the Cerebellum and Cerebellum-Like Circuits of Zebrafish

    Science.gov (United States)

    Robra, Lena; Thirumalai, Vatsala

    2016-01-01

    The dopamine and cAMP regulated phosphoprotein of apparent molecular weight 32 kDa (Darpp-32) is an inhibitory subunit of protein phosphatase-1 (PP-1). Darpp-32 activity is regulated by multiple ligand-activated G-protein coupled receptors (GPCRs). This protein is coded for by the protein phosphatase-1 regulatory subunit 1b (ppp1r1b) gene. Here, we provide experimental evidence for the presence of multiple isoforms of ppp1r1b in zebrafish. We show that these isoforms are differentially expressed during development with the full-length isoform being maternally deposited. Next, with a custom polyclonal antibody generated against the full-length protein, we show that in the adult, Darpp-32 is strongly expressed in principal neurons of the cerebellum and cerebellum-like circuits. These include Purkinje neurons in the cerebellum, Type-I neurons in the optic tectum, and crest cells in the medial octavolateralis nucleus (MON). We confirmed the identity of these neurons through their colocalization with Parvalbumin 7 immunoreactivity. Darpp-32 is seen in the somata and dendrites of these neurons with faint staining in the axons. In all of these regions, Darpp-32-immunoreactive cells were in close proximity to tyrosine hydroxylase (TH) immunoreactive puncta indicating the presence of direct catecholaminergic input to these neurons. Darpp-32 immunoreactivity was seen in Purkinje neurons as early as 3 days post-fertilization (dpf) when Purkinje neurons are first specified. In sum, we show that Darpp-32, a signaling integrator, is a specific marker of principal neurons in the cerebellum and cerebellum-like circuits in zebrafish. PMID:27540357

  10. Effect of low frequency rTMS stimulation over lateral cerebellum: a FDG PET study

    International Nuclear Information System (INIS)

    Several lines of evidence suggested the involvement of cerebellum in cognitive function as well as motor function. Because of the measurement difficulty of functional connectivity, little is known about the underlying mechanism involvement of cerebellum in motor and cognitive function in living human brain. To understand the role of cerebellum within the neural network, we investigated the changes of neuronal activity elicited by the cerebellar repetitive transcranial magnetic stimulation (rTMS). 11 right-handed normal volunteers (age: 23.4±2.5 y;6 males) were studied with FDG PET under two conditions; sham and 1Hz rTMS over left lateral cerebellum. With 10 min inter-block interval, three blocks of rTMS were started with the intravenous injection of [18F]FDG. In each block, 5min rTMS were delivered with an intensity of 90% of the resting motor threshold (RMT). Sham rTMS was delivered with same protocol but the coil was positioned perpendicular to the target area with 50% RMT. PET scans were acquired immediately after the rTMS stimulation. Sham and 1Hz rTMS images compared using paired t-test with SPM2. Inhibited neuronal activity compare to the sham condition were revealed in the stimulated left lateral cerebellum and orbitofrontal gyrus and right motor related areas (S1, SMA and posterior parietal cortex). While enhanced neuronal activity compare to the sham condition were revealed in the bilateral inferior frontal gyri including Broca's area and superior temporal gyrus including primary auditory cortex. Bilateral middle temporal, left precentral and right middle occipital gyri were also showed enhanced neuronal activity. This result showed that rTMS over left lateral cerebellum modulate direct vicinity of the targeted region and a large network of remote interconnected contralateral motor and ipsilateral language related brain regions. Present result provide evidence that cerebellum may contribute to language related cognitive function as well as motor control

  11. Expression of thrombin and its associated protein in cerebellum of human and rat after intracerebral hemorrhage

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhi-yi; QI Ji-ping; ZHU Hong; SONG Yue-jia; WU He; JIA Ying; ZHANG Guang-mei

    2010-01-01

    Background Intracerebral hemorrhage (ICH) can cause brain damage through a number of pathways.The purpose of the study was to explore the effect of thrombin, protease nexin-1 (PN-1) and protease activated receptor-1 (PAR-1) in rat and human cerebellum after ICH.Methods A model of ICH was produced in adult Sprague-Dawley rats by direct injection of autologous blood (50 μl) into caudate nucleus.Patients with injured hemorrhage were also enrolled in this study.Different expressions of thrombin,PAR-1, PN-1 were detected in rat and human cerebellum by immunohistochemistry and in situ hybridization.Results In rat cerebellum, thrombin protein significantly increased at 6 hours and reached the maximum 2 days afterICH.The expression of PAR-1 protein reached the maximum at 24-48 hours, and then began to decrease.The expression of PN-1 protein reached the maximum at 3 hours, decreased somewhat after that and increased a little at 5days after ICH.While in human cerebellum, the changing tendency of thrombin, PAR-1 and PN-1 was almost conform to the rat.Conclusion In cerebellum, thrombin can activate PAR-1 expression after ICH, and PN-1 appears quickly after ICH in order to control the deleterious effect of thrombin.

  12. Analysis of β-N-methylamino-L-alanine (L-BMAA) neurotoxicity in rat cerebellum.

    Science.gov (United States)

    Muñoz-Sáez, Emma; de Munck García, Estefanía; Arahuetes Portero, Rosa Ma; Martínez, Ana; Solas Alados, Ma Teresa; Miguel, Begoña Gómez

    2015-05-01

    Due to its structural similarity to glutamate, L-BMAA could be a trigger for neurodegenerative disorders caused by changes in the intracellular medium, such as increased oxidative stress, mitochondrial dysfunction, impaired synthesis and protein degradation and the imbalance of some enzymes. It is also important to note that according to some published studies, L-BMAA will be incorporated into proteins, causing the alteration of protein homeostasis. Neuronal cells are particularly prone to suffer damage in protein folding and protein accumulation because they have not performed cellular division. In this work, we will analyse the cerebellum impairment triggered by L-BMAA in treated rats. The cerebellum is one of the most important subcortical motor centres and ensures that movements are performed with spatial and temporal precision. Cerebellum damage caused by L-BMAA can contribute to motor impairment. To characterize this neurodegenerative pathology, we first carried out ultrastructure analysis in Purkinje cells showing altered mitochondria, endoplasmic reticulum (ER), and Golgi apparatus (GA). We then performed biochemical assays of GSK3 and TDP-43 in cerebellum, obtaining an increase of both biomarkers with L-BMAA treatment and, finally, performed autophagy studies that revealed a higher level of these processes after treatment. This work provides evidence of cerebellar damage in rats after treatment with L-BMAA. Three months after treatment, affected rats cannot restore the normal functions of the cerebellum regarding motor coordination and postural control. PMID:25898785

  13. Arrangement and Applying of Movement Patterns in the Cerebellum Based on Semi-supervised Learning.

    Science.gov (United States)

    Solouki, Saeed; Pooyan, Mohammad

    2016-06-01

    Biological control systems have long been studied as a possible inspiration for the construction of robotic controllers. The cerebellum is known to be involved in the production and learning of smooth, coordinated movements. Therefore, highly regular structure of the cerebellum has been in the core of attention in theoretical and computational modeling. However, most of these models reflect some special features of the cerebellum without regarding the whole motor command computational process. In this paper, we try to make a logical relation between the most significant models of the cerebellum and introduce a new learning strategy to arrange the movement patterns: cerebellar modular arrangement and applying of movement patterns based on semi-supervised learning (CMAPS). We assume here the cerebellum like a big archive of patterns that has an efficient organization to classify and recall them. The main idea is to achieve an optimal use of memory locations by more than just a supervised learning and classification algorithm. Surely, more experimental and physiological researches are needed to confirm our hypothesis. PMID:26109488

  14. Dysfunctional Activation of the Cerebellum in Schizophrenia: A Functional Neuroimaging Meta-Analysis

    Science.gov (United States)

    Bernard, Jessica A.; Mittal, Vijay A.

    2014-01-01

    The cognitive dysmetria framework postulates that the deficits seen in schizophrenia are due to underlying cerebello-thalamo-cortical dysfunction. The cerebellum is thought to be crucial in the formation of internal models for both motor and cognitive behaviors. In healthy individuals there is a functional topography within the cerebellum. Alterations in the functional topography and activation of the cerebellum in schizophrenia patients may be indicative of altered internal models, providing support for this framework. Using state-of-the-art neuroimaging meta-analysis, we investigated cerebellar activation across a variety of task domains affected in schizophrenia and in comparison to healthy controls. Our results indicate an altered functional topography in patients. This was especially apparent for emotion and working memory tasks, and may be related to deficits in these domains. Results suggest that an altered cerebellar functional topography in schizophrenia may be contributing to the many deficits associated with the disease, perhaps due to dysfunctional internal models. PMID:26392921

  15. Effects of Cinnamon Extract on Cerebellum Histomorphometry in Diabetic Rats’ Fetus

    Directory of Open Access Journals (Sweden)

    AR Rafati

    2013-10-01

    Full Text Available Abstract Background & aim: In pregnant women, maternal diabetes occurs when the pancreas does not produce enough insulin, so glucose increases in the mother's blood and the blood of the fetus therefore causing many complications in children. The aim of this study was to evaluate the effects of cinnamon on morphometric histologic changes on fetal cerebellum of diabetic rats at days 18 and 20. Methods: In this study, 32 healthy female Wistar rats were prepared and randomly divided into four groups, normal control, diabetic, healthy subjects treated with cinnamon and cinnamon extract-treated diabetic groups. Diabetic groups were subjected by intraperitoneal of streptozotocin. All groups were charged with natural mating and they received a dose of 60 mg/ kg of cinnamon at the first day off pregnancy. After formation of the nervous system, in the eighteenth and twentieth day of pregnancy, the mother of the four mice were anesthetized and the fetus was removed for sampling. The histological slides were prepared and various parameters were studied in the cerebellum. Data were analyzed using one-way ANOVA and Duncan test. Results: The thickness of gray matter, and the gray matter white cells in the cerebellum of diabetic rats compared to other groups tested at days of18 and 20 and embryonic cells in the white matter of the cerebellum at day 18 was significantly decreased (p< 0.05. Conclusion: Administration of cinnamon extract reduces mothers’ blood sugar levels therefore preventing the complications of diabetes on the fetal cerebellum. Key words: cinnamon extract, Diabetes, cerebellum, Rat.

  16. Automatic Segmentation of the Cerebellum in Ultrasound Volumes of the Fetal Brain

    OpenAIRE

    G. Velásquez Rodríguez; F. Arámbula Cosío; M.E. Guzmán Huerta; L. Camargo Marín; H. Borboa Olivares; Boris Escalante Ramírez

    2015-01-01

    The size of the cerebellum in ultrasound volumes of the fetal brain has shown a high correlation with gestational age, which makes it a valuable feature to detect fetal growth restrictions. Manual annotation of the 3D surface of the cerebellum in an ultrasound volume is a time consuming task, which needs to be performed by a highly trained expert. In order to assist the experts in the evaluation of cerebellar dimensions, we developed an automatic scheme for the segmentation of the 3D surface ...

  17. fMRI Activities in the Emotional Cerebellum: A Preference for Negative Stimuli and Goal-Directed Behavior

    NARCIS (Netherlands)

    C.K. Schraa-Tam (Caroline); W.J.R. Rietdijk (Wim); W.J.M.I. Verbeke (Willem); R.C. Dietvorst (Roeland); W.E. van den Berg (Wouter); R.P. Bagozzi (Richard); C.I. de Zeeuw (Chris)

    2012-01-01

    textabstractSeveral studies indicate that the cerebellum might play a role in experiencing and/or controlling emphatic emotions, but it remains to be determined whether there is a distinction between positive and negative emotions, and, if so, which specific parts of the cerebellum are involved in t

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

    Directory of Open Access Journals (Sweden)

    Rosa M López-Pedrajas

    2015-07-01

    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.

  19. The Cerebellum Generates Motor-to-Auditory Predictions: ERP Lesion Evidence

    Science.gov (United States)

    Knolle, Franziska; Schroger, Erich; Baess, Pamela; Kotz, Sonja A.

    2012-01-01

    Forward predictions are crucial in motor action (e.g., catching a ball, or being tickled) but may also apply to sensory or cognitive processes (e.g., listening to distorted speech or to a foreign accent). According to the "internal forward model," the cerebellum generates predictions about somatosensory consequences of movements. These predictions…

  20. A single episode of neonatal seizures alters the cerebellum of immature rats

    Czech Academy of Sciences Publication Activity Database

    Lomoio, S.; Necchi, D.; Mareš, Vladislav; Scherini, E.

    2011-01-01

    Roč. 93, č. 1 (2011), s. 17-24. ISSN 0920-1211 Institutional research plan: CEZ:AV0Z50110509 Keywords : metrazol seizures * cerebellum * Purkinje cells * GluR2/3 * GLT1 Subject RIV: FH - Neurology Impact factor: 2.290, year: 2011

  1. The Role of the Pediatric Cerebellum in Motor Functions, Cognition, and Behavior: A Clinical Perspective.

    Science.gov (United States)

    Salman, Michael S; Tsai, Peter

    2016-08-01

    This article discusses the contribution of the pediatric cerebellum to locomotion, ocular motor control, speech articulation, cognitive function, and behavior modulation. Hypotheses on cerebellar function are discussed. Clinical features in patients with cerebellar disorders are outlined. Cerebellar abnormalities in cognitive and behavioral disorders are detailed. PMID:27423796

  2. Modulating the expression level of secreted Wnt3 influences cerebellum development in zebrafish transgenics.

    Science.gov (United States)

    Teh, Cathleen; Sun, Guangyu; Shen, Hongyuan; Korzh, Vladimir; Wohland, Thorsten

    2015-11-01

    The boundaries of brain regions are associated with the tissue-specific secretion of ligands from different signaling pathways. The dynamics of these ligands in vivo and the impact of its disruption remain largely unknown. Using light and fluorescence microscopy for the overall imaging of the specimen and fluorescence correlation spectroscopy (FCS) to determine Wnt3 dynamics, we demonstrated that Wnt3 regulates cerebellum development during embryogenesis using zebrafish wnt3 transgenics with either tissue-specific expression of an EGFP reporter or a functionally active fusion protein, Wnt3EGFP. The results suggest a state of dynamic equilibrium of Wnt3EGFP mobility in polarized neuroepithelial-like progenitors in the dorsal midline and cerebellar progenitors on the lateral side. Wnt3EGFP is secreted from the cerebellum as shown by measurements of its mobility in the ventricular cavity. The importance of Wnt secretion in brain patterning was validated with the Porcn inhibitor Wnt-C59 (C59), which, when applied early, reduced membrane-bound and secreted fractions of Wnt3EGFP and led to a malformed brain characterized by the absence of epithalamus, optic tectum and cerebellum. Likewise, interference with Wnt secretion later on during cerebellar development negatively impacted cerebellar growth and patterning. Our work, supported by quantitative analysis of protein dynamics in vivo, highlights the importance of membrane-localized and secreted Wnt3 during cerebellum development. PMID:26395493

  3. Origins of oligodendrocytes in the cerebellum, whose development is controlled by the transcription factor, Sox9.

    Science.gov (United States)

    Hashimoto, Ryoya; Hori, Kei; Owa, Tomoo; Miyashita, Satoshi; Dewa, Kenichi; Masuyama, Norihisa; Sakai, Kazuhisa; Hayase, Yoneko; Seto, Yusuke; Inoue, Yukiko U; Inoue, Takayoshi; Ichinohe, Noritaka; Kawaguchi, Yoshiya; Akiyama, Haruhiko; Koizumi, Schuichi; Hoshino, Mikio

    2016-05-01

    Development of oligodendrocytes, myelin-forming glia in the central nervous system (CNS), proceeds on a protracted schedule. Specification of oligodendrocyte progenitor cells (OPCs) begins early in development, whereas their terminal differentiation occurs at late embryonic and postnatal periods. However, for oligodendrocytes in the cerebellum, the developmental origins and the molecular machinery to control these distinct steps remain unclear. By in vivo fate mapping and immunohistochemical analyses, we obtained evidence that the majority of oligodendrocytes in the cerebellum originate from the Olig2-expressing neuroepithelial domain in the ventral rhombomere 1 (r1), while about 6% of cerebellar oligodendrocytes are produced in the cerebellar ventricular zone. Furthermore, to elucidate the molecular determinants that regulate their development, we analyzed mice in which the transcription factor Sox9 was specifically ablated from the cerebellum, ventral r1 and caudal midbrain by means of the Cre/loxP recombination system. This resulted in a delay in the birth of OPCs and subsequent developmental aberrations in these cells in the Sox9-deficient mice. In addition, we observed altered proliferation of OPCs, resulting in a decrease in oligodendrocyte numbers that accompanied an attenuation of the differentiation and an increased rate of apoptosis. Results from in vitro assays using oligodendrocyte-enriched cultures further supported our observations from in vivo experiments. These data suggest that Sox9 participates in the development of oligodendrocytes in the cerebellum, by regulating the timing of their generation, proliferation, differentiation and survival. PMID:26940020

  4. The role of the cerebellum in schizophrenia: from cognition to molecular pathways

    Directory of Open Access Journals (Sweden)

    Peyman Yeganeh-Doost

    2011-01-01

    Full Text Available Beside its role in motor coordination, the cerebellum is involved in cognitive function such as attention, working memory, verbal learning, and sensory discrimination. In schizophrenia, a disturbed prefronto-thalamo-cerebellar circuit has been proposed to play a role in the pathophysiology. In addition, a deficit in the glutamatergic N-methyl-D-aspartate (NMDAf receptor has been hypothesized. The risk gene neuregulin 1 may play a major role in this process. We demonstrated a higher expression of the NMDA receptor subunit 2D in the right cerebellar regions of schizophrenia patients, which may be a secondary upregulation due to a dysfunctional receptor. In contrast, the neuregulin 1 risk variant containing at least one C-allele was associated with decreased expression of NMDA receptor subunit 2C, leading to a dysfunction of the NMDA receptor, which in turn may lead to a dysfunction of the gamma amino butyric acid (GABA system. Accordingly, from post-mortem studies, there is accumulating evidence that GABAergic signaling is decreased in the cerebellum of schizophrenia patients. As patients in these studies are treated with antipsychotics long term, we evaluated the effect of long-term haloperidol and clozapine treatment in an animal model. We showed that clozapine may be superior to haloperidol in restoring a deficit in NMDA receptor subunit 2C expression in the cerebellum. We discuss the molecular findings in the light of the role of the cerebellum in attention and cognitive deficits in schizophrenia.

  5. Social cognition and the cerebellum: A meta-analytic connectivity analysis.

    Science.gov (United States)

    Van Overwalle, Frank; D'aes, Tine; Mariën, Peter

    2015-12-01

    This meta-analytic connectivity modeling (MACM) study explores the functional connectivity of the cerebellum with the cerebrum in social cognitive processes. In a recent meta-analysis, Van Overwalle, Baetens, Mariën, and Vandekerckhove (2014) documented that the cerebellum is implicated in social processes of "body" reading (mirroring; e.g., understanding other persons' intentions from observing their movements) and "mind" reading (mentalizing, e.g., inferring other persons' beliefs, intentions or personality traits, reconstructing persons' past, future, or hypothetical events). In a recent functional connectivity study, Buckner et al. (2011) offered a novel parcellation of cerebellar topography that substantially overlaps with the cerebellar meta-analytic findings of Van Overwalle et al. (2014). This overlap suggests that the involvement of the cerebellum in social reasoning depends on its functional connectivity with the cerebrum. To test this hypothesis, we explored the meta-analytic co-activations as indices of functional connectivity between the cerebellum and the cerebrum during social cognition. The MACM results confirm substantial and distinct connectivity with respect to the functions of (a) action understanding ("body" reading) and (b) mentalizing ("mind" reading). The consistent and strong connectivity findings of this analysis suggest that cerebellar activity during social judgments reflects distinct mirroring and mentalizing functionality, and that these cerebellar functions are connected with corresponding functional networks in the cerebrum. PMID:26419890

  6. Automatic segmentation of the fetal cerebellum using spherical harmonics and gray level profiles

    Science.gov (United States)

    Velásquez-Rodríguez, Gustavo; Arámbula Cosío, Fernando; Escalate Ramírez, Boris

    2015-12-01

    The cerebellum is an important structure to determine the gestational age, cerebellar diameter obtained by ultrasound volumes of the fetal brain has shown a high correlation with gestational age, therefore is useful to determine fetal growth restrictions. The manual annotation of 3D surfaces from the fetal brain is time consuming and needs to be done by a highly trained expert. To help with the annotation in the evaluation of cerebellar diameter, we developed a new automatic scheme for the segmentation of the 3D surface of the cerebellum in ultrasound volumes, using a spherical harmonics model and the optimization of an objective function based on gray level voxel profiles. The results on 10 ultrasound volumes of the fetal brain show an accuracy in the segmentation of the cerebellum (mean Dice coefficient of 0.7544). The method reported shows potential to effectively assist the experts in the assessment of fetal growth in ultrasound volumes. We consider the proposed cerebellum segmentation method a contribution for the SPHARM segmentations models, because it is capable to run without hardware restriction, (GPU), and gives adequate results in a reasonable amount of time.

  7. Alcohol hangover induces mitochondrial dysfunction and free radical production in mouse cerebellum.

    Science.gov (United States)

    Karadayian, A G; Bustamante, J; Czerniczyniec, A; Lombardi, P; Cutrera, R A; Lores-Arnaiz, S

    2015-09-24

    Alcohol hangover (AH) is defined as the temporary state after alcohol binge-like drinking, starting when ethanol (EtOH) is absent in plasma. Previous data indicate that AH induces mitochondrial dysfunction and free radical production in mouse brain cortex. The aim of this work was to study mitochondrial function and reactive oxygen species production in mouse cerebellum at the onset of AH. Male mice received a single i.p. injection of EtOH (3.8g/kg BW) or saline solution. Mitochondrial function was evaluated 6h after injection (AH onset). At the onset of AH, malate-glutamate and succinate-supported state 4 oxygen uptake was 2.3 and 1.9-fold increased leading to a reduction in respiratory control of 55% and 48% respectively, as compared with controls. Decreases of 38% and 16% were found in Complex I-III and IV activities. Complex II-III activity was not affected by AH. Mitochondrial membrane potential and mitochondrial permeability changes were evaluated by flow cytometry. Mitochondrial membrane potential and permeability were decreased by AH in cerebellum mitochondria. Together with this, AH induced a 25% increase in superoxide anion and a 92% increase in hydrogen peroxide production in cerebellum mitochondria. Related to nitric oxide (NO) metabolism, neuronal nitric oxide synthase (nNOS) protein expression was 52% decreased by the hangover condition compared with control group. No differences were found in cerebellum NO production between control and treated mice. The present work demonstrates that the physiopathological state of AH involves mitochondrial dysfunction in mouse cerebellum showing the long-lasting effects of acute EtOH exposure in the central nervous system. PMID:26192095

  8. De Sedibus et Causis Morborum: is Essential Tremor a Primary Disease of the Cerebellum?

    Science.gov (United States)

    Louis, Elan D

    2016-06-01

    Morgagni's 1761 publication of De sedibus et causis morborum (i.e., of the Seats and Causes of Diseases) represented a paradigmatic moment in the history of medicine. The book ushered in a new way of conceptualizing human disease, shattering old dogma, and linking constellations of symptoms and signs (i.e., clinical disease) with anatomic pathology in specific organs (i.e., organ disease). This was the anatomical-clinical method, and it attempted to unveil "the seat" of each disease in a specific organ. Essential tremor (ET) is among the most common neurological diseases. There is little debate that the origin of ET lies in the brain, but if one tries to delve more deeply than this, things become murky. The dogma for the past 40 years has been that the seat of ET is the inferior olivary nucleus. Closer scrutiny of this model, however, has revealed its many flaws, and the model, based on little if any empiric evidence, has increasingly lost favor. Arising from a wealth of research in recent years is a growing body of knowledge that links ET to a disarrangement of the cerebellum. Data from a variety of sources reviewed in this issue (clinical, neuroimaging, neurochemical, animal model, physiological, and pathological) link ET to the cerebellum. That the cerebellum is involved in an abnormal brain loop that is responsible for ET is not debated. The tantalizing question is whether an abnormality in the cerebellum is the prime mover, and whether the cerebellum is the seat of this particular disease. PMID:26093616

  9. Effects of Estrogen on ER, NGF, and ChAT Expression in Cerebellum of Aging Female Sprague-Dawley Rat

    Institute of Scientific and Technical Information of China (English)

    CHEN Zheng-li; FAN Guang-li; LUO Qi-hui; ZHU Chun-mei; HUANG Yi-dan

    2007-01-01

    This article discusses the effects of estrogen on the expression of estrogen receptor (ER), nerve growth factor (NGF), and choline acetyltransferase (ChAT) in the cerebellum of rats. The model of aging female rat was established to study the expression and distribution of ER, NGF, and ChAT in the cerebellum following 17β-estradiol treatment using the technique of immunohistochemical ultrasensitive SP in sprague-dawley rat. The immunoreactive productions were distributed in stratum Purkinje cell, nucleus dentatus, nucleus interpositus, and nucleus fastigii of cerebellum, and the ER positive production was mainly located in the plasma, cytoplasmic membrane, and neurite, and also existed in nucleus. The general tendency of the expression of ER, NGF, and ChAT positive production in the cerebellum cortex and nuclei of aging rat significantly decreases, while the intensity and quantity of the immunoreactive production ascends predominantly after 17β-estradiol treatment. Simultaneously, the positive neurite of Purkinje cell shows a similar tendency. The abovementioned results suggest that the estrogen upregulates the expression of NGF and ChAT, and plays a vital role in sustaining and protecting the structure and function of cerebellum neurons. Furthermore, the similarity of their changing tendency implies that they were correlated and cooperated during the course in effect of estrogen on cerebellum. It also showed that the action of estrogen in cerebellum could be via genomic and nongenomic mechanism.

  10. Real-Time Simulation of Passage-of-Time Encoding in Cerebellum Using a Scalable FPGA-Based System.

    Science.gov (United States)

    Luo, Junwen; Coapes, Graeme; Mak, Terrence; Yamazaki, Tadashi; Tin, Chung; Degenaar, Patrick

    2016-06-01

    The cerebellum plays a critical role for sensorimotor control and learning. However, dysmetria or delays in movements' onsets consequent to damages in cerebellum cannot be cured completely at the moment. Neuroprosthesis is an emerging technology that can potentially substitute such motor control module in the brain. A pre-requisite for this to become practical is the capability to simulate the cerebellum model in real-time, with low timing distortion for proper interfacing with the biological system. In this paper, we present a frame-based network-on-chip (NoC) hardware architecture for implementing a bio-realistic cerebellum model with  ∼ 100 000 neurons, which has been used for studying timing control or passage-of-time (POT) encoding mediated by the cerebellum. The simulation results verify that our implementation reproduces the POT representation by the cerebellum properly. Furthermore, our field-programmable gate array (FPGA)-based system demonstrates excellent computational speed that it can complete 1sec real world activities within 25.6 ms. It is also highly scalable such that it can maintain approximately the same computational speed even if the neuron number increases by one order of magnitude. Our design is shown to outperform three alternative approaches previously used for implementing spiking neural network model. Finally, we show a hardware electronic setup and illustrate how the silicon cerebellum can be adapted as a potential neuroprosthetic platform for future biological or clinical application. PMID:26452290

  11. Effect of Cerebellum Radiation Dosimetry on Cognitive Outcomes in Children With Infratentorial Ependymoma

    International Nuclear Information System (INIS)

    Purpose: Cognitive decline is a recognized effect of radiation therapy (RT) in children treated for brain tumors. The importance of the cerebellum and its contribution to cognition have been recognized; however, the effect of RT on cerebellum-linked neurocognitive deficits has yet to be explored. Methods and Materials: Seventy-six children (39 males) at a median 3.3 years of age (range, 1-17 years old) were irradiated for infratentorial ependymoma from 1997 to 2008. The total prescribed dose was 54 to 59.4 Gy administered to the postoperative tumor bed with 5- or 10-mm clinical target volume margin. Age-appropriate cognitive and academic testing was performed prior to the start of RT and was then repeated at 6 months and annually throughout 5 years. The anterior and posterior cerebellum and other normal brain volumes were contoured on postcontrast, T1-weighted postoperative magnetic resonance images registered to treatment planning computed tomography images. Mean doses were calculated and used with time after RT and other clinical covariates to model their effect on neurocognitive test scores. Results: Considering only the statistically significant rates in longitudinal changes for test scores and models that included mean dose, there was a correlation between mean infratentorial dose and intelligence quotient (IQ; −0.190 patients/Gy/year; P=.001), math (−0.164 patients/Gy/year; P=.010), reading (−0.137 patients/Gy/year; P=.011), and spelling scores (−0.147 patients/Gy/year; P=.012), where Gy was measured as the difference between the mean dose received by an individual patient and the mean dose received by the patient group. There was a correlation between mean anterior cerebellum dose and IQ scores (−0.116 patients/Gy/year; P=.042) and mean posterior cerebellum dose and IQ (−0.150 patients/Gy/year; P=.002), math (−0.120 patients/Gy/year; P=.023), reading (−0.111 patients/Gy/year; P=.012), and spelling (−0.117 patients/Gy/year; P=.015

  12. Effect of Cerebellum Radiation Dosimetry on Cognitive Outcomes in Children With Infratentorial Ependymoma

    Energy Technology Data Exchange (ETDEWEB)

    Merchant, Thomas E., E-mail: thomas.merchant@stjude.org [Division of Radiation Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Sharma, Shelly [Division of Radiation Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Xiong, Xiaoping; Wu, Shengjie [Department of Biostatistics, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Conklin, Heather [Department of Psychology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States)

    2014-11-01

    Purpose: Cognitive decline is a recognized effect of radiation therapy (RT) in children treated for brain tumors. The importance of the cerebellum and its contribution to cognition have been recognized; however, the effect of RT on cerebellum-linked neurocognitive deficits has yet to be explored. Methods and Materials: Seventy-six children (39 males) at a median 3.3 years of age (range, 1-17 years old) were irradiated for infratentorial ependymoma from 1997 to 2008. The total prescribed dose was 54 to 59.4 Gy administered to the postoperative tumor bed with 5- or 10-mm clinical target volume margin. Age-appropriate cognitive and academic testing was performed prior to the start of RT and was then repeated at 6 months and annually throughout 5 years. The anterior and posterior cerebellum and other normal brain volumes were contoured on postcontrast, T1-weighted postoperative magnetic resonance images registered to treatment planning computed tomography images. Mean doses were calculated and used with time after RT and other clinical covariates to model their effect on neurocognitive test scores. Results: Considering only the statistically significant rates in longitudinal changes for test scores and models that included mean dose, there was a correlation between mean infratentorial dose and intelligence quotient (IQ; −0.190 patients/Gy/year; P=.001), math (−0.164 patients/Gy/year; P=.010), reading (−0.137 patients/Gy/year; P=.011), and spelling scores (−0.147 patients/Gy/year; P=.012), where Gy was measured as the difference between the mean dose received by an individual patient and the mean dose received by the patient group. There was a correlation between mean anterior cerebellum dose and IQ scores (−0.116 patients/Gy/year; P=.042) and mean posterior cerebellum dose and IQ (−0.150 patients/Gy/year; P=.002), math (−0.120 patients/Gy/year; P=.023), reading (−0.111 patients/Gy/year; P=.012), and spelling (−0.117 patients/Gy/year; P=.015

  13. MRI measurements of the brain stem and cerebellum in high functioning autistic children

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Toshiaki; Tayama, Masanobu; Miyazaki, Masahito; Murakawa, Kazuyoshi; Kuroda, Yasuhiro (Tokushima Univ. (Japan). School of Medicine)

    1994-01-01

    To determine involvements of the brain stem and/or cerebellum in autism, we compared midsagittal magnetic resonance images of the brains of high functioning autistic children with those of normal controls. We found that the midbrain and medulla oblongata were significantly smaller in these autistic children than in the control children. The pons area did not differ between the two groups, nor was there any difference in the cerebellar vermis area. The ratio of the brain stem and cerebellum to the posterior fossa area did not differ significantly between the high functioning autistic and the control children. The development of the cerebellar vermis area was delayed in autistic children as compared with that in the control children. Thus, it was suggested that significant anatomical changes in the midbrain and medulla oblongata existed in the autistic children. (author).

  14. Chronological changes in nonhaemorrhagic brain infarcts with short T1 in the cerebellum and basal ganglia

    International Nuclear Information System (INIS)

    Our purpose was to investigate nonhaemorrhagic infarcts with a short T1 in the cerebellum and basal ganglia. We carried out repeat MRI on 12 patients with infarcts in the cerebellum or basal ganglia with a short T1. Cerebellar cortical lesions showed high signal on T1-weighted spin-echo images beginning at 2 weeks, which became prominent from 3 weeks to 2 months, and persisted for as long as 14 months after the ictus. The basal ganglia lesions demonstrated slightly high signal from a week after the ictus, which became more intense thereafter. Signal intensity began to fade gradually after 2 months. High signal could be seen at the periphery until 5 months, and then disappeared, while low or isointense signal, seen in the central portion from day 20, persisted thereafter. (orig.)

  15. Tri-layer wrinkling as a mechanism for anchoring center initiation in the developing cerebellum.

    Science.gov (United States)

    Lejeune, Emma; Javili, Ali; Weickenmeier, Johannes; Kuhl, Ellen; Linder, Christian

    2016-07-01

    During cerebellar development, anchoring centers form at the base of each fissure and remain fixed in place while the rest of the cerebellum grows outward. Cerebellar foliation has been extensively studied; yet, the mechanisms that control anchoring center initiation and position remain insufficiently understood. Here we show that a tri-layer model can predict surface wrinkling as a potential mechanism to explain anchoring center initiation and position. Motivated by the cerebellar microstructure, we model the developing cerebellum as a tri-layer system with an external molecular layer and an internal granular layer of similar stiffness and a significantly softer intermediate Purkinje cell layer. Including a weak intermediate layer proves key to predicting surface morphogenesis, even at low stiffness contrasts between the top and bottom layers. The proposed tri-layer model provides insight into the hierarchical formation of anchoring centers and establishes an essential missing link between gene expression and evolution of shape. PMID:27252048

  16. MRI measurements of the brain stem and cerebellum in high functioning autistic children

    International Nuclear Information System (INIS)

    To determine involvements of the brain stem and/or cerebellum in autism, we compared midsagittal magnetic resonance images of the brains of high functioning autistic children with those of normal controls. We found that the midbrain and medulla oblongata were significantly smaller in these autistic children than in the control children. The pons area did not differ between the two groups, nor was there any difference in the cerebellar vermis area. The ratio of the brain stem and cerebellum to the posterior fossa area did not differ significantly between the high functioning autistic and the control children. The development of the cerebellar vermis area was delayed in autistic children as compared with that in the control children. Thus, it was suggested that significant anatomical changes in the midbrain and medulla oblongata existed in the autistic children. (author)

  17. A comprehensive volumetric analysis of the cerebellum in children and adolescents with autism spectrum disorder

    OpenAIRE

    Scott, Julia A.; Schumann, Cynthia Mills; Goodlin-Jones, Beth L.; Amaral, David G.

    2009-01-01

    Magnetic resonance imaging (MRI) and postmortem neuropathological studies have implicated the cerebellum in the pathophysiology of autism. Controversy remains, however, concerning the nature and the consistency of cerebellar alterations. MRI studies of the cross-sectional area of the vermis have found both decreases and no difference in autism groups. Volumetric analysis of the vermis, which is less prone to “plane of section artifacts” may provide a more reliable assessment of size differenc...

  18. Effects of Cinnamon Extract on Cerebellum Histomorphometry in Diabetic Rats’ Fetus

    OpenAIRE

    AR Rafati; SS Hashemi; O Hashemi

    2013-01-01

    Abstract Background & aim: In pregnant women, maternal diabetes occurs when the pancreas does not produce enough insulin, so glucose increases in the mother's blood and the blood of the fetus therefore causing many complications in children. The aim of this study was to evaluate the effects of cinnamon on morphometric histologic changes on fetal cerebellum of diabetic rats at days 18 and 20. Methods: In this study, 32 healthy female Wistar rats were prepared and randomly divided into...

  19. Influence of Transcranial Direct Current Stimulation to the Cerebellum on Standing Posture Control

    Science.gov (United States)

    Inukai, Yasuto; Saito, Kei; Sasaki, Ryoki; Kotan, Shinichi; Nakagawa, Masaki; Onishi, Hideaki

    2016-01-01

    Damage to the vestibular cerebellum results in dysfunctional standing posture control. Patients with cerebellum dysfunction have a larger sway in the center of gravity while standing compared with healthy subjects. Transcranial direct current stimulation (tDCS) is a noninvasive technique for selectively exciting or inhibiting specific neural structures with potential applications in functional assessment and treatment of neural disorders. However, the specific stimulation parameters for influencing postural control have not been assessed. In this study, we investigated the influence of tDCS when applied over the cerebellum on standing posture control. Sixteen healthy subjects received tDCS (20 min, 2 mA) over the scalp 2 cm below the inion. In Experiment 1, all 16 subjects received tDCS under three stimulus conditions, Sham, Cathodal, and Anodal, in a random order with the second electrode placed on the forehead. In Experiment 2, five subjects received cathodal stimulation only with the second electrode placed over the right buccinator muscle. Center of gravity sway was measured twice for 60 s before and after tDCS in a standing posture with eyes open and legs closed, and average total locus length, locus length per second, rectangular area, and enveloped area were calculated. In Experiment 1, total locus length and locus length per second decreased significantly after cathodal stimulation but not after anodal or sham stimulation, while no tDCS condition influenced rectangular or enveloped areas. In Experiment 2, cathodal tDCS again significantly reduced total locus length and locus length per second but not rectangular and enveloped areas. The effects of tDCS on postural control are polarity-dependent, likely reflecting the selective excitation or inhibition of cerebellar Purkinje cells. Cathodal tDCS to the cerebellum of healthy subjects can alter body sway (velocity).

  20. Models of basal ganglia and cerebellum for sensorimotor integration and predictive control

    Science.gov (United States)

    Jabri, Marwan A.; Huang, Jerry; Coenen, Olivier J. D.; Sejnowski, Terrence J.

    2000-10-01

    This paper presents a sensorimotor architecture integrating computational models of a cerebellum and a basal ganglia and operating on a microrobot. The computational models enable a microrobot to learn to track a moving object and anticipate future positions using a CCD camera. The architecture features pre-processing modules for coordinate transformation and instantaneous orientation extraction. Learning of motor control is implemented using predictive Hebbian reinforcement-learning algorithm in the basal ganglia model. Learning of sensory predictions makes use of a combination of long-term depression (LTD) and long-term potentiation (LTP) adaptation rules within the cerebellum model. The basal ganglia model uses the visual inputs to develop sensorimotor mapping for motor control, while the cerebellum module uses robot orientation and world- coordinate transformed inputs to predict the location of the moving object in a robot centered coordinate system. We propose several hypotheses about the functional role of cell populations in the cerebellum and argue that mossy fiber projections to the deep cerebellar nucleus (DCN) could play a coordinate transformation role and act as gain fields. We propose that such transformation could be learnt early in the brain development stages and could be guided by the activity of the climbing fibers. Proprioceptor mossy fibers projecting to the DCN and providing robot orientation with respect to a reference system could be involved in this case. Other mossy fibers carrying visual sensory input provide visual patterns to the granule cells. The combined activities of the granule and the Purkinje cells store spatial representations of the target patterns. The combinations of mossy and Purkinje projections to the DCN provide a prediction of the location of the moving target taking into consideration the robot orientation. Results of lesion simulations based on our model show degradations similar to those reported in cerebellar lesion

  1. Rapid evolution of the cerebellum in humans and other great apes

    OpenAIRE

    Barton, Robert A.; Venditti, Chris

    2014-01-01

    Humans’ unique cognitive abilities are usually attributed to a greatly expanded neocortex, which has been described as “the crowning achievement of evolution and the biological substrate of human mental prowess” [1]. The human cerebellum, however, contains four times more neurons than the neocortex [2] and is attracting increasing attention for its wide range of cognitive functions. Using a method for detecting evolutionary rate changes along the branches of phylogenetic trees, we show that t...

  2. Rapid evolution of the cerebellum in humans and other great apes.

    OpenAIRE

    Barton, R. A.; Venditti, C.

    2014-01-01

    Humans’ unique cognitive abilities are usually attributed to a greatly expanded neocortex, which has been described as ‘‘the crowning achievement of evolution and the biological substrate of human mental prowess’’ [1]. The human cerebellum, however, contains four times more neurons than the neocortex [2] and is attracting increasing attention for its wide range of cognitive functions. Using a method for detecting evolutionary rate changes along the branches of phylogenetic trees, we show that...

  3. The Pediatric Cerebellum in Inherited Neurodegenerative Disorders: A Pattern-recognition Approach.

    Science.gov (United States)

    Blaser, Susan I; Steinlin, Maja; Al-Maawali, Almundher; Yoon, Grace

    2016-08-01

    Evaluation of imaging studies of the cerebellum in inherited neurodegenerative disorders is aided by attention to neuroimaging patterns based on anatomic determinants, including biometric analysis, hyperintense signal of structures, including the cerebellar cortex, white matter, dentate nuclei, brainstem tracts, and nuclei, the presence of cysts, brain iron, or calcifications, change over time, the use of diffusion-weighted/diffusion tensor imaging and T2*-weighted sequences, magnetic resonance spectroscopy; and, in rare occurrences, the administration of contrast material. PMID:27423800

  4. Specific regions within the embryonic midbrain and cerebellum require different levels of FGF signaling during development

    Science.gov (United States)

    Basson, M. Albert; Echevarria, Diego; Ahn, Christina Petersen; Sudarov, Anamaria; Joyner, Alexandra L.; Mason, Ivor J.; Martinez, Salvador; Martin, Gail R.

    2008-01-01

    SUMMARY Development of the prospective midbrain and cerebellum are coordinated by FGF ligands produced by the isthmic organizer. Previous studies have suggested that the midbrain and cerebellum require different levels of FGF signaling for their development. However, little is known about the extent to which specific regions within these two parts of the brain differ in their requirement for FGF signaling during embryogenesis. In this study, we have explored the effects of inhibiting FGF signaling within the embryonic midbrain (mesencephalon) and cerebellum (rhombomere 1) by misexpressing Sprouty2 (Spry2) specifically in the mouse mesencephalon and rhombomere 1 from an early stage. We show that such Spry2 misexpression moderately reduces FGF signaling, and that this reduction causes the death of cells in the anterior mesencephalon, the region furthest from the source of FGF ligands. Interestingly, the remaining cells in the posterior mesencephalon develop into anterior midbrain, indicating that a low level of FGF signaling is sufficient to promote only anterior midbrain development. Spry2 misexpression also affects development of the vermis, the medial part of the cerebellum that spans the midline. We found that whereas misexpression of Spry2 alone caused loss of the anterior vermis, reducing FGF signaling further, by decreasing Fgf8 gene dosage, resulted in loss of the entire vermis. We provide evidence that cell death is not responsible for this tissue loss. Instead, our data suggest that the vermis fails to develop because reducing FGF signaling perturbs the balance between vermis and roof plate development in rhombomere 1. We suggest a molecular explanation for this phenomenon by providing evidence that FGF signaling functions to inhibit the BMP signaling that promotes roof plate development. PMID:18216176

  5. Branching patterns of olivocerebellar axons in relation to the compartmental organization of the cerebellum

    Directory of Open Access Journals (Sweden)

    Hirofumi eFujita

    2013-02-01

    Full Text Available A single olivocerebellar (OC axon gives rise to about seven branches that terminate as climbing fibers (CFs. Branching patterns of an OC axon, which are classified into local, transverse and longitudinal types, are highly organized, in relation to the longitudinal molecular (aldolase C or zebrin II compartmentalization and the transverse lobulation of the cerebellum. Local branching is involved in forming a narrow band-shaped functional subarea within a molecular compartment. On the other hand, transverse and longitudinal branchings appear to be involved in linking mediolaterally separated molecular compartments and rostrocaudally separated lobular areas, respectively. Longitudinal branching occurs frequently between equivalent molecular compartments of specific combinations of lobules. These combinations include lobule V-simple lobule and crus II-paramedian lobule in the pars intermedia and hemisphere, and lobules I-V and lobule VIII in the vermis. The longitudinal branching pattern not only fits with mirror-imaged somatosensory double representation of the body in the pars intermedia, but it also suggests a general rostrocaudal link exists for the whole cerebellum across the putative rostrocaudal boundary in lobule VIc-crus I. Molecular compartments of the cerebellar cortex originate from the Purkinje cell (PC clusters that appear in the late embryonic stage, when the immature OC projection is formed. Some clusters split rostrocaudally across crus I during the development of cortical compartments, which would result in longitudinal branching of OC projection across crus I. Supposing that the branching pattern of OC axons represents an essential organization of the cerebellum, longitudinal branching suggests a functional and developmental links between the rostral and caudal cerebellum across lobule VIc-crus I throughout the cerebellar cortex.

  6. Immunocytochemical localization of microtubule-associated protein 1 in rat cerebellum using monoclonal antibodies

    OpenAIRE

    1984-01-01

    Immunohistochemical staining with monoclonal antibodies showed that microtubule-associated protein 1 (MAP1) has a restricted cellular distribution in the rat cerebellum. Anti-MAP1 staining was found only in neurons, where it was much stronger in dendrites than in axons. There were striking variations in the apparent concentration of MAP1 in different classes of neurons. Purkinje cells were the most strongly labeled, while granule cell neurons gave a faint, threshold-level reaction with the an...

  7. Brain stem and cerebellum volumetric analysis of Machado Joseph disease patients

    Directory of Open Access Journals (Sweden)

    S T Camargos

    2011-01-01

    Full Text Available Machado-Joseph disease, or spinocerebellar ataxia type 3(MJD/SCA3, is the most frequent late onset spinocerebellar ataxia and results from a CAG repeat expansion in the ataxin-3 gene. Previous studies have found correlation between atrophy of cerebellum and brainstem with age and CAG repeats, although no such correlation has been found with disease duration and clinical manifestations. In this study we test the hypothesis that atrophy of cerebellum and brainstem in MJD/SCA3 is related to clinical severity, disease duration and CAG repeat length as well as to other variables such as age and ICARS (International Cooperative Ataxia Rating Scale. Whole brain high resolution MRI and volumetric measurement with cranial volume normalization were obtained from 15 MJD/SCA3 patients and 15 normal, age and sex-matchedcontrols. We applied ICARS and compared the score with volumes and CAG number, disease duration and age. We found significant correlation of both brain stem and cerebellar atrophy with CAG repeat length, age, disease duration and degree of disability. The Spearman rank correlation was stronger with volumetric reduction of the cerebellum than with brain stem. Our data allow us to conclude that volumetric analysis might reveal progressive degeneration after disease onset, which in turn is linked to both age and number of CAG repeat expansions in SCA 3.

  8. The effect of trichlorfon and methylazoxymethanol on the development of guinea pig cerebellum

    International Nuclear Information System (INIS)

    The pesticide trichlorfon (125 mg/kg on days 42-44 in gestation) gives hypoplasia of Brain of the offspring without any significant reduction in their body weights. The hypoplasia may be caused by trichlorfon itself or by its metabolite dichlorvos. This period of development coincides with the growth spurt period of guinea pig brain. The largest changes occurred in the cerebellum. Electron microscopic examination of the cerebellar cortex showed increased apoptotic death of cells in the granule cell layer after trichlorfon treatment. A reduction in thickness of the external germinal layer of the cerebellar cortex and an elevated amount of pyknotic and karyorrhexic cells in the granule cell layer was found. There was a significant reduction in choline esterase, choline acetyltransferase and glutamate decarboxylase activities in the cerebellum. Methylazoxymethanol (15 mg/kg body weight, day 43) was examined for comparison and caused similar hypoplasia of the guinea pig cerebellum, but did also induce a reduction in body weight. Trichloroethanol, the main metabolite of trichlorfon, did not give brain hypoplasia

  9. Electrophysiological representation of scratching CpG activity in the cerebellum.

    Science.gov (United States)

    Martínez-Silva, Lourdes; Manjarrez, Elias; Gutiérrez-Ospina, Gabriel; Quevedo, Jorge N

    2014-01-01

    We analyzed the electrical activity of neuronal populations in the cerebellum and the lumbar spinal cord during fictive scratching in adult decerebrate cats before and after selective sections of the Spino-Reticulo Cerebellar Pathway (SRCP) and the Ventral-Spino Cerebellar Tract (VSCT). During fictive scratching, we found a conspicuous sinusoidal electrical activity, called Sinusoidal Cerebellar Potentials (SCPs), in the cerebellar vermis, which exhibited smaller amplitude in the paravermal and hemisphere cortices. There was also a significant spino-cerebellar coherence between these SCPs and the lumbar sinusoidal cord dorsum potentials (SCDPs). However, during spontaneous activity such spino-cerebellar coherence between spontaneous potentials recorded in the same regions decreased. We found that the section of the SRCP and the VSCT did not abolish the amplitude of the SCPs, suggesting that there are additional pathways conveying information from the spinal CPG to the cerebellum. This is the first evidence that the sinusoidal activity associated to the spinal CPG circuitry for scratching has a broad representation in the cerebellum beyond the sensory representation from hindlimbs previously described. Furthermore, the SCPs represent the global electrical activity of the spinal CPG for scratching in the cerebellar cortex. PMID:25350378

  10. Neurotrophins and their Trk-receptors in the cerebellum of zebrafish.

    Science.gov (United States)

    Gatta, Claudia; Altamura, Gennaro; Avallone, Luigi; Castaldo, Luciana; Corteggio, Annunziata; D'Angelo, Livia; de Girolamo, Paolo; Lucini, Carla

    2016-06-01

    Neurotrophins (NTs) and their specific Trk-receptors are key molecules involved in the regulation of survival, proliferation, and differentiation of central nervous system during development and adulthood in vertebrates. In the present survey, we studied the expression and localization of neurotrophins and their Trk-receptors in the cerebellum of teleost fish Danio rerio (zebrafish). Teleostean cerebellum is composed of a valvula, body and vestibulolateral lobe. Valvula and body show the same three-layer structure as cerebellar cortex in mammals. The expression of NTs and Trk-receptors in the whole brain of zebrafish has been studied by Western blotting analysis. By immunohistochemistry, the localization of NTs has been observed mainly in Purkinje cells; TrkA and TrkB-receptors in cells and fibers of granular and molecular layers. TrkC was faintly detected. The occurrence of NTs and Trk-receptors suggests that they could have a synergistic action in the cerebellum of zebrafish. J. Morphol. 277:725-736, 2016. © 2016 Wiley Periodicals, Inc. PMID:27197756

  11. Cutaneous and periodontal inputs to the cerebellum of the naked mole-rat (Heterocephalus glaber

    Directory of Open Access Journals (Sweden)

    Diana K Sarko

    2013-11-01

    Full Text Available The naked mole-rat (Heterocephalus glaber is a small fossorial rodent with specialized dentition that is reflected by the large cortical area dedicated to representation of the prominent incisors. Due to naked mole-rats’ behavioral reliance on the incisors for digging and for manipulating objects, as well as their ability to move the lower incisors independently, we hypothesized that expanded somatosensory representations of the incisors would be present within the cerebellum in order to accommodate a greater degree of proprioceptive, cutaneous, and periodontal input. Multiunit electrophysiological recordings targeting the ansiform lobule were used to investigate tactile inputs from receptive fields on the entire body with a focus on the incisors. Similar to other rodents, a fractured somatotopy appeared to be present with discrete representations of the same receptive fields repeated within each folium of the cerebellum. These findings confirm the presence of somatosensory inputs to a large area of the naked mole-rat cerebellum with particularly extensive representations of the lower incisors and mystacial vibrissae. We speculate that these extensive inputs facilitate processing of tactile cues as part of a sensorimotor integration network that optimizes how sensory stimuli are acquired through active exploration and in turn adjusts motor outputs (such as independent movement of the lower incisors. These results highlight the diverse sensory specializations and corresponding brain organizational schemes that have evolved in different mammals to facilitate exploration of and interaction with their environment.

  12. The Cerebellum: New Computational Model that Reveals its Primary Function to Calculate Multibody Dynamics Conform to Lagrange-Euler Formulation

    OpenAIRE

    Kurtaj, Lavdim; Limani, Ilir; Shatri, Vjosa; Skeja, Avni

    2014-01-01

    Cerebellum is part of the brain that occupies only 10% of the brain volume, but it contains about 80% of total number of brain neurons. New cerebellar function model is developed that sets cerebellar circuits in context of multibody dynamics model computations, as important step in controlling balance and movement coordination, functions performed by two oldest parts of the cerebellum. Model gives new functional interpretation for granule cells-Golgi cell circuit, including distinct function ...

  13. Involvement of the ipsilateral and contralateral cerebellum in the acquisition of unilateral classical eyeblink conditioning in guinea pigs

    Institute of Scientific and Technical Information of China (English)

    Bo HU; Xi LIN; Lushuai HUANG; Li YANG; Hua FENG; Jianfeng SUI

    2009-01-01

    Aim:The aim of this study was to evaluate the relative contributions of the ipsilateral and contralateral cerebellum to the acquisition of unilateral classical eyeblink conditioning (EBCC).Methods: The unilateral EBCC was achieved using a binaural tone conditioned stimulus (CS) paired with a left airpuff unconditioned stimulus (US).A high-resolution potentiometer was used to monitor eyeblink responses.Guinea pigs received one CS-US session followed by three CS-US sessions (sessions 2 to 4),during which microinjections of muscimol,a GABAA receptor agonist,were performed to reversibly inactivate the cerebellum unilaterally prior to training.To test whether any learning had occurred during these inactivation sessions,training was continued for six more CS-US sessions (sessions 5 to 10) without any inactivation.Results: Animals with inactivation of the left cerebellum had no signs of left conditioned response (CR) during sessions 2 to 4,and their CR acquisition during sessions 5 to 10 was not distinguishable from that of control animals during sessions 2 to 7.In contrast,animals with inactivation of the right cerebellum acquired left CRs during sessions 2 to 4,although their CR acquisition was significantly retarded during session 2.In addition,microinjections of muscimol into the right cerebellum did not affect left neuro-behavioral activity.Finally,microinjections of muscimol into either the left or the right cerebellum did not affect the performance of tone-airpuff evoked unconditioned response (UR).Conclusion: In contrast to the essential role of the ipsilateral cerebellum,the contralateral cerebellum is potentially involved in the acquisition of unilateral EBCC during the early stage of training.

  14. Robust Machine Learning-Based Correction on Automatic Segmentation of the Cerebellum and Brainstem.

    Directory of Open Access Journals (Sweden)

    Jun Yi Wang

    Full Text Available Automated segmentation is a useful method for studying large brain structures such as the cerebellum and brainstem. However, automated segmentation may lead to inaccuracy and/or undesirable boundary. The goal of the present study was to investigate whether SegAdapter, a machine learning-based method, is useful for automatically correcting large segmentation errors and disagreement in anatomical definition. We further assessed the robustness of the method in handling size of training set, differences in head coil usage, and amount of brain atrophy. High resolution T1-weighted images were acquired from 30 healthy controls scanned with either an 8-channel or 32-channel head coil. Ten patients, who suffered from brain atrophy because of fragile X-associated tremor/ataxia syndrome, were scanned using the 32-channel head coil. The initial segmentations of the cerebellum and brainstem were generated automatically using Freesurfer. Subsequently, Freesurfer's segmentations were both manually corrected to serve as the gold standard and automatically corrected by SegAdapter. Using only 5 scans in the training set, spatial overlap with manual segmentation in Dice coefficient improved significantly from 0.956 (for Freesurfer segmentation to 0.978 (for SegAdapter-corrected segmentation for the cerebellum and from 0.821 to 0.954 for the brainstem. Reducing the training set size to 2 scans only decreased the Dice coefficient ≤0.002 for the cerebellum and ≤ 0.005 for the brainstem compared to the use of training set size of 5 scans in corrective learning. The method was also robust in handling differences between the training set and the test set in head coil usage and the amount of brain atrophy, which reduced spatial overlap only by <0.01. These results suggest that the combination of automated segmentation and corrective learning provides a valuable method for accurate and efficient segmentation of the cerebellum and brainstem, particularly in large

  15. Cerebellum and psychiatric disorders O cerebelo e os transtornos psiquiátricos

    Directory of Open Access Journals (Sweden)

    Leonardo Baldaçara

    2008-09-01

    Full Text Available OBJECTIVE: The objective of this update article is to report structural and functional neuroimaging studies exploring the potential role of cerebellum in the pathophysiology of psychiatric disorders. METHOD: A non-systematic literature review was conducted by means of Medline using the following terms as a parameter: "cerebellum", "cerebellar vermis", "schizophrenia", "bipolar disorder", "depression", "anxiety disorders", "dementia" and "attention deficit hyperactivity disorder". The electronic search was done up to April 2008. DISCUSSION: Structural and functional cerebellar abnormalities have been reported in many psychiatric disorders, namely schizophrenia, bipolar disorder, major depressive disorder, anxiety disorders, dementia and attention deficit hyperactivity disorder. Structural magnetic resonance imaging studies have reported smaller total cerebellar and vermal volumes in schizophrenia, mood disorders and attention deficit hyperactivity disorder. Functional magnetic resonance imaging studies using cognitive paradigms have shown alterations in cerebellar activity in schizophrenia, anxiety disorders and attention deficit hyperactivity disorder. In dementia, the cerebellum is affected in later stages of the disease. CONCLUSION: Contrasting with early theories, cerebellum appears to play a major role in different brain functions other than balance and motor control, including emotional regulation and cognition. Future studies are clearly needed to further elucidate the role of cerebellum in both normal and pathological behavior, mood regulation, and cognitive functioning.OBJETIVO: Este artigo de atualização tem como objetivo avaliar estudos em neuroimagem estrutural e funcional a fim de explorar o papel do cerebelo na patofisiologia dos transtornos psiquiátricos. MÉTODO: Uma revisão não sistemática foi realizada através do Medline utilizando-se como parâmetro os seguintes termos: "cerebellum", "cerebellar vermis", "schizophrenia

  16. Subchronic Exposure to Arsenic Represses the TH/TRβ1-CaMK IV Signaling Pathway in Mouse Cerebellum.

    Science.gov (United States)

    Guan, Huai; Li, Shuangyue; Guo, Yanjie; Liu, Xiaofeng; Yang, Yi; Guo, Jinqiu; Li, Sheng; Zhang, Cong; Shang, Lixin; Piao, Fengyuan

    2016-01-01

    We previously reported that arsenic (As) impaired learning and memory by down-regulating calmodulin-dependent protein kinase IV (CaMK IV) in mouse cerebellum. It has been documented that the thyroid hormone receptor (TR)/retinoid X receptor (RXR) heterodimer and thyroid hormone (TH) may be involved in the regulation of CaMK IV. To investigate whether As affects the TR/RXR heterodimer and TH, we determined As concentration in serum and cerebellum, 3,5,3'-triiodothyronine (T3) and thyroxin (T4) levels in serum, and expression of CaMK IV, TR and RXR in cerebellum of mice exposed to As. Cognition function was examined by the step-down passive avoidance task and Morris water maze (MWM) tests. Morphology of the cerebellum was observed by Hematoxylin-Eosin staining under light microscope. Our results showed that the concentrations of As in the serum and cerebellum of mice both increased with increasing As-exposure level. A significant positive correlation was found between the two processes. Adeficit in learning and memory was found in the exposed mice. Abnormal morphologic changes of Purkinje cells were observed in cerebellum of the exposed mice. Moreover, the cerebellar expressions of CaMK IV protein and the TRβ gene, and TRβ1 protein were significantly lower in As-exposed mice than those in controls. Subchronic exposure to As appears to increase its level in serum and cerebella of mice, impairing learning and memory and down-regulating expression of TRβ1 as well as down-stream CaMK IV. It is also suggested that the increased As may be responsible for down-regulation of TRβ1 and CaMK IV in cerebellum and that the down-regulated TRβ1 may be involved in As-induced impairment of learning and memory via inhibiting CaMK IV and its down-stream pathway. PMID:26821021

  17. Subchronic Exposure to Arsenic Represses the TH/TRβ1-CaMK IV Signaling Pathway in Mouse Cerebellum

    Directory of Open Access Journals (Sweden)

    Huai Guan

    2016-01-01

    Full Text Available We previously reported that arsenic (As impaired learning and memory by down-regulating calmodulin-dependent protein kinase IV (CaMK IV in mouse cerebellum. It has been documented that the thyroid hormone receptor (TR/retinoid X receptor (RXR heterodimer and thyroid hormone (TH may be involved in the regulation of CaMK IV. To investigate whether As affects the TR/RXR heterodimer and TH, we determined As concentration in serum and cerebellum, 3,5,3’-triiodothyronine (T3 and thyroxin (T4 levels in serum, and expression of CaMK IV, TR and RXR in cerebellum of mice exposed to As. Cognition function was examined by the step-down passive avoidance task and Morris water maze (MWM tests. Morphology of the cerebellum was observed by Hematoxylin-Eosin staining under light microscope. Our results showed that the concentrations of As in the serum and cerebellum of mice both increased with increasing As-exposure level. A significant positive correlation was found between the two processes. Adeficit in learning and memory was found in the exposed mice. Abnormal morphologic changes of Purkinje cells were observed in cerebellum of the exposed mice. Moreover, the cerebellar expressions of CaMK IV protein and the TRβ gene, and TRβ1 protein were significantly lower in As-exposed mice than those in controls. Subchronic exposure to As appears to increase its level in serum and cerebella of mice, impairing learning and memory and down-regulating expression of TRβ1 as well as down-stream CaMK IV. It is also suggested that the increased As may be responsible for down-regulation of TRβ1 and CaMK IV in cerebellum and that the down-regulated TRβ1 may be involved in As-induced impairment of learning and memory via inhibiting CaMK IV and its down-stream pathway.

  18. Processing of Visual Signals Related to Self-motion in the Cerebellum of Pigeons

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    Douglas Richard Wylie

    2013-02-01

    Full Text Available In this paper I describe the key features of optic flow processing in pigeons. Optic flow is the visual motion that occurs across the entire retina as a result of self-motion and is processed by subcortical visual pathways that project to the cerebellum. These pathways originate in two retinal-recipient nuclei, the nucleus of the basal optic root and the nucleus lentiformis mesencephali, which project to the vestibulocerebellum (folia IXcd and X, directly as mossy fibres, and indirectly as climbing fibres from the inferior olive. Optic flow information is integrated with vestibular input in the vestibulocerebellum. There is a clear separation of function in the vestibulocerebellum: Purkinje cells in the flocculus process optic flow resulting from self-rotation, whereas Purkinje cells in the uvula/nodulus process optic flow resulting from self-translation. Furthermore, Purkinje cells with particular optic flow preferences are organized topographically into parasagittal zones. These zones are correlated with expression of the isoenzyme aldolase C, also known as zebrin II (ZII. ZII expression is heterogeneous such that there are parasagittal stripes of Purkinje cells that have high expression (ZII+ alternating with stripes of Purkinje cells with low expression (ZII-. A functional zone spans a ZII+/- stripe pair. That is, each zone that contains Purkinje cells responsive to a particular pattern of optic flow is subdivided into a strip containing ZII+ Purkinje cells and a strip containing ZII- Purkinje cells. Additionally, there is optic flow input to folia VI-VIII of the cerebellum from lentiformis mesencephali. These folia also receive visual input from the tectofugal system via pontine nuclei. As the tectofugal system is involved in the analysis of local motion, there is integration of optic flow and local motion information in VI-VIII. This part of the cerebellum may be important for moving through a cluttered environment.

  19. Thyroxine, triiodothyronine, and reverse triiodothyronine processing in the cerebellum: Autoradiographic studies in adult rats

    International Nuclear Information System (INIS)

    Well confirmed evidence has demonstrated that the cerebellum is an important target of thyroid hormone action during development. Moreover, the presence of nuclear receptors and strong 5'-deiodinase activity in cerebella of adult rats have suggested that this region may continue to respond to thyroid hormones during maturity. Recent autoradiographic observations have focused attention on the cerebellar granular layer, in that [125I]T3 administered iv to adult rats was found to be selectively and saturably concentrated there. To determine the specificity of iodothyronine localization in the granular layer, we have now compared film autoradiographic observations made after iv [125I]T4 and iv [125I]rT3 with those found after iv [125I]T3. The results demonstrated that, as in the case of the latter hormone, labeling within the cerebellar cortex after iv [125I]T4 was both selective and saturable. Moreover, except for a lag in time to resolution and a longer retention time, the distribution of cerebellar radioactivity after iv labeled T4 was qualitatively similar to that seen after iv [125I]T3. However, the ability of T4 to become differentially concentrated in the granular layer of cerebellum was absolutely dependent on its ability to be converted intracerebrally to T3. Thus, pretreatment with ipodate, which blocks brain 5'-deiodinase activity and, therefore, the intracerebral formation of T3 from T4, completely prevented cerebellar granular layer labeling after iv [125I]T4 even though it did not interfere with differential labeling of this region by iv delivered [125I]T3. In the same experiments, propylthiouracil, a potent peripheral, but not central, 5'-deiodinase inhibitor, had no qualitative effect on the distribution of either T4 or T3 in cerebellum

  20. Cerebellum in levodopa-induced dyskinesias: the unusual suspect in the motor network

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    Asha eKishore

    2014-08-01

    Full Text Available The exact mechanisms that generate levodopa-induced dyskinesias (LID during chronic levodopa therapy for Parkinson’s disease (PD are not yet fully established. The most widely accepted theories incriminate the non-physiological synthesis, release and reuptake of dopamine generated by exogenously administered levodopa in the striatum, and the aberrant plasticity in the corticostriatal loops. However, normal motor performance requires the correct recruitment of motor maps. This depends on a high level of synergy within the primary motor cortex (M1 as well as between M1 and other cortical and subcortical areas, for which dopamine is necessary. The plastic mechanisms within M1 which are crucial for the maintenance of this synergy are disrupted both during OFF and dyskinetic states in PD. When tested without levodopa, dyskinetic patients show loss of treatment benefits on long-term potentiation and long-term depression-like plasticity of the intracortical circuits. When tested with the regular pulsatile levodopa doses, they show further impairment of the M1 plasticity, such as inability to depotentiate an already facilitated synapse and paradoxical facilitation in response to afferent input aimed at synaptic inhibition. Dyskinetic patients have also severe impairment of the associative, sensorimotor plasticity of M1 attributed to deficient cerebellar modulation of sensory afferents to M1. Here we review the anatomical and functional studies, including the recently described bidirectional connections between the cerebellum and the basal ganglia that support a key role of the cerebellum in the generation of LID. This model stipulates that aberrant neuronal synchrony in PD with LID may propagate from the sub thalamic nucleus to the cerebellum and lock the cerebellar cortex in a hyperactive state. This could affect critical cerebellar functions such as the dynamic and discrete modulation of M1 plasticity and the matching of motor commands with sensory

  1. In vivo binding of [11C]nemonapride to sigma receptors in the cortex and cerebellum

    International Nuclear Information System (INIS)

    Radiolabeled nemonapride (NEM, YM-09151-2) is widely used as a representative dopamine D2-like receptor ligand in pharmacological and neurological studies, and 11C-labeled analog ([11C]NEM) has been developed for positron emission tomography (PET) studies. The aim of this study was to evaluate whether [11C]NEM binds in vivo to sigma receptors. [11C]NEM and one of six dopamine D2-like receptor ligands or seven sigma receptor ligands were co-injected into mice, and the regional brain uptake of [11C]NEM was measured by a tissue dissection method. The striatal uptake of [11C]NEM was reduced by D2-like receptor ligands, NEM, haloperidol, (+)-butaclamol, raclopride, and sulpiride, but not by a D4 receptor ligand clozapine. In the cortex and cerebellum the uptake was also reduced by D2-like receptor ligands with affinity for sigma receptors, but not by raclopride. Although none of seven sigma receptor ligands, SA6298, N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine hydrochloride (NE-100), (+)-pentazocine, R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2-aminopropane hydrochloride ([-]-PPAP), (-)-pentazocine, R(+)-3-(3-hydroxyphenyl)-N-propylpiperidine hydrochloride ([+]-3-PPP), and (+)-N-allylnormetazocine hydrochloride ([+]-SKF 10047), blocked the striatal uptake, five of them with relatively higher affinity significantly reduced the [11C]NEM uptake by the cortex, and four of them reduced that by the cerebellum. We concluded that [11C]NEM binds in vivo not only to dopamine D2-like receptors in the striatum but also to sigma receptors in other regions such as cortex and cerebellum

  2. Chronic exposure to hypergravity affects thyrotropin-releasing hormone levels in rat brainstem and cerebellum

    Science.gov (United States)

    Daunton, N. G.; Tang, F.; Corcoran, M. L.; Fox, R. A.; Man, S. Y.

    1998-01-01

    In studies to determine the neurochemical mechanisms underlying adaptation to altered gravity we have investigated changes in neuropeptide levels in brainstem, cerebellum, hypothalamus, striatum, hippocampus, and cerebral cortex by radioimmunoassay. Fourteen days of hypergravity (hyperG) exposure resulted in significant increases in thyrotropin-releasing hormone (TRH) content of brainstem and cerebellum, but no changes in levels of other neuropeptides (beta-endorphin, cholecystokinin, met-enkephalin, somatostatin, and substance P) examined in these areas were found, nor were TRH levels significantly changed in any other brain regions investigated. The increase in TRH in brainstem and cerebellum was not seen in animals exposed only to the rotational component of centrifugation, suggesting that this increase was elicited by the alteration in the gravitational environment. The only other neuropeptide affected by chronic hyperG exposure was met-enkephalin, which was significantly decreased in the cerebral cortex. However, this alteration in met-enkephalin was found in both hyperG and rotation control animals and thus may be due to the rotational rather than the hyperG component of centrifugation. Thus it does not appear as if there is a generalized neuropeptide response to chronic hyperG following 2 weeks of exposure. Rather, there is an increase only of TRH and that occurs only in areas of the brain known to be heavily involved with vestibular inputs and motor control (both voluntary and autonomic). These results suggest that TRH may play a role in adaptation to altered gravity as it does in adaptation to altered vestibular input following labyrinthectomy, and in cerebellar and vestibular control of locomotion, as seen in studies of ataxia.

  3. Maturational Patterns of Iodothyronine Phenolic and Tyrosyl Ring Deiodinase Activities in Rat Cerebrum, Cerebellum, and Hypothalamus

    OpenAIRE

    Kaplan, Michael M.; Yaskoski, Kimberlee A.

    1981-01-01

    To explore the control of thyroid hormone metabolism in brain during maturation, we have measured iodothyronine deiodination in homogenates of rat cerebrum, cerebellum, and hypothalamus from 1 d postnatally through adulthood. Homogenates were incubated with 125I-l-thyroxine (T4) + [131I]3,5,3′-l-triiodothyronine (T3) + 100 mM dithiothreitol. Nonradioactive T4, T3, and 3,3′,5′-triiodothyronine (rT3) were included, as appropriate. The net production rate of [125I]T3 from T4 in 1-d cerebral homo...

  4. Prion and doppel proteins bind to granule cells of the cerebellum

    OpenAIRE

    Legname, Giuseppe; Nelken, Peter; Guan, Zhengyu; Kanyo, Zoltan F.; DeArmond, Stephen J.; Prusiner, Stanley B.

    2002-01-01

    We reported that expression of the cellular prion protein (PrPC) rescues doppel (Dpl)-induced cerebellar degeneration in mice. To search for protein(s) that mediate this process, we fused the C-termini of mouse (Mo) PrP and Dpl to the Fc portion of an IgG. Although both MoPrP-Fc and MoDpl-Fc bound to many regions of the brain, we observed restricted binding to granule cells in the cerebellum, suggesting a scenario in which granule cells express a protein that mediates Dpl-induced neurodegener...

  5. Interaction of plasticity and circuit organization during the acquisition of cerebellum-dependent motor learning

    OpenAIRE

    Yang, Yan; Lisberger, Stephen G.

    2013-01-01

    eLife digest Practice makes perfect in many areas of life, such as playing sport or even just drinking coffee from a cup without spilling any. Our brains can learn and improve these motor skills through trial, error and learning, with such “motor learning” depending on the cerebellum, a part of the brain that helps to coordinate all kinds of movements. Motor learning is a product of the organization of the cerebellar circuit, which is well understood, and the “plasticity” in the synapses that...

  6. Chronic lithium treatment with or without haloperidol fails to affect the morphology of the rat cerebellum

    DEFF Research Database (Denmark)

    Licht, R W; Larsen, Jytte Overgaard; Smith, D; Braendgaard, H

    2003-01-01

    We used unbiased stereological principles to determine whether long-term administration of lithium at human therapeutic levels, with or without haloperidol, affects the number or sizes of cerebellar Purkinje cells or the volume of histological layers in the rat cerebellum. Twenty-eight rats were...... randomly divided into three groups, receiving either no treatment, lithium, or lithium combined with haloperidol. The serum lithium levels ranged from 0.50 to 0.77 mmol/l. Haloperidol was given at a daily dose of 1 mg/kg. After 30 weeks of treatment, the animals were killed and the cerebelli were...

  7. Neuroprotection by taurine in ethanol-induced apoptosis in the developing cerebellum

    OpenAIRE

    Taranukhin Andrey G; Taranukhina Elena Y; Saransaari Pirjo; Podkletnova Irina M; Pelto-Huikko Markku; Oja Simo S

    2010-01-01

    Abstract Background Acute ethanol administration leads to massive apoptotic neurodegeneration in the developing central nervous system. We studied whether taurine is neuroprotective in ethanol-induced apoptosis in the mouse cerebellum during the postnatal period. Methods The mice were divided into three groups: ethanol-treated, ethanol+taurine-treated and controls. Ethanol (20% solution) was administered subcutaneously at a total dose of 5 g/kg (2.5 g/kg at time 1 h and 2.5 g/kg at 3 h) to th...

  8. Early-stage hemangioblastoma presenting as a small lesion with significant edema in the cerebellum.

    Science.gov (United States)

    Nie, Quanmin; Guo, Pin; Shen, Lin; Li, Xiaoxiong; Qiu, Yongming

    2015-03-01

    Hemangioblastomas are benign tumors that are frequently associated with peritumoral cysts; however, their early characteristics before cyst formation remain unclear. In this article, the authors present a novel case of a cerebellar hemangioblastoma presenting as a small solid lesion with significant edema. Surgery was performed to resect the tumor, and a follow-up magnetic resonance imaging scan revealed complete excision of the mass and resolution of the cerebellar edema. Histological examination confirmed that the lesion was a hemangioblastoma. This is the only report in the literature to describe the imaging and histopathologic characteristics of an initial hemangioblastoma in the cerebellum. PMID:25699527

  9. Neuroimaging of Infectious and Inflammatory Diseases of the Pediatric Cerebellum and Brainstem.

    Science.gov (United States)

    Rossi, Andrea; Martinetti, Carola; Morana, Giovanni; Severino, Mariasavina; Tortora, Domenico

    2016-08-01

    Cerebellar involvement by infectious-inflammatory conditions is rare in children. Most patients present with acute ataxia, and are typically previously healthy, young (often preschool) children. Viral involvement is the most common cause and ranges from acute postinfectious ataxia to acute cerebellitis MR imaging plays a crucial role in the evaluation of patients suspected of harboring inflammatory-infectious involvement of the cerebellum and brainstem. Knowledge of the imaging features of these disorders and technical competence on pediatric MR imaging are necessary for a correct interpretation of findings, which in turn prompts further management. PMID:27423804

  10. Information to cerebellum on spinal motor networks mediated by the dorsal spinocerebellar tract

    DEFF Research Database (Denmark)

    Stecina, Katinka; Fedirchuk, Brent; Hultborn, Hans

    peripheral sensory input to the cerebellum in general, and during rhythmic movements such as locomotion and scratch. In contrast, the VSCT was seen as conveying a copy of the output of spinal neuronal circuitry, including those circuits generating rhythmic motor activity (the spinal central pattern generator......, overall, there is a greater similarity between DSCT and VSCT activity than previously acknowledged. Indeed the majority of DSCT cells can be driven by spinal CPGs for locomotion and scratch without phasic sensory input. It thus seems natural to propose the possibility that CPG input to some of these...

  11. Cerebellum and processing of negative facial emotions: cerebellar transcranial DC stimulation specifically enhances the emotional recognition of facial anger and sadness

    OpenAIRE

    Ferrucci, Roberta; Giannicola, Gaia; Rosa, Manuela; Fumagalli, Manuela; Boggio, Paulo Sergio; Hallett, Mark; Zago, Stefano; Priori, Alberto

    2011-01-01

    Some evidence suggests that the cerebellum participates in the complex network processing emotional facial expression. To evaluate the role of the cerebellum in recognizing facial expressions we delivered transcranial direct current stimulation (tDCS) over the cerebellum and prefrontal cortex. A facial emotion recognition task was administered to 21 healthy subjects before and after cerebellar tDCS; we also tested subjects with a visual attention task and a visual analogue scale (VAS) for mood.

  12. Sperm whales and killer whales with the largest brains of all toothed whales show extreme differences in cerebellum.

    Science.gov (United States)

    Ridgway, Sam H; Hanson, Alicia C

    2014-01-01

    Among cetaceans, killer whales and sperm whales have the widest distribution in the world's oceans. Both species use echolocation, are long-lived, and have the longest periods of gestation among whales. Sperm whales dive much deeper and much longer than killer whales. It has long been thought that sperm whales have the largest brains of all living things, but our brain mass evidence, from published sources and our own specimens, shows that big males of these two species share this distinction. Despite this, we also find that cerebellum size is very different between killer whales and sperm whales. The sperm whale cerebellum is only about 7% of the total brain mass, while the killer whale cerebellum is almost 14%. These results are significant because they contradict claims that the cerebellum scales proportionally with the rest of the brain in all mammals. They also correct the generalization that all cetaceans have enlarged cerebella. We suggest possible reasons for the existence of such a large cerebellar size difference between these two species. Cerebellar function is not fully understood, and comparing the abilities of animals with differently sized cerebella can help uncover functional roles of the cerebellum in humans and animals. Here we show that the large cerebellar difference likely relates to evolutionary history, diving, sensory capability, and ecology. PMID:24852603

  13. Multiagent data warehousing and multiagent data mining for cerebrum/cerebellum modeling

    Science.gov (United States)

    Zhang, Wen-Ran

    2002-03-01

    An algorithm named Neighbor-Miner is outlined for multiagent data warehousing and multiagent data mining. The algorithm is defined in an evolving dynamic environment with autonomous or semiautonomous agents. Instead of mining frequent itemsets from customer transactions, the new algorithm discovers new agents and mining agent associations in first-order logic from agent attributes and actions. While the Apriori algorithm uses frequency as a priory threshold, the new algorithm uses agent similarity as priory knowledge. The concept of agent similarity leads to the notions of agent cuboid, orthogonal multiagent data warehousing (MADWH), and multiagent data mining (MADM). Based on agent similarities and action similarities, Neighbor-Miner is proposed and illustrated in a MADWH/MADM approach to cerebrum/cerebellum modeling. It is shown that (1) semiautonomous neurofuzzy agents can be identified for uniped locomotion and gymnastic training based on attribute relevance analysis; (2) new agents can be discovered and agent cuboids can be dynamically constructed in an orthogonal MADWH, which resembles an evolving cerebrum/cerebellum system; and (3) dynamic motion laws can be discovered as association rules in first order logic. Although examples in legged robot gymnastics are used to illustrate the basic ideas, the new approach is generally suitable for a broad category of data mining tasks where knowledge can be discovered collectively by a set of agents from a geographically or geometrically distributed but relevant environment, especially in scientific and engineering data environments.

  14. An fMRI Study of Intra-Individual Functional Topography in the Human Cerebellum

    Directory of Open Access Journals (Sweden)

    Catherine J. Stoodley

    2010-01-01

    Full Text Available Neuroimaging studies report cerebellar activation during both motor and non-motor paradigms, and suggest a functional topography within the cerebellum. Sensorimotor tasks activate the anterior lobe, parts of lobule VI, and lobule VIII, whereas higher-level tasks activate lobules VI and VII in the posterior lobe. To determine whether these activation patterns are evident at a single-subject level, we conducted functional magnetic resonance imaging (fMRI during five tasks investigating sensorimotor (finger tapping, language (verb generation, spatial (mental rotation, working memory (N-back, and emotional processing (viewing images from the International Affective Picture System. Finger tapping activated the ipsilateral anterior lobe (lobules IV-V as well as lobules VI and VIII. Activation during verb generation was found in right lobules VII and VIIIA. Mental rotation activated left-lateralized clusters in lobules VII-VIIIA, VI-Crus I, and midline VIIAt. The N-back task showed bilateral activation in right lobules VI-Crus I and left lobules VIIB-VIIIA. Cerebellar activation was evident bilaterally in lobule VI while viewing arousing vs. neutral images. This fMRI study provides the first proof of principle demonstration that there is topographic organization of motor execution vs. cognitive/emotional domains within the cerebellum of a single individual, likely reflecting the anatomical specificity of cerebro-cerebellar circuits underlying different task domains. Inter-subject variability of motor and non-motor topography remains to be determined.

  15. Sprouty genes prevent excessive FGF signalling in multiple cell types throughout development of the cerebellum

    Science.gov (United States)

    Yu, Tian; Yaguchi, Yuichiro; Echevarria, Diego; Martinez, Salvador; Basson, M. Albert

    2011-01-01

    Fibroblast growth factors (FGFs) and regulators of the FGF signalling pathway are expressed in several cell types within the cerebellum throughout its development. Although much is known about the function of this pathway during the establishment of the cerebellar territory during early embryogenesis, the role of this pathway during later developmental stages is still poorly understood. Here, we investigated the function of sprouty genes (Spry1, Spry2 and Spry4), which encode feedback antagonists of FGF signalling, during cerebellar development in the mouse. Simultaneous deletion of more than one of these genes resulted in a number of defects, including mediolateral expansion of the cerebellar vermis, reduced thickness of the granule cell layer and abnormal foliation. Analysis of cerebellar development revealed that the anterior cerebellar neuroepithelium in the early embryonic cerebellum was expanded and that granule cell proliferation during late embryogenesis and early postnatal development was reduced. We show that the granule cell proliferation deficit correlated with reduced sonic hedgehog (SHH) expression and signalling. A reduction in Fgfr1 dosage during development rescued these defects, confirming that the abnormalities are due to excess FGF signalling. Our data indicate that sprouty acts both cell autonomously in granule cell precursors and non-cell autonomously to regulate granule cell number. Taken together, our data demonstrate that FGF signalling levels have to be tightly controlled throughout cerebellar development in order to maintain the normal development of multiple cell types. PMID:21693512

  16. Gating of long-term potentiation by nicotinic acetylcholine receptors at the cerebellum input stage.

    Directory of Open Access Journals (Sweden)

    Francesca Prestori

    Full Text Available The brain needs mechanisms able to correlate plastic changes with local circuit activity and internal functional states. At the cerebellum input stage, uncontrolled induction of long-term potentiation or depression (LTP or LTD between mossy fibres and granule cells can saturate synaptic capacity and impair cerebellar functioning, which suggests that neuromodulators are required to gate plasticity processes. Cholinergic systems innervating the cerebellum are thought to enhance procedural learning and memory. Here we show that a specific subtype of acetylcholine receptors, the α7-nAChRs, are distributed both in cerebellar mossy fibre terminals and granule cell dendrites and contribute substantially to synaptic regulation. Selective α7-nAChR activation enhances the postsynaptic calcium increase, allowing weak mossy fibre bursts, which would otherwise cause LTD, to generate robust LTP. The local microperfusion of α7-nAChR agonists could also lead to in vivo switching of LTD to LTP following sensory stimulation of the whisker pad. In the cerebellar flocculus, α7-nAChR pharmacological activation impaired vestibulo-ocular-reflex adaptation, probably because LTP was saturated, preventing the fine adjustment of synaptic weights. These results show that gating mechanisms mediated by specific subtypes of nicotinic receptors are required to control the LTD/LTP balance at the mossy fibre-granule cell relay in order to regulate cerebellar plasticity and behavioural adaptation.

  17. Brain metabolites in the hippocampus-amygdala region and cerebellum in autism: an {sup 1}H-MR spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, H.; Harada, M.; Hisaoka, S.; Nishitani, H. [Dept. of Radiology, Univ. of Tokushima, Tokushima City (Japan); Mori, K. [Dept. of Pediatrics, Univ. of Tokushima (Japan)

    1999-07-01

    Histological abnormalities of the brain in autism have been investigated extensively. We studied metabolites in the hippocampusamygdala (HA) region and cerebellum. We examined the right HA region and left cerebellar hemisphere of 27 autistic patients 2-18 years old, 21 boys and 6 girls and 10 normal children 6-14 years old, 4 boys and 6 girls, using the STEAM sequence. This sequence was used to minimise the influence of relaxation times. The N-acetyl aspartate (NAA) concentration was significantly lower (P=0.042) in autistic patients than in normal children (9.37 and 10.95 mM, respectively). There was no significant difference in other metabolites. The correlation coefficient (r value) of NAA between the HA region and cerebellum was 0.616. The decreased NAA concentration may be due to neuronal hypofunction or immature neurons. The NAA concentration in the HA region and cerebellum may be related, because of neuronal circuits or networks. (orig.)

  18. Brain metabolites in the hippocampus-amygdala region and cerebellum in autism: an 1H-MR spectroscopy study

    International Nuclear Information System (INIS)

    Histological abnormalities of the brain in autism have been investigated extensively. We studied metabolites in the hippocampusamygdala (HA) region and cerebellum. We examined the right HA region and left cerebellar hemisphere of 27 autistic patients 2-18 years old, 21 boys and 6 girls and 10 normal children 6-14 years old, 4 boys and 6 girls, using the STEAM sequence. This sequence was used to minimise the influence of relaxation times. The N-acetyl aspartate (NAA) concentration was significantly lower (P=0.042) in autistic patients than in normal children (9.37 and 10.95 mM, respectively). There was no significant difference in other metabolites. The correlation coefficient (r value) of NAA between the HA region and cerebellum was 0.616. The decreased NAA concentration may be due to neuronal hypofunction or immature neurons. The NAA concentration in the HA region and cerebellum may be related, because of neuronal circuits or networks. (orig.)

  19. Metabolic changes and DNA hypomethylation in cerebellum are associated with behavioral alterations in mice exposed to trichloroethylene postnatally

    Energy Technology Data Exchange (ETDEWEB)

    Blossom, Sarah J., E-mail: blossomsarah@uams.edu [Department of Pediatrics, University of Arkansas for Medical Sciences, College of Medicine, Arkansas Children' s Hospital Research Institute, 13 Children' s Way, Little Rock, AR 72202 (United States); Cooney, Craig A. [Department of Research and Development, Central Arkansas Veterans Healthcare System, John L. McClellan Memorial Veterans Hospital, 4300 West 7th St., Little Rock, AR 72205-5484 (United States); Melnyk, Stepan B.; Rau, Jenny L.; Swearingen, Christopher J. [Department of Pediatrics, University of Arkansas for Medical Sciences, College of Medicine, Arkansas Children' s Hospital Research Institute, 13 Children' s Way, Little Rock, AR 72202 (United States); Wessinger, William D. [Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, College of Medicine, 4301 West Markham St., Little Rock, AR 72205 (United States)

    2013-06-15

    Previous studies demonstrated that low-level postnatal and early life exposure to the environmental contaminant, trichloroethylene (TCE), in the drinking water of MRL +/+ mice altered glutathione redox homeostasis and increased biomarkers of oxidative stress indicating a more oxidized state. Plasma metabolites along the interrelated transmethylation pathway were also altered indicating impaired methylation capacity. Here we extend these findings to further characterize the impact of TCE exposure in mice exposed to water only or two doses of TCE in the drinking water (0, 2, and 28 mg/kg/day) postnatally from birth until 6 weeks of age on redox homeostasis and biomarkers of oxidative stress in the cerebellum. In addition, pathway intermediates involved in methyl metabolism and global DNA methylation patterns were examined in cerebellar tissue. Because the cerebellum is functionally important for coordinating motor activity, including exploratory and social approach behaviors, these parameters were evaluated in the present study. Mice exposed to 28 mg/kg/day TCE exhibited increased locomotor activity over time as compared with control mice. In the novel object exploration test, these mice were more likely to enter the zone with the novel object as compared to control mice. Similar results were obtained in a second test when an unfamiliar mouse was introduced into the testing arena. The results show for the first time that postnatal exposure to TCE causes key metabolic changes in the cerebellum that may contribute to global DNA methylation deficits and behavioral alterations in TCE-exposed mice. - Highlights: • We exposed male mice to low-level trichloroethylene from postnatal days 1 through 42. • This exposure altered redox potential and increased oxidative stress in cerebellum. • This exposure altered metabolites important in cellular methylation in cerebellum. • This exposure promoted DNA hypomethylation in cerebellum. • This exposure enhanced locomotor

  20. Metabolic changes and DNA hypomethylation in cerebellum are associated with behavioral alterations in mice exposed to trichloroethylene postnatally

    International Nuclear Information System (INIS)

    Previous studies demonstrated that low-level postnatal and early life exposure to the environmental contaminant, trichloroethylene (TCE), in the drinking water of MRL +/+ mice altered glutathione redox homeostasis and increased biomarkers of oxidative stress indicating a more oxidized state. Plasma metabolites along the interrelated transmethylation pathway were also altered indicating impaired methylation capacity. Here we extend these findings to further characterize the impact of TCE exposure in mice exposed to water only or two doses of TCE in the drinking water (0, 2, and 28 mg/kg/day) postnatally from birth until 6 weeks of age on redox homeostasis and biomarkers of oxidative stress in the cerebellum. In addition, pathway intermediates involved in methyl metabolism and global DNA methylation patterns were examined in cerebellar tissue. Because the cerebellum is functionally important for coordinating motor activity, including exploratory and social approach behaviors, these parameters were evaluated in the present study. Mice exposed to 28 mg/kg/day TCE exhibited increased locomotor activity over time as compared with control mice. In the novel object exploration test, these mice were more likely to enter the zone with the novel object as compared to control mice. Similar results were obtained in a second test when an unfamiliar mouse was introduced into the testing arena. The results show for the first time that postnatal exposure to TCE causes key metabolic changes in the cerebellum that may contribute to global DNA methylation deficits and behavioral alterations in TCE-exposed mice. - Highlights: • We exposed male mice to low-level trichloroethylene from postnatal days 1 through 42. • This exposure altered redox potential and increased oxidative stress in cerebellum. • This exposure altered metabolites important in cellular methylation in cerebellum. • This exposure promoted DNA hypomethylation in cerebellum. • This exposure enhanced locomotor

  1. Derivation of high-resolution MRI atlases of the human cerebellum at 3T and segmentation using multiple automatically generated templates.

    Science.gov (United States)

    Park, Min Tae M; Pipitone, Jon; Baer, Lawrence H; Winterburn, Julie L; Shah, Yashvi; Chavez, Sofia; Schira, Mark M; Lobaugh, Nancy J; Lerch, Jason P; Voineskos, Aristotle N; Chakravarty, M Mallar

    2014-07-15

    The cerebellum has classically been linked to motor learning and coordination. However, there is renewed interest in the role of the cerebellum in non-motor functions such as cognition and in the context of different neuropsychiatric disorders. The contribution of neuroimaging studies to advancing understanding of cerebellar structure and function has been limited, partly due to the cerebellum being understudied as a result of contrast and resolution limitations of standard structural magnetic resonance images (MRI). These limitations inhibit proper visualization of the highly compact and detailed cerebellar foliations. In addition, there is a lack of robust algorithms that automatically and reliably identify the cerebellum and its subregions, further complicating the design of large-scale studies of the cerebellum. As such, automated segmentation of the cerebellar lobules would allow detailed population studies of the cerebellum and its subregions. In this manuscript, we describe a novel set of high-resolution in vivo atlases of the cerebellum developed by pairing MR imaging with a carefully validated manual segmentation protocol. Using these cerebellar atlases as inputs, we validate a novel automated segmentation algorithm that takes advantage of the neuroanatomical variability that exists in a given population under study in order to automatically identify the cerebellum, and its lobules. Our automatic segmentation results demonstrate good accuracy in the identification of all lobules (mean Kappa [κ]=0.731; range 0.40-0.89), and the entire cerebellum (mean κ=0.925; range 0.90-0.94) when compared to "gold-standard" manual segmentations. These results compare favorably in comparison to other publically available methods for automatic segmentation of the cerebellum. The completed cerebellar atlases are available freely online (http://imaging-genetics.camh.ca/cerebellum) and can be customized to the unique neuroanatomy of different subjects using the proposed

  2. Cerebellum segmentation in MRI using atlas registration and local multi-scale image descriptors

    DEFF Research Database (Denmark)

    van der Lijn, F.; de Bruijne, M.; Hoogendam, Y.Y.; Klein, S.; Hameeteman, R.; Breteler, M.; Niessen, W.

    We propose a novel cerebellum segmentation method for MRI, based on a combination of statistical models of the structure's expected location in the brain and its local appearance. The appearance model is obtained from a k-nearest-neighbor classifier, which uses a set of multi-scale local image...... descriptors as features. The spatial model is constructed by registering multiple manually annotated datasets to the unlabeled target image. The two components are then combined in a Bayesian framework. The method is quantitatively validated in a leave-one-out experiment using 18 MR images of elderly subjects....... The experiment showed that the method produces accurate segmentations. The mean Dice similarity index compared to the manual reference was 0.953 for left and right, and the mean surface distance was 0.49 mm for left and 0.50 mm for right. The combined atlas- and appearance-based method was found to be...

  3. Plastic corollary discharge predicts sensory consequences of movements in a cerebellum-like circuit.

    Science.gov (United States)

    Requarth, Tim; Sawtell, Nathaniel B

    2014-05-21

    The capacity to predict the sensory consequences of movements is critical for sensory, motor, and cognitive function. Though it is hypothesized that internal signals related to motor commands, known as corollary discharge, serve to generate such predictions, this process remains poorly understood at the neural circuit level. Here we demonstrate that neurons in the electrosensory lobe (ELL) of weakly electric mormyrid fish generate negative images of the sensory consequences of the fish's own movements based on ascending spinal corollary discharge signals. These results generalize previous findings describing mechanisms for generating negative images of the effects of the fish's specialized electric organ discharge (EOD) and suggest that a cerebellum-like circuit endowed with associative synaptic plasticity acting on corollary discharge can solve the complex and ubiquitous problem of predicting sensory consequences of movements. PMID:24853945

  4. Cell death in the Purkinje cells of the cerebellum of senescence accelerated mouse (SAMP(8)).

    Science.gov (United States)

    Zhu, Yonghong; Lee, Cleo C L; Lam, W P; Wai, Maria S M; Rudd, John A; Yew, David T

    2007-10-01

    The cerebella of SAMP(8) (accelerated aging mouse) and SAMR(1) controls were analyzed by Western Blotting of tyrosine hydroxylase and choline acetyltransferase, as well as by TUNEL and histological silver staining. Both tyrosine hydroxylase and choline acetyltransferase levels were higher in SAMR(1) than in SAMP(8). There was also an age-related decrease in enzyme levels in SAMP(8), with the reduction of tyrosine hydroxylase being more apparent. Concomitantly, there was an age-related increase of apoptosis in the medial neocerebellum and the vermis as revealed by TUNEL, with changes being significant in the SAMP(8) strain. Histologically, some Purkinje cells appeared to disappear during aging. Taken together, the data suggests that the aging SAMP(8) strain displays differential Purkinje cell death in the medial cerebellum and that some of the dying cells are likely to be catecholaminergic. PMID:17415677

  5. Ethanol influences on Bax associations with mitochondrial membrane proteins in neonatal rat cerebellum.

    Science.gov (United States)

    Heaton, Marieta Barrow; Siler-Marsiglio, Kendra; Paiva, Michael; Kotler, Alexandra; Rogozinski, Jonathan; Kubovec, Stacey; Coursen, Mary; Madorsky, Vladimir

    2013-02-01

    These studies investigated interactions taking place at the mitochondrial membrane in neonatal rat cerebellum following ethanol exposure and focused on interactions between proapoptotic Bax and proteins of the permeability transition pore (PTP), voltage-dependent anion channel (VDAC) and adenine nucleotide translocator (ANT) of the outer and inner mitochondrial membranes, respectively. Cultured cerebellar granule cells were used to assess the role of these interactions in ethanol neurotoxicity. Analyses were made at the age of maximal cerebellar ethanol vulnerability (P4), compared to the later age of relative resistance (P7), to determine whether differential ethanol sensitivity was mirrored by differences in these molecular interactions. We found that, following ethanol exposure, Bax proapoptotic associations with both VDAC and ANT were increased, particularly at the age of greater ethanol sensitivity, and these interactions were sustained at this age for at least 2 h postexposure. Since Bax:VDAC interactions disrupt protective VDAC interactions with mitochondrial hexokinase (HXK), we also assessed VDAC:HXK associations following ethanol treatment and found such interactions were altered by ethanol treatment, but only at 2 h postexposure and only in the P4, ethanol-sensitive cerebellum. Ethanol neurotoxicity in cultured neuronal preparations was abolished by pharmacological inhibition of both VDAC and ANT interactions with Bax but not by a Bax channel blocker. Therefore, we conclude that, at this age, within the constraints of our experimental model, a primary mode of Bax-induced initiation of the apoptosis cascade following ethanol insult involves interactions with proteins of the PTP complex and not channel formation independent of PTP constituents. PMID:22767450

  6. Development of the cerebellum in the platypus (Ornithorhynchus anatinus) and short-beaked echidna (Tachyglossus aculeatus).

    Science.gov (United States)

    Ashwell, Ken W S

    2012-01-01

    The monotremes are a unique group of mammals whose young are incubated in a leathery-shelled egg and fed with milk from teatless areolae after hatching. As soon as they hatch, monotreme young must be able to maneuver around the nest or maternal pouch to locate the areolae and stimulate milk ejection. In the present study, the embryological collections at the Museum für Naturkunde, Berlin, have been used to follow the development of the monotreme cerebellum through incubation and lactational phases, to determine whether cerebellar circuitry is able to contribute to the coordination of locomotion in the monotreme hatchling, and to correlate cerebellar development with behavioral maturation. The structure of the developing monotreme cerebellum and the arrangement of transitory neuronal populations are similar to those reported for fetal and neonatal eutherians, but the time course of the key events of later cerebellar development is spread over a much longer period. Expansion of the rostral rhombic lip and formation of the nuclear and cortical transitory zones occurs by the time of hatching, but it is not until after the end of the first post-hatching week that deep cerebellar neurons begin to settle in their definitive positions and the Purkinje cell layer can be distinguished. Granule cell formation is also prolonged over many post-hatching months and the external granular layer persists for more than 20 weeks after hatching. The findings indicate that cerebellar circuitry is unlikely to contribute to the coordination of movements in the monotreme peri-hatching period. Those activities are most likely controlled by the spinal cord and medullary reticular formation circuitry. PMID:22572119

  7. CDKL5 knockout leads to altered inhibitory transmission in the cerebellum of adult mice.

    Science.gov (United States)

    Sivilia, S; Mangano, C; Beggiato, S; Giuliani, A; Torricella, R; Baldassarro, V A; Fernandez, M; Lorenzini, L; Giardino, L; Borelli, A C; Ferraro, L; Calzà, L

    2016-06-01

    Mutations in the X-linked cyclin-dependent kinase-like 5 gene (CDKL5) are associated to severe neurodevelopmental alterations including motor symptoms. In order to elucidate the neurobiological substrate of motor symptoms in CDKL5 syndrome, we investigated the motor function, GABA and glutamate pathways in the cerebellum of CDKL5 knockout female mice. Behavioural data indicate that CDKL5-KO mice displayed impaired motor coordination on the Rotarod test, and altered steps, as measured by the gait analysis using the CatWalk test. A higher reduction in spontaneous GABA efflux, than that in glutamate, was observed in CDKL5-KO mouse cerebellar synaptosomes, leading to a significant increase of spontaneous glutamate/GABA efflux ratio in these animals. On the contrary, there were no differences between groups in K(+) -evoked GABA and glutamate efflux. The anatomical analysis of cerebellar excitatory and inhibitory pathways showed a selective defect of the GABA-related marker GAD67 in the molecular layer in CDKL5-KO mice, while the glutamatergic marker VGLUT1 was unchanged in the same area. Fine cerebellar structural abnormalities such as a reduction of the inhibitory basket 'net' estimated volume and an increase of the pinceau estimated volume were also observed in CDKL5-KO mice. Finally, the BDNF mRNA expression level in the cerebellum, but not in the hippocampus, was reduced compared with WT animals. These data suggest that CDKL5 deletion during development more markedly impairs the establishment of a correct GABAergic cerebellar network than that of glutamatergic one, leading to the behavioural symptoms associated with CDKL5 mutation. PMID:27108663

  8. Role of the flocculus of the cerebellum in motor learning of the vestibulo-ocular reflex

    Science.gov (United States)

    Highstein, S. M.

    1998-01-01

    Structure-function studies at the systems level are an effective method for understanding the relationship of the central nervous system to behavior. Motor learning or adaptation of the vestibulo-ocular reflex is a clear example wherein this approach has been productive. During a vestibulo-ocular reflex the brain converts a head velocity signal, transduced through the vestibular semicircular canals, into an eye movement command delivered to the extraocular muscles. If the viewed target remains on the fovea of the retina, the reflex is compensatory, and its gain, eye velocity/head velocity, is one. When the image of the viewed object slips across the retina, visual acuity decreases, and the gain of the reflex, which is no longer one, is plastically adapted or adjusted until retinal stability is restored. The anatomic substrate for this plasticity thus involves brain structures in which visual-vestibular interaction can potentially occur, as well as vestibular and visual sensory and oculomotor motor structures. Further, it has been known for many years that removal of the flocculus of the cerebellum permanently precludes further vestibulo-ocular reflex adaptation, demonstrating the involvement of the cerebellum in this behavior. Maekawa and Simpson (J Neurophysiol 1973;36: 649-66) discovered that one visual input to the flocculus involved the accessory optic system and the inferior olive. Ensuing work has demonstrated that the visual signals used to adapt the vestibulo-ocular reflex are transmitted by this accessory optic system to the flocculus and subsequently to brain stem structures involved in vestibulo-ocular reflex plasticity. Presently the inclusive list of anatomic sites involved in vestibulo-ocular reflex circuitry and its adaptive plasticity is small. Our laboratory continues to believe that this behavior should be caused by interactions within this small class of neurons. By studying each class of identified neuron and its interactions with others within

  9. Reduction of GABA/sub B/ receptor binding induced by climbing fiber degeneration in the rat cerebellum

    International Nuclear Information System (INIS)

    When the rat cerebellar climbing fibers degenerated, as induced by lesioning the inferior olive with 3-acetylpyridine (3-AP), GABA/sub B/ receptor binding determined with 3H-(+/-)baclofen was reduced in the cerebellum but not in the cerebral cortex of rats. Computer analysis of saturation data revealed two components of the binding sites, and indicated that decrease of the binding in the cerebellum was due to reduction in receptor density, mainly of the high-affinity sites, the B/sub max/ of which was reduced to one-third that in the control animals. In vitro treatment with 3-AP, of the membranes prepared from either the cerebellum or the cerebral cortex, induced no alteration in the binding sites, thereby indicating that the alteration of GABA/sub B/ sites induced by in vivo treatment with 3-AP is not due to a direct action of 3-AP on the receptor. GABA/sub A/ and benzodiazepine receptor binding labelled with 3H-muscimol and 3H-diazepam, respectively, in both of brain regions was not affected by destruction of the inferior olive. These results provide evidence that some of the GABA/sub B/ sites but neither GABA/sub A/ nor benzodiazepine receptors in the cerebellum are located at the climbing fiber terminals. 28 references, 4 figures, 2 tables

  10. Reduction of GABA/sub B/ receptor binding induced by climbing fiber degeneration in the rat cerebellum

    Energy Technology Data Exchange (ETDEWEB)

    Kato, K.; Fukuda, H.

    1985-07-22

    When the rat cerebellar climbing fibers degenerated, as induced by lesioning the inferior olive with 3-acetylpyridine (3-AP), GABA/sub B/ receptor binding determined with /sup 3/H-(+/-)baclofen was reduced in the cerebellum but not in the cerebral cortex of rats. Computer analysis of saturation data revealed two components of the binding sites, and indicated that decrease of the binding in the cerebellum was due to reduction in receptor density, mainly of the high-affinity sites, the B/sub max/ of which was reduced to one-third that in the control animals. In vitro treatment with 3-AP, of the membranes prepared from either the cerebellum or the cerebral cortex, induced no alteration in the binding sites, thereby indicating that the alteration of GABA/sub B/ sites induced by in vivo treatment with 3-AP is not due to a direct action of 3-AP on the receptor. GABA/sub A/ and benzodiazepine receptor binding labelled with /sup 3/H-muscimol and /sup 3/H-diazepam, respectively, in both of brain regions was not affected by destruction of the inferior olive. These results provide evidence that some of the GABA/sub B/ sites but neither GABA/sub A/ nor benzodiazepine receptors in the cerebellum are located at the climbing fiber terminals. 28 references, 4 figures, 2 tables.

  11. Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus

    Science.gov (United States)

    Title (20 words): Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus. Introduction (120 words): Polybrominated diphenyl ethers (PBDE5) possess neurotoxic effects similar to those of PCBs. The cellular a...

  12. Effects of sub-lethal dose of gamma-irradiation on levels of acid phosphatase in cerebellum of pigeons

    International Nuclear Information System (INIS)

    The changes in the activities of acid phosphatase in the sham-irradiated and γ-irradiated cerebellum of pigeons have been studied both biochemically as well as histochemically after 400 rads. The specific activity of acid phosphatase decreased significantly after 48h and 72h of irradiation. The histochemical observations following total body irradiation confirmed the results obtained by quantitative biochemical studies. (author)

  13. SELECTIVE EFFECTS OF DATURA STRAMONIUM ON THE GRANULAR PARALLEL FIBRES AND PURKINJE CELLS OF THE CEREBELLUM IN WISTAR RATS

    Directory of Open Access Journals (Sweden)

    Peter E. Ekanem

    2015-12-01

    Full Text Available Introduction: Datura stramonium (DS is a tropical ubiquitous shrub which is often used to increase intoxication in some beverages and is also freely used as a hallucinogen. It is a depressant of the central nervous system, yet commonly smoked in like manner tobacco. The present study investigated changes induced by intoxication with DS on the purkinje cells and parallel fibres of the cerebellum in Wistar rats to further elucidate the effects of this drug on cerebellar structure. Materials and Methods: The study was conducted on both male and female Wistar rats (200-250 g. They were placed into three batches and four groups were derived from each batch, with eight animals per group. Ethanolic dried seed extract of DS was diluted in normal saline and administered intraperitoneally (I.P. at a dose of 750mg/kg and given to the treatment groups: once in batch 1, twice in batch 2, twelve hourly and thrice in batch 3, eight hourly per day respectively for 4 weeks, while the control groups received an equivalent of normal saline. The rats were euthanized and sections of the cerebellum were histologically processed in all groups. Silver impregnation stain for degenerating axons and neurons was used to elucidate the actions of DS on purkinje cells and the parallel fibres of the cerebellum. Results: The result of IP administration of DS extract (750 mg/kg given three times daily to the treated rats showed significant histological changes, which included atrophy of the parallel fibres but no significant changes in the purkinje cells of the cerebellum. Conclusions: Intoxication of DS seed as a result of excessive ingestion may have a selective degenerative effect on the parallel fibres of the granule cells of the cerebellum while the purkinje cells are spared; the implication being motor dysfunction.

  14. Exploratory investigation on nitro- and phospho-proteome cerebellum changes in hyperammonemia and hepatic encephalopathy rat models.

    Science.gov (United States)

    Brunelli, Laura; Campagna, Roberta; Airoldi, Luisa; Cauli, Omar; Llansola, Marta; Boix, Jordi; Felipo, Vicente; Pastorelli, Roberta

    2012-03-01

    Hepatic encephalopathy (HE) is a neurological disease associated with hepatic dysfunction. Current knowledge suggests that hyperammonemia, related to liver failure, is a main factor contributing to the cerebral alterations in HE and that hyperammonemia might impair signal transduction associated with post-translational modification of proteins such as tyrosine-nitration and phosphorylation. However, the molecular bases of the HE remain unclear and very little is known about the occurrence of post-translational modification on in vivo proteins. In this exploratory study we look for evidence of post-translation modifications of proteins in the cerebellum of experimental HE rat models using a proteomic approach. For the first time we showed that hyperammonemia without liver failure (HA rats) and experimental HE with liver failure due to portacaval shunt (PCS rats) lead to a reduced protein nitration in rat cerebellum, where the undernitrated proteins were involved in energy metabolism and cytoskeleton remodelling. Moreover we showed that tyrosine nitration loss of these proteins was not necessarily associated to a change in their phosphorylation state as result of the disease. Interestingly the rat cerebellum phosphoproteome was mainly perturbed in PCS rats, whereas HA rats did not shown appreciable changes in their phosphoprotein profile. Since the protein nitration level decreased similarly in the cerebellum of both HA and PCS rats, this implies that the two disease models share common effects but also present some differential signalling effects in the cerebellum of the same animals. This study highlights the interest for studying the concerted action of multiple signalling pathways in HE development. PMID:22083566

  15. Ethanol sensitivity: a central role for CREB transcription regulation in the cerebellum

    Directory of Open Access Journals (Sweden)

    Biswal Shyam

    2006-12-01

    Full Text Available Abstract Background Lowered sensitivity to the effects of ethanol increases the risk of developing alcoholism. Inbred mouse strains have been useful for the study of the genetic basis of various drug addiction-related phenotypes. Inbred Long-Sleep (ILS and Inbred Short-Sleep (ISS mice differentially express a number of genes thought to be implicated in sensitivity to the effects of ethanol. Concomitantly, there is evidence for a mediating role of cAMP/PKA/CREB signalling in aspects of alcoholism modelled in animals. In this report, the extent to which CREB signalling impacts the differential expression of genes in ILS and ISS mouse cerebella is examined. Results A training dataset for Machine Learning (ML and Exploratory Data Analyses (EDA was generated from promoter region sequences of a set of genes known to be targets of CREB transcription regulation and a set of genes whose transcription regulations are potentially CREB-independent. For each promoter sequence, a vector of size 132, with elements characterizing nucleotide composition features was generated. Genes whose expressions have been previously determined to be increased in ILS or ISS cerebella were identified, and their CREB regulation status predicted using the ML scheme C4.5. The C4.5 learning scheme was used because, of four ML schemes evaluated, it had the lowest predicted error rate. On an independent evaluation set of 21 genes of known CREB regulation status, C4.5 correctly classified 81% of instances with F-measures of 0.87 and 0.67 respectively for the CREB-regulated and CREB-independent classes. Additionally, six out of eight genes previously determined by two independent microarray platforms to be up-regulated in the ILS or ISS cerebellum were predicted by C4.5 to be transcriptionally regulated by CREB. Furthermore, 64% and 52% of a cross-section of other up-regulated cerebellar genes in ILS and ISS mice, respectively, were deemed to be CREB-regulated. Conclusion These

  16. Bilateral contributions of the cerebellum to the complex motor tasks on EPI fMRI

    International Nuclear Information System (INIS)

    To demonstrate activation signals within the cerebellar cortex and to determine the side of the cerebellar cortex eliciting activation signals in response to complex motor tasks, as seen on EPI fMRI. Seven right-handed subjects (M : F=3 : 4; mean age, 30.3 years) underwent repetitive finger apposition with the dominant right hand. Using a 1.5 T MRI scanner, EPI fMR images were obtained. MR parameters used for EPI fMRI were TR/TE/Flip angle : 0.96 msec/64msec/90 deg FOV 22cm, 128 X 128 matrix, 10 slices, 10mm thickness while those for SE T1 weighted localized images were TR/TE : 450/16, FOV 23cm, 256 X 256 matrix. The paradigm was three sets of alternate resting and moving fingers for six cycles, resulting in times of 360 seconds (10 slices X 15 EPI X 6 cycles = 900 images). Image processing involved the use of a 200mHz Dual Pentium PC with homemade software. T-testing (p < 0.005 approx.= p < 0.0005) and time series analysis were performed, and to verify the locations of activated regions, resulting images were analyzed in a color-coded overlay to reference T1-weighted spin echo coronal images. Percentage change in signal intensity (PCSI) was calculated from the processed data. All normal subjects showed significant activation signals in both the contralateral (left) primary motor cortex (PCSI = 3.12% 0.96) and ipsilateral (right) cerebellar cortex (PCSI = 3.09% ±1.14). Signal activation was detected in the contralateral supplemental motor area (2.91% ±0.82), and motor activation in the anterior upper half of the contralateral cerebellum (PCSI 2.50% ±0.69). The difference in activation signals between both sides of the cerebellar cortex was not statistically significant. All data were matched with time-series analysis. Bilateral cerebellar activation is associated with unilateral complex finger movements, as seen on fMRI. This result may support the recent neurological observation that the cerebellum may exert bilateral effects on motor performance

  17. Muscarinic receptor subtypes differentially control synaptic input and excitability of cerebellum-projecting medial vestibular nucleus neurons.

    Science.gov (United States)

    Zhu, Yun; Chen, Shao-Rui; Pan, Hui-Lin

    2016-04-01

    Neurons in the vestibular nuclei have a vital function in balance maintenance, gaze stabilization, and posture. Although muscarinic acetylcholine receptors (mAChRs) are expressed and involved in regulating vestibular function, it remains unclear how individual mAChR subtypes regulate vestibular neuronal activity. In this study, we determined which specific subtypes of mAChRs control synaptic input and excitability of medial vestibular nucleus (MVN) neurons that project to the cerebellum. Cerebellum-projecting MVN neurons were labeled by a fluorescent retrograde tracer and then identified in rat brainstem slices. Quantitative PCR analysis suggested that M2 and M3 were the possible major mAChR subtypes expressed in the MVN. The mAChR agonist oxotremorine-M significantly reduced the amplitude of glutamatergic excitatory post-synaptic currents evoked by stimulation of vestibular primary afferents, and this effect was abolished by the M2-preferring antagonist AF-DX 116. However, oxotremorine-M had no effect on GABA-mediated spontaneous inhibitory post-synaptic currents of labeled MVN neurons. Furthermore, oxotremorine-M significantly increased the firing activity of labeled MVN neurons, and this effect was blocked by the M3-preferring antagonist J104129 in most neurons tested. In addition, AF-DX 116 reduced the onset latency and prolonged the excitatory effect of oxotremorine-M on the firing activity of labeled MVN neurons. Our findings suggest that M3 is the predominant post-synaptic mAChR involved in muscarinic excitation of cerebellum-projecting MVN neurons. Pre-synaptic M2 mAChR regulates excitatory glutamatergic input from vestibular primary afferents, which in turn influences the excitability of cerebellum-projecting MVN neurons. This new information has important therapeutic implications for treating vestibular disorders with mAChR subtype-selective agents. Medial vestibular nucleus (MVN) neurons projecting to the cerebellum are involved in balance control. We

  18. Noradrenergic modulation of the parallel fiber-Purkinje cell synapse in mouse cerebellum.

    Science.gov (United States)

    Lippiello, Pellegrino; Hoxha, Eriola; Volpicelli, Floriana; Lo Duca, Giuseppina; Tempia, Filippo; Miniaci, Maria Concetta

    2015-02-01

    The signals arriving to Purkinje cells via parallel fibers are essential for all tasks in which the cerebellum is involved, including motor control, learning new motor skills and calibration of reflexes. Since learning also requires the activation of adrenergic receptors, we investigated the effects of adrenergic receptor agonists on the main plastic site of the cerebellar cortex, the parallel fiber-Purkinje cell synapse. Here we show that noradrenaline serves as an endogenous ligand for both α1-and α2-adrenergic receptors to produce synaptic depression between parallel fibers and Purkinje cells. On the contrary, PF-EPSCs were potentiated by the β-adrenergic receptor agonist isoproterenol. This short-term potentiation was postsynaptically expressed, required protein kinase A, and was mimicked by the β2-adrenoceptor agonist clenbuterol, suggesting that the β2-adrenoceptors mediate the noradrenergic facilitation of synaptic transmission between parallel fibers and Purkinje cells. Moreover, β-adrenoceptor activation lowered the threshold for cerebellar long-term potentiation induced by 1 Hz parallel fiber stimulation. The presence of both α and β adrenergic receptors on Purkinje cells suggests the existence of bidirectional mechanisms of regulation allowing the noradrenergic afferents to refine the signals arriving to Purkinje cells at particular arousal states or during learning. PMID:25218865

  19. Structural brain abnormalities in the frontostriatal system and cerebellum in pedophilia.

    Science.gov (United States)

    Schiffer, Boris; Peschel, Thomas; Paul, Thomas; Gizewski, Elke; Forsting, Michael; Leygraf, Norbert; Schedlowski, Manfred; Krueger, Tillmann H C

    2007-11-01

    Even though previous neuropsychological studies and clinical case reports have suggested an association between pedophilia and frontocortical dysfunction, our knowledge about the neurobiological mechanisms underlying pedophilia is still fragmentary. Specifically, the brain morphology of such disorders has not yet been investigated using MR imaging techniques. Whole brain structural T1-weighted MR images from 18 pedophile patients (9 attracted to males, 9 attracted to females) and 24 healthy age-matched control subjects (12 hetero- and 12 homosexual) from a comparable socioeconomic stratum were processed by using optimized automated voxel-based morphometry within multiple linear regression analyses. Compared to the homosexual and heterosexual control subjects, pedophiles showed decreased gray matter volume in the ventral striatum (also extending into the nucl. accumbens), the orbitofrontal cortex and the cerebellum. These observations further indicate an association between frontostriatal morphometric abnormalities and pedophilia. In this respect these findings may support the hypothesis that there is a shared etiopathological mechanism in all obsessive-compulsive spectrum disorders. PMID:16876824

  20. Is Autism a Disease of the Cerebellum?: An integration of clinical and pre-clinical results

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    Tiffany D. Rogers

    2013-05-01

    Full Text Available Autism spectrum disorders are a group of neurodevelopmental disorders characterized by deficits in social skills and communication, unusual and repetitive behavior, and a range of deficits in cognitive function. While the etiology of autism is unknown, current research indicates that abnormalities of the cerebellum, now believed to be involved in cognitive function and the prefrontal cortex (PFC, are associated with autism. The current paper proposes that impaired cerebello-cortical circuitry could, at least in part, underlie autistic symptoms. The use of animal models that allow for manipulation of genetic and environmental influences are an effective means of elucidating both distal and proximal etiological factors in autism and their potential impact on cerebello-cortical circuitry. Some existing rodent models of autism, as well as some models not previously applied to the study of the disorder, display cerebellar and behavioral abnormalities that parallel those commonly seen in autistic patients. The novel findings produced from research utilizing rodent models could provide a better understanding of the neurochemical and behavioral impact of changes in cerebello-cortical circuitry in autism.

  1. The Proteome Profiles of the Cerebellum of Juvenile, Adult and Aged Rats—An Ontogenetic Study

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    Michael Wille

    2015-09-01

    Full Text Available In this study, we searched for proteins that change their expression in the cerebellum (Ce of rats during ontogenesis. This study focuses on the question of whether specific proteins exist which are differentially expressed with regard to postnatal stages of development. A better characterization of the microenvironment and its development may result from these study findings. A differential two-dimensional polyacrylamide gel electrophoresis (2DE and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS analysis of the samples revealed that the number of proteins of the functional classes differed depending on the developmental stages. Especially members of the functional classes of biosynthesis, regulatory proteins, chaperones and structural proteins show the highest differential expression within the analyzed stages of development. Therefore, members of these functional protein groups seem to be involved in the development and differentiation of the Ce within the analyzed development stages. In this study, changes in the expression of proteins in the Ce at different postnatal developmental stages (postnatal days (P 7, 90, and 637 could be observed. At the same time, an identification of proteins which are involved in cell migration and differentiation was possible. Especially proteins involved in processes of the biosynthesis and regulation, the dynamic organization of the cytoskeleton as well as chaperones showed a high amount of differentially expressed proteins between the analyzed dates.

  2. Effects of microwave exposure on motor learning and GluR2 phosphorylation in rabbit cerebellum

    International Nuclear Information System (INIS)

    Objective: To investigate the effects of microwave exposure on motor learning and Glutamate receptor 2(GluR2) phosphorylation in rat cerebellum. Methods: The rabbits were trained for seven days to form eye-blink conditioning, and then divided randomly into control and microwave exposure group (at hours 0,3,24 and 72 subgroups after exposure, respectively). The rabbits were accepted 90 mW/cm2 microwave exposure for 30 minutes, and the rectal temperature were detected immediately after exposure and specific absorption rate (SAR) value were calculated. Eye-blink conditioning were detected immediately after exposure, and cerebellar GluR2 protein and GluR2 phosphorylation were detected with Western blotting. Results: Rectal temperature of rabbits were increased by 3.02 degree C after exposure, and SAR value was 8.74 W/kg. The eye-blink conditioning decreased significantly after exposure, and cerebellar GluR2 protein expression had no significant alteration but phosphorylation reduced significantly after exposure. Conclusions: 90 mW/cm2 microwave exposure has injurious effects on cerebellar GluR2 phosphorylation and motor learning. (authors)

  3. 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.

  4. Differential effects of benzodiazepines on phospholipid methylation in hippocampus and cerebellum of rats

    International Nuclear Information System (INIS)

    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 (3H)-phosphatidyl-N-monomethylethanolamine which was elevated by 40 to 70% at doses ranging from 10-9 to 10-6M. 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

  5. Cerebellum as Initial Site of Distant Metastasis from Papillary Carcinoma of Thyroid: Review of Three Cases

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    Mutahir A. Tunio

    2015-01-01

    Full Text Available Background. The cerebellum as initial site of distant metastasis from differentiated thyroid carcinoma (DTC including papillary (PTC and follicular thyroid carcinoma (FTC is rare manifestation. Case Presentations. Herein, we present three cases of cerebellar metastasis (CBM of PTC. Mean age of patients was 67 years (range: 64–72, and mean duration between initial diagnosis and CBM was 49.6 months (range: 37–61. Frequent location was left cerebellar hemisphere and was associated with hydrocephalus. All patients underwent suboccipital craniectomy, and in two patients postoperative intensity modulated radiation therapy (IMRT was given to deliver 5000 cGy in 25 fractions to residual lesions. Patient without postoperative IMRT had cerebellar recurrence along with lung and bone metastasis after 38 months. However, two patients were found alive and free of disease at the time of last follow-up. Conclusion. CBM from PTC is a rare clinical entity and is often associated with hydrocephalus. Histopathological diagnosis is important to initiate effective treatment, which relies on multidisciplinary approach to prolong the disease-free and overall survival rates.

  6. Lithium delays the radiation-induced apoptotic process in external granule cells of mouse cerebellum

    International Nuclear Information System (INIS)

    Proliferating cells of the external granular layer (EGL) in the developing cerebellum are highly sensitive to ionizing radiation. We examined the effect of lithium, an inhibitor of intracellular signaling, on the manifestation of radiation-induced apoptosis. Newborn mice were exposed to 0.5 Gy gamma-irradiation alone, or first were treated with lithium (10 μmol/g, SC) then given 0.5 Gy irradiation 2 hr later. The EGL was examined histologically for apoptosis at various times after treatment. Apoptotic cells increased rapidly, peaked (about 14%) 6 hr after irradiation, then decreased gradually to the control level by 24 hr. Prior treatment with lithium delayed the manifestation of apoptosis, the peak appearing at 12 hr. The disappearance of dead cells was delayed for about one day. The lithium concentration in the whole brain increased rapidly, being 30 μg/g at the time of irradiation and remaining at more than 40 μg/g for 40 hr. Lithium is reported to inhibit guanine-nucleotide binding to G proteins as well as phosphoinositide turnover. Of the variety of lesions induced by radiation, DNA double strand breaks are the most important source of cell lethality. The present findings, however, suggest that cyclic AMP-mediated and/or phosphoinositide-mediated signaling systems regulate radiation-induced apoptosis. (author)

  7. Cerebellum and Integration of Neural Networks in Dual-Task Processing

    Science.gov (United States)

    Wu, Tao; Liu, Jun; Hallett, Mark; Zheng, Zheng; Chan, Piu

    2014-01-01

    Performing two tasks simultaneously (dual-task) is common in human daily life. The neural correlates of dual-task processing remain unclear. In the current study, we used a dual motor and counting task with functional MRI (fMRI) to determine whether there are any areas additionally activated for dual-task performance. Moreover, we investigated the functional connectivity of these added activated areas, as well as the training effect on brain activity and connectivity. We found that the right cerebellar vermis, left lobule V of the cerebellar anterior lobe and precuneus are additionally activated for this type of dual-tasking. These cerebellar regions had functional connectivity with extensive motor- and cognitive-related regions. Dual-task training induced less activation in several areas, but increased the functional connectivity between these cerebellar regions and numbers of motor- and cognitive-related areas. Our findings demonstrate that some regions within the cerebellum can be additionally activated with dual-task performance. Their role in dual motor and cognitive task processes is likely to integrate motor and cognitive networks, and may be involved in adjusting these networks to be more efficient in order to perform dual-tasking properly. The connectivity of the precuneus differs from the cerebellar regions. A possible role of the precuneus in dual-task may be monitoring the operation of active brain networks. PMID:23063842

  8. Altered functional connectivity of the language network in ASD: Role of classical language areas and cerebellum

    Directory of Open Access Journals (Sweden)

    Marjolein Verly

    2014-01-01

    Full Text Available The development of language, social interaction and communicative skills is remarkably different in the child with autism spectrum disorder (ASD. Atypical brain connectivity has frequently been reported in this patient population. However, the neural correlates underlying their disrupted language development and functioning are still poorly understood. Using resting state fMRI, we investigated the functional connectivity properties of the language network in a group of ASD patients with clear comorbid language impairment (ASD-LI; N = 19 and compared them to the language related connectivity properties of 23 age-matched typically developing children. A verb generation task was used to determine language components commonly active in both groups. Eight joint language components were identified and subsequently used as seeds in a resting state analysis. Interestingly, both the interregional and the seed-based whole brain connectivity analysis showed preserved connectivity between the classical intrahemispheric language centers, Wernicke's and Broca's areas. In contrast however, a marked loss of functional connectivity was found between the right cerebellar region and the supratentorial regulatory language areas. Also, the connectivity between the interhemispheric Broca regions and modulatory control dorsolateral prefrontal region was found to be decreased. This disruption of normal modulatory control and automation function by the cerebellum may underlie the abnormal language function in children with ASD-LI.

  9. The Contribution of the Cerebellum to Cognition in Spinocerebellar Ataxia Type 6

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    Freya E. Cooper

    2010-01-01

    Full Text Available This study sought evidence for a specific cerebellar contribution to cognition by characterising the cognitive phenotype of Spinocerebellar Ataxia Type 6 (SCA-6; an autosomal dominant genetic disease which causes a highly specific late-onset cerebellar degeneration. A comprehensive neuropsychological assessment was administered to 27 patients with genetically confirmed SCA-6. General intellectual ability, memory and executive function were examined using internationally standardised tests (Wechsler Adult Intelligence Scale-III, Wechsler Memory Scale-III, Delis and Kaplan Executive Function System, Brixton Spatial Anticipation test. The patient group showed no evidence of intellectual or memory decline. However, tests of executive function involving skills of cognitive flexibility, inhibition of response and verbal reasoning and abstraction demonstrated significant impairment at the group level with large effect sizes. The results demonstrate an executive deficit due to SCA-6 that can be conceptualised as parallel to the motor difficulties suffered by these patients: the data support a role for the cerebellum in the regulation and coordination of cognitive, as well as motor processes that is relevant to individual performance.

  10. Coenzyme Q10 Levels Are Decreased in the Cerebellum of Multiple-System Atrophy Patients.

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    Lucia V Schottlaender

    Full Text Available The objective of this study was to evaluate whether the levels of coenzyme Q10 (CoQ10 in brain tissue of multiple system atrophy (MSA patients differ from those in elderly controls and in patients with other neurodegenerative diseases.Flash frozen brain tissue of a series of 20 pathologically confirmed MSA patients [9 olivopontocerebellar atrophy (OPCA type, 6 striatonigral degeneration (SND type, and 5 mixed type] was used for this study. Elderly controls (n = 37 as well as idiopathic Parkinson's disease (n = 7, dementia with Lewy bodies (n = 20, corticobasal degeneration (n = 15 and cerebellar ataxia (n = 18 patients were used as comparison groups. CoQ10 was measured in cerebellar and frontal cortex tissue by high performance liquid chromatography.We detected a statistically significant decrease (by 3-5% in the level of CoQ10 in the cerebellum of MSA cases (P = 0.001, specifically in OPCA (P = 0.001 and mixed cases (P = 0.005, when compared to controls as well as to other neurodegenerative diseases [dementia with Lewy bodies (P<0.001, idiopathic Parkinson's disease (P<0.001, corticobasal degeneration (P<0.001, and cerebellar ataxia (P = 0.001].Our results suggest that a perturbation in the CoQ10 biosynthetic pathway is associated with the pathogenesis of MSA but the mechanism behind this finding remains to be elucidated.

  11. Acupuncture Enhances Effective Connectivity between Cerebellum and Primary Sensorimotor Cortex in Patients with Stable Recovery Stroke

    Directory of Open Access Journals (Sweden)

    Zijing Xie

    2014-01-01

    Full Text Available Recent neuroimaging studies have demonstrated that stimulation of acupuncture at motor-implicated acupoints modulates activities of brain areas relevant to the processing of motor functions. This study aims to investigate acupuncture-induced changes in effective connectivity among motor areas in hemiparetic stroke patients by using the multivariate Granger causal analysis. A total of 9 stable recovery stroke patients and 8 healthy controls were recruited and underwent three runs of fMRI scan: passive finger movements and resting state before and after manual acupuncture stimuli. Stroke patients showed significantly attenuated effective connectivity between cortical and subcortical areas during passive motor task, which indicates inefficient information transmissions between cortical and subcortical motor-related regions. Acupuncture at motor-implicated acupoints showed specific modulations of motor-related network in stroke patients relative to healthy control subjects. This specific modulation enhanced bidirectionally effective connectivity between the cerebellum and primary sensorimotor cortex in stroke patients, which may compensate for the attenuated effective connectivity between cortical and subcortical areas during passive motor task and, consequently, contribute to improvement of movement coordination and motor learning in subacute stroke patients. Our results suggested that further efficacy studies of acupuncture in motor recovery can focus on the improvement of movement coordination and motor learning during motor rehabilitation.

  12. A case report of rod migration into cerebellum through foramen magnum after lateral mass fixation of cervical spine.

    Science.gov (United States)

    Kiran, Belsare; Sharma, Ayush; Prashant, Gedam; Parekh, Aseem

    2016-04-01

    We report on a rare case of connecting rod migration into the posterior cranial fossa after posterior cervical decompression and lateral mass screw fixation. A 55-year-old male patient who was operated on for ossification of posterior longitudinal ligament complained of sudden-onset giddiness followed by loss of consciousness one and half year following surgery. CT scan showed migration of left-sided connecting rod into the right cerebellum through foramen magnum. The patient was operated on for rod removal but he sustained a cardiorespiratory arrest and died on the eighth postoperative day. Autopsy confirmed damage to the right cerebellum due to rod migration. The clinician should be aware that superior rod migration is a rare but potentially disastrous complication. Regular follow-up with radiological evaluation should be done to look for implant loosening, migration, and non-union even in asymptomatic patients. The implant should be subsequently removed after it has served its purpose. PMID:26748502

  13. Production rates and turnover of triiodothyronine in rat-developing cerebral cortex and cerebellum. Responses to hypothyroidism

    International Nuclear Information System (INIS)

    Local 5'-deiodination of serum thyroxine (T4) is the main source of triiodothyronine (T3) for the brain. Since we noted in previous studies that the cerebral cortex of neonatal rats tolerated marked reductions in serum T4 without biochemical hypothyroidism, we examined the in vivo T4 and T3 metabolism in that tissue and in the cerebellum of euthyroid and hypothyroid 2-wk-old rats. We also assessed the contribution of enhanced tissue T4 to T3 conversion and decreased T3 removal from the tissues to the T3 homeostasis in hypothyroid brain. Congenital and neonatal hypothyroidism was induced by adding methimazole to the drinking water. Serum, cerebral cortex (Cx), cerebellum (Cm), liver (L) and kidney (R) concentrations of 125I-T4, 125I-T3(T4), and 131I-T3 were measured at various times after injecting 125I-T4 and 131I-T3. The rate of T3 removal from the tissues was measured after injecting an excess of anti-T3-antibody to rats previously injected with tracer T3. In hypothyroidism, the fractional removal rates and clearances were reduced in all tissues, in cortex and cerebellum by 70%, and in liver and kidney ranging from 30 to 50%. While greater than 80% of the 125I-T3(T4) in the brain tissues of euthyroid rats was locally produced, in hypothyroid cerebral cortex and cerebellum the integrated concentrations of 125I-T3(T4) were 2.7- and 1.5-fold greater than in euthyroid rats

  14. Induction of brain CYP2E1 by chronic ethanol treatment and related oxidative stress in hippocampus, cerebellum, and brainstem

    International Nuclear Information System (INIS)

    Ethanol is one of the most commonly abused substances, and oxidative stress is an important causative factor in ethanol-induced neurotoxicity. Cytochrome P450 2E1 (CYP2E1) is involved in ethanol metabolism in the brain. This study investigates the role of brain CYP2E1 in the susceptibility of certain brain regions to ethanol neurotoxicity. Male Wistar rats were intragastrically treated with ethanol (3.0 g/kg, 30 days). CYP2E1 protein, mRNA expression, and catalytic activity in various brain regions were respectively assessed by immunoblotting, quantitative quantum dot immunohistochemistry, real-time RT-PCR, and LC–MS. The generation of reactive oxygen species (ROS) was analyzed using a laser confocal scanning microscope. The hippocampus, cerebellum, and brainstem were selectively damaged after ethanol treatment, indicated by both lactate dehydrogenase (LDH) activity and histopathological analysis. Ethanol markedly increased the levels of CYP2E1 protein, mRNA expression, and activity in the hippocampus and cerebellum. CYP2E1 protein and activity were significantly increased by ethanol in the brainstem, with no change in mRNA expression. ROS levels induced by ethanol paralleled the enhanced CYP2E1 proteins in the hippocampus, granular layer and white matter of cerebellum as well as brainstem. Brain CYP2E1 activity was positively correlated with the damage to the hippocampus, cerebellum, and brainstem. These results suggest that the selective sensitivity of brain regions to ethanol neurodegeneration may be attributed to the regional and cellular-specific induction of CYP2E1 by ethanol. The inhibition of CYP2E1 levels may attenuate ethanol-induced oxidative stress via ROS generation.

  15. Regional expression and ultrastructural localization of EphA7 in the hippocampus and cerebellum of adult rat.

    Science.gov (United States)

    Amegandjin, Clara A; Jammow, Wafaa; Laforest, Sylvie; Riad, Mustapha; Baharnoori, Moogeh; Badeaux, Frédérique; DesGroseillers, Luc; Murai, Keith K; Pasquale, Elena B; Drolet, Guy; Doucet, Guy

    2016-08-15

    EphA7 is expressed in the adult central nervous system (CNS), where its roles are yet poorly defined. We mapped its distribution using in situ hybridization (ISH) and immunohistochemistry (IHC) combined with light (LM) and electron microscopy (EM) in adult rat and mouse brain. The strongest ISH signal was in the hippocampal pyramidal and granule cell layers. Moderate levels were detected in habenula, striatum, amygdala, the cingulate, piriform and entorhinal cortex, and in cerebellum, notably the Purkinje cell layer. The IHC signal distribution was consistent with ISH results, with transport of the protein to processes, as exemplified in the hippocampal neuropil layers and weakly stained pyramidal cell layers. In contrast, in the cerebellum, the Purkinje cell bodies were the most strongly immunolabeled elements. EM localized the cell surface-expression of EphA7 essentially in postsynaptic densities (PSDs) of dendritic spines and shafts, and on some astrocytic leaflets, in both hippocampus and cerebellum. Perikaryal and dendritic labeling was mostly intracellular, associated with the synthetic and trafficking machineries. Immunopositive vesicles were also observed in axons and axon terminals. Quantitative analysis in EM showed significant differences in the frequency of labeled elements between regions. Notably, labeled dendrites were ∼3-5 times less frequent in cerebellum than in hippocampus, but they were individually endowed with ∼10-40 times higher frequencies of PSDs, on their shafts and spines. The cell surface localization of EphA7, being preferentially in PSDs, and in perisynaptic astrocytic leaflets, provides morphologic evidence that EphA7 plays key roles in adult CNS synaptic maintenance, plasticity, or function. J. Comp. Neurol. 524:2462-2478, 2016. © 2016 Wiley Periodicals, Inc. PMID:26780036

  16. Rapid development of Purkinje cell excitability, functional cerebellar circuit, and afferent sensory input to cerebellum in zebrafish

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    Jui-Yi Hsieh

    2014-12-01

    Full Text Available The zebrafish has significant advantages for studying the morphological development of the brain. However, little is known about the functional development of the zebrafish brain. We used patch clamp electrophysiology in live animals to investigate the emergence of excitability in cerebellar Purkinje cells, functional maturation of the cerebellar circuit, and establishment of sensory input to the cerebellum. Purkinje cells are born at 3 days post-fertilization (dpf. By 4 dpf, Purkinje cells spontaneously fired action potentials in an irregular pattern. By 5 dpf, the frequency and regularity of tonic firing had increased significantly and most cells fired complex spikes in response to climbing fiber activation. Our data suggest that, as in mammals, Purkinje cells are initially innervated by multiple climbing fibers that are winnowed to a single input. To probe the development of functional sensory input to the cerebellum, we investigated the response of Purkinje cells to a visual stimulus consisting of a rapid change in light intensity. At 4 dpf, sudden darkness increased the rate of tonic firing, suggesting that afferent pathways carrying visual information are already active by this stage. By 5 dpf, visual stimuli also activated climbing fibers, increasing the frequency of complex spiking. Our results indicate that the electrical properties of zebrafish and mammalian Purkinje cells are highly conserved and suggest that the same ion channels, Nav1.6 and Kv3.3, underlie spontaneous pacemaking activity. Interestingly, functional development of the cerebellum is temporally correlated with the emergence of complex, visually-guided behaviors such as prey capture. Because of the rapid formation of an electrically-active cerebellum, optical transparency, and ease of genetic manipulation, the zebrafish has great potential for functionally mapping cerebellar afferent and efferent pathways and for investigating cerebellar control of motor behavior.

  17. Expression of Brain-derived Neurotrophic Factor and Tyrosine Kinase B in Cerebellum of Poststroke Depression Rat Model

    Institute of Scientific and Technical Information of China (English)

    Yun Li; Chun Peng; Xu Guo; Jun-Jie You; Harishankar Prasad Yadav

    2015-01-01

    Background:The pathophysiology of poststroke depression (PSD) remains elusive because of its proposed multifactorial nature.Accumulating evidence suggests that brain-derived neurotrophic factor (BDNF) plays a key role in the pathophysiology of depression and PSD.And the cerebellar dysfunction may be important in the etiology of depression;it is not clear whether it also has a major effect on the risk of PSD.This study aimed to explore the expression of BDNF and high-affinity receptors tyrosine kinase B (TrkB) in the cerebellum of rats with PSD.Methods:The rat models with focal cerebral ischemic were made using a thread embolization method.PSD rat models were established with comprehensive separate breeding and unpredicted chronic mild stress (UCMS) on this basis.A normal control group,depression group,and a stroke group were used to compare with the PSD group.Thirteen rats were used in each group.Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) for detecting the expression of BDNF and TrkB protein and mRNA in the cerebellum were used at the 29th day following the UCMS.Results:Compared with the normal control group and the stroke group,the number ofBDNF immunoreactive (IR) positive neurons was less in the PSD group (P < 0.05).Furthermore,the number ofTrkB IR positive cells was significantly less in the PSD group than that in the normal control group (P < 0.05).The gene expression of BDNF and TrkB in the cerebellum of PSD rats also decreased compared to the normal control group (P < 0.05).Conclusions:These findings suggested a possible association between expression of BDNF and TrkB in the cerebellum and the pathogenesis of PSD.

  18. Presence of diadenosine polyphosphates in microdialysis samples from rat cerebellum in vivo: effect of mild hyperammonemia on their receptors

    OpenAIRE

    Gualix, Javier; Gómez-Villafuertes, Rosa; Pintor, Jesús; Llansola, Marta; Felipo, Vicente; Miras-Portugal, M. Teresa

    2013-01-01

    Diadenosine triphosphate (Ap3A), diadenosine tetraphosphate (Ap4A), and diadenosine pentaphosphate (Ap5A) have been identified in microdialysis samples from the cerebellum of conscious freely moving rats, under basal conditions, by means of a high-performance liquid chromatography method. The occurrence of Ap3A in the cerebellar microdyalisates is noteworthy, as the presence of this compound in the interstitial medium in neural tissues has not been previously described. The concentrations mea...

  19. Occult left atrial ball-like thrombus in a patient referred for surgical removal of suspected cerebellum tumor

    International Nuclear Information System (INIS)

    Atrial fibrillation and related cardio-embolic cerebrovascular accidents are two well-defined major healthcare problems worldwide. It has been approximated that 2.2 million people in America and 4.5 million in European Union have paroxysmal or persistent atrial fibrillation. And atrial fibrillation itself is an independent long-term risk factor of stroke. We present a case of patient referred to our center for surgical removal of suspected cerebellum tumor, a case that had a rather unexpected ending. A 58-year-old male patient with a history of atrial fibrillation, congestive heart failure (NYHA II/III), stable coronary artery disease, diabetes type 2 and hyperlipidemia presented with vertigo, headaches, mainly during physical activity and increased tiredness. Performed computer tomography revealed two lesions in the cerebellum and in the left lateral chamber. The diagnosis of a proliferative disease of the cerebellum was established and patient was referred to the Neurosurgical Department. Fortunately, before the operation the echocardiography was performed, which revealed two lesions in left atrium. The decision of the Heart Team was to refer the patient for an open-heart surgery, in which two thrombi were removed. Neurosurgeons decided to withdraw from further surgery and proceed with head MRI and conservative treatment, deciding that the lesion in the cerebellum was most likely an ischemic area. Looking at the brain lesion should always be done from the whole patient’s perspective. And using mutlimodality imaging may lead to appropriate diagnosis, correct course of therapeutic action and unexpected ending of a rather non-extraordinary case

  20. Links from complex spikes to local plasticity and motor learning in the cerebellum of awake-behaving monkeys

    OpenAIRE

    Medina, Javier F.; Lisberger, Stephen G.

    2008-01-01

    The hypothesis of cerebellar learning proposes that complex spikes in Purkinje cells engage mechanisms of plasticity in the cerebellar cortex; in turn, changes in the cerebellum depress the simple spike response of Purkinje cells to a given stimulus and cause the adaptive modification of a motor behavior. Although many elements of this hypothesis have been supported by prior experiments, the links between complex spikes, simple spike plasticity, and behavior have not yet been examined simulta...

  1. Cerebellum as a forward but not inverse model in visuomotor adaptation task: a tDCS-based and modeling study.

    Science.gov (United States)

    Yavari, Fatemeh; Mahdavi, Shirin; Towhidkhah, Farzad; Ahmadi-Pajouh, Mohammad-Ali; Ekhtiari, Hamed; Darainy, Mohammad

    2016-04-01

    Despite several pieces of evidence, which suggest that the human brain employs internal models for motor control and learning, the location of these models in the brain is not yet clear. In this study, we used transcranial direct current stimulation (tDCS) to manipulate right cerebellar function, while subjects adapt to a visuomotor task. We investigated the effect of this manipulation on the internal forward and inverse models by measuring two kinds of behavior: generalization of training in one direction to neighboring directions (as a proxy for inverse models) and localization of the hand position after movement without visual feedback (as a proxy for forward model). The experimental results showed no effect of cerebellar tDCS on generalization, but significant effect on localization. These observations support the idea that the cerebellum is a possible brain region for internal forward, but not inverse model formation. We also used a realistic human head model to calculate current density distribution in the brain. The result of this model confirmed the passage of current through the cerebellum. Moreover, to further explain some observed experimental results, we modeled the visuomotor adaptation process with the help of a biologically inspired method known as population coding. The effect of tDCS was also incorporated in the model. The results of this modeling study closely match our experimental data and provide further evidence in line with the idea that tDCS manipulates FM's function in the cerebellum. PMID:26706039

  2. Impaired redox state and respiratory chain enzyme activities in the cerebellum of vitamin A-treated rats

    International Nuclear Information System (INIS)

    Vitamin A is a micronutrient that participates in the maintenance of the mammalian cells homeostasis. However, excess of vitamin A, which may be achieved through increased intake of the vitamin either therapeutically or inadvertently, induces several deleterious effects in a wide range of mammalian cells, including neuronal cells. Vitamin A is a redox-active molecule, and it was previously demonstrated that it induces oxidative stress in several cell types. Therefore, in the present work, we investigated the effects of vitamin A supplementation at clinical doses (1000-9000 IU/(kg day)) on redox environment and respiratory chain activity in the adult rat cerebellum. Glutathione-S-transferase (GST) enzyme activity was also measured here. The animals were treated for 3, 7, or 28 days with vitamin A as retinol palmitate. We found increased levels of molecular markers of oxidative damage in the rat cerebellum in any period analyzed. Additionally, vitamin A supplementation impaired cerebellar mitochondrial electron transfer chain (METC) activity. GST enzyme activity was increased in the cerebellum of rats chronically treated with vitamin A. Based on our results and data previously published, we recommend more caution in prescribing vitamin A at high doses even clinically, since there is a growing concern regarding toxic effects associated to vitamin A intake

  3. Apparent diffusion coefficient evaluation for secondary changes in the cerebellum of rats after middle cerebral artery occlusion.

    Science.gov (United States)

    Yang, Yunjun; Gao, Lingyun; Fu, Jun; Zhang, Jun; Li, Yuxin; Yin, Bo; Chen, Weijian; Geng, Daoying

    2013-11-01

    Supratentorial cerebral infarction can cause functional inhibition of remote regions such as the cerebellum, which may be relevant to diaschisis. This phenomenon is often analyzed using positron emission tomography and single photon emission CT. However, these methods are expensive and radioactive. Thus, the present study quantified the changes of infarction core and remote regions after unilateral middle cerebral artery occlusion using apparent diffusion coefficient values. Diffusion-weighted imaging showed that the area of infarction core gradually increased to involve the cerebral cortex with increasing infarction time. Diffusion weighted imaging signals were initially increased and then stabilized by 24 hours. With increasing infarction time, the apparent diffusion coefficient value in the infarction core and remote bilateral cerebellum both gradually decreased, and then slightly increased 3-24 hours after infarction. Apparent diffusion coefficient values at remote regions (cerebellum) varied along with the change of supratentorial infarction core, suggesting that the phenomenon of diaschisis existed at the remote regions. Thus, apparent diffusion coefficient values and diffusion weighted imaging can be used to detect early diaschisis. PMID:25206615

  4. Development of passive CLARITY and immunofluorescent labelling of multiple proteins in human cerebellum: understanding mechanisms of neurodegeneration in mitochondrial disease

    Science.gov (United States)

    Phillips, Jonathan; Laude, Alex; Lightowlers, Robert; Morris, Chris M.; Turnbull, Doug M.; Lax, Nichola Z.

    2016-01-01

    CLARITY enables immunofluorescent labelling and imaging of large volumes of tissue to provide a better insight into the three dimensional relationship between cellular morphology and spatial interactions between different cell types. In the current study, we optimise passive CLARITY and immunofluorescent labelling of neurons and mitochondrial proteins in mouse and human brain tissues to gain further insights into mechanisms of neurodegeneration occurring in mitochondrial disease. This is the first study to utilise human cerebellum fixed in paraformaldehyde and cryoprotected in conjunction with formalin-fixed tissues opening up further avenues for use of archived tissue. We optimised hydrogel-embedding and passive clearance of lipids from both mouse (n = 5) and human (n = 9) cerebellum as well as developing an immunofluorescent protocol that consistently labels different neuronal domains as well as blood vessels. In addition to visualising large structures, we were able to visualise mitochondrial proteins in passively cleared tissues to reveal respiratory chain deficiency associated with mitochondrial disease. We also demonstrate multiple use of tissues by stripping antibodies and re-probing the cerebellum. This technique allows interrogation of large volumes intact brain samples for better understanding of the complex pathological changes taking place in mitochondrial disease. PMID:27181107

  5. Marrow Stromal Cells Migrate Throughout Forebrain and Cerebellum, and They Differentiate into Astrocytes after Injection into Neonatal Mouse Brains

    Science.gov (United States)

    Kopen, Gene C.; Prockop, Darwin J.; Phinney, Donald G.

    1999-09-01

    Stem cells are a valuable resource for treating disease, but limited access to stem cells from tissues such as brain restricts their utility. Here, we injected marrow stromal cells (MSCs) into the lateral ventricle of neonatal mice and asked whether these multipotential mesenchymal progenitors from bone marrow can adopt neural cell fates when exposed to the brain microenvironment. By 12 days postinjection, MSCs migrated throughout the forebrain and cerebellum without disruption to the host brain architecture. Some MSCs within the striatum and the molecular layer of the hippocampus expressed glial fibrillary acidic protein and, therefore, differentiated into mature astrocytes. MSCs also populated neuron rich regions including the Islands of Calleja, the olfactory bulb, and the internal granular layer of the cerebellum. A large number of MSCs also were found within the external granular layer of the cerebellum. In addition, neurofilament positive donor cells were found within the reticular formation of the brain stem, suggesting that MSCs also may have differentiated into neurons. Therefore, MSCs are capable of producing differentiated progeny of a different dermal origin after implantation into neonatal mouse brains. These results suggest that MSCs are potentially useful as vectors for treating a variety of central nervous system disorders.

  6. Functional magnetic resonance imaging of the rat cerebellum during electrical stimulation of the fore- and hindpaw at 7 T

    Science.gov (United States)

    Peeters, Ronald; Verhoye, Marleen; Vos, Bart; De Schutter, Erik; Van der Linden, Anne-Marie

    1999-05-01

    Blood oxygenation level dependent contrast (BOLD) functional MRI responses at 7T were observed in the cerebellum of alpha- chloralose anesthetized rats in response to innocuous electrical stimulation of a forepaw or hindpaw. The responses were imaged in both coronal and sagittal slices which allowed for a clear delineation and localization of the observed activations. We demonstrate the validity of our fMRI protocol by imaging the responses in somatosensory cortex to the same stimuli and by showing a high level of reproducibility of the cerebellar responses. Widespread bilateral activations were found with mainly a patchy and medio-lateral band organization, more pronounced ipsilaterally. There was no overlap between the cerebellar activations caused by forepaw or hindpaw stimulation. Most remarkable was the overall horizontal organization of these responses: for both stimulation paradigms the patches and bands of activation were roughly positioned in either a cranial or caudal plane running antero-posteriorly through the whole cerebellum. This is the first fMRI study in the cerebellum of the rat. We relate our findings to the known projection patterns found with other techniques and to human fMRI studies. The horizontal organization found wasn't observed before in other studies using other techniques.

  7. Interaction between hippocampus and cerebellum Crus I in sequence-based but not place-based navigation

    Science.gov (United States)

    Iglói, Kinga; Doeller, Christian F.; Paradis, Anne-Lise; Benchenane, Karim; Berthoz, Alain; Burgess, Neil; Rondi-Reig, Laure

    2016-01-01

    To examine the cerebellar contribution to human spatial navigation we used fMRI and virtual reality. Our findings show that the sensory-motor requirements of navigation induce activity in cerebellar lobules and cortical areas known to be involved in the motor loop and vestibular processing. By contrast, cognitive aspects of navigation mainly induce activity in a different cerebellar lobule (VIIA Crus I). Our results demonstrate a functional link between cerebellum and hippocampus in humans and identify specific functional circuits linking lobule VIIA Crus I of the cerebellum to medial parietal, medial prefrontal and hippocampal cortices in non motor aspects of navigation. They further suggest that Crus I belongs to two non-motor loops, involved in different strategies: place-based navigation is supported by coherent activity between left cerebellar lobule VIIA Crus I and medial parietal cortex along with right hippocampus activity, while sequence-based navigation is supported by coherent activity between right lobule VIIA Crus I, medial prefrontal cortex and left hippocampus. These results highlight the prominent role of the human cerebellum in both motor and cognitive aspects of navigation, and specify the cortico-cerebellar circuits by which it acts depending on the requirements of the task. PMID:24947462

  8. Participação do cerebelo no processamento auditivo Participation of the cerebellum in auditory processing

    Directory of Open Access Journals (Sweden)

    Patrícia Maria Sens

    2007-04-01

    Full Text Available O cerebelo era tradicionalmente visto como um órgão coordenador da motricidade, entretanto é atualmente considerado como um importante centro de integração de sensibilidades e coordenação de várias fases do processo cognitivo. OBJETIVO: é sistematizar as informações da literatura quanto à participação do cerebelo na percepção auditiva. MÉTODOS: foram selecionados na literatura trabalhos em animais sobre a fisiologia e anatomia das vias auditivas do cerebelo, além de trabalhos em humanos sobre diversas funções do cerebelo na percepção auditiva. Foram discutidos os achados da literatura, que há evidências que o cerebelo participa das seguintes funções cognitivas relacionadas à audição: geração verbal; processamento auditivo; atenção auditiva; memória auditiva; raciocínio abstrato; timing; solução de problemas; discriminação sensorial; informação sensorial; processamento da linguagem; operações lingüísticas. CONCLUSÃO: Foi constatado que são incompletas as informações sobre as estruturas, funções e vias auditivas do cerebelo.The cerebellum, traditionally conceived as a controlling organ of motricity, it is today considered an all-important integration center for both sensitivity and coordination of the various phases of the cognitive process. AIM: This paper aims at gather and sort literature information on the cerebellum’s role in the auditory perception. METHODS: We have selected animal studies of both the physiology and the anatomy of the cerebellum auditory pathway, as well as papers on humans discussing several functions of the cerebellum in auditory perception. As for the literature, it has been discussed and concluded that there is evidence that the cerebellum participates in many cognitive functions related to hearing: speech generation, auditory processing, auditory memory, abstract reasoning, timing, solution of problems, sensorial discrimination, sensorial information, language

  9. Effect of Nonionizing Radiation onThe Cerebellum of Neonatal Mice

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    Samir A. Nassar

    2009-09-01

    Full Text Available Introduction: Although the use of mobile telephones is common, increasing and beneficial, it is still considered as an environmental pollutant nowaday. This is because these devices require to be held close to the head and the exposure effects on the brain remain controversial. Being so, we designed this study. Aim: The present study was done in an attempt to investigate the morphological, histochemical and ultrastructural changes produced in the cerebellum of neonatal mice as a result of exposure to the nonionizing radiation of the mobile phone. Material and Methods: Eleven neonatal mice were used in this study. Five of them were exposed (as experimental group to mobile phone microwaves (900- 1800 MHz, SAR: 0.92 w/kg during their late prenatal and early postnatal life (1 hour/day for 30 consecutive days. While the other six served as control animals. Comparable parts of cerebella were removed from all animals and processed for the examination by the light and the transmission electron microscopes. Results: The whole body exposure of the neonatal mice to this type of nonionizing radiation resulted in several morphological, histochemical and ultrastructural changes. These changes included a statistically significant decrease in the mean cell distribution, DNA content and total protein content of Purkinje cells and other cerebellar elements of exposed animals. On the other hand an increase in the Purkinje cell volume was recorded. In addition, the ultrastructural observations were corrugated plasma and nuclear membranes, ruptured mitochondria, destruction of Golgi apparatus , dilatation and disintegration of RER, scarcity of ribosomes and Nissl bodies in Purkinje cells. Damage in the cell membranes, chromatin clumping and increase in electron density of the cells of granular layer also observed. In the molecular layer; degeneration of axons and dendrites, increased electron density and damage of neurons occurred. Conclusion: The whole

  10. The cerebellum: A neural system for the study of reinforcement learning

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    Rodney A. Swain

    2011-03-01

    Full Text Available In its strictest application, the term reinforcement learning refers to a computational approach to learning in which an agent (often a machine interacts with a mutable environment to maximize reward through trial and error. The approach borrows essentials from several fields, most notably Computer Science, Behavioral Neuroscience, and Psychology. At the most basic level, a neural system capable of mediating reinforcement learning must be able to acquire sensory information about the external environment and internal milieu (either directly or through connectivities with other brain regions, must be able to select a behavior to be executed, and must be capable of providing evaluative feedback about the success of that behavior. Given that Psychology informs us that reinforcers, both positive and negative, are stimuli or consequences that increase the probability that the immediately antecedent behavior will be repeated and that reinforcer strength or viability is modulated by the organism’s past experience with the reinforcer, its affect, and even the state of its muscles (e.g., eyes open or closed; it is the case that any neural system that supports reinforcement learning must also be sensitive to these same considerations. Once learning is established, such a neural system must finally be able to maintain continued response expression and prevent response drift. In this report, we examine both historical and recent evidence that the cerebellum satisfies all of these requirements. While we report evidence from a variety of learning paradigms, the majority of our discussion will focus on classical conditioning of the rabbit eye blink response as an ideal model system for the study of reinforcement and reinforcement learning.

  11. Direct neural current imaging in an intact cerebellum with magnetic resonance imaging.

    Science.gov (United States)

    Sundaram, Padmavathi; Nummenmaa, Aapo; Wells, William; Orbach, Darren; Orringer, Daniel; Mulkern, Robert; Okada, Yoshio

    2016-05-15

    The ability to detect neuronal currents with high spatiotemporal resolution using magnetic resonance imaging (MRI) is important for studying human brain function in both health and disease. While significant progress has been made, we still lack evidence showing that it is possible to measure an MR signal time-locked to neuronal currents with a temporal waveform matching concurrently recorded local field potentials (LFPs). Also lacking is evidence that such MR data can be used to image current distribution in active tissue. Since these two results are lacking even in vitro, we obtained these data in an intact isolated whole cerebellum of turtle during slow neuronal activity mediated by metabotropic glutamate receptors using a gradient-echo EPI sequence (TR=100ms) at 4.7T. Our results show that it is possible (1) to reliably detect an MR phase shift time course matching that of the concurrently measured LFP evoked by stimulation of a cerebellar peduncle, (2) to detect the signal in single voxels of 0.1mm(3), (3) to determine the spatial phase map matching the magnetic field distribution predicted by the LFP map, (4) to estimate the distribution of neuronal current in the active tissue from a group-average phase map, and (5) to provide a quantitatively accurate theoretical account of the measured phase shifts. The peak values of the detected MR phase shifts were 0.27-0.37°, corresponding to local magnetic field changes of 0.67-0.93nT (for TE=26ms). Our work provides an empirical basis for future extensions to in vivo imaging of neuronal currents. PMID:26899788

  12. Metabotropic glutamate receptor subtypes modulating neurotransmission at parallel fibre-Purkinje cell synapses in rat cerebellum.

    Science.gov (United States)

    Neale, S A; Garthwaite, J; Batchelor, A M

    2001-07-01

    The actions of reportedly group-selective metabotropic glutamate (mGlu) receptor agonists and antagonists on neurotransmission at parallel fibre-Purkinje cell synapses in the rat cerebellum have been characterised using sharp microelectrode recording and an in vitro slice preparation. Application of the group I agonist (S)-3,5-dihydroxyphenylglycine (DHPG) or the group III selective agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) depressed synaptic transmission in a reversible and concentration-dependent manner (EC(50)=18 and 5 microM, respectively). The depression produced by DHPG was unrelated to the depolarisation observed in some Purkinje cells. The group II agonist (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV, 1 microM) had no effect. The effects of DHPG were inhibited by the group I-selective antagonist 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt), but not by the group II/III antagonist alpha-methyl-4-phosphonophenylglycine (MPPG). The effect of L-AP4 was inhibited by MPPG, but not by the group I/II antagonist (S)-alpha-methyl-4-carboxyphenylglycine (MCPG). By themselves, the antagonists did not affect the EPSPs, suggesting that neither receptor is activated during low frequency neurotransmission. It is concluded that, in addition to the excitatory role for group I receptors described previously, both group I and III (but not group II) mGlu receptors operate at this synapse to inhibit synaptic transmission. The specific receptor subtypes involved are likely to be mGlu1 and mGlu4. PMID:11445184

  13. The output signal of Purkinje cells of the cerebellum and circadian rhythmicity.

    Directory of Open Access Journals (Sweden)

    Jérôme Mordel

    Full Text Available Measurement of clock gene expression has recently provided evidence that the cerebellum, like the master clock in the SCN, contains a circadian oscillator. The cerebellar oscillator is involved in anticipation of mealtime and possibly resides in Purkinje cells. However, the rhythmic gene expression is likely transduced into a circadian cerebellar output signal to exert an effective control of neuronal brain circuits that are responsible for feeding behavior. Using electrophysiological recordings from acute and organotypic cerebellar slices, we tested the hypothesis whether Purkinje cells transmit a circadian modulated signal to their targets in the brain. Extracellular recordings from brain slices revealed the typical discharge pattern previously described in vivo in single cell recordings showing basically a tonic or a trimodal-like firing pattern. However, in acute sagittal cerebellar slices the average spike rate of randomly selected Purkinje cells did not exhibit significant circadian variations, irrespective of their specific firing pattern. Also, frequency and amplitude of spontaneous inhibitory postsynaptic currents and the amplitude of GABA- and glutamate-evoked currents did not vary with circadian time. Long-term recordings using multielectrode arrays (MEA allowed to monitor neuronal activity at multiple sites in organotypic cerebellar slices for several days to weeks. With this recording technique we observed oscillations of the firing rate of cerebellar neurons, presumably of Purkinje cells, with a period of about 24 hours which were stable for periods up to three days. The daily renewal of culture medium could induce circadian oscillations of the firing rate of Purkinje cells, a feature that is compatible with the behavior of slave oscillators. However, from the present results it appears that the circadian expression of cerebellar clock genes exerts only a weak influence on the electrical output of cerebellar neurons.

  14. Ictal hyperperfusion of cerebellum and basal ganglia in temporal lobe epilepsy: SPECT subtraction

    International Nuclear Information System (INIS)

    The ictal perfusion patterns of cerebellum and basal ganglia have not been systematically investigated in patients with temporal lobe epilepsy (TLE). Their ictal perfusion patterns were analyzed in relation with temporal lobe and frontal lobe hyperperfusion during TLE seizures using SPECT subtraction. Thirty-three TLE patients had interictal and ictal SPECT, video-EEG monitoring. SPGR MRI, and SPECT subtraction with MRI co-registration. The vermian cerebellar hyperperfusion (CH) was observed in 26 patients (78.8%) and hemispheric CH in 25 (75.8%). Compared to the side of epileptogenic temporal lobe, there were seven ipsilateral hemispheric CH (28.0%), fifteen contralateral hemispheric CH( 60.0%) and three bilateral hemispheric CH( 12.0%). CH was more frequently observed in patients with additional frontal hyperperfusion (15/15, 93.3%) than in patients without frontal hyperperfusion (11/18, 61.1 %). The basal ganglia hyperperfusion (14/15, 93.3%) than in patients without frontal hyperperfusion (BGH) was seen in 11 of the 15 patients with frontotemporal hyperperfusion (73.3%) and 11 of the 18 with temporal hyperperfusion only (61.1%). In 17 patients with unilateral BGH, contralateral CH to the BGH was observed in 14 (82.5%) and ipsilateral CH to BGH in 2 (11.8%) and bilateral CH in 1 (5.9%). The cerebellar hyperperfusion and basal ganglia hyperperfusion during seizures of TLE can be contralateral, ipsilateral or bilateral to the seizure focus. The presence of additional frontal or basal ganglia hyperperfusion was more frequently associated with contralateral hemispheric CH to their sides. However, temporal lobe hyperperfusion appears to be related with both ipsilateral and contralateral hemispheric CH

  15. Purkinje cell NMDA receptors assume a key role in synaptic gain control in the mature cerebellum.

    Science.gov (United States)

    Piochon, Claire; Levenes, Carole; Ohtsuki, Gen; Hansel, Christian

    2010-11-10

    A classic view in cerebellar physiology holds that Purkinje cells do not express functional NMDA receptors and that, therefore, postsynaptic NMDA receptors are not involved in the induction of long-term depression (LTD) at parallel fiber (PF) to Purkinje cell synapses. Recently, it has been demonstrated that functional NMDA receptors are postsynaptically expressed at climbing fiber (CF) to Purkinje cell synapses in mice, reaching full expression levels at ∼2 months after birth. Here, we show that in the mature mouse cerebellum LTD (induced by paired PF and CF activation), but not long-term potentiation (LTP; PF stimulation alone) at PF to Purkinje cell synapses is blocked by bath application of the NMDA receptor antagonist D-2-amino-5-phosphonovaleric acid (D-APV). A blockade of LTD, but not LTP, was also observed when the noncompetitive NMDA channel blocker MK-801 was added to the patch-pipette saline, suggesting that postsynaptically expressed NMDA receptors are required for LTD induction. Using confocal calcium imaging, we show that CF-evoked calcium transients in dendritic spines are reduced in the presence of D-APV. This observation confirms that NMDA receptor signaling occurs at CF synapses and suggests that NMDA receptor-mediated calcium transients at the CF input site might contribute to LTD induction. Finally, we performed dendritic patch-clamp recordings from rat Purkinje cells. Dendritically recorded CF responses were reduced when D-APV was bath applied. Together, these data suggest that the late developmental expression of postsynaptic NMDA receptors at CF synapses onto Purkinje cells is associated with a switch toward an NMDA receptor-dependent LTD induction mechanism. PMID:21068337

  16. Clinical significance of brain SPECT abnormalities of thalami and cerebellum in cerebral palsy with normal MRI

    Energy Technology Data Exchange (ETDEWEB)

    Park, C. H.; Lim, S. Y.; Lee, I. Y.; Kim, O. H.; Bai, M. S.; Kim, S. J.; Yoon, S. N.; Cho, C. W. [College of Medicine, Ajou Univ., Suwon (Korea, Republic of)

    1997-07-01

    The cerebral palsy(CP) encephalopathies are often of uncertain etiology and various functional image findings comparing with anatomical image findings have been reported. However, only a few have mentioned its clinical implications. The purpose of our report is to compare clinical severity and functional SPECT abnormalities of thalami and cerebellum in CP patients with normal MRI. Thirty six CP patients with bilateral spastic palsy who had normal MRI and brain SPECT were studied from July 1996 to September 1997. The patients' age at the time of SPECT was 22.84{+-}17.69 months. The patients were divided into two groups according to motor quotient(MQ); moderate defect (>50MQ : n=27 MQ=22.78{+-}10.36), mild defect (<50MQ : n=9, MQ=66.11{+-}13.87). The degree of rCBF decrease between the two groups was evaluated by {chi}{sup 2} test. Brain SPECT was performed following IV administration of 0.05-0.1 mCi/kg (minimum 2.0 mCi) of Tc-99m ECD and chloral hydrate sedation (50-80 mg/kg p.o) using a triple head system (MS 3, Siemens). Interpretation of brain SPECT was visual analysis: severe decrease is defined when the defect is moderate to marked and mild decrease in rCBF as mild. Seven of 36 (19.4%) showed unilateral or bilateral moderate decrease in rCBF in thalami, 20(55.6%) showed mild decrease, and 9(25.0%) showed no decreased rCBF. All 7 who had moderate thalamic defect reveled moderate motor defect clinically. Ten of 36(27.9%) revealed unilateral or bilateral moderate rCBF defect, 23 (63.9%) depicted mild defect, and 3(8.3%) showed no defect. Sixteen with moderate thalamic rCBF defect showed moderate motor defect in 15 patients. There was statistically significant (p=0.02605) relationship between rCBF defect and motor defect in our CP patients. In conclusion, brain SPECT appears sensitive, non-invasive tool in the evaluation as well as in the prognostication of bilateral spastic cerebral palsy patients and deserves further study using larger number of patients.

  17. Barhl1 is directly regulated by thyroid hormone in the developing cerebellum of mice

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Hongyan, E-mail: hongyan_dong@hc-sc.gc.ca [Hazard Identification Division, Environmental Health Science and Research Bureau, Health Canada, 50 Columbine Driveway, Ottawa, Ontario, Canada K1A 0K9 (Canada); Yauk, Carole L. [Mechanistic Studies Division, Environmental Health Science and Research Bureau, Health Canada, 50 Columbine Driveway, Ottawa, Ontario, Canada K1A 0K9 (Canada); Wade, Michael G. [Hazard Identification Division, Environmental Health Science and Research Bureau, Health Canada, 50 Columbine Driveway, Ottawa, Ontario, Canada K1A 0K9 (Canada)

    2011-11-11

    Highlights: Black-Right-Pointing-Pointer Thyroid hormone receptor binds to the promoter region of Barhl1. Black-Right-Pointing-Pointer Barhl1 expression in cerebellum is negatively regulated by thyroid hormone. Black-Right-Pointing-Pointer Negative regulation of Barhl1 by thyroid hormone was confirmed in vitro. Black-Right-Pointing-Pointer Thyroid hormone may play a role in normal brain development through transcriptional control of Barhl1. -- Abstract: Thyroid hormones (THs) are essential for the brain development. Despite considerable effort, few genes directly regulated by THs have been identified. In this study, we investigate the effects of THs on the regulation of Barhl1, a transcription factor that regulates sensorineural development. Using DNA microarray combined with chromatin immunoprecipitation (ChIP-chip), we identified a TR{beta} binding site in the promoter of Barhl1. The binding was further confirmed by ChIP-PCR. The site is located approximately 755 bp upstream of the transcription start site. Reporter vectors containing the binding site or mutated fragments were transfected into GH3 cells. T3 treatment decreased the transcriptional activity of the wild fragment but not the mutant. Two 28 bp oligonucleotides containing sequences that resemble known TH response elements (TREs) were derived from this binding site and DNA-protein interaction was performed using electrophoretic mobility shift assays (EMSA). Binding analysis in a nuclear extract containing TR{beta} revealed that one of these fragments bound TR{beta}. This complex was shifted with the addition of anti-TR{beta} antibody. We investigated Barhl1 expression in animal models and TH-treated cultured cells. Both long term treatment with 6-propyl-2-thiouracil and short-term treatment with 0.05% methimazole/1% sodium perchlorate (both treatments render mice hypothyroid) resulted in up-regulation of Barhl1. TH supplementation of hypothyroid mice caused a decrease in the expression of Barhl1

  18. Clinical significance of brain SPECT abnormalities of thalami and cerebellum in cerebral palsy with normal MRI

    International Nuclear Information System (INIS)

    The cerebral palsy(CP) encephalopathies are often of uncertain etiology and various functional image findings comparing with anatomical image findings have been reported. However, only a few have mentioned its clinical implications. The purpose of our report is to compare clinical severity and functional SPECT abnormalities of thalami and cerebellum in CP patients with normal MRI. Thirty six CP patients with bilateral spastic palsy who had normal MRI and brain SPECT were studied from July 1996 to September 1997. The patients' age at the time of SPECT was 22.84±17.69 months. The patients were divided into two groups according to motor quotient(MQ); moderate defect (>50MQ : n=27 MQ=22.78±10.36), mild defect (2 test. Brain SPECT was performed following IV administration of 0.05-0.1 mCi/kg (minimum 2.0 mCi) of Tc-99m ECD and chloral hydrate sedation (50-80 mg/kg p.o) using a triple head system (MS 3, Siemens). Interpretation of brain SPECT was visual analysis: severe decrease is defined when the defect is moderate to marked and mild decrease in rCBF as mild. Seven of 36 (19.4%) showed unilateral or bilateral moderate decrease in rCBF in thalami, 20(55.6%) showed mild decrease, and 9(25.0%) showed no decreased rCBF. All 7 who had moderate thalamic defect reveled moderate motor defect clinically. Ten of 36(27.9%) revealed unilateral or bilateral moderate rCBF defect, 23 (63.9%) depicted mild defect, and 3(8.3%) showed no defect. Sixteen with moderate thalamic rCBF defect showed moderate motor defect in 15 patients. There was statistically significant (p=0.02605) relationship between rCBF defect and motor defect in our CP patients. In conclusion, brain SPECT appears sensitive, non-invasive tool in the evaluation as well as in the prognostication of bilateral spastic cerebral palsy patients and deserves further study using larger number of patients

  19. Neural correlates of sensory prediction errors in monkeys: evidence for internal models of voluntary self-motion in the cerebellum.

    Science.gov (United States)

    Cullen, Kathleen E; Brooks, Jessica X

    2015-02-01

    During self-motion, the vestibular system makes essential contributions to postural stability and self-motion perception. To ensure accurate perception and motor control, it is critical to distinguish between vestibular sensory inputs that are the result of externally applied motion (exafference) and that are the result of our own actions (reafference). Indeed, although the vestibular sensors encode vestibular afference and reafference with equal fidelity, neurons at the first central stage of sensory processing selectively encode vestibular exafference. The mechanism underlying this reafferent suppression compares the brain's motor-based expectation of sensory feedback with the actual sensory consequences of voluntary self-motion, effectively computing the sensory prediction error (i.e., exafference). It is generally thought that sensory prediction errors are computed in the cerebellum, yet it has been challenging to explicitly demonstrate this. We have recently addressed this question and found that deep cerebellar nuclei neurons explicitly encode sensory prediction errors during self-motion. Importantly, in everyday life, sensory prediction errors occur in response to changes in the effector or world (muscle strength, load, etc.), as well as in response to externally applied sensory stimulation. Accordingly, we hypothesize that altering the relationship between motor commands and the actual movement parameters will result in the updating in the cerebellum-based computation of exafference. If our hypothesis is correct, under these conditions, neuronal responses should initially be increased--consistent with a sudden increase in the sensory prediction error. Then, over time, as the internal model is updated, response modulation should decrease in parallel with a reduction in sensory prediction error, until vestibular reafference is again suppressed. The finding that the internal model predicting the sensory consequences of motor commands adapts for new

  20. In vivo binding of [{sup 11}C]nemonapride to sigma receptors in the cortex and cerebellum

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Kiichi E-mail: ishiwata@pet.tmig.or.jp; Senda, Michio

    1999-08-01

    Radiolabeled nemonapride (NEM, YM-09151-2) is widely used as a representative dopamine D{sub 2}-like receptor ligand in pharmacological and neurological studies, and {sup 11}C-labeled analog ([{sup 11}C]NEM) has been developed for positron emission tomography (PET) studies. The aim of this study was to evaluate whether [{sup 11}C]NEM binds in vivo to sigma receptors. [{sup 11}C]NEM and one of six dopamine D{sub 2}-like receptor ligands or seven sigma receptor ligands were co-injected into mice, and the regional brain uptake of [{sup 11}C]NEM was measured by a tissue dissection method. The striatal uptake of [{sup 11}C]NEM was reduced by D{sub 2}-like receptor ligands, NEM, haloperidol, (+)-butaclamol, raclopride, and sulpiride, but not by a D{sub 4} receptor ligand clozapine. In the cortex and cerebellum the uptake was also reduced by D{sub 2}-like receptor ligands with affinity for sigma receptors, but not by raclopride. Although none of seven sigma receptor ligands, SA6298, N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine hydrochloride (NE-100), (+)-pentazocine, R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2-aminopropane hydrochloride ([-]-PPAP), (-)-pentazocine, R(+)-3-(3-hydroxyphenyl)-N-propylpiperidine hydrochloride ([+]-3-PPP), and (+)-N-allylnormetazocine hydrochloride ([+]-SKF 10047), blocked the striatal uptake, five of them with relatively higher affinity significantly reduced the [{sup 11}C]NEM uptake by the cortex, and four of them reduced that by the cerebellum. We concluded that [{sup 11}C]NEM binds in vivo not only to dopamine D{sub 2}-like receptors in the striatum but also to sigma receptors in other regions such as cortex and cerebellum.

  1. Aroclor 1254, a developmental neurotoxicant, alters energy metabolism- and intracellular signaling-associated protein networks in rat cerebellum and hippocampus

    International Nuclear Information System (INIS)

    The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and learning and memory in humans. Although the molecular mechanisms for PCB effects are unclear, several studies indicate that the disruption of Ca2+-mediated signal transduction plays significant roles in PCB-induced developmental neurotoxicity. Culminating events in signal transduction pathways include the regulation of gene and protein expression, which affects the growth and function of the nervous system. Our previous studies showed changes in gene expression related to signal transduction and neuronal growth. In this study, protein expression following developmental exposure to PCB is examined. Pregnant rats (Long Evans) were dosed with 0.0 or 6.0 mg/kg/day of Aroclor-1254 from gestation day 6 through postnatal day (PND) 21, and the cerebellum and hippocampus from PND14 animals were analyzed to determine Aroclor 1254-induced differential protein expression. Two proteins were found to be differentially expressed in the cerebellum following PCB exposure while 18 proteins were differentially expressed in the hippocampus. These proteins are related to energy metabolism in mitochondria (ATP synthase, sub unit β (ATP5B), creatine kinase, and malate dehydrogenase), calcium signaling (voltage-dependent anion-selective channel protein 1 (VDAC1) and ryanodine receptor type II (RyR2)), and growth of the nervous system (dihydropyrimidinase-related protein 4 (DPYSL4), valosin-containing protein (VCP)). Results suggest that Aroclor 1254-like persistent chemicals may alter energy metabolism and intracellular signaling, which might result in developmental neurotoxicity. -- Highlights: ► We performed brain proteomic analysis of rats exposed to the neurotoxicant, Aroclor 1254. ► Cerebellum and

  2. Presence of diadenosine polyphosphates in microdialysis samples from rat cerebellum in vivo: effect of mild hyperammonemia on their receptors.

    Science.gov (United States)

    Gualix, Javier; Gómez-Villafuertes, Rosa; Pintor, Jesús; Llansola, Marta; Felipo, Vicente; Miras-Portugal, M Teresa

    2014-01-01

    Diadenosine triphosphate (Ap(3)A), diadenosine tetraphosphate (Ap(4)A), and diadenosine pentaphosphate (Ap(5)A) have been identified in microdialysis samples from the cerebellum of conscious freely moving rats, under basal conditions, by means of a high-performance liquid chromatography method. The occurrence of Ap(3)A in the cerebellar microdyalisates is noteworthy, as the presence of this compound in the interstitial medium in neural tissues has not been previously described. The concentrations measured for the diadenosine polyphosphates in the cerebellar dialysate were (in nanomolar) 10.5 ± 2.9, 5.4 ± 1.2, and 5.8 ± 1.3 for Ap(3)A, Ap(4)A, and Ap(5)A, respectively. These concentrations are in the range that allows the activation of the presynaptic dinucleotide receptor in nerve terminals. However, a possible interaction of these dinucleotides with other purinergic receptors cannot be ruled out, as rat cerebellum expresses a variety of P2X or P2Y receptors susceptible to be activated by diadenosine polyphosphates, such as the P2X1-4, P2Y(1), P2Y(2), P2Y(4), and P2Y(12) receptors, as demonstrated by quantitative real-time PCR. Also, the ecto-nucleotide pyrophosphatases/phosphodiesterases NPP1 and NPP3, able to hydrolyze the diadenosine polyphosphates and terminate their extracellular actions, are expressed in the rat cerebellum. All these evidences contribute to reinforce the role of diadenosine polyphosphates as signaling molecules in the central nervous system. Finally, we have analyzed the possible differences in the concentration of diadenosine polyphosphates in the cerebellar extracellular medium and changes in the expression levels of their receptors and hydrolyzing enzymes in an animal model of moderate hyperammonemia. PMID:23943472

  3. Production rates and turnover of triiodothyronine in rat-developing cerebral cortex and cerebellum. Responses to hypothyroidism.

    OpenAIRE

    J.E. Silva; Matthews, P S

    1984-01-01

    Local 5'-deiodination of serum thyroxine (T4) is the main source of triiodothyronine (T3) for the brain. Since we noted in previous studies that the cerebral cortex of neonatal rats tolerated marked reductions in serum T4 without biochemical hypothyroidism, we examined the in vivo T4 and T3 metabolism in that tissue and in the cerebellum of euthyroid and hypothyroid 2-wk-old rats. We also assessed the contribution of enhanced tissue T4 to T3 conversion and decreased T3 removal from the tissue...

  4. A Low Ethanol Dose Affects all Types of Cells in Mixed Long-Term Embryonic Cultures of the Cerebellum

    DEFF Research Database (Denmark)

    Pickering, Chris; Wicher, Grzegorz; Rosendahl, Sofi;

    2010-01-01

    . We exposed a primary culture of rat cerebellum from embryonic day 17 (corresponding to second trimester in humans) to ethanol at a concentration of 17.6 mM which is roughly equivalent to one glass of wine. Acutely, there was no change in cell viability after 5 or 8 days of exposure relative to...... of this ethanol dose, cultures were exposed for 30 days. After this period, virtually no neurons or myelinating oligodendrocytes were present in the ethanol-treated cultures. In conclusion, chronic exposure to ethanol, even at small doses, dramatically and persistently affects normal development....

  5. [3H]GABA uptake as a marker for cell type in primary cultures of cerebellum and olfactory bulb

    International Nuclear Information System (INIS)

    Uptake of [3H]GABA into cell cultures of rat cerebellum and olfactory bulb was studied by autoradiography, using β-alanine and aminocyclohexane carboxylic acid to distinguish neuronal-specific and glial-specific uptake. Neurons and astrocytes were also labelled by tetanus toxin and anti-GFAP respectively. This combination of markers allowed identification and quantification of several cell types. Cerebellar cultures were found to contain 77% granule neurons, 7.5% inhibitory neurons (probably stellate and basket cells) and 15% astrocytes. Olfactory bulb cultures were over 50% in small neurons which accumulated GABA, the olfactory bulb granule neuron being GABAergic in vivo. (Auth.)

  6. The role of the cerebellum in auditory processing using the SSI test A participação do cerebelo no processamento auditivo com o uso do teste SSI

    OpenAIRE

    Patricia Maria Sens; Clemente Isnard Ribeiro de Almeida; Marisa Mara Neves de Souza; Josyane Borges A. Gonçalves; Luiz Claudio do Carmo

    2011-01-01

    The Synthetic Sentence Identification (SSI) test assesses central auditory pathways by measuring auditory and visual sensitivity and testing selective attention. Cerebellum activation in auditory attention and sensorial activity modulation have already been described. Assessing patients with cerebellar lesions alone using the SSI test can confirm the role of the cerebellum in auditory processing. AIM: To evaluate the role of the cerebellum in auditory processing in individuals with normal hea...

  7. Ginsenoside rb1 modulates level of monoamine neurotransmitters in mice frontal cortex and cerebellum in response to immobilization stress.

    Science.gov (United States)

    Lee, Sang Hee; Hur, Jinyoung; Lee, Eunjoo H; Kim, Sun Yeou

    2012-09-01

    Cerebral monoamines play important roles as neurotransmitters that are associated with various stressful stimuli. Some components such as ginsenosides (triterpenoidal glycosides derived from the Ginseng Radix) may interact with monoamine systems. The aim of this study was to determine whether ginsenoside Rb1 can modulate levels of the monoamines such as dihydroxyphenylalanine (DOPA), dopamine (DA), norepinephrine (NE), epinephrine (EP), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydorxytryptamine (5-HT), 5-hydroxindole-3-acetic acid (5-HIAA), and 5-hydroxytryptophan (5-HTP) in mice frontal cortex and cerebellum in response to immobilization stress. Mice were treated with ginsenoside Rb1 (10 mg/kg, oral) before a single 30 min immobilization stress. Acute immobilization stress resulted in elevation of monoamine levels in frontal cortex and cerebellum. Pretreatment with ginsenoside Rb1 attenuated the stress-induced changes in the levels of monoamines in each region. The present findings showed the anti-stress potential of ginsenoside Rb1 in relation to regulation effects on the cerebral monoaminergic systems. Therefore, the ginsenoside Rb1 may be a useful candidate for treating several brain symptoms related with stress. PMID:24009838

  8. PEX13 deficiency in mouse brain as a model of Zellweger syndrome: abnormal cerebellum formation, reactive gliosis and oxidative stress

    Directory of Open Access Journals (Sweden)

    C. Catharina Müller

    2011-01-01

    Delayed cerebellar development is a hallmark of Zellweger syndrome (ZS, a severe neonatal neurodegenerative disorder. ZS is caused by mutations in PEX genes, such as PEX13, which encodes a protein required for import of proteins into the peroxisome. The molecular basis of ZS pathogenesis is not known. We have created a conditional mouse mutant with brain-restricted deficiency of PEX13 that exhibits cerebellar morphological defects. PEX13 brain mutants survive into the postnatal period, with the majority dying by 35 days, and with survival inversely related to litter size and weaning body weight. The impact on peroxisomal metabolism in the mutant brain is mixed: plasmalogen content is reduced, but very-long-chain fatty acids are normal. PEX13 brain mutants exhibit defects in reflex and motor development that correlate with impaired cerebellar fissure and cortical layer formation, granule cell migration and Purkinje cell layer development. Astrogliosis and microgliosis are prominent features of the mutant cerebellum. At the molecular level, cultured cerebellar neurons from E19 PEX13-null mice exhibit elevated levels of reactive oxygen species and mitochondrial superoxide dismutase-2 (MnSOD, and show enhanced apoptosis together with mitochondrial dysfunction. PEX13 brain mutants show increased levels of MnSOD in cerebellum. Our findings suggest that PEX13 deficiency leads to mitochondria-mediated oxidative stress, neuronal cell death and impairment of cerebellar development. Thus, PEX13-deficient mice provide a valuable animal model for investigating the molecular basis and treatment of ZS cerebellar pathology.

  9. The quantification of COMT mRNA in post mortem cerebellum tissue: diagnosis, genotype, methylation and expression

    Directory of Open Access Journals (Sweden)

    Craig Ian W

    2006-02-01

    Full Text Available Abstract Background The COMT gene is located on chromosome 22q11, a region strongly implicated in the aetiology of several psychiatric disorders, in particular schizophrenia. Previous research has suggested that activity and expression of COMT is altered in schizophrenia, and is mediated by one or more polymorphisms within the gene, including the functional Val158Met polymorphism. Method In this study we examined the expression levels of COMT mRNA using quantitative RT-PCR in 60 post mortem cerebellum samples derived from individuals with schizophrenia, bipolar disorder, depression, and no history of psychopathology. Furthermore, we have examined the methylation status of two CpG sites in the promoter region of the gene. Results We found no evidence of altered COMT expression or methylation in any of the psychiatric diagnoses examined. We did, however, find evidence to suggest that genotype is related to COMT gene expression, replicating the findings of two previous studies. Specifically, val158met (rs165688; Val allele rs737865 (G allele and rs165599 (G allele all showed reduced expression (P COMT expression, with females exhibiting significantly greater levels of COMT mRNA. Conclusion The expression of COMT does not appear to be altered in the cerebellum of individuals suffering from schizophrenia, bipolar disorder or depression, but does appear to be influenced by single nucleotide polymorphisms within the gene.

  10. tDCS of the Cerebellum: Where Do We Stand in 2016? Technical Issues and Critical Review of the Literature

    Science.gov (United States)

    van Dun, Kim; Bodranghien, Florian C. A. A.; Mariën, Peter; Manto, Mario U.

    2016-01-01

    Transcranial Direct Current Stimulation (tDCS) is an up-and-coming electrical neurostimulation technique increasingly used both in healthy subjects and in selected groups of patients. Due to the high density of neurons in the cerebellum, its peculiar anatomical organization with the cortex lying superficially below the skull and its diffuse connections with motor and associative areas of the cerebrum, the cerebellum is becoming a major target for neuromodulation of the cerebellocerebral networks. We discuss the recent studies based on cerebellar tDCS with a focus on the numerous technical and open issues which remain to be solved. Our current knowledge of the physiological impacts of tDCS on cerebellar circuitry is criticized. We provide a comparison with transcranial Alternating Current Stimulation (tACS), another promising transcranial electrical neurostimulation technique. Although both tDCS and tACS are becoming established techniques to modulate the cerebellocerebral networks, it is surprising that their impacts on cerebellar disorders remains unclear. A major reason is that the literature lacks large trials with a double-blind, sham-controlled, and cross-over experimental design in cerebellar patients. PMID:27242469

  11. Prophylactic role of melatonin against radiation induced damage in mouse cerebellum with special reference to Purkinje cells

    Energy Technology Data Exchange (ETDEWEB)

    Sisodia, Rashmi; Kumari, Seema; Verma, Rajesh Kumar; Bhatia, A L [Neurobiology Laboratory, Department of Zoology, University of Rajasthan, Jaipur 302004 (India)

    2006-06-15

    Melatonin, a hormone with a proven antioxidative efficacy, crosses all morphophysiological barriers, including the blood-brain barrier, and distributes throughout the cell. The present study is an attempt to investigate the prophylactic influence of a chronic low level of melatonin against an acute radiation induced oxidative stress in the cerebellum of Swiss albino mice, with special reference to Purkinje cells. After 15 days of treatment the mice were sacrificed at various intervals from 1 to 30 days. Biochemical parameters included lipid peroxidation (LPO) and glutathione (GSH) levels as the endpoints. The quantitative study included alterations in number and volume of Purkinje cells. Swiss albino mice were orally administered a very low dose of melatonin (0.25 mg/mouse/day) for 15 consecutive days before single exposure to 4 Gy gamma radiation. Melatonin checked the augmented levels of LPO, by approximately 55%, by day 30 day post-exposure. Radiation induced depleted levels of GSH could be raised by 68.9% by day 30 post-exposure. Radiation exposure resulted in a reduction of the volume of Purkinje cells and their total number. The administration of melatonin significantly protected against the radiation induced decreases in Purkinje cell volume and number. Results indicate the antioxidative properties of melatonin resulting in its prophylactic property against radiation induced biochemical and cellular alterations in the cerebellum. The findings support the idea that melatonin may be used as an anti-irradiation drug due to its potent free radical scavenging and antioxidative efficacy.

  12. Defects in myelination, paranode organization and Purkinje cell innervation in the ether lipid-deficient mouse cerebellum.

    Science.gov (United States)

    Teigler, Andre; Komljenovic, Dorde; Draguhn, Andreas; Gorgas, Karin; Just, Wilhelm W

    2009-06-01

    Ether lipids (ELs), particularly plasmalogens, are essential constituents of the mammalian central nervous system. The physiological role of ELs, in vivo, however is still enigmatic. In the present study, we characterized a mouse model carrying a targeted deletion of the peroxisomal dihydroxyacetonephosphate acyltransferase gene that results in the complete lack of ELs. Investigating the cerebellum of these mice, we observed: (i) defects in foliation patterning and delay in precursor granule cell migration, (ii) defects in myelination and concomitant reduction in the level of myelin basic protein, (iii) disturbances in paranode organization by extending the Caspr distribution and disrupting axo-glial septate-like junctions, (iv) impaired innervation of Purkinje cells by both parallel fibers and climbing fibers and (v) formation of axon swellings by the accumulation of inositol-tris-phosphate receptor 1 containing smooth ER-like tubuli. Functionally, conduction velocity of myelinated axons in the corpus callosum was significantly reduced. Most of these phenotypes were already apparent at P20 but still persisted in 1-year-old animals. In summary, these data show that EL deficiency results in severe developmental and lasting structural alterations at the cellular and network level of the cerebellum, and reveal an important role of ELs for proper brain function. Common molecular mechanisms that may underlie these phenotypes are discussed. PMID:19270340

  13. Cerebellum proteomics addressing the cognitive deficit of rats perinatally exposed to the food-relevant polychlorinated biphenyl 138.

    Science.gov (United States)

    Campagna, Roberta; Brunelli, Laura; Airoldi, Luisa; Fanelli, Roberto; Hakansson, Helen; Heimeier, Rachel A; De Boever, Patrick; Boix, Jordi; Llansola, Marta; Felipo, Vicente; Pastorelli, Roberta

    2011-09-01

    Developmental exposure to polychlorinated biphenyls (PCBs) has been associated with cognitive deficits in humans and laboratory animals by mechanisms that remain unknown. Recently, it has been shown that developmental exposure to 2,2',3,4,4',5'-hexachlorobiphenyl (PCB138), a food-relevant PCB congener, decreases the learning ability of young rats. The aim of this study was to characterize the effect of perinatal exposure to PCB138 on the brain proteome profile in young rats in order to gain insight into the mechanisms underlying PCB138 neurotoxicity. Comparison of the cerebellum proteome from 3-month-old unexposed and PCB138-exposed male offspring was performed using state-of-the-art label-free semiquantitative mass spectrometry method. Biological pathways associated with Ca(2+) homeostasis and androgen receptor signaling pathways were primarily disrupted. These perturbations may contribute toward a premature ageing-like proteome profile of the cerebellum that is triggered by PCB138 exposure in males. Our proteomic data provide insights into the phenomena that may be contributing to the PCB138 neurotoxicity effects observed in laboratory rodents and correlate with PCB exposure and decreased cognitive functions in humans. As such, this study highlights the importance of PCB138 as a risk factor in developmental neurotoxicity in laboratory rodents and humans. PMID:21673325

  14. Extracellular alkaline-acid pH shifts evoked by iontophoresis of glutamate and aspartate in turtle cerebellum.

    Science.gov (United States)

    Chesler, M; Rice, M E

    1991-01-01

    The effect of glutamate and aspartate iontophoresis on extracellular pH was investigated in the turtle cerebellum in vitro. Both amino acids produced a rapid alkaline transient, typically followed by a prolonged acidification. These responses could be evoked in all layers of the cerebellum. Transition from bicarbonate to N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered media amplified the pH shifts. Similar alkaline-acid transients could be evoked in the molecular layer by electrical stimulation of the parallel fibers or the ipsilateral peduncle, or by superfusion of glutamate or aspartate. However, no alkaline shifts were evoked in the granular layer by either parallel fiber or peduncle stimulation. In contrast, the iontophoretically induced alkaline shifts were largest in the granular layer. Compared with the stimulus-evoked alkalinizations, the iontophoretic alkaline shifts were relatively insensitive to Mn2+ or Cd2+. These data suggest that the activity-dependent alkalinization of brain extracellular space is generated by a bicarbonate-independent mechanism related to excitatory synaptic transmission. The results are consistent with a flux of hydrogen ions through cationic channels, but do not support a direct role for voltage-dependent Ca2+ channels. In view of the sensitivity of ion channels to changes in external pH, and the magnitude of the amino acid-induced pH shifts, these results indicate that extracellular pH could play an important modulatory role in excitatory synaptic transmission. PMID:1711651

  15. Theta Burst Stimulation of the Cerebellum Modifies the TMS-Evoked N100 Potential, a Marker of GABA Inhibition.

    Directory of Open Access Journals (Sweden)

    Allanah Harrington

    Full Text Available Theta burst stimulation (TBS of the cerebellum, a potential therapy for neurological disease, can modulate corticospinal excitability via the dentato-thalamo-cortical pathway, but it is uncertain whether its effects are mediated via inhibitory or facilitatory networks. The aim of this study was to investigate the effects of 30Hz cerebellar TBS on the N100 waveform of the TMS-evoked potential (TEP, a marker of intracortical GABAB-mediated inhibition. 16 healthy participants (aged 18-30 years; 13 right handed and 3 left handed received 30Hz intermittent TBS (iTBS, continuous TBS (cTBS or sham stimulation over the right cerebellum, in three separate sessions. The first 8 participants received TBS at a stimulus intensity of 80% of active motor threshold (AMT, while the remainder received 90% of AMT. Motor evoked potentials (MEP and TEP were recorded before and after each treatment, by stimulating the first dorsal interosseus area of the left motor cortex. Analysis of the 13 right handed participants showed that iTBS at 90% of AMT increased the N100 amplitude compared to sham and cTBS, without significantly altering MEP amplitude. cTBS at 80% of active motor threshold decreased the N100 amplitude and cTBS overall reduced resting MEP amplitude. The study demonstrates effects of 30Hz cerebellar TBS on inhibitory cortical networks that may be useful for treatment of neurological conditions associated with dysfunctional intracortical inhibition.

  16. Curcumin modulates dopaminergic receptor, CREB and phospholipase c gene expression in the cerebral cortex and cerebellum of streptozotocin induced diabetic rats

    Directory of Open Access Journals (Sweden)

    George Naijil

    2010-05-01

    Full Text Available Abstract Curcumin, an active principle component in rhizome of Curcuma longa, has proved its merit for diabetes through its anti-oxidative and anti-inflammatory properties. This study aims at evaluating the effect of curcumin in modulating the altered dopaminergic receptors, CREB and phospholipase C in the cerebral cortex and cerebellum of STZ induced diabetic rats. Radioreceptor binding assays and gene expression was done in the cerebral cortex and cerebellum of male Wistar rats using specific ligands and probes. Total dopaminergic receptor binding parameter, Bmax showed an increase in cerebral cortex and decrease in the cerebellum of diabetic rats. Gene expression studies using real time PCR showed an increased expression of dopamine D1 and D2 receptor in the cerebral cortex of diabetic rats. In cerebellum dopamine D1 receptor was down regulated and D2 receptor showed an up regulation. Transcription factor CREB and phospholipase C showed a significant down regulation in cerebral cortex and cerebellum of diabetic rats. We report that curcumin supplementation reduces diabetes induced alteration of dopamine D1, D2 receptors, transcription factor CREB and phospholipase C to near control. Our results indicate that curcumin has a potential to regulate diabetes induced malfunctions of dopaminergic signalling, CREB and Phospholipase C expression in cerebral cortex and cerebellum and thereby improving the cognitive and emotional functions associated with these regions. Furthermore, in line with these studies an interaction between curcumin and dopaminergic receptors, CREB and phospholipase C is suggested, which attenuates the cortical and cerebellar dysfunction in diabetes. These results suggest that curcumin holds promise as an agent to prevent or treat CNS complications in diabetes.

  17. Loss of NCB5OR in the cerebellum disturbs iron pathways, potentiates behavioral abnormalities, and exacerbates harmaline-induced tremor in mice.

    Science.gov (United States)

    Stroh, Matthew A; Winter, Michelle K; Swerdlow, Russell H; McCarson, Kenneth E; Zhu, Hao

    2016-08-01

    Iron dyshomeostasis has been implicated in many diseases, including a number of neurological conditions. Cytosolic NADH cytochrome b5 oxidoreductase (NCB5OR) is ubiquitously expressed in animal tissues and is capable of reducing ferric iron in vitro. We previously reported that global gene ablation of NCB5OR resulted in early-onset diabetes and altered iron homeostasis in mice. To further investigate the specific effects of NCB5OR deficiency on neural tissue without contributions from known phenotypes, we generated a conditional knockout (CKO) mouse that lacks NCB5OR only in the cerebellum and midbrain. Assessment of molecular markers in the cerebellum of CKO mice revealed changes in pathways associated with cellular and mitochondrial iron homeostasis. (59)Fe pulse-feeding experiments revealed cerebellum-specific increased or decreased uptake of iron by 7 and 16 weeks of age, respectively. Additionally, we characterized behavioral changes associated with loss of NCB5OR in the cerebellum and midbrain in the context of dietary iron deprivation-evoked generalized iron deficiency. Locomotor activity was reduced and complex motor task execution was altered in CKO mice treated with an iron deficient diet. A sucrose preference test revealed that the reward response was intact in CKO mice, but that iron deficient diet consumption altered sucrose preference in all mice. Detailed gait analysis revealed locomotor changes in CKO mice associated with dysfunctional proprioception and locomotor activation independent of dietary iron deficiency. Finally, we demonstrate that loss of NCB5OR in the cerebellum and midbrain exacerbated harmaline-induced tremor activity. Our findings suggest an essential role for NCB5OR in maintaining both iron homeostasis and the proper functioning of various locomotor pathways in the mouse cerebellum and midbrain. PMID:27188291

  18. Cerebelo: más allá de la coordinación motora Anatomía y conexiones del cerebelo Cerebellum: beyond motor coordination

    OpenAIRE

    José William Cornejo Ochoa; Jaime Carrizosa Moog

    2003-01-01

    Siempre se ha reconocido la función que ejerce el cerebelo sobre la motricidad. Sin embargo, en las últimas dos décadas son cada vez más frecuentes los reportes del papel que puede tener esta estructura sobre varias funciones cognitivas como la atención, el aprendizaje y la memoria o sobre algunos síndromes como el autismo. Se revisa la literatura sobre este tópico. The motor function of the cerebellum has ever been recognized. During the last two decades the cerebellum has been implicated in...

  19. Aroclor 1254, a developmental neurotoxicant, alters energy metabolism- and intracellular signaling-associated protein networks in rat cerebellum and hippocampus

    Energy Technology Data Exchange (ETDEWEB)

    Kodavanti, Prasada Rao S., E-mail: kodavanti.prasada@epa.gov [Neurotoxicology Branch, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina (United States); Osorio, Cristina [Systems Proteomics Center, University of North Carolina at Chapel Hill, North Carolina (United States); Program on Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, North Carolina (United States); Royland, Joyce E.; Ramabhadran, Ram [Genetic and Cellular Toxicology Branch, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina (United States); Alzate, Oscar [Department of Cellular and Developmental Biology, University of North Carolina at Chapel Hill, North Carolina (United States); Systems Proteomics Center, University of North Carolina at Chapel Hill, North Carolina (United States); Program on Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, North Carolina (United States)

    2011-11-15

    The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and learning and memory in humans. Although the molecular mechanisms for PCB effects are unclear, several studies indicate that the disruption of Ca{sup 2+}-mediated signal transduction plays significant roles in PCB-induced developmental neurotoxicity. Culminating events in signal transduction pathways include the regulation of gene and protein expression, which affects the growth and function of the nervous system. Our previous studies showed changes in gene expression related to signal transduction and neuronal growth. In this study, protein expression following developmental exposure to PCB is examined. Pregnant rats (Long Evans) were dosed with 0.0 or 6.0 mg/kg/day of Aroclor-1254 from gestation day 6 through postnatal day (PND) 21, and the cerebellum and hippocampus from PND14 animals were analyzed to determine Aroclor 1254-induced differential protein expression. Two proteins were found to be differentially expressed in the cerebellum following PCB exposure while 18 proteins were differentially expressed in the hippocampus. These proteins are related to energy metabolism in mitochondria (ATP synthase, sub unit {beta} (ATP5B), creatine kinase, and malate dehydrogenase), calcium signaling (voltage-dependent anion-selective channel protein 1 (VDAC1) and ryanodine receptor type II (RyR2)), and growth of the nervous system (dihydropyrimidinase-related protein 4 (DPYSL4), valosin-containing protein (VCP)). Results suggest that Aroclor 1254-like persistent chemicals may alter energy metabolism and intracellular signaling, which might result in developmental neurotoxicity. -- Highlights: Black-Right-Pointing-Pointer We performed brain proteomic analysis of rats exposed to the neurotoxicant

  20. More consistently altered connectivity patterns for cerebellum and medial temporal lobes than for amygdala and striatum in schizophrenia

    Directory of Open Access Journals (Sweden)

    Henning ePeters

    2016-02-01

    Full Text Available Background: Brain architecture can be divided into a cortico-thalamic system and modulatory ‘subcortical-cerebellar’ systems containing key structures such as striatum, medial temporal lobes (MTLs, amygdala, and cerebellum. Subcortical-cerebellar systems are known to be altered in schizophrenia. In particular, intrinsic functional brain connectivity (iFC between these systems has been consistently demonstrated in patients. While altered connectivity is known for each subcortical-cerebellar system separately, it is unknown whether subcortical-cerebellar systems’ connectivity patterns with the cortico-thalamic system are comparably altered across systems, i.e., if separate subcortical-cerebellar systems’ connectivity patterns are consistent across patients. Methods: To investigate this question, 18 patients with schizophrenia (3 unmedicated, 15 medicated with atypical antipsychotics and 18 healthy controls were assessed by resting-state functional magnetic resonance imaging (fMRI. Independent component analysis of fMRI data revealed cortical intrinsic brain networks (NWs with time courses representing proxies for cortico-thalamic system activity. Subcortical-cerebellar systems’ activity was represented by fMRI-based time courses of selected regions-of-interest (ROIs (i.e., striatum, MTL, amygdala, cerebellum. Correlation analysis among ROI- and NWs-time courses yielded individual connectivity matrices (i.e. connectivity between NW and ROIs (allROIs-NW, separateROI-NW, only NWs (NWs-NWs, and only ROIs (allROIs-allROIs as main outcome measures, which were classified by support-vector-machine-based leave-one-out cross-validation. Differences in classification accuracy were statistically evaluated for consistency across subjects and systems. Results: Correlation matrices based on allROIs-NWs yielded 91% classification accuracy, which was significantly superior to allROIs-allROIs and NWs-NWs (56% and 74%, respectively. Considering separate

  1. Abscesso actinomicótico do cerebelo: relato de caso Actinomycotic abscess of the cerebellum: case report

    Directory of Open Access Journals (Sweden)

    Mário H. Tsubouchi

    1995-09-01

    Full Text Available Acometimento do sistema nervoso central por actinomicetos é extremamente raro. Os autores descrevem um caso de actinomicose de cerebelo, com diagnóstico estabelecido após remoção cirúrgica da lesão e tratamento com sucesso com penicilina endovenosa e oral. Breve revisão da literatura sobre o envolvimento do sistema nervoso na actinomicose é apresentada.A 38 year-old man presented fever and a clinical picture of intracranial hypertension and ataxic syndrome. A CT-scan disclosed an expanding lesion of the cerebellum. Surgical excision of the lesion was performed and pathological examination made the diagnosis of an actinomycotic abscess. The probable primary source of infection were the lungs and/or oral cavity. The postoperative course was uneventful, with complete recovery after a long period of treatment with penicillin (IV and PO. The authors review some aspects about central nervous system involvement in actinomycosis.

  2. Essential Function of Dicer in Resolving DNA Damage in the Rapidly Dividing Cells of the Developing and Malignant Cerebellum

    Directory of Open Access Journals (Sweden)

    Vijay Swahari

    2016-01-01

    Full Text Available Maintenance of genomic integrity is critical during neurodevelopment, particularly in rapidly dividing cerebellar granule neuronal precursors that experience constitutive replication-associated DNA damage. As Dicer was recently recognized to have an unexpected function in the DNA damage response, we examined whether Dicer was important for preserving genomic integrity in the developing brain. We report that deletion of Dicer in the developing mouse cerebellum resulted in the accumulation of DNA damage leading to cerebellar progenitor degeneration, which was rescued with p53 deficiency; deletion of DGCR8 also resulted in similar DNA damage and cerebellar degeneration. Dicer deficiency also resulted in DNA damage and death in other rapidly dividing cells including embryonic stem cells and the malignant cerebellar progenitors in a mouse model of medulloblastoma. Together, these results identify an essential function of Dicer in resolving the spontaneous DNA damage that occurs during the rapid proliferation of developmental progenitors and malignant cells.

  3. Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum

    Directory of Open Access Journals (Sweden)

    Ana ePalomino

    2014-03-01

    Full Text Available Growing awareness of cerebellar involvement in addiction is based on the cerebellum’s intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression (CB1 receptors and enzymes that produce (DAGLα/β and NAPE-PLD and degrade (MAGL and FAAH eCB were altered. In addition, we analyzed the gene expression of relevant components of the glutamate signaling system (glutamate synthesizing enzymes LGA and KGA, mGluR3/5 metabotropic receptors, and NR1/2A/2B/2C-NMDA and GluR1/2/3/4-AMPA ionotropic receptor subunits and the gene expression of tyrosine hydroxylase (TH, the rate-limiting enzyme in catecholamine biosynthesis, because noradrenergic terminals innervate the cerebellar cortex. Results indicated that acute cocaine exposure decreased DAGLα expression, suggesting a down-regulation of 2-AG production, as well as gene expression of TH, KGA, mGluR3 and all ionotropic receptor subunits analyzed in the cerebellum. The acquisition of conditioned locomotion and sensitization after repeated cocaine exposure were associated with an increased NAPE-PLD/FAAH ratio, suggesting enhanced anandamide production, and a decreased DAGLβ/MAGL ratio, suggesting decreased 2-AG generation. Repeated cocaine also increased LGA gene expression but had no effect on glutamate receptors. These findings indicate that acute cocaine modulates the expression of the eCB and glutamate systems. Repeated cocaine results in normalization of glutamate receptor expression, although sustained changes in eCB is observed. We suggest that cocaine-induced alterations to cerebellar eCB should be considered when analyzing the adaptations imposed by psychostimulants that

  4. Gene expression profiles in the cerebellum and hippocampus following exposure to a neurotoxicant, Aroclor 1254: Developmental effects

    International Nuclear Information System (INIS)

    The developmental consequences of exposure to the polychlorinated biphenyls (PCBs) have been widely studied, making PCBs a unique model to understand issues related to environmental mixture of persistent chemicals. PCB exposure in humans adversely affects neurocognitive development, causes psychomotor difficulties, and contributes to attention deficits in children, all of which seem to be associated with altered patterns of neuronal connectivity. In the present study, we examined gene expression profiles in the rat nervous system following PCB developmental exposure. Pregnant rats (Long-Evans) were dosed perinatally with 0 or 6 mg/kg/day of Aroclor 1254 from gestation day 6 through postnatal day (PND) 21. Gene expression in cerebellum and hippocampus from PND7 and PND14 animals was analyzed with an emphasis on developmental aspects. Changes in gene expression (≥ 1.5 fold) in control animals identified normal developmental changes. These basal levels of expression were compared to data from Aroclor 1254-treated animals to determine the impact of gestational PCB exposure on developmental parameters. The results indicate that the expression of a number of developmental genes related to cell cycle, synaptic function, cell maintenance, and neurogenesis is significantly altered from PND7 to PND14. Aroclor 1254 treatment appears to dampen the overall growth-related gene expression levels in both regions with the effect being more pronounced in the cerebellum. Functional analysis suggests that Aroclor 1254 delays maturation of the developing nervous system, with the consequences dependent on the ontological state of the brain area and the functional role of the individual gene. Such changes may underlie learning and memory deficits observed in PCB exposed animals and humans

  5. IL-6 is increased in the cerebellum of autistic brain and alters neural cell adhesion, migration and synaptic formation

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    Dobkin Carl

    2011-05-01

    Full Text Available Abstract Background Although the cellular mechanisms responsible for the pathogenesis of autism are not understood, a growing number of studies have suggested that localized inflammation of the central nervous system (CNS may contribute to the development of autism. Recent evidence shows that IL-6 has a crucial role in the development and plasticity of CNS. Methods Immunohistochemistry studies were employed to detect the IL-6 expression in the cerebellum of study subjects. In vitro adenoviral gene delivery approach was used to over-express IL-6 in cultured cerebellar granule cells. Cell adhesion and migration assays, DiI labeling, TO-PRO-3 staining and immunofluorescence were used to examine cell adhesion and migration, dendritic spine morphology, cell apoptosis and synaptic protein expression respectively. Results In this study, we found that IL-6 was significantly increased in the cerebellum of autistic subjects. We investigated how IL-6 affects neural cell development and function by transfecting cultured mouse cerebellar granule cells with an IL-6 viral expression vector. We demonstrated that IL-6 over-expression in granule cells caused impairments in granule cell adhesion and migration but had little effect on the formation of dendritic spines or granule cell apoptosis. However, IL-6 over-expression stimulated the formation of granule cell excitatory synapses, without affecting inhibitory synapses. Conclusions Our results provide further evidence that aberrant IL-6 may be associated with autism. In addition, our results suggest that the elevated IL-6 in the autistic brain could alter neural cell adhesion, migration and also cause an imbalance of excitatory and inhibitory circuits. Thus, increased IL-6 expression may be partially responsible for the pathogenesis of autism.

  6. An interspecies comparison of mercury inhibition on muscarinic acetylcholine receptor binding in the cerebral cortex and cerebellum

    International Nuclear Information System (INIS)

    Mercury (Hg) is a ubiquitous pollutant that can disrupt neurochemical signaling pathways in mammals. It is well documented that inorganic Hg (HgCl2) and methyl Hg (MeHg) can inhibit the binding of radioligands to the muscarinic acetylcholine (mACh) receptor in rat brains. However, little is known concerning this relationship in specific anatomical regions of the brain or in other species, including humans. The purpose of this study was to explore the inhibitory effects of HgCl2 and MeHg on [3H]-quinuclidinyl benzilate ([3H]-QNB) binding to the mACh receptor in the cerebellum and cerebral cortex regions from human, rat, mouse, mink, and river otter brain tissues. Saturation binding curves were obtained from each sample to calculate receptor density (B max) and ligand affinity (K d). Subsequently, samples were exposed to HgCl2 or MeHg to derive IC50 values and inhibition constants (K i). Results demonstrate that HgCl2 is a more potent inhibitor of mACh receptor binding than MeHg, and the receptors in the cerebellum are more sensitive to Hg-mediated mACh receptor inhibition than those in the cerebral cortex. Species sensitivities, irrespective of Hg type and brain region, can be ranked from most to least sensitive: river otter > rat > mink > mouse > humans. In summary, our data demonstrate that Hg can inhibit the binding [3H]-QNB to the mACh receptor in a range of mammalian species. This comparative study provides data on interspecies differences and a framework for interpreting results from human, murine, and wildlife studies

  7. Increased expression of fatty acid synthase and acetyl-CoA carboxylase in the prefrontal cortex and cerebellum in the valproic acid model of autism

    Science.gov (United States)

    Chen, Jianling; Wu, Wei; Fu, Yingmei; Yu, Shunying; Cui, Donghong; Zhao, Min; Du, Yasong; Li, Jijun; Li, Xiaohong

    2016-01-01

    The primary aim of the present study was to investigate alterations in enzymes associated with fatty acid synthesis, namely fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC), in the prefrontal cortex and cerebellum of the valproic acid (VPA)-induced animal model of autism. In this model, pregnant rats were given a single intraperitoneal injection of VPA, and prefrontal cortex and cerebellum samples from their pups were analyzed. The results of western blotting and reverse transcription-quantitative polymerase chain reaction analyses demonstrated that the protein and mRNA expression levels of FASN, ACC and phospho-ACC (pACC) were increased in the prefrontal cortex and cerebellum of the VPA model of autism. Furthermore, in the prefrontal cortex and cerebellum of the VPA model of autism, AMPK expression is increased, whereas PI3K and Akt expression are unchanged. This suggests that disorder of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt/FASN and/or adenosine 5′-monophosphate-activated protein kinase (AMPK)/ACC pathway may be involved in the pathogenesis of autism. It is hypothesized that fatty acid synthesis participates in autism through PI3K/Akt/FASN and AMPK/ACC pathways. PMID:27602061

  8. Internal modeling of upcoming speech: A causal role of the right posterior cerebellum in non-motor aspects of language production.

    Science.gov (United States)

    Runnqvist, Elin; Bonnard, Mireille; Gauvin, Hanna S; Attarian, Shahram; Trébuchon, Agnès; Hartsuiker, Robert J; Alario, F-Xavier

    2016-08-01

    Some language processing theories propose that, just as for other somatic actions, self-monitoring of language production is achieved through internal modeling. The cerebellum is the proposed center of such internal modeling in motor control, and the right cerebellum has been linked to an increasing number of language functions, including predictive processing during comprehension. Relating these findings, we tested whether the right posterior cerebellum has a causal role for self-monitoring of speech errors. Participants received 1 Hz repetitive transcranial magnetic stimulation during 15 min to lobules Crus I and II in the right hemisphere, and, in counterbalanced orders, to the contralateral area in the left cerebellar hemisphere (control) in order to induce a temporary inactivation of one of these zones. Immediately afterwards, they engaged in a speech production task priming the production of speech errors. Language production was impaired after right compared to left hemisphere stimulation, a finding that provides evidence for a causal role of the cerebellum during language production. We interpreted this role in terms of internal modeling of upcoming speech through a verbal working memory process used to prevent errors. PMID:27249802

  9. Organohalogen contaminants and metabolites in cerebrospinal fluid and cerebellum gray matter in short-beaked common dolphins and Atlantic white-sided dolphins from the western North Atlantic

    Energy Technology Data Exchange (ETDEWEB)

    Montie, Eric W., E-mail: emontie@marine.usf.ed [Departments of Biology (EWM and MEH) and Marine Chemistry and Geochemistry (CMR), Woods Hole Oceanographic Institution - WHOI, Woods Hole, MA 02543 (United States); Reddy, Christopher M. [Departments of Biology (EWM and MEH) and Marine Chemistry and Geochemistry (CMR), Woods Hole Oceanographic Institution - WHOI, Woods Hole, MA 02543 (United States); Gebbink, Wouter A. [Wildlife and Landscape Science Directorate, Science and Technology Branch, Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, Ontario K1A OH3 (Canada); Touhey, Katie E. [Cape Cod Stranding Network, Buzzards Bay, MA 02542 (United States); Hahn, Mark E. [Departments of Biology (EWM and MEH) and Marine Chemistry and Geochemistry (CMR), Woods Hole Oceanographic Institution - WHOI, Woods Hole, MA 02543 (United States); Letcher, Robert J. [Wildlife and Landscape Science Directorate, Science and Technology Branch, Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, Ontario K1A OH3 (Canada)

    2009-08-15

    Concentrations of several congeners and classes of organohalogen contaminants (OHCs) and/or their metabolites, namely organochlorine pesticides (OCs), polychlorinated biphenyls (PCBs), hydroxylated-PCBs (OH-PCBs), methylsulfonyl-PCBs (MeSO{sub 2}-PCBs), polybrominated diphenyl ether (PBDE) flame retardants, and OH-PBDEs, were measured in cerebrospinal fluid (CSF) of short-beaked common dolphins (n = 2), Atlantic white-sided dolphins (n = 8), and gray seal (n = 1) from the western North Atlantic. In three Atlantic white-sided dolphins, cerebellum gray matter (GM) was also analyzed. The levels of OCs, PCBs, MeSO{sub 2}-PCBs, PBDEs, and OH-PBDEs in cerebellum GM were higher than the concentrations in CSF. 4-OH-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) was the only detectable OH-PCB congener present in CSF. The sum (SIGMA) OH-PCBs/SIGMA PCB concentration ratio in CSF was approximately two to three orders of magnitude greater than the ratio in cerebellum GM for dolphins. - Organohalogens and/or metabolites in cerebrospinal fluid and cerebellum gray matter in short-beaked common dolphins, Atlantic white-sided dolphins, and gray seal.

  10. Organohalogen contaminants and metabolites in cerebrospinal fluid and cerebellum gray matter in short-beaked common dolphins and Atlantic white-sided dolphins from the western North Atlantic

    International Nuclear Information System (INIS)

    Concentrations of several congeners and classes of organohalogen contaminants (OHCs) and/or their metabolites, namely organochlorine pesticides (OCs), polychlorinated biphenyls (PCBs), hydroxylated-PCBs (OH-PCBs), methylsulfonyl-PCBs (MeSO2-PCBs), polybrominated diphenyl ether (PBDE) flame retardants, and OH-PBDEs, were measured in cerebrospinal fluid (CSF) of short-beaked common dolphins (n = 2), Atlantic white-sided dolphins (n = 8), and gray seal (n = 1) from the western North Atlantic. In three Atlantic white-sided dolphins, cerebellum gray matter (GM) was also analyzed. The levels of OCs, PCBs, MeSO2-PCBs, PBDEs, and OH-PBDEs in cerebellum GM were higher than the concentrations in CSF. 4-OH-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) was the only detectable OH-PCB congener present in CSF. The sum (Σ) OH-PCBs/Σ PCB concentration ratio in CSF was approximately two to three orders of magnitude greater than the ratio in cerebellum GM for dolphins. - Organohalogens and/or metabolites in cerebrospinal fluid and cerebellum gray matter in short-beaked common dolphins, Atlantic white-sided dolphins, and gray seal.

  11. BRAF Fusion Analysis in Pilocytic Astrocytomas: KIAA1549-BRAF 15-9 Fusions Are More Frequent in the Midline Than Within the Cerebellum.

    Science.gov (United States)

    Faulkner, Claire; Ellis, Hayley Patricia; Shaw, Abigail; Penman, Catherine; Palmer, Abigail; Wragg, Christopher; Greenslade, Mark; Haynes, Harry Russell; Williams, Hannah; Lowis, Stephen; White, Paul; Williams, Maggie; Capper, David; Kurian, Kathreena Mary

    2015-09-01

    Pilocytic astrocytomas (PAs) are increasingly tested for KIAA1549-BRAF fusions. We used reverse transcription polymerase chain reaction for the 3 most common KIAA1549-BRAF fusions, together with BRAF V600E and histone H3.3 K27M analyses to identify relationships of these molecular characteristics with clinical features in a cohort of 32 PA patients. In this group, the overall BRAF fusion detection rate was 24 (75%). Ten (42%) of the 24 had the 16-9 fusion, 8 (33%) had only the 15-9 fusion, and 1 (4%) of the patients had only the 16-11 fusion. In the PAs with only the 15-9 fusion, 1 PA was in the cerebellum and 7 were centered in the midline outside of the cerebellum, that is, in the hypothalamus (n = 4), optic pathways (n = 2), and brainstem (n = 1). Tumors within the cerebellum were negatively associated with fusion 15-9. Seven (22%) of the 32 patients had tumor-related deaths and 25 of the patients (78%) were alive between 2 and 14 years after initial biopsy. Age, sex, tumor location, 16-9 fusion, and 15-9 fusion were not associated with overall survival. Thus, in this small cohort, 15-9 KIAA1549-BRAF fusion was associated with midline PAs located outside of the cerebellum; these tumors, which are generally difficult to resect, are prone to recurrence. PMID:26222501

  12. [Rearrangements of efferent activity parameters in generators of cyclic motor reactions during electric stimulation of cerebellum inputs and outputs in the cat].

    Science.gov (United States)

    Degtiarenko, A M

    1992-01-01

    Rearrangements of the activity parameters of scratching and locomotor generators conditioned by electric stimulation of the inferior olive, nucleus reticularis lateralis as well as of the fastigial nucleus and nucleus interpositus of the cerebellum were investigated on decerebrate immobilized animals. Scratching and locomotor generators were characterized by the ability to effectively rearrange the time structure of their activity in response to certain changes in phase and amplitude characteristics of signals arriving both by the mossy and climbing inputs of the cerebellum. The flexor half-centre of the locomotor generator and aiming half-centre of the scratching generator increased both the period and intensity of their activity under influence of signals arriving to the cerebellum from the inferior olive and nucleus reticularis lateralis at the first half of the working phase of these half-centres. Stimulation of the inferior olive and nucleus reticularis lateralis during the second half of the flexor and aiming phases evoked somewhat different changes in correlation of activity for half-centres of the locomotor and scratching generators. A slight shortening of the activity period of the aiming half-centre during scratching and a decrease of the activity period of the extensor half-centre during locomotion were observed. Stimulation of the structures mentioned above during the working phase of half-centres controlling limb extensor movements evoked shortening of the extensor half-centres activity period during locomotion and exerted no effect on the scratching jerk half-centre activity period during scratching. The scratching generator, unlike the locomotor generator is characterized by a significant degree of resemblance of the rearrangement of generator efferent activity parameters evoked by electric stimulation of the cerebellum nuclei and its afferent inputs. Possible mechanisms of forming the correcting influences on scratching and locomotor generators from

  13. Binding kinetics of 11C-N-methyl piperidyl benzilate (11C-NMPB) in a rhesus monkey brain using the cerebellum as a reference region

    International Nuclear Information System (INIS)

    The binding kinetics of' 11C-N-methyl piperidyl benzilate (11C-NMPB) in rhesus monkey brain were studied using animal positron emission tomography (PET) (SHR2000). This study is intended to assess the validity of the method using the cerebellum as a reference region, and to evaluate the effects of anesthesia on 11C -NMPB binding. Two monkeys, anesthetized with ketamine, received intravenous 11C-NMPB alone (370-760 MBq, 11C-NMPB accumulated densely in the striatum and cerebral cortex with time. In contrast, the tracer accumulation significantly decreased with increased doses of nonradioactive NMPB. In the cerebellum, on the other hand, the accumulation of 11C-NMPB remained low and the tracer was slowly eliminated from the brain following the injection. 11C-NMPB binding in the cerebellum was barely affected by the increased dose of nonradioactive NMPB. We thus concluded that the specific 11C-NMPB binding was negligible in the cerebellum, and performed simplified evaluation of 11C-NMPB binding in each brain region by a graphical method using the cerebellum as a reference region. PET was conducted 26 times, in total both in ketamine-anesthetized and awake monkeys (n=3 each). Measurements of 11C-NMPB binding showed good run-to-run reproducibility within individual animals. When 11C-NMPB binding was compared between ketamine-treated and awake animals, a significant increase in 11C-NMPB binding was observed in the striatum but not in other brain regions of ketamine-treated animals. (author)

  14. Preliminary morphological and morphometric study of rat cerebellum following sodium arsenite exposure during rapid brain growth (RBG) period

    International Nuclear Information System (INIS)

    The effects of arsenic exposure during rapid brain growth (RBG) period were studied in rat brains with emphasis on the Purkinje cells of the cerebellum. The RBG period in rats extends from postnatal day 4 (PND 4) to postnatal day 10 (PND 10) and is reported to be highly vulnerable to environmental insults. Mother reared Wistar rat pups were administered intraperitoneal injections (i.p.) of sodium arsenite (aqueous solution) in doses of 1.0, 1.5 and 2.0 mg/kg body weight (bw) to groups II, III and IV (n = 6 animals/group) from PND 4 to 10 (sub acute). Control animals (group I) received distilled water by the same route. On PND 11, the animals were perfusion fixed with 4% paraformaldehyde in 0.1 M phosphate buffer (PB) with pH 7.4. The cerebellum obtained from these animals was post-fixed and processed for paraffin embedding. Besides studying the morphological characteristics of Purkinje cells in cresyl violet (CV) stained paraffin sections (10 μm), morphometric analysis of Purkinje cells was carried out using Image Analysis System (Image Proplus software version 4.5) attached to Nikon Microphot-FX microscope. The results showed that on PND 11, the Purkinje cells were arranged in multiple layers extending from Purkinje cell layer (PL) to outer part of granule cell layer (GL) in experimental animals (contrary to monolayer arrangement within PL in control animals). Also, delayed maturation (well defined apical cytoplasmic cones and intense basal basophilia) was evident in Purkinje cells of experimental animals on PND 11. The mean Purkinje cell nuclear area was significantly increased in the arsenic treated animals compared to the control animals. The observations of the present study (faulty migration, delayed maturation and alteration in nuclear area measurements of Purkinje cells subsequent to arsenic exposure) thus provided the morphological evidence of structural alterations subsequent to arsenite induced developmental neurotoxicity which could be presumed to be

  15. Effects of acute versus repeated cocaine exposure on the expression of endocannabinoid signaling-related proteins in the mouse cerebellum

    Science.gov (United States)

    Palomino, Ana; Pavón, Francisco-Javier; Blanco-Calvo, Eduardo; Serrano, Antonia; Arrabal, Sergio; Rivera, Patricia; Alén, Francisco; Vargas, Antonio; Bilbao, Ainhoa; Rubio, Leticia; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2014-01-01

    Growing awareness of cerebellar involvement in addiction is based on the cerebellum’s intermediary position between motor and reward, potentially acting as an interface between motivational and cognitive functions. Here, we examined the impact of acute and repeated cocaine exposure on the two main signaling systems in the mouse cerebellum: the endocannabinoid (eCB) and glutamate systems. To this end, we investigated whether eCB signaling-related gene and protein expression {cannabinoid receptor type 1 receptors and enzymes that produce [diacylglycerol lipase alpha/beta (DAGLα/β) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD)] and degrade [monoacylglycerol lipase (MAGL) and fatty acid amino hydrolase (FAAH)] eCB} were altered. In addition, we analyzed the gene expression of relevant components of the glutamate signaling system [glutamate synthesizing enzymes liver-type glutaminase isoform (LGA) and kidney-type glutaminase isoform (KGA), metabotropic glutamatergic receptor (mGluR3/5), NMDA-ionotropic glutamatergic receptor (NR1/2A/2B/2C) and AMPA-ionotropic receptor subunits (GluR1/2/3/4)] and the gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, because noradrenergic terminals innervate the cerebellar cortex. Results indicated that acute cocaine exposure decreased DAGLα expression, suggesting a down-regulation of 2-arachidonylglycerol (2-AG) production, as well as gene expression of TH, KGA, mGluR3 and all ionotropic receptor subunits analyzed in the cerebellum. The acquisition of conditioned locomotion and sensitization after repeated cocaine exposure were associated with an increased NAPE-PLD/FAAH ratio, suggesting enhanced anandamide production, and a decreased DAGLβ/MAGL ratio, suggesting decreased 2-AG generation. Repeated cocaine also increased LGA gene expression but had no effect on glutamate receptors. These findings indicate that acute cocaine modulates the expression of the eCB and

  16. Quantitative proteomic analysis of Niemann-Pick disease, type C1 cerebellum identifies protein biomarkers and provides pathological insight.

    Directory of Open Access Journals (Sweden)

    Stephanie M Cologna

    Full Text Available Niemann-Pick disease, type C1 (NPC1 is a fatal, neurodegenerative disorder for which there is no definitive therapy. In NPC1, a pathological cascade including neuroinflammation, oxidative stress and neuronal apoptosis likely contribute to the clinical phenotype. While the genetic cause of NPC1 is known, we sought to gain a further understanding into the pathophysiology by identifying differentially expressed proteins in Npc1 mutant mouse cerebella. Using two-dimensional gel electrophoresis and mass spectrometry, 77 differentially expressed proteins were identified in Npc1 mutant mice cerebella compared to controls. These include proteins involved in glucose metabolism, detoxification/oxidative stress and Alzheimer disease-related proteins. Furthermore, members of the fatty acid binding protein family, including FABP3, FABP5 and FABP7, were found to have altered expression in the Npc1 mutant cerebellum relative to control. Translating our findings from the murine model to patients, we confirm altered expression of glutathione s-transferase α, superoxide dismutase, and FABP3 in cerebrospinal fluid of NPC1 patients relative to pediatric controls. A subset of NPC1 patients on miglustat, a glycosphingolipid synthesis inhibitor, showed significantly decreased levels of FABP3 compared to patients not on miglustat therapy. This study provides an initial report of dysregulated proteins in NPC1 which will assist with further investigation of NPC1 pathology and facilitate implementation of therapeutic trials.

  17. High-pass filtering and dynamic gain regulation enhance vertical bursts transmission along the mossy fiber pathway of cerebellum

    Directory of Open Access Journals (Sweden)

    Jonathan Mapelli

    2010-05-01

    Full Text Available Signal elaboration in the cerebellum mossy fiber input pathway presents controversial aspects, especially concerning gain regulation and the spot-like (rather than beam-like appearance of granular-to-molecular layer transmission. By using voltage-sensitive dye (VSD imaging in rat cerebellar slices (Mapelli et al., 2010, we found that mossy fiber bursts optimally excited the granular layer above ~50 Hz and the overlaying molecular layer above ~100 Hz, thus generating a cascade of high-pass filters. NMDA receptors enhanced transmission in the granular, while GABA-A receptors depressed transmission in both the granular and molecular layer. Burst transmission gain was controlled through a dynamic frequency-dependent involvement of these receptors. Moreover, while high-frequency transmission was enhanced along vertical lines connecting the granular to molecular layer, no high-frequency enhancement was observed along the parallel fiber axis in the molecular layer. This was probably due to the stronger effect of Purkinje cell GABA-A receptor-mediated inhibition occurring along the parallel fibers than along the granule cell axon ascending branch. The consequent amplification of burst responses along vertical transmission lines could explain the spot-like activation of Purkinje cells observed following punctuate stimulation in vivo .

  18. Spike timing regulation on the millisecond scale by distributed synaptic plasticity at the cerebellum input stage: a simulation study

    Directory of Open Access Journals (Sweden)

    Jesus A Garrido

    2013-05-01

    Full Text Available The way long-term synaptic plasticity regulates neuronal spike patterns is not completely understood. This issue is especially relevant for the cerebellum, which is endowed with several forms of long-term synaptic plasticity and has been predicted to operate as a timing and a learning machine. Here we have used a computational model to simulate the impact of multiple distributed synaptic weights in the cerebellar granular layer network. In response to mossy fiber bursts, synaptic weights at multiple connections played a crucial role to regulate spike number and positioning in granule cells. The weight at mossy fiber to granule cell synapses regulated the delay of the first spike and the weight at mossy fiber and parallel fiber to Golgi cell synapses regulated the duration of the time-window during which the first-spike could be emitted. Moreover, the weights of synapses controlling Golgi cell activation regulated the intensity of granule cell inhibition and therefore the number of spikes that could be emitted. First spike timing was regulated with millisecond precision and the number of spikes ranged from 0 to 3. Interestingly, different combinations of synaptic weights optimized either first-spike timing precision or spike number, efficiently controlling transmission and filtering properties. These results predict that distributed synaptic plasticity regulates the emission of quasi-digital spike patterns on the millisecond time scale and allows the cerebellar granular layer to flexibly control burst transmission along the mossy fiber pathway.

  19. The contribution of delta subunit-containing GABAA receptors to phasic and tonic conductance changes in cerebellum, thalamus and neocortex.

    Directory of Open Access Journals (Sweden)

    Stephen G Brickley

    2013-12-01

    Full Text Available We have made use of the delta subunit-selective allosteric modulator DS2 (4-chloro-N-[2-(2-thienylimidazo[1,2-a]pyridine-3-yl benzamide to assay the contribution of delta-GABAARs to tonic and phasic conductance changes in the cerebellum, thalamus and neocortex. In cerebellar granule cells, an enhancement of the tonic conductance was observed for DS2 and the orthosteric agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol. As expected, DS2 did not alter the properties of GABAA receptor-mediated inhibitory postsynaptic synaptic currents (IPSCs supporting a purely extrasynaptic role for delta-GABAARs in cerebellar granule cells. DS2 also enhanced the tonic conductance recorded from thalamic relay neurons of the visual thalamus with no alteration in IPSC properties. However, in addition to enhancing the tonic conductance DS2 also slowed the decay of IPSCs recorded from layer II/III neocortical neurons. A slowing of the IPSC decay also occurred in the presence of the voltage-gated sodium channel blocker TTX. Moreover, under conditions of reduced GABA release the ability of DS2 to enhance the tonic conductance was attenuated. These results indicate that delta-GABAARs can be activated following vesicular GABA release onto neocortical neurons and that the actions of DS2 on the tonic conductance may be influenced by the ambient GABA levels present in particular brain regions.

  20. Seizure-related 6,a brain-specific expression gene,is highly expressed in the human cerebellum

    Institute of Scientific and Technical Information of China (English)

    Jianming Jiang; Long Yu; Yangtai Guan; Zhiliang Yu; Xinghua Huang; Xiaosong Chen; Lisha Tang; Xianning Zhang

    2010-01-01

    Epilepsy is a complex,Mendelian disease,and most cases are sporadic.Genomic comparisons of tissue from identified monogenic epilepsies with multigenic and acquired syndromes could ultimately reveal crucial molecular neuropathology for an epileptic phenotype.In the present study,a novel gene,human seizure-related(hSEZ)-6,was isolated from a human brain cDNA library.hSEZ-6 comprises 17 exons and spans a region of at least 55.6 kb,which was localized to 17q12 by radiation hybridization,hSEZ-6 exhibits two isoform types,hSEZ-6A and hSEZ-6B,which encode996 and 995 amino acids,respectively.The two putative hSEZ-6 proteins contain similar motifs and share 82% and 84% identity with mouse SEZ-6A protein,whose expression level increased in mouse cerebral cortex-derived cells treated with a convulsant drug,pentylentetrazole.Northern blot analysis demonstrated that hSEZ-6 is expressed highly in the cerebellum and in nucleus of the extrapyramidal system,such as the caudate nucleus and putamen.Reverse transcription polymerase chain reaction revealed that hSEZ-6 is expressed in neurons rather than gliocytes,which suggests that hSEZ-6 is a seizure-related gene.

  1. Curcumin alters motor coordination but not total number of Purkinje cells in the cerebellum of adolescent male Wistar rats

    Institute of Scientific and Technical Information of China (English)

    Ginus Partadiredja; Sutarman; Taufik Nur Yahya; Christiana Tri Nuryana; Rina Susilowati

    2013-01-01

    OBJECTIVE:The present study aimed at investigating the effects of curcumin on the motor coordination and the estimate of the total number of cerebellar Purkinje cells of adolescent Wistar rats exposed to ethanol.METHODS:The total of 21 male Wistar rats aged 37 d old were divided into three groups,namely ethanol,ethanol-curcumin,and control groups.The ethanol group received 1.5 g/kg ethanol injected intraperitoneally and water given per oral; the ethanol-curcumin group received 1.5 g/kg ethanol injected intraperitoneally and curcumin extract given per oral; the control group received saline injection and oral water.The treatment was carried out daily for one month,after which the motor coordination performance of the rats was examined using revolving drum apparatus at test days 1,8,and 15.The rats were finally sacrificed and the cerebellum of the rats was further processed for stereological analysis.The estimate of the total number of Purkinje cells was calculated using physical fractionator method.RESULTS:The ethanol-curcumin group performed better than both ethanol and control groups in the motor coordination ability at day 8 of testing (P< 0.01).No Purkinje cell loss was observed as a result of one month intraperitoneal injection of ethanol.CONCLUSION:Curcumin may exert beneficial effects on the motor coordination of adolescent rats exposed to ethanol via undetermined hormetic mechanisms.

  2. Infrared spectroscopic imaging of the biochemical modifications induced in the cerebellum of the Niemann-Pick type C mouse

    Science.gov (United States)

    Kidder, Linda H.; Colarusso, Pina; Stewart, Sarah A.; Levin, Ira W.; Appel, Nathan M.; Lester, David S.; Pentchev, Peter G.; Lewis, E. N.

    1999-01-01

    WE have applied Fourier transform infrared (IR) spectroscopic imaging to the investigation of the neuropathologic effects of a genetic lipid storage disease, Niemann-Pick type C (NPC). Tissue sections both from the cerebella of a strain of BALB/c mice that demonstrated morphology and pathology of the human disease and from control animals were used. These samples were analyzed by standard histopathological procedures as well as this new IR imaging approach. The IR absorbance images exhibit contrast based on biochemical variations and allow for the identification of the cellular layers within the tissue samples. Furthermore, these images provide a qualitative description of the localized biochemical differences existing between the diseased and control tissue in the absence of histological staining. Statistical analyses of the IR spectra extracted from individual cell layers of the imaging data sets provide concise quantitative descriptions of these biochemical changes. The results indicate that lipid is depleted specifically in the white matter of the NPC mouse in comparison to the control samples. Minor differences were noted for the granular layers, but no significant differences were observed in the molecular layers of the cerebellar tissue. These changes are consistent with significant demyelination within the cerebellum of the NPC mouse.

  3. A realistic bi-hemispheric model of the cerebellum uncovers the purpose of the abundant granule cells during motor control.

    Science.gov (United States)

    Pinzon-Morales, Ruben-Dario; Hirata, Yutaka

    2015-01-01

    The cerebellar granule cells (GCs) have been proposed to perform lossless, adaptive spatio-temporal coding of incoming sensory/motor information required by downstream cerebellar circuits to support motor learning, motor coordination, and cognition. Here we use a physio-anatomically inspired bi-hemispheric cerebellar neuronal network (biCNN) to selectively enable/disable the output of GCs and evaluate the behavioral and neural consequences during three different control scenarios. The control scenarios are a simple direct current motor (1 degree of freedom: DOF), an unstable two-wheel balancing robot (2 DOFs), and a simulation model of a quadcopter (6 DOFs). Results showed that adequate control was maintained with a relatively small number of GCs (< 200) in all the control scenarios. However, the minimum number of GCs required to successfully govern each control plant increased with their complexity (i.e., DOFs). It was also shown that increasing the number of GCs resulted in higher robustness against changes in the initialization parameters of the biCNN model (i.e., synaptic connections and synaptic weights). Therefore, we suggest that the abundant GCs in the cerebellar cortex provide the computational power during the large repertoire of motor activities and motor plants the cerebellum is involved with, and bring robustness against changes in the cerebellar microcircuit (e.g., neuronal connections). PMID:25983678

  4. A realistic bi-hemispheric model of the cerebellum uncovers the purpose of the abundant granule cells during motor control

    Directory of Open Access Journals (Sweden)

    Ruben Dario Pinzon Morales

    2015-05-01

    Full Text Available The cerebellar granule cells (GCs have been proposed to perform lossless, adaptive spatio-temporal coding of incoming sensory/motor information required by downstream cerebellar circuits to \\textcolor{red}{support} motor learning, motor coordination, and cognition. Here we use a physio-anatomically inspired bi-hemispheric cerebellar neuronal network (biCNN to selectively enable/disable the output of GCs and evaluate the behavioral and neural consequences during three different control scenarios. The control scenarios are a simple direct current motor (1 degree of freedom: DOF, an unstable two-wheel balancing robot (2 DOFs, and a simulation model of a quadcopter (6 DOFs. Results showed that adequate control was maintained with a relatively small number of GCs ($<$ 200 in all the control scenarios. However, the minimum number of GCs required to successfully govern each control plant increased with their complexity (i.e., DOFs. It was also shown that increasing the number of GCs resulted in higher robustness against changes in the initialization parameters of the biCNN model (i.e., synaptic connections and synaptic weights. Therefore, we suggest that the abundant GCs in the cerebellar cortex provide the computational power during the large repertoire of motor activities and motor plants the cerebellum is involved with, and bring robustness against changes in the cerebellar microcircuit (e.g., neuronal connections.

  5. Electron microscopic autoradiography of the uptake of [3H]GABA in dispersed cell cultures of rat cerebellums. II

    International Nuclear Information System (INIS)

    The formation of GABAergic synapses in dispersed cell cultures of the rat cerebellum was followed from 7 to 21 days in vitro(DIV). The majority of GABAergic synapses appeared between 10 and 14 DIV, and apparently no additional GABAergic synapses formed after 14 DIV. The first step in the development of GABAergic synapses appeared to be the formation of a larger diameter swelling in a GABAergic neuronal process. After the initial contact between the pre - and postsynaptic elements was established, both the number of synaptic vesicles and the thickness of the postsynaptic density increased, while the cross-sectional area of the presynaptic element decreased. The length of the postsynaptic density showed some increase, but no changes were noted in the synaptic cleft thickness, size of the synaptic vesicles or the shape of the synaptic vesicles. The findings indicate that the formation of GABAergic synapses was not preceded by the formation of other types of junction or performed synaptic elements. In addition, the timing and the rate of formation of GABAergic synapses appears not to depend on contact with a single type of postynaptic neuron, but rather to depend upon intrinsic properties of the development of the GABAergic neuron. (Auth.)

  6. Histopathological and Behavioral Assessment of Toxin-Produced Cerebellar Lesion: A Potent Model for Cell Transplantation Studies in The Cerebellum

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    Mohammad Amin Edalatmanesh

    2014-04-01

    Full Text Available cognition, learning and memory functions. This study presents a permanent model of a toxin produced cerebellar lesion characterized according to contemporary motor and cognitive abnormalities. Materials and Methods: In this experimental study, slow administration of quinolinic acid (QA, 5 μl of 200 μmol, 1 μl/minute in the right cerebellar hemisphere (lobule VI caused noticeable motor and cognitive disturbances along with cellular degeneration in all treated animals. We assessed behavioral and histopathological studies over ten weeks after QA treatment. The data were analyzed with ANOVA and the student’s t test. Results: The QA treated group showed marked motor learning deficits on the rotating rod test (p≤0.0001, locomotor asymmetry on the cylinder test (p≤0.0001, dysmetria on the beam balance test (p≤0.0001, abnormalities in neuromuscular strength on the hang wire test (p≤0.0001, spatial memory deficits in the Morris water maze (MWM, p≤0.001 and fear conditioned memory on the passive avoidance test (p≤0.01 over a ten-week period compared with the control animals. Histopathological analysis showed loss of Purkinje cells (p≤0.001 and granular cell density (p≤0.0001 in the lesioned hemisphere of the cerebellum. Conclusion: Results of the present study show that QA can remove numerous cells which respond to this toxin in hemispheric lobule VI and thus provide a potential model for functional and cell-based studies.

  7. Cerebelo: más allá de la coordinación motora Anatomía y conexiones del cerebelo Cerebellum: beyond motor coordination

    Directory of Open Access Journals (Sweden)

    José William Cornejo Ochoa

    2003-02-01

    Full Text Available Siempre se ha reconocido la función que ejerce el cerebelo sobre la motricidad. Sin embargo, en las últimas dos décadas son cada vez más frecuentes los reportes del papel que puede tener esta estructura sobre varias funciones cognitivas como la atención, el aprendizaje y la memoria o sobre algunos síndromes como el autismo. Se revisa la literatura sobre este tópico. The motor function of the cerebellum has ever been recognized. During the last two decades the cerebellum has been implicated in cognitive functions like memory, attention and learning or in syndromes such as the autistic spectrum. These topics are reviewed in this article.

  8. [123I]epidepride binding to cerebellar dopamine D2/D3 receptors is displaceable: implications for the use of cerebellum as a reference region.

    Science.gov (United States)

    Pinborg, Lars H; Videbaek, Charlotte; Ziebell, Morten; Mackeprang, Torben; Friberg, Lars; Rasmussen, Hans; Knudsen, Gitte M; Glenthoj, Birte Y

    2007-02-15

    The low density of cerebellar dopamine D(2)/D(3) receptors provides the basis for using the cerebellum as a representation of free- and non-specifically bound radioligand in positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies. With the development of ultra high-affinity dopamine D(2)/D(3) ligands like [(123)I]epidepride, [(18)F]fallypride, and [(11)C]FLB-457, quantification of extrastriatal low density receptor populations including the cerebellum is possible with important implications for calculation of binding parameters. [(123)I]epidepride-SPECT was performed in 23 patients with schizophrenia before and after 3 months of antipsychotic treatment with either risperidone (n=14) or zuclopenthixol (n=9). In the unblocked situation and partially blocked situation, the average distribution volumes were 5.2+/-1.3 mL/mL and 4.0+/-0.8 mL/mL, respectively. The paired distribution volumes were reduced by 22+/-15% (mean+/-SD) after antipsychotic treatment (pepidepride was calculated to be 3.3+/-0.8 mL/mL. Both the % [(123)I]epidepride fraction of plasma radioactivity (p>0.76) and the plasma [(123)I]epidepride concentration (p>0.45) were unchanged after antipsychotic treatment (paired Student's t-test). These results strongly suggest the presence of "non-negligible" specific [(123)I]epidepride binding to dopamine D(2)/D(3) receptors in the cerebellum. Using the cerebellum as a representation of free and non-specifically bound radioligand and neglecting the specifically bound component may lead to results that erroneously imply that antipsychotic drugs bind to extrastriatal dopamine D(2)/D(3) receptors with a higher affinity than to striatal dopamine D(2)/D(3) receptors. PMID:17175177

  9. Study of surgical management of spontaneous hemorrhage of cerebellum%小脑血肿的急诊外科处置

    Institute of Scientific and Technical Information of China (English)

    栾新平; 丛海平; 木依提·阿不力米提; 党金山; 刘继新; 贾宏宇; 木塔力甫

    2001-01-01

    Objective For heightening horizon of surgical management 21 cases with spontaneous hemorrhage of cerebellum were retrospectively analysed.Methods In the 21 patients with spontaneous hemorrhage of cerebellum,3 cases were treated by paraventriculostomy of anterior horn,14 cases by scavenging intracerebral hemorrhage of cerebellum through posterior cranial fossa approach,after scavenging intracerebral hemorrhage 4 cases were treaded by paraventriculostomy of anterior horn.Results 6 cases were died after operation,2 cases supervened dysdipsia,4 cases supervened dysphonia,1 case supervened communicating hydrocephalus and 7 cases without any complications.Conclusion The most effective means of preventing subsequent pathological process that patient with spontaneous hemorrhage of cerebellum is operation which is carried out as early as possible.%目的通过对21例经过手术的自发性小脑出血病例的回顾性分析,以期提高对此病的手术治疗水平。方法 21例病例,行侧脑室前角穿刺外引流3例,行后颅窝开颅清除血肿14例,开颅清除血肿后又行侧脑室前角穿刺引流术4例。结果术后死亡6例,饮水呛咳2例,发音障碍4例,交通性脑积水1例,无后遗症7例。结论对小脑出血病人尽早实施手术治疗是阻断继发性病理改变最有效的手段。

  10. Ganglioneuroblastoma of the cerebellum: neuroimaging and pathological features of a case Ganglioneuroblastoma no cerebelo: achados de neuroimagem e patologia em um caso

    OpenAIRE

    Emerson L. Gasparetto; Sérgio Rosemberg; Hamilton Matushita; Claudia da Costa Leite

    2007-01-01

    OBJECTIVE: To report a case of ganglioneuroblastoma of cerebellum, with emphasis to the neuroimaging and pathological findings. CASE REPORT: A one year and eight-month-old girl presented with a two-month history of hypoactivity and tremor in the legs. The MRI showed an enhancing cerebellar mass hypointense on T1 and hyperintense on T2-weighted images. The patient underwent a craniotomy with resection of the lesion. The histological and immunohistochemical studies defined the diagnosis of gang...

  11. Effect of an antioxidant combination on the distribution of acetylcholinesterase and adenosine triphosphatase activities in the cerebellum of in lindane-intoxicated mice

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    Devendra Kumar Bhatt

    2013-04-01

    Full Text Available Objective: The present investigation ascertains a protective potential of a combination of antioxidants against lindane-induced toxicity in cerebellum of mice. Methods: For the study, animals are divided into four groups. First group is control and it is given only vehicle. Second group is treated with lindane and analysed if there are any lesions in the brain. Third group is purely antioxidants treated group; four antioxidants, i.e. resveratrol, ascorbic acid, alpha lipoic acid and vitamin E, are subcutaneously administered in a suitable combination to the animals of this group. Fourth group is treated with both lindane and antioxidants. Acetylcholinesterase (AChE and adenosine triphosphatase (ATPase activities are used as histochemical markers for manifestation of lindane-induced acute toxicity. Biochemical levels of glutathione (GSH and thiobarbituric acid reactive substances (TBARS were also evaluated for different groups to confirm the toxicity of lindane in cerebellum. Results: Treatment with lindane caused decrease in AChE and ATPase activities, and GSH levels in cerebellum whereas a significant increase was recorded in TBARS. Antioxidants treatment increased the enzymatic activities. A significant rise in GSH level was recorded in the antioxidant treatment group as compared to group I and group II whereas TBARS levels were significantly reduced. GSH and TBARS levels altered significantly in group IV as compared to control group and lindane-treated group. In group III, AChE and ATPase activities increased in layers and nuclei of cerebellum as compared to control group. Conclusions: Since the use of antioxidants prevents the inhibition of AChE and ATPase, functions which are altered due to lindane-toxicity may be protected. [J Exp Integr Med 2013; 3(2.000: 103-112

  12. Microarray Analysis Reveals Higher Gestational Folic Acid Alters Expression of Genes in the Cerebellum of Mice Offspring—A Pilot Study

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    Subit Barua

    2015-01-01

    Full Text Available Folate is a water-soluble vitamin that is critical for nucleotide synthesis and can modulate methylation of DNA by altering one-carbon metabolism. Previous studies have shown that folate status during pregnancy is associated with various congenital defects including the risk of aberrant neural tube closure. Maternal exposure to a methyl supplemented diet also can alter DNA methylation and gene expression, which may influence the phenotype of offspring. We investigated if higher gestational folic acid (FA in the diet dysregulates the expression of genes in the cerebellum of offspring in C57BL/6 J mice. One week before gestation and throughout the pregnancy, groups of dams were supplemented with FA either at 2 mg/kg or 20 mg/kg of diet. Microarray analysis was used to investigate the genome wide gene expression profile in the cerebellum from day old pups. Our results revealed that exposure to the higher dose FA diet during gestation dysregulated expression of several genes in the cerebellum of both male and female pups. Several transcription factors, imprinted genes, neuro-developmental genes and genes associated with autism spectrum disorder exhibited altered expression levels. These findings suggest that higher gestational FA potentially dysregulates gene expression in the offspring brain and such changes may adversely alter fetal programming and overall brain development.

  13. Presymptomatic Alterations in Amino Acid Metabolism and DNA Methylation in the Cerebellum of a Murine Model of Niemann-Pick Type C Disease.

    Science.gov (United States)

    Kennedy, Barry E; Hundert, Amos S; Goguen, Donna; Weaver, Ian C G; Karten, Barbara

    2016-06-01

    The fatal neurodegenerative disorder Niemann-Pick type C (NPC) is caused in most cases by mutations in NPC1, which encodes the late endosomal NPC1 protein. Loss of NPC1 disrupts cholesterol trafficking from late endosomes to the endoplasmic reticulum and plasma membrane, causing cholesterol accumulation in late endosomes/lysosomes. Neurons are particularly vulnerable to this cholesterol trafficking defect, but the pathogenic mechanisms through which NPC1 deficiency causes neuronal dysfunction remain largely unknown. Herein, we have investigated amino acid metabolism in cerebella of NPC1-deficient mice at different stages of NPC disease. Imbalances in amino acid metabolism were evident from increased branched chain amino acid and asparagine levels and altered expression of key enzymes of glutamine/glutamate metabolism in presymptomatic and early symptomatic NPC1-deficient cerebellum. Increased levels of several amino acid intermediates of one-carbon metabolism indicated disturbances in folate and methylation pathways. Alterations in DNA methylation were apparent in decreased expression of DNA methyltransferase 3a and methyl-5'-cytosine-phosphodiester-guanine-domain binding proteins, reduced 5-methylcytosine immunoreactivity in the molecular and Purkinje cell layers, demethylation of genome-wide repetitive LINE-1 elements, and hypermethylation in specific promoter regions of single-copy genes in NPC1-deficient cerebellum at early stages of the disease. Alterations in amino acid metabolism and epigenetic changes in the cerebellum at presymptomatic stages of NPC disease represent previously unrecognized mechanisms of NPC pathogenesis. PMID:27083515

  14. Antioxidant Activity of Grapevine Leaf Extracts against Oxidative Stress Induced by Carbon Tetrachloride in Cerebral Cortex, Hippocampus and Cerebellum of Rats

    Science.gov (United States)

    Wohlenberg, Mariane; Almeida, Daniela; Bokowski, Liane; Medeiros, Niara; Agostini, Fabiana; Funchal, Cláudia; Dani, Caroline

    2014-01-01

    In recent years, it has become increasingly important to study the beneficial properties of derivatives of grapes and grapevine. The objective of this study was to determine the antioxidant activity of Vitis labrusca leaf extracts, comparing conventional and organic grapevines, in different brain areas of rats. We used male Wistar rats treated with grapevine leaf extracts for a period of 14 days, and on the 15th day, we administered in half of the rats, mineral oil and the other half, carbon tetrachloride (CCl4). The animals were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum were removed to assess oxidative stress parameters and the activity of antioxidant enzymes. Lipid peroxidation levels (TBARS) were unchanged. However, CCl4 induced oxidative damage to proteins in all tissues studied, and this injury was prevented by both extracts. Superoxide dismutase (SOD) activity was increased by CCl4 in the cerebral cortex and decreased in other tissues. However, CCl4 increased catalase (CAT) activity in the cerebellum and decreased it in the cerebral cortex. The SOD/CAT ratio was restored in the cerebellum by both extracts and only in the cerebral cortex by the organic extract. PMID:26784867

  15. Antioxidant Activity of Grapevine Leaf Extracts against Oxidative Stress Induced by Carbon Tetrachloride in Cerebral Cortex, Hippocampus and Cerebellum of Rats

    Directory of Open Access Journals (Sweden)

    Mariane Wohlenberg

    2014-04-01

    Full Text Available In recent years, it has become increasingly important to study the beneficial properties of derivatives of grapes and grapevine. The objective of this study was to determine the antioxidant activity of Vitis labrusca leaf extracts, comparing conventional and organic grapevines, in different brain areas of rats. We used male Wistar rats treated with grapevine leaf extracts for a period of 14 days, and on the 15th day, we administered in half of the rats, mineral oil and the other half, carbon tetrachloride (CCl4. The animals were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum were removed to assess oxidative stress parameters and the activity of antioxidant enzymes. Lipid peroxidation levels (TBARS were unchanged. However, CCl4 induced oxidative damage to proteins in all tissues studied, and this injury was prevented by both extracts. Superoxide dismutase (SOD activity was increased by CCl4 in the cerebral cortex and decreased in other tissues. However, CCl4 increased catalase (CAT activity in the cerebellum and decreased it in the cerebral cortex. The SOD/CAT ratio was restored in the cerebellum by both extracts and only in the cerebral cortex by the organic extract.

  16. Pregnenolone sulfate restores the glutamate-nitric-oxide-cGMP pathway and extracellular GABA in cerebellum and learning and motor coordination in hyperammonemic rats.

    Science.gov (United States)

    Gonzalez-Usano, Alba; Cauli, Omar; Agusti, Ana; Felipo, Vicente

    2014-02-19

    Around 40% of cirrhotic patients show minimal hepatic encephalopathy (MHE), with mild cognitive impairment which reduces their quality of life and life span. Treatment of MHE is unsatisfactory, and there are no specific treatments for the neurological alterations in MHE. Hyperammonemia is the main contributor to neurological alterations in MHE. New agents acting on molecular targets involved in brain mechanisms leading to neurological alterations are needed to treat MHE. Chronic hyperammonemia impairs learning of a Y-maze task by impairing the glutamate-nitric-oxide (NO)-cGMP pathway in cerebellum, in part by enhancing GABA(A) receptor activation, which also induces motor in-coordination. Acute pregnenolone sulfate (PregS) restores the glutamate-NO-cGMP pathway in hyperammonemic rats. This work aimed to assess whether chronic treatment of hyperammonemic rats with PregS restores (1) motor coordination; (2) extracellular GABA in cerebellum; (3) learning of the Y-maze task; (4) the glutamate-NO-cGMP pathway in cerebellum. Chronic intracerebral administration of PregS normalizes motor coordination likely due to extracellular GABA reduction. PregS restores learning ability by restoring the glutamate-NO-cGMP pathway, likely due to both enhanced NMDA receptor activation and reduced GABA(A) receptor activation. Similar treatments would improve cognitive and motor alterations in patients with MHE. PMID:24256194

  17. Bacopa monnieri Extract (CDRI-08 Modulates the NMDA Receptor Subunits and nNOS-Apoptosis Axis in Cerebellum of Hepatic Encephalopathy Rats

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    Papia Mondal

    2015-01-01

    Full Text Available Hepatic encephalopathy (HE, characterized by impaired cerebellar functions during chronic liver failure (CLF, involves N-methyl-D-aspartate receptor (NMDAR overactivation in the brain cells. Bacopa monnieri (BM extract is a known neuroprotectant. The present paper evaluates whether BM extract is able to modulate the two NMDAR subunits (NR2A and NR2B and its downstream mediators in cerebellum of rats with chronic liver failure (CLF, induced by administration of 50 mg/kg bw thioacetamide (TAA i.p. for 14 days, and in the TAA group rats orally treated with 200 mg/kg bw BM extract from days 8 to 14. NR2A is known to impart neuroprotection and that of NR2B induces neuronal death during NMDAR activation. Neuronal nitric oxide synthase- (nNOS- apoptosis pathway is known to mediate NMDAR led excitotoxicity. The level of NR2A was found to be significantly reduced with a concomitant increase of NR2B in cerebellum of the CLF rats. This was consistent with significantly enhanced nNOS expression, nitric oxide level, and reduced Bcl2/Bax ratio. Moreover, treatment with BM extract reversed the NR2A/NR2B ratio and also normalized the levels of nNOS-apoptotic factors in cerebellum of those rats. The findings suggest modulation of NR2A and NR2B expression by BM extract to prevent neurochemical alterations associated with HE.

  18. Metabotropic glutamate receptor 5 modulates the nitric oxide-cGMP pathway in cerebellum in vivo through activation of AMPA receptors.

    Science.gov (United States)

    Boix, Jordi; Llansola, Marta; Cabrera-Pastor, Andrea; Felipo, Vicente

    2011-04-01

    Metabotropic glutamate receptors (mGluRs) modulate important processes in cerebellum including long-term depression, which also requires formation of nitric oxide (NO) and cGMP. Some reports suggest that mGluRs could modulate the NO-cGMP pathway in cerebellum. However this modulation has not been studied in detail. The aim of this work was to assess by microdialysis in freely moving rats whether activation of mGluR5 modulates the NO-cGMP pathway in cerebellum in vivo and to analyze the underlying mechanisms. We show that mGluR5 activation increases extracellular glutamate, citrulline and cGMP in cerebellum. Blocking NMDA receptors with MK-801 does not prevent any of these effects, indicating that NMDA receptors activation is not required. However in the presence of MK-801 the effects are more transient, returning faster to basal levels. Blocking AMPA receptors prevents the increase in citrulline and cGMP induced by mGluR5 activation, but not the increase in glutamate. The release of glutamate is prevented by tetrodotoxin but not by fluoroacetate, indicating that glutamate is released from neurons and not from astrocytes. Activation of AMPA receptors increases citrulline and cGMP. These data indicate that activation of mGluR5 induces an increase of extracellular glutamate which activates AMPA receptors, leading to activation of nitric oxide synthase and increased NO, which activates guanylate cyclase, increasing cGMP. The response mediated by AMPA receptors desensitize rapidly. Activation of AMPA receptors also induces a mild depolarization, allowing activation of NMDA receptors which prolongs the duration of the effect initiated by activation of AMPA receptors. These data support that the three types of glutamate receptors: mGluR5, AMPA and NMDA cooperate in the modulation of the grade and duration of activation of the NO-cGMP pathway in cerebellum in vivo. This pathway would modulate cerebellar processes such as long-term depression. PMID:21300123

  19. The determination of trace metals by INAA in cortex cerebellum and putamen of human brain and in their neuromelanins

    International Nuclear Information System (INIS)

    Instrumental Neutron Activation Analysis (INAA) was used for all the measurements. Irradiations were performed at the Triga Mark II (General Atomic - USA) research reactor of the University of Pavia. Depending on the elements to be determined, two different irradiation procedures were followed: Short irradiations were performed in the pneumatic irradiation facility at a neutron flux of 5x1012 n x cm-2 x s-1 . Samples and standards sealed in plastic vials were irradiated for 5 minutes. Long irradiations were carried out in the central thimble facility at a nominal neutron flux of 1013 n x cm-2 x s-1. Samples and standards were sealed in quartz vials and then neutron irradiated for 40 h. For the gamma spectra evaluation HPGe (gamma -x) detectors (ORTEC - USA) coupled to computerized multichannel analysers (ORTEC ADCAM - USA) were used. The concentrations of trace elements in Cortex, Cerebellum, Putamen and in their Neuromelanins are reported. Fe is the most abundant element in tissues, followed by Zinc. The ability of NMs to sequestrate metals is well shown, being their concentrations in NMs much higher than in their respective tissues, where some of them (Hg, Mo) were not even detectable. Strong differences are shown between the different pigments in interaction with metals. NM from SN shows a higher affinity for iron than all the other pigments isolated from other brain areas; nevertheless, the tissue that contains the highest concentration of this metal is PU and not SN. These results would confirm that NM from SN plays a protective role in neurons by quenching Fenton's reaction, so far considered the cause of the pathogenesis of PD. A protective role could be played by the other pigments as well, as the concentrations of analysed elements show that they bind large amounts of potentially toxic metals different from iron. This might be explained as the need of the neurons to defend themselves from the toxicity of this metal by the development of a specific pigment

  20. Potential role of oxidative stress in mediating the effect of altered gravity on the developing rat cerebellum

    Science.gov (United States)

    Sajdel-Sulkowska, Elizabeth M.; Nguon, Kosal; Sulkowski, Zachary L.; Lipinski, Boguslaw

    We have previously reported that perinatal exposure to hypergravity affects cerebellar structure and motor coordination in rat neonates. In the present study, we explored the hypothesis that exposure to hypergravity results in oxidative stress that may contribute to the decrease in Purkinje cell number and the impairment of motor coordination in hypergravity-exposed rat neonates. To test this hypothesis we compared cerebellar oxidative stress markers 3-nitrotyrosine (3-NT; an index of oxidative protein modification) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG; an index of oxidative DNA damage) between stationary control (SC) and rat neonates exposed to 1.65 G (HG) on a 24-ft centrifuge from gestational day (G) 8 to postnatal day (P) 21. The levels of 3-NT and 8-OH-dG were determined by specific ELISAs. We also compared the Purkinje cell number (stereorologically) and rotarod performance between the two groups. The levels of 3-NT were increased only in HG females on P6 and on P12 in the cerebellum, and only in HG females on P12 in the extracellabellar tissue. Limited cerebellar data suggests an increase in the levels of 8-OH-dG on P12 only in HG females. In extracerebellar tissue the increase in 8-OH-dG levels was observed in both HG males and HG females except on P6 when it was only observed in HG males. While preliminary, these data suggest that the effect of hypergravity on the developing brain is sex-dependent and may involve oxidative stress. Oxidative stress may, in turn, contribute to the decrease Purkinje cell number and impaired motor behavior observed in hypergravity-exposed rats.

  1. The effects of heavy ion particles on the developing murine cerebellum, with special reference to cell death

    International Nuclear Information System (INIS)

    We report here the effects of heavy ion beams on postnatal mouse cerebellar development, with reference to cell death. Eight-day-old B6C3F1 mice were irradiated with single doses of 0.1, 0.25, 0.5, 1.0, and 2.0 Gy, using a carbon beam of 290 MeV delivered from a heavy ion medical accelerator in Chiba (HIMAC). To compare the effects of X-rays with those of accelerated carbon ions, 8-day-old mice were exposed to X-rays single doses of 0.1, 0.25, 0.5, 1.0, and 2.0 Gy, respectively. Pups were fixed at 1, 6, 12 and 24 hr after exposure to HIMAC beams or X-rays. Four-μm-thick parasagittal sections of the cerebella were processed for hematoxylin-eosin staining as well as for staining with the TUNEL (terminal dUTP nick-end labeling) technique. The density of fragmented nuclei in the external granular layer increased with time, peaking at 6 hr after exposure, in both the HIMAC and X-irradiated groups. In the HIMAC groups, the density was significantly higher in those animals exposed to 0.25 Gy or more compared to 0 Gy, whereas in the X-irradiated groups it was significantly higher in those mice exposed to 0.5 Gy or more. Electron microscopic examinations revealed chromatin condensation in the cell nuclei in the HIMAC groups. This is the first in vivo evidence that apoptotic cell death is induced in developing mouse cerebellum after exposure to heavy ion particles. The difference in the frequency of dying cells between exposure to heavy ion particles and to X-rays may reflect the high linear energy transfer (LET) associated with a heavy ion beam. (author)

  2. Effects of cyclooxygenase inhibitor pretreatment on nitric oxide production, nNOS and iNOS expression in rat cerebellum.

    Science.gov (United States)

    Di Girolamo, G; Farina, M; Riberio, M L; Ogando, D; Aisemberg, J; de los Santos, A R; Martí, M L; Franchi, A M

    2003-07-01

    1. The therapeutic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is thought to be due mainly to its inhibition of cyclooxygenase (COX) enzymes, but there is a growing body of research that now demonstrates a variety of NSAIDs effects on cellular signal transduction pathways other than those involving prostaglandins. 2. Nitric oxide (NO) as a free radical and an agent that gives rise to highly toxic oxidants (peroxynitrile, nitric dioxide, nitron ion), becomes a cause of neuronal damage and death in some brain lesions such as Parkinson and Alzheimer disease, and Huntington's chorea. 3. In the present study, the in vivo effect of three NSAIDs (lysine clonixinate (LC), indomethacine (INDO) and meloxicam (MELO)) on NO production and nitric oxide synthase expression in rat cerebellar slices was analysed. Rats were treated with (a) saline, (b) lipopolysaccharide (LPS) (5 mg kg(-1), i.p.), (c) saline in combination with different doses of NSAIDs and (d) LPS in combination with different doses of NSAIDs and then killed 6 h after treatment. 4. NO synthesis, evaluated by Bred and Snyder technique, was increased by LPS. This augmentation was inhibited by coadministration of the three NSAIDs assayed. None of the NSAIDs tested was able to modify control NO synthesis. 5. Expression of iNOS and neural NOS (nNOS) was detected by Western blotting in control and LPS-treated rats. LC and INDO, but not MELO, were able to inhibit the expression of these enzymes. 6. Therefore, reduction of iNOS and nNOS levels in cerebellum may explain, in part, the anti-inflammatory effect of these NSAIDs and may also have importance in the prevention of NO-mediated neuronal injury. PMID:12871835

  3. The microstructural effects of aqueous extract of Garcinia kola (Linn) on the hippocampus and cerebellum of malnourished mice

    Institute of Scientific and Technical Information of China (English)

    Sunday A Ajayi; David A Ofusori; Gideon B Ojo; Oladele A Ayoka; Taiwo A Abayomi; Adekilekun A Tijani

    2011-01-01

    Objective: To assess the neuroprotective effects of aqueous extract of Garcinia kola on neurotoxin administered malnourished mice adopting histological procedure. Methods: The study was carried out using thirty-two adult malnourished mice which were randomly assigned into four groups (n=8): A, B, C and D. Group A served as control, while the other groups served as the experimental groups. Animals in group A were fed malnourished diet ad libitum and given water liberally. Animals in group B were administered with 3-Nitropropionic acid (3-NP) (neurotoxin) only at 20 mg/kg body weight, group C were given only Garcinia kola extracts, and group D were pre-treated with Garcinia kola extracts at 200 mg/kg for seven days prior to administration of neurotoxin at 20 mg/kg body weight. After three days of neurotoxins administration in the relevant groups, the brains were excised and fixed in formal calcium for histological processing. Results:The study showed that hippocampal and cerebellar neurons of animals in group B exhibited some cellular degeneration and blood vessel blockage, which were not seen in groups A, C and D. Cresyl violet staining was least intense in group B than in groups A, C and D. Despite the fact that animals in group D has equal administration of 3-Nitropropionic acid concentration, there were no traces of neural degeneration as it was evidenced in group B. Conclusions: It is concluded that Garcinia kola has protective effects on the neurons of the hippocampus and cerebellum of malnourished mice.

  4. Single session imaging of cerebellum at 7 Tesla: obtaining structure and function of multiple motor subsystems in individual subjects.

    Directory of Open Access Journals (Sweden)

    Melissa A Batson

    Full Text Available The recent increase in the use of high field MR systems is accompanied by a demand for acquisition techniques and coil systems that can take advantage of increased power and accuracy without being susceptible to increased noise. Physical location and anatomical complexity of targeted regions must be considered when attempting to image deeper structures with small nuclei and/or complex cytoarchitechtonics (i.e. small microvasculature and deep nuclei, such as the brainstem and the cerebellum (Cb. Once these obstacles are overcome, the concomitant increase in signal strength at higher field strength should allow for faster acquisition of MR images. Here we show that it is technically feasible to quickly and accurately detect blood oxygen level dependent (BOLD signal changes and obtain anatomical images of Cb at high spatial resolutions in individual subjects at 7 Tesla in a single one-hour session. Images were obtained using two high-density multi-element surface coils (32 channels in total placed beneath the head at the level of Cb, two channel transmission, and three-dimensional sensitivity encoded (3D, SENSE acquisitions to investigate sensorimotor activations in Cb. Two classic sensorimotor tasks were used to detect Cb activations. BOLD signal changes during motor activity resulted in concentrated clusters of activity within the Cb lobules associated with each task, observed consistently and independently in each subject: Oculomotor vermis (VI/VII and CrusI/II for pro- and anti-saccades; ipsilateral hemispheres IV-VI for finger tapping; and topographical separation of eye- and hand- activations in hemispheres VI and VIIb/VIII. Though fast temporal resolution was not attempted here, these functional patches of highly specific BOLD signal changes may reflect small-scale shunting of blood in the microvasculature of Cb. The observed improvements in acquisition time and signal detection are ideal for individualized investigations such as

  5. Regulation of synaptic transmission in the mossy fibre-granule cell pathway of rat cerebellum by metabotropic glutamate receptors.

    Science.gov (United States)

    Vetter, P; Garthwaite, J; Batchelor, A M

    1999-06-01

    The role of metabotropic glutamate receptors (mGluRs) in the mossy fibre-granule cell pathway in rat cerebellum was studied using slice preparations and electrophysiological techniques. Application of the group I selective agonist (S)-3,5-dihydroxyphenylglycine (DHPG) evoked, in a concentration-dependent manner (EC50 = 33 microM), a depolarising/hyperpolarising complex response from granule cells which was preferentially inhibited by the group I selective antagonist (S)-4-carboxyphenylglycine (4CPG). The group III selective agonist L-amino-4-phosphonobutyrate (AP4) evoked a hyperpolarising response (EC50 = 10 microM) which was inhibited by the group II/III selective antagonist (S)-alpha-methyl-4-phosphonophenylglycine (MPPG). The group II agonist (2S,2'R,3'R)-2-(2',3'-dicarboxylcyclopropyl)glycine (DCG-IV) elicited no measurable voltage change. The amplitude of the synaptically-mediated mossy fibre response in granule cells was unaffected during application of AP4, was reduced by DHPG and was enhanced by DCG-IV (EC50 = 80 nM). These effects were inhibited by the group selective antagonists 4CPG and (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine (PCCG-4), respectively. Further investigation using patch-clamp recording revealed that DCG-IV potently inhibited spontaneous GABAergic currents. We conclude that group I and III (but not group II) mGluRs are functionally expressed by granule cells, whereas unexpectedly group II or III mGluRs do not appear to be present presynaptically on mossy fibre terminals. Group II mGluRs are located on Golgi cell terminals; when activated these receptors cause disinhibition, a function which may be important for gating information transfer from the mossy fibres to the granule cells. PMID:10465684

  6. Identification of thyroid hormone receptor binding sites and target genes using ChIP-on-chip in developing mouse cerebellum.

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    Hongyan Dong

    Full Text Available Thyroid hormone (TH is critical to normal brain development, but the mechanisms operating in this process are poorly understood. We used chromatin immunoprecipitation to enrich regions of DNA bound to thyroid receptor beta (TRbeta of mouse cerebellum sampled on post natal day 15. Enriched target was hybridized to promoter microarrays (ChIP-on-chip spanning -8 kb to +2 kb of the transcription start site (TSS of 5000 genes. We identified 91 genes with TR binding sites. Roughly half of the sites were located in introns, while 30% were located within 1 kb upstream (5' of the TSS. Of these genes, 83 with known function included genes involved in apoptosis, neurodevelopment, metabolism and signal transduction. Two genes, MBP and CD44, are known to contain TREs, providing validation of the system. This is the first report of TR binding for 81 of these genes. ChIP-on-chip results were confirmed for 10 of the 13 binding fragments using ChIP-PCR. The expression of 4 novel TH target genes was found to be correlated with TH levels in hyper/hypothyroid animals providing further support for TR binding. A TRbeta binding site upstream of the coding region of myelin associated glycoprotein was demonstrated to be TH-responsive using a luciferase expression system. Motif searches did not identify any classic binding elements, indicating that not all TR binding sites conform to variations of the classic form. These findings provide mechanistic insight into impaired neurodevelopment resulting from TH deficiency and a rich bioinformatics resource for developing a better understanding of TR binding.

  7. Identification of Thyroid Hormone Receptor Binding Sites and Target Genes Using ChIP-on-Chip in Developing Mouse Cerebellum

    Science.gov (United States)

    Dong, Hongyan; Yauk, Carole L.; Rowan-Carroll, Andrea; You, Seo-Hee; Zoeller, R. Thomas; Lambert, Iain; Wade, Michael G.

    2009-01-01

    Thyroid hormone (TH) is critical to normal brain development, but the mechanisms operating in this process are poorly understood. We used chromatin immunoprecipitation to enrich regions of DNA bound to thyroid receptor beta (TRβ) of mouse cerebellum sampled on post natal day 15. Enriched target was hybridized to promoter microarrays (ChIP-on-chip) spanning −8 kb to +2 kb of the transcription start site (TSS) of 5000 genes. We identified 91 genes with TR binding sites. Roughly half of the sites were located in introns, while 30% were located within 1 kb upstream (5′) of the TSS. Of these genes, 83 with known function included genes involved in apoptosis, neurodevelopment, metabolism and signal transduction. Two genes, MBP and CD44, are known to contain TREs, providing validation of the system. This is the first report of TR binding for 81 of these genes. ChIP-on-chip results were confirmed for 10 of the 13 binding fragments using ChIP-PCR. The expression of 4 novel TH target genes was found to be correlated with TH levels in hyper/hypothyroid animals providing further support for TR binding. A TRβ binding site upstream of the coding region of myelin associated glycoprotein was demonstrated to be TH-responsive using a luciferase expression system. Motif searches did not identify any classic binding elements, indicating that not all TR binding sites conform to variations of the classic form. These findings provide mechanistic insight into impaired neurodevelopment resulting from TH deficiency and a rich bioinformatics resource for developing a better understanding of TR binding. PMID:19240802

  8. Methylphenidate induces lipid and protein damage in prefrontal cortex, but not in cerebellum, striatum and hippocampus of juvenile rats.

    Science.gov (United States)

    Schmitz, Felipe; Scherer, Emilene B S; Machado, Fernanda R; da Cunha, Aline A; Tagliari, Bárbara; Netto, Carlos A; Wyse, Angela T S

    2012-12-01

    The use of psychostimulant methylphenidate has increased in recent years for the treatment of attention-deficit hyperactivity disorder in children and adolescents. However, the behavioral and neurochemical changes promoted by its use are not yet fully understood, particularly when used for a prolonged period during stages of brain development. Thus, the aim of this study was to determine some parameters of oxidative stress in encephalic structures of juvenile rats subjected to chronic methylphenidate treatment. Wistar rats received intraperitoneal injections of methylphenidate (2.0 mg/kg) once a day, from the 15th to the 45th day of age or an equivalent volume of 0.9% saline solution (controls). Two hours after the last injection, animals were euthanized and the encephalic structures obtained for determination of oxidative stress parameters. Results showed that methylphenidate administration increased the activities of superoxide dismutase and catalase, but did not alter the levels of reactive species, thiobarbituric acid reactive substances levels and sulfhydryl group in cerebellum of rats. In striatum and hippocampus, the methylphenidate-treated rats presented a decrease in the levels of reactive species and thiobarbituric acid reactive substances, but did not present changes in the sulfhydryl groups levels. In prefrontal cortex, methylphenidate promoted an increase in reactive species formation, SOD/CAT ratio, and increased the lipid peroxidation and protein damage. These findings suggest that the encephalic structures respond differently to methylphenidate treatment, at least, when administered chronically to young rats. Notably, the prefrontal cortex of juvenile rats showed greater sensitivity to oxidative effects promoted by methylphenidate in relation to other encephalic structures analyzed. PMID:22968482

  9. Disruption of the LTD dialogue between the cerebellum and the cortex in Angelman syndrome model: a timing hypothesis

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    Guy eCheron

    2014-11-01

    Full Text Available Angelman syndrome is a genetic neurodevelopmental disorder in which cerebellar functioning impairment has been documented despite the absence of gross structural abnormalities. Characteristically, a spontaneous 160 Hz oscillation emerges in the Purkinje cells network of the Ube3am-/p+ Angelman mouse model. This abnormal oscillation is induced by enhanced Purkinje cell rhythmicity and hypersynchrony along the parallel fiber beam. We present a pathophysiological hypothesis for the neurophysiology underlying major aspects of the clinical phenotype of Angelman syndrome, including cognitive, language and motor deficits, involving long-range connection between the cerebellar and the cortical networks. This hypothesis states that the alteration of the cerebellar rhythmic activity impinges cerebellar long-term depression (LTD plasticity, which in turn alters the LTD plasticity in the cerebral cortex. This hypothesis was based on preliminary experiments using electrical stimulation of the whiskers pad performed in alert mice showing that after a 8 Hz LTD-inducing protocol, the cerebellar LTD accompanied by a delayed response in the wild type mice is missing in Ube3am-/p+ mice and that the LTD induced in the barrel cortex following the same peripheral stimulation in wild mice is reversed into a LTP in the Ube3am-/p+ mice. The control exerted by the cerebellum on the excitation vs inhibition balance in the cerebral cortex and possible role played by the timing plasticity of the Purkinje cell LTD on the spike–timing dependent plasticity (STDP of the pyramidal neurons are discussed in the context of the present hypothesis.

  10. The effects of heavy ion particles on the developing murine cerebellum, with special reference to cell death

    Energy Technology Data Exchange (ETDEWEB)

    Kinoshita, Chikako; Yaoi, Takeshi; Fushiki, Shinji [Kyoto Prefectural Univ. of Medicine (Japan). Research Inst. for Neurological Diseases and Geriatrics; Nojima, Kumie [National Inst. of Radiological Sciences, Chiba (Japan). Internatinal Space Radiation Lab.

    2003-07-01

    We report here the effects of heavy ion beams on postnatal mouse cerebellar development, with reference to cell death. Eight-day-old B6C3F1 mice were irradiated with single doses of 0.1, 0.25, 0.5, 1.0, and 2.0 Gy, using a carbon beam of 290 MeV delivered from a heavy ion medical accelerator in Chiba (HIMAC). To compare the effects of X-rays with those of accelerated carbon ions, 8-day-old mice were exposed to X-rays single doses of 0.1, 0.25, 0.5, 1.0, and 2.0 Gy, respectively. Pups were fixed at 1, 6, 12 and 24 hr after exposure to HIMAC beams or X-rays. Four-{mu}m-thick parasagittal sections of the cerebella were processed for hematoxylin-eosin staining as well as for staining with the TUNEL (terminal dUTP nick-end labeling) technique. The density of fragmented nuclei in the external granular layer increased with time, peaking at 6 hr after exposure, in both the HIMAC and X-irradiated groups. In the HIMAC groups, the density was significantly higher in those animals exposed to 0.25 Gy or more compared to 0 Gy, whereas in the X-irradiated groups it was significantly higher in those mice exposed to 0.5 Gy or more. Electron microscopic examinations revealed chromatin condensation in the cell nuclei in the HIMAC groups. This is the first in vivo evidence that apoptotic cell death is induced in developing mouse cerebellum after exposure to heavy ion particles. The difference in the frequency of dying cells between exposure to heavy ion particles and to X-rays may reflect the high linear energy transfer (LET) associated with a heavy ion beam. (author)

  11. Differential modulation of the glutamate-nitric oxide-cyclic GMP pathway by distinct neurosteroids in cerebellum in vivo.

    Science.gov (United States)

    Cauli, O; González-Usano, A; Agustí, A; Felipo, V

    2011-09-01

    The glutamate-nitric oxide (NO)-cGMP pathway mediates many responses to activation of N-methyl-d-aspartate (NMDA) receptors, including modulation of some types of learning and memory. The glutamate-NO-cGMP pathway is modulated by GABAergic neurotransmission. Activation of GABA(A) receptors reduces the function of the pathway. Several neurosteroids modulate the activity of GABA(A) and/or NMDA receptors, suggesting that they could modulate the function of the glutamate-NO-cGMP pathway. The aim of this work was to assess, by in vivo microdialysis, the effects of several neurosteroids with different effects on GABA(A) and NMDA receptors on the function of the glutamate-NO-cGMP pathway in cerebellum in vivo. To assess the effects of the neurosteroids on the glutamate-NO-cGMP pathway, they were administered through the microdialysis probe before administration of NMDA and the effects on NMDA-induced increase in extracellular cGMP were analyzed. We also assessed the effects of the neurosteroids on basal levels of extracellular cGMP. To assess the effects of neurosteroids on nitric oxide synthase (NOS) activity and on NMDA-induced activation of NOS, we also measured the effects of the neurosteroids on extracellular citrulline. Pregnanolone and tetrahydrodeoxy-corticosterone (THDOC) behave as agonists of GABA(A) receptors and completely block NMDA-induced increase in cGMP. Pregnanolone but not THDOC also reduced basal levels of extracellular cGMP. Pregnenolone did not affect extracellular cGMP or its increase by NMDA administration. Pregnenolone sulfate increased basal extracellular cGMP and potentiated NMDA-induced increase in cGMP, behaving as an enhancer of NMDA receptors activation. Allopregnanolone and dehydroepiandrosterone sulphate behave as antagonists of NMDA receptors, increasing basal cGMP and blocking completely NMDA-induced increase in cGMP. Dehydroepiandrosterone sulphate seems to do this by activating sigma receptors. These data support the concept that, at

  12. Grey matter volume and resting-state functional connectivity of the motor cortex-cerebellum network reflect the individual variation in masticatory performance in the healthy elderly people

    Directory of Open Access Journals (Sweden)

    Chia-Shu eLin

    2016-01-01

    Full Text Available Neuroimaging studies have consistently identified brain activation in the motor area and the cerebellum during chewing. In this study, we further investigated the structural and functional brain signature associated with masticatory performance, which is a widely used index for evaluating overall masticatory function in the elderly. Twenty-five healthy elderly participants underwent oral examinations, masticatory performance tests, and behavioral assessments, including the Cognitive Abilities Screening Instrument and the short-form Geriatric Depression Scale. Masticatory performance was assessed with the validated colorimetric method, using color-changeable chewing gum. T1-weighted structural magnetic resonance imaging (MRI and resting-state function MRI were performed. We analyzed alterations in grey matter volume (GMV using voxel-based morphometry and resting-state functional connectivity (rsFC between brain regions using the seed-based method. The structural and functional MRI analyses revealed the following findings: (1 the GMV change in the premotor cortex was positively correlated with masticatory performance. (2 The rsFC between the cerebellum and the premotor cortex was positively correlated with masticatory performance. (3 The GMV changes in the dorsolateral prefrontal cortex (DLPFC, as well as the rsFC between the cerebellum and the DLPFC, was positively correlated with masticatory performance. The findings showed that in the premotor cortex, a reduction of GMV and rsFC would reflect declined masticatory performance. The positive correlation between DLPFC connectivity and masticatory performance implies that masticatory ability is associated with cognitive function in the elderly. Our findings highlighted the role of the central nervous system in masticatory performance and increased our understanding of the structural and functional brain signature underlying individual variations in masticatory performance in the elderly.

  13. Implication of Tryptophan 2,3-Dioxygenase and its Novel Variants in the Hippocampus and Cerebellum During the Developing and Adult Brain

    Directory of Open Access Journals (Sweden)

    Masaaki Kanai

    2010-07-01

    Full Text Available Tryptophan 2,3-dioxygenase (TDO is a first and rate-limiting enzyme for the kynurenine pathway of tryptophan metabolism. Using Tdo-/-mice, we have recently shown that TDO plays a pivotal role in systemic tryptophan metabolism and brain serotonin synthesis as well as emotional status and adult neurogenesis. However, the expression of TDO in the brain has not yet been well characterized, in contrast to its predominant expression in the liver. To further examine the possible role of local TDO in the brain, we quantified the levels of tdo mRNA in various nervous tissues, using Northern blot and quantitative real-time RT-PCR. Higher levels of tdo mRNA expression were detected in the cerebellum and hippocampus. We also identified two novel variants of the tdo gene, termed tdo variant1 and variant2, in the brain. Similar to the known TDO form (TDO full-form, tetramer formation and enzymatic activity were obtained when these variant forms were expressed in vitro. While quantitative real-time RT-PCR revealed that the tissue distribution of these variants was similar to that of tdo full-form, the expression patterns of these variants during early postnatal development in the hippocampus and cerebellum differed. Our findings indicate that in addition to hepatic TDO, TDO and its variants in the brain might function in the developing and adult nervous system. Given the previously reported associations of tdo gene polymorphisms in the patients with autism and Tourette syndrome, the expression of TDO in the brain suggests the possible influence of TDO on psychiatric status. Potential functions of TDOs in the cerebellum, hippocampus and cerebral cortex under physiological and pathological conditions are discussed.

  14. A bi-hemispheric neuronal network model of the cerebellum with spontaneous climbing fiber firing produces asymmetrical motor learning during robot control.

    Science.gov (United States)

    Pinzon-Morales, Ruben-Dario; Hirata, Yutaka

    2014-01-01

    To acquire and maintain precise movement controls over a lifespan, changes in the physical and physiological characteristics of muscles must be compensated for adaptively. The cerebellum plays a crucial role in such adaptation. Changes in muscle characteristics are not always symmetrical. For example, it is unlikely that muscles that bend and straighten a joint will change to the same degree. Thus, different (i.e., asymmetrical) adaptation is required for bending and straightening motions. To date, little is known about the role of the cerebellum in asymmetrical adaptation. Here, we investigate the cerebellar mechanisms required for asymmetrical adaptation using a bi-hemispheric cerebellar neuronal network model (biCNN). The bi-hemispheric structure is inspired by the observation that lesioning one hemisphere reduces motor performance asymmetrically. The biCNN model was constructed to run in real-time and used to control an unstable two-wheeled balancing robot. The load of the robot and its environment were modified to create asymmetrical perturbations. Plasticity at parallel fiber-Purkinje cell synapses in the biCNN model was driven by error signal in the climbing fiber (cf) input. This cf input was configured to increase and decrease its firing rate from its spontaneous firing rate (approximately 1 Hz) with sensory errors in the preferred and non-preferred direction of each hemisphere, as demonstrated in the monkey cerebellum. Our results showed that asymmetrical conditions were successfully handled by the biCNN model, in contrast to a single hemisphere model or a classical non-adaptive proportional and derivative controller. Further, the spontaneous activity of the cf, while relatively small, was critical for balancing the contribution of each cerebellar hemisphere to the overall motor command sent to the robot. Eliminating the spontaneous activity compromised the asymmetrical learning capabilities of the biCNN model. Thus, we conclude that a bi

  15. A bi-hemispheric neuronal network model of the cerebellum with spontaneous climbing fiber firing produces asymmetrical motor learning during robot control

    Directory of Open Access Journals (Sweden)

    Ruben Dario Pinzon Morales

    2014-11-01

    Full Text Available To acquire and maintain precise movement controls over a lifespan, changes in the physical and physiological characteristics of muscles must be compensated for adaptively. The cerebellum plays a crucial role in such adaptation. Changes in muscle characteristics are not always symmetrical. For example, it is unlikely that muscles that bend and straighten a joint will change to the same degree. Thus, different (i.e., asymmetrical adaptation is required for bending and straightening motions. To date, little is known about the role of the cerebellum in asymmetrical adaptation. Here, we investigate the cerebellar mechanisms required for asymmetrical adaptation using a bi-hemispheric cerebellar neuronal network model (biCNN. The bi-hemispheric structure is inspired by the observation that lesioning one hemisphere reduces motor performance asymmetrically. The biCNN model was constructed to run in real-time and used to control an unstable two-wheeled balancing robot. The load of the robot and its environment were modified to create asymmetrical perturbations. Plasticity at parallel fiber-Purkinje cell synapses in the biCNN model was driven by error signal in the climbing fiber (cf input. This cf input was configured to increase and decrease its firing rate from its spontaneous firing rate (approximately 1 Hz with sensory errors in the preferred and non-preferred direction of each hemisphere, as demonstrated in the monkey cerebellum. Our results showed that asymmetrical conditions were successfully handled by the biCNN model, in contrast to a single hemisphere model or a classical non-adaptive proportional and derivative controller. Further, the spontaneous activity of the cf, while relatively small, was critical for balancing the contribution of each cerebellar hemisphere to the overall motor command sent to the robot. Eliminating the spontaneous activity compromised the asymmetrical learning capabilities of the biCNN model. Thus, we conclude that a bi

  16. Acute liver failure in rats activates glutamine-glutamate cycle but declines antioxidant enzymes to induce oxidative stress in cerebral cortex and cerebellum.

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    Santosh Singh

    Full Text Available BACKGROUND AND PURPOSE: Liver dysfunction led hyperammonemia (HA causes a nervous system disorder; hepatic encephalopathy (HE. In the brain, ammonia induced glutamate-excitotoxicity and oxidative stress are considered to play important roles in the pathogenesis of HE. The brain ammonia metabolism and antioxidant enzymes constitute the main components of this mechanism; however, need to be defined in a suitable animal model. This study was aimed to examine this aspect in the rats with acute liver failure (ALF. METHODS: ALF in the rats was induced by intraperitoneal administration of 300 mg thioacetamide/Kg. b.w up to 2 days. Glutamine synthetase (GS and glutaminase (GA, the two brain ammonia metabolizing enzymes vis a vis ammonia and glutamate levels and profiles of all the antioxidant enzymes vis a vis oxidative stress markers were measured in the cerebral cortex and cerebellum of the control and the ALF rats. RESULTS: The ALF rats showed significantly increased levels of ammonia in the blood (HA but little changes in the cortex and cerebellum. This was consistent with the activation of the GS-GA cycle and static levels of glutamate in these brain regions. However, significantly increased levels of lipid peroxidation and protein carbonyl contents were consistent with the reduced levels of all the antioxidant enzymes in both the brain regions of these ALF rats. CONCLUSION: ALF activates the GS-GA cycle to metabolize excess ammonia and thereby, maintains static levels of ammonia and glutamate in the cerebral cortex and cerebellum. Moreover, ALF induces oxidative stress by reducing the levels of all the antioxidant enzymes which is likely to play important role, independent of glutamate levels, in the pathogenesis of acute HE.

  17. Neuromodulatory adaptive combination of correlation-based learning in cerebellum and reward-based learning in basal ganglia for goal-directed behavior control.

    Science.gov (United States)

    Dasgupta, Sakyasingha; Wörgötter, Florentin; Manoonpong, Poramate

    2014-01-01

    Goal-directed decision making in biological systems is broadly based on associations between conditional and unconditional stimuli. This can be further classified as classical conditioning (correlation-based learning) and operant conditioning (reward-based learning). A number of computational and experimental studies have well established the role of the basal ganglia in reward-based learning, where as the cerebellum plays an important role in developing specific conditioned responses. Although viewed as distinct learning systems, recent animal experiments point toward their complementary role in behavioral learning, and also show the existence of substantial two-way communication between these two brain structures. Based on this notion of co-operative learning, in this paper we hypothesize that the basal ganglia and cerebellar learning systems work in parallel and interact with each other. We envision that such an interaction is influenced by reward modulated heterosynaptic plasticity (RMHP) rule at the thalamus, guiding the overall goal directed behavior. Using a recurrent neural network actor-critic model of the basal ganglia and a feed-forward correlation-based learning model of the cerebellum, we demonstrate that the RMHP rule can effectively balance the outcomes of the two learning systems. This is tested using simulated environments of increasing complexity with a four-wheeled robot in a foraging task in both static and dynamic configurations. Although modeled with a simplified level of biological abstraction, we clearly demonstrate that such a RMHP induced combinatorial learning mechanism, leads to stabler and faster learning of goal-directed behaviors, in comparison to the individual systems. Thus, in this paper we provide a computational model for adaptive combination of the basal ganglia and cerebellum learning systems by way of neuromodulated plasticity for goal-directed decision making in biological and bio-mimetic organisms. PMID:25389391

  18. Neuromodulatory Adaptive Combination of Correlation-based Learning in Cerebellum and Reward-based Learning in Basal Ganglia for Goal-directed Behavior Control

    Directory of Open Access Journals (Sweden)

    Sakyasingha eDasgupta

    2014-10-01

    Full Text Available Goal-directed decision making in biological systems is broadly based on associations between conditional and unconditional stimuli. This can be further classified as classical conditioning (correlation-based learning and operant conditioning (reward-based learning. A number of computational and experimental studies have well established the role of the basal ganglia in reward-based learning, where as the cerebellum plays an important role in developing specific conditioned responses. Although viewed as distinct learning systems, recent animal experiments point towards their complementary role in behavioral learning, and also show the existence of substantial two-way communication between these two brain structures. Based on this notion of co-operative learning, in this paper we hypothesize that the basal ganglia and cerebellar learning systems work in parallel and interact with each other. We envision that such an interaction is influenced by reward modulated heterosynaptic plasticity (RMHP rule at the thalamus, guiding the overall goal directed behavior. Using a recurrent neural network actor-critic model of the basal ganglia and a feed-forward correlation-based learning model of the cerebellum, we demonstrate that the RMHP rule can effectively balance the outcomes of the two learning systems. This is tested using simulated environments of increasing complexity with a four-wheeled robot in a foraging task in both static and dynamic configurations. Although modeled with a simplified level of biological abstraction, we clearly demonstrate that such a RMHP induced combinatorial learning mechanism, leads to stabler and faster learning of goal-directed behaviors, in comparison to the individual systems. Thus in this paper we provide a computational model for adaptive combination of the basal ganglia and cerebellum learning systems by way of neuromodulated plasticity for goal-directed decision making in biological and bio-mimetic organisms.

  19. Maternal exposure to a continuous 900-MHz electromagnetic field provokes neuronal loss and pathological changes in cerebellum of 32-day-old female rat offspring.

    Science.gov (United States)

    Odacı, Ersan; Hancı, Hatice; İkinci, Ayşe; Sönmez, Osman Fikret; Aslan, Ali; Şahin, Arzu; Kaya, Haydar; Çolakoğlu, Serdar; Baş, Orhan

    2016-09-01

    Large numbers of people are unknowingly exposed to electromagnetic fields (EMF) from wireless devices. Evidence exists for altered cerebellar development in association with prenatal exposure to EMF. However, insufficient information is still available regarding the effects of exposure to 900 megahertz (MHz) EMF during the prenatal period on subsequent postnatal cerebellar development. This study was planned to investigate the 32-day-old female rat pup cerebellum following exposure to 900MHz EMF during the prenatal period using stereological and histopathological evaluation methods. Pregnant rats were divided into control, sham and EMF groups. Pregnant EMF group (PEMFG) rats were exposed to 900MHz EMF for 1h inside an EMF cage during days 13-21 of pregnancy. Pregnant sham group (PSG) rats were also placed inside the EMF cage during days 13-21 of pregnancy for 1h, but were not exposed to any EMF. No procedure was performed on the pregnant control group (PCG) rats. Newborn control group (CG) rats were obtained from the PCG mothers, newborn sham group (SG) rats from the PSG and newborn EMF group (EMFG) rats from the PEMFG rats. The cerebellums of the newborn female rats were extracted on postnatal day 32. The number of Purkinje cells was estimated stereologically, and histopathological evaluations were also performed on cerebellar sections. Total Purkinje cell numbers calculated using stereological analysis were significantly lower in EMFG compared to CG (pprenatal exposure to EMF affects the development of Purkinje cells in the female rat cerebellum and that the consequences of this pathological effect persist after the postnatal period. PMID:26391347

  20. Rapid Thyroxine to 3,5,3′-Triiodothyronine Conversion and Nuclear 3,5,3′-Triiodothyronine Binding in Rat Cerebral Cortex and Cerebellum

    OpenAIRE

    Crantz, F R; Larsen, P R

    1980-01-01

    Thyroxine (T4) to 3,5,3′-triiodothyronine (T3) conversion was evaluated in vivo in cerebral cortex, cerebellum, and anterior pituitary of male euthyroid Sprague-Dawley rats. Tracer quantities of 125I-T4 and 131I-T3 were injected into controls and iopanoic acid-pretreated rats 3 h before isolation of nuclei from these tissues. Specifically-bound nuclear 131I-T3, denoted T3(T3); 125I-T3, denoted T3(T4); and 125I-T4 were extracted and identified by chromatography. Plasma iodothyronines were simi...

  1. Accurate Measurement of 5-Methylcytosine and 5-Hydroxymethylcytosine in Human Cerebellum DNA by Oxidative Bisulfite on an Array (OxBS-Array)

    OpenAIRE

    Field, Sarah F.; Beraldi, Dario; Bachman, Martin; Stewart, Sabrina K.; Beck, Stephan; Balasubramanian, Shankar

    2015-01-01

    The Infinium 450K Methylation array is an established tool for measuring methylation. However, the bisulfite (BS) reaction commonly used with the 450K array cannot distinguish between 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). The oxidative-bisulfite assay disambiguates 5mC and 5hmC. We describe the use of oxBS in conjunction with the 450K array (oxBS-array) to analyse 5hmC/5mC in cerebellum DNA. The “methylation” level derived by the BS reaction is the combined level of 5mC a...

  2. Grey Matter Volume in the Cerebellum is Related to the Processing of Grammatical Rules in a Second Language: A Structural Voxel-based Morphometry Study

    OpenAIRE

    Pliatsikas, Christos; Johnstone, Tom; Marinis, Theodoros

    2014-01-01

    The experience of learning and using a second language (L2) has been shown to affect the grey matter (GM) structure of the brain. Importantly, GM density in several cortical and subcortical areas has been shown to be related to performance in L2 tasks. Here, we show that bilingualism can lead to increased GM volume in the cerebellum, a structure that has been related to the processing of grammatical rules. Additionally, the cerebellar GM volume of highly proficient L2 speakers is correlated t...

  3. Total Phenolic Content and Antioxidant Activity of Different Types of Chocolate, Milk, Semisweet, Dark, and Soy, in Cerebral Cortex, Hippocampus, and Cerebellum of Wistar Rats

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    Niara da Silva Medeiros

    2015-01-01

    Full Text Available Chocolate is a product consumed worldwide and it stands out for presenting an important amount of phenolic compounds. In this study, the total phenolic content and antioxidant activity in the cerebral cortex, hippocampus, and cerebellum of male Wistar rats when consuming different types of chocolate, including milk, semisweet, dark, and soy, was evaluated. The total polyphenols concentration and antioxidant activity in vitro by the method of DPPH radical-scavenging test were evaluated in chocolate samples. Lipid peroxidation (TBARS, protein oxidation (carbonyl, sulfhydryl groups, and activity of SOD enzyme in cerebral cortex, hippocampus, and cerebellum of rats treated or not with hydrogen peroxide and/or chocolate were also evaluated. The dark chocolate demonstrated higher phenolic content and antioxidant activity, followed by semisweet, soy, and milk chocolates. The addition of chocolate in the diet of the rats reduced lipid peroxidation and protein oxidation caused by hydrogen peroxide. In the sulfhydryl assay, we observed that the levels of nonenzymatic defenses only increased with the chocolate treatments The SOD enzyme activity was modulated in the tissues treated with the chocolates. We observed in the samples of chocolate a significant polyphenol content and an important antioxidant activity; however, additional studies with different chocolates and other tissues are necessary to further such findings.

  4. Increased anxiety-like behaviour and altered GABAergic system in the amygdala and cerebellum of VPA rats - An animal model of autism.

    Science.gov (United States)

    Olexová, Lucia; Štefánik, Peter; Kršková, Lucia

    2016-08-26

    Anxiety is one of the associated symptoms of autism spectrum disorder. According to the literature, increases in anxiety are accompanied by GABAergic system deregulation. The aim of our study, performed using an animal model of autism in the form of rats prenatally treated with valproic acid (VPA rats), was to investigate changes in anxiety-like behaviour and the gene expression of molecules that control levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain. Anxiety-like behaviours were investigated using zone preferences in the open field test. The levels of the 65 and 67kDa enzymes of l-glutamic acid decarboxylase (GAD) mRNAs and type 1 GABA transporter (GAT1) were evaluated in the amygdala, as well as GABA producing enzymes in the cortex layer of the cerebellum. Our research showed that adult VPA rats spent less time in the inner zone of the testing chamber and more time in the outer zone of the testing chamber in the open field test. We also found that adult VPA rats had increased expression of GAT1 in the amygdala, as well as decreased levels of GAD65 and GAD67 mRNA in the cerebellum compared to control animals. These findings support the existence of a relationship between increased anxiety-like behaviour and changes in the regulation of the GABAergic system in VPA rats. PMID:27353514

  5. The alterations in regional homogeneity of parieto-cingulate and temporo-cerebellum regions of first-episode medication-naïve depression patients.

    Science.gov (United States)

    Lai, Chien-Han; Wu, Yu-Te

    2016-03-01

    This study surveyed the characteristics of the indicator for the synchrony of brain activities, regional homogeneity (ReHo), in patients who were diagnosed with major depressive disorder (MDD) without co-morbidities. Forty-four patients with MDD and twenty-seven normal controls were enrolled in our study. The ReHo outputs of patients and controls were compared by a nonparametric permutation-based method with global brain volume, age, and gender as covariates. In addition, the correlations between the clinical variables (such as depression severity, anxiety severity, illness duration) and ReHo values were also estimated in each group and across both groups. The patients with MDD had lower ReHo values than the controls for the cognitive division of right anterior cingulate cortex and the left inferior parietal lobule. In contrast, the patients had higher values of ReHo than controls for the right inferior temporal lobe and the right cerebellum. Additionally, the ReHo values were negatively correlated with the depression severity and with illness duration in the right anterior cingulate cortex. MDD patients had significant alterations in the ReHo of the parieto-cingulate and temporo-cerebellum regions with opposite trends. PMID:25904155

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

    International Nuclear Information System (INIS)

    Irreversible incorporation of [3H]flunitrazepam and [3H]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 [3H]flunitrazepam was greater in the pellet than in the suspension. The incorporation was identical for [3H]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 [3H]flunitrazepam photo-labeled receptor revealed the same number of major sites in both brain regions. In contrast, [3H]Ro15-4513 appears to label fewer sites in cortex and cerebellum. Photoaffinity labeling with [3H]flunitrazepam in ligand-bound membrane pellet provides a more selective and reliable method for studying the subunit structure of GABA/benzodiazepine receptor complex

  7. Hyperammonemia alters the modulation by different neurosteroids of the glutamate-nitric oxide-cyclic GMP pathway through NMDA- GABAA - or sigma receptors in cerebellum in vivo.

    Science.gov (United States)

    González-Usano, Alba; Cauli, Omar; Agustí, Ana; Felipo, Vicente

    2013-04-01

    Several neurosteroids modulate the glutamate-nitric oxide (NO)-cGMP pathway in cerebellum through modulation of NMDA- GABAA - or sigma receptors. Hyperammonemia alters the concentration of several neurosteroids and impairs the glutamate-NO-cGMP pathway, leading to impaired learning ability. This work aimed to assess whether chronic hyperammonemia alters the modulation by different neurosteroids of GABAA, NMDA, and/or sigma receptors and of the glutamate-NO-cGMP pathway in cerebellum. Neurosteroids were administered through microdialysis probes, and extracellular cGMP and citrulline were measured. Then NMDA was administered to assess the effects on the glutamate-NO-cGMP pathway activation. Hyperammonemia completely modifies the effects of pregnanolone and pregnenolone. Pregnanolone acts as a GABAA receptor agonist in controls, but as an NMDA receptor antagonist in hyperammonemic rats. Pregnenolone does not induce any effect in controls, but acts as a sigma receptor agonist in hyperammonemic rats. Hyperammonemia potentiates the actions of tetrahydrodeoxy-corticosterone (THDOC) as a GABAA receptor agonist, allopregnanolone as an NMDA receptor antagonist, and pregnenolone sulfate as an NMDA receptor activation enhancer. Neurosteroids that reduce the pathway (pregnanolone, THDOC, allopregnanolone, DHEAS) may contribute to cognitive impairment in hyperammonemia and hepatic encephalopathy. Pregnenolone would impair cognitive function in hyperammonemia. Neurosteroids that restore the pathway in hyperammonemia (pregnenolone sulfate) could restore cognitive function in hyperammonemia and encephalopathy. PMID:23227932

  8. Connectivity pattern differences bilaterally in the cerebellum posterior lobe in healthy subjects after normal sleep and sleep deprivation: a resting-state functional MRI study

    Directory of Open Access Journals (Sweden)

    Liu XM

    2015-05-01

    Full Text Available Xuming Liu,1 Zhihan Yan,2 Tingyu Wang,1 Xiaokai Yang,1 Feng Feng,3 Luping Fan,1 Jian Jiang4 1Department of Radiology, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, 2Department of Radiology, The 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou, 3Peking Union Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 4Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China Objective: The aim of this study was to use functional magnetic resonance imaging (fMRI technique to explore the resting-state functional connectivity (rsFC differences of the bilaterial cerebellum posterior lobe (CPL after normal sleep (NS and after sleep deprivation (SD. Methods: A total of 16 healthy subjects (eight males, eight females underwent an fMRI scan twice at random: once following NS and the other following 24 hours’ SD, with an interval of 1 month between the two scans. The fMRI scanning included resting state and acupuncture stimulation. The special activated regions located during the acupuncture stimulation were selected as regions of interest for rsFC analysis. Results: Bilateral CPLs were positively activated by acupuncture stimulation. In the NS group, the left CPL showed rsFC with the bilateral CPL, bilateral frontal lobe (BFL, left precuneus and right inferior parietal lobule, while the right CPL showed rsFC with the bilateral temporal lobe, right cerebellum anterior lobe, right CPL, left frontal lobe, left anterior cingulate, right posterior cingulate, and bilateral inferior parietal lobule. In the SD group, the left CPL showed rsFC with the left posterior cingulate gyrus bilateral CPL, left precuneus, left precentral gyrus, BFL, and the left parietal lobe, while the right CPL showed rsFC with bilateral cerebellum anterior lobe, bilateral CPL, left frontal lobe and left temporal lobe. Compared with the NS group, the

  9. Protective Effects of N-Acetyl-L-cystein on 3,4-Methylene Dioxymethamphetamie-Induced Neurotoxicity in Cerebellum of Male Rats

    Directory of Open Access Journals (Sweden)

    Sara Soleimani Asl

    2011-10-01

    Full Text Available Objective(s: 3-4, methylenedioxymethamphetamine (MDMA causes apoptosis in nervous system and several studies suggest that oxidative stress contributes to MDMA-induced neurotoxicity. The aim of this study is to examine the effects of N-acetyl-L-Cystein (NAC as an antioxidant on MDMA-induced apoptosis. Materials and Methods: 21 Sprague dawley male rats (200-250mg were treated with MDMA (2×0,5mg/kg or MDMA plus NAC (100mg/kg IP for 7 day. After last administration of MDMA, rats were killed, cerebellum was removed and Bax and Bcl-2 expression was assessed by western blotting method. Results: The results of this study showed that MDMA causes up-regulation of Bax and down-regulation of Bcl-2 and NAC administration attenuated MDMA-induced apoptosis. Conclusion: The present study suggests that NAC treatment may improve MDMA-induced neurotoxicity.

  10. Neuroprotective Effect of Portulaca oleraceae Ethanolic Extract Ameliorates Methylmercury Induced Cognitive Dysfunction and Oxidative Stress in Cerebellum and Cortex of Rat Brain.

    Science.gov (United States)

    Sumathi, Thangarajan; Christinal, Johnson

    2016-07-01

    Methylmercury (MeHg) is highly toxic, and its principal target tissue in human is the nervous system, which has made MeHg intoxication a public health concern for many decades. Portulaca oleraceae (purslane), a member of the Portulacaceae family, is widespread as a weed and has been ranked the eighth most common plant in the world. In this study, we sought for potential beneficial effects of Portulaca oleracea ethanolic extract (POEE) against the neurotoxicity induced by MeHg in cerebellum and cortex of rats. Male Wistar rats were administered with MeHg orally at a dose of 5 mg/kg b.w. for 21 days. Experimental rats were given MeHg and also administered with POEE (4 mg/kg, orally) 1 h prior to the administration of MeHg for 21 days. After MeHg exposure, we determine the mercury concentration by atomic absorption spectroscopy (AAS); mercury content was observed high in MeHg-induced group. POEE reduced the mercury content. We also observed that the activities of catalase, superoxide dismutase, glutathione peroxidase, and the level of glutathione were reduced. The levels of glutathione reductase and thiobarbituric acid reactive substance were found to be increased. The above biochemical changes were found to be reversed with POEE. Behavioral changes like decrease tail flick response, longer immobility time, and decreased motor activity were noted down during MeHg exposure. POEE pretreatment offered protection from these behavioral changes. MeHg intoxication also caused histopathological changes in cerebellum and cortex, which was found to be normalized by treatment with POEE. The present results indicate that POEE has protective effect against MeHg-induced neurotoxicity. PMID:26563420

  11. Sex Differences in the Cerebellum and its Correlates with Some Body Traits in the African Grasscutter (Thryonomys swinderianus – Temminck, 1827: Morphometric Study

    Directory of Open Access Journals (Sweden)

    Obadiah Byanet

    2012-09-01

    Full Text Available Introduction: Sexual dimorphisms in biological structures such as brain and behaviour have been widely recognized in animals and humans. The purpose of this study was to examine whether there are sex differences in the size of the cerebellum with other body traits, such as the head, tail and brain.Methods:Twelve grasscutters comprising of 6 males and 6 females were used in this study. Each brain was extracted from the skull by standard procedures and the mean values of the weights, dimensions and volumes of the brain, cerebellum, head and tail were compared in male and female using quantitative analytical statistical method.Results:The results showed that the absolute mean brain weight and volume obtained in the male was slightly higher than that of the female, while the cerebellar mean weight was slightly higher in the female; although these values were not statistically significant (P> 0.05. The mean cerebellar lengths and widths did not differ between the two sexes (> 0.05, but the mean cerebellar circumference in the male was statistically higher than in the female (P< 0.05. The female cerebellar length was positively correlated with the length of the brain, head, body and tail.Discussion:In conclusion, the brain weight was slightly higher in the male than female, while the cerebellar weight was higher in the female than male. The significantly higher value of the cerebellar circumference in the male may partly be responsible for the big round head seen in the live male grasscutter.

  12. Metabolic changes of prefrontal cerebral lobe ,white matter and cerebellum in patients with post-stroke depression A proton magnetic resonance spectroscopy study

    Institute of Scientific and Technical Information of China (English)

    Qinggang Xu; Hong Cao; Qingwei Song; Jianlin Wu

    2008-01-01

    BACKGROUND:Proton magnetic resonance spectroscopy(1H-MRS)non-invasively detects changes in chemical substances in the brain,which reflects the pathological metabolism.OBJECTIVE:To investigate changes in N-acetyl-aspartate(NAA),choline(Cho),creatine(Cr),and myoinositol(MI)in the gray and white matter of cerebral prefrontal lobe and cerebellum of patients with differential degrees of post-stroke depression(PSD)using 1H-MRS.DESIGN:A case control study.SETTING:The First Affiliated Hospital of the Dalian Medical University.PARTICIPANTS:A total of 38 patients with stroke(28 male and 10 female patients,aged 40 to 79 years)were selected from the Department of Neurology,1st Atfiliated Hospital,Dalian Medical University,from February to October in 2004.All subjects met the DSM-IV criteria for cerebrovascular disease and depression.The degree of depression was defined according to Hamilton criteria.38 patients with PSD were divided into two groups according to the time after ischemia,20 patients in the acute group with less than 10 days after ischemic attack(mild:16 patients,moderate/severe:4 patients)and 18 patients in the chronic group with more than 11 days after ischemic attack(mild:15 patients,moderate/severe:3 patients).Seventeen healthy volunteers with matching age from 41 to 80 years were examined as a control group.The study was approved by the Medical Ethics Committee of the University Medical Center Utrecht,and each participant signed an informed consent form.METHODS:Spectra were acquired by multi-voxel point-resolved spectroscopy(PRESS)sequence with GE signal.ST MP-di,localized in prefrontal cerebral lobe and cerebellum.Values of NAA,Cho,MI,and Cr ere compared between different graded PSD patients and control subjects with one-way analysis of variance in software SPSS11.5.MAIN OUTCOME MEASURES:Metabolite concentration in different brain regions of interest.Difference in metabolites between distinctly graded PSD patients and control subjects.Exclusion of age

  13. Hyperammonemia alters glycinergic neurotransmission and modulation of the glutamate-nitric oxide-cGMP pathway by extracellular glycine in cerebellum in vivo.

    Science.gov (United States)

    Cabrera-Pastor, Andrea; Taoro-Gonzalez, Lucas; Felipo, Vicente

    2016-05-01

    The glutamate-nitric oxide (NO)-cGMP pathway modulates some forms of learning. How glycine modulates this pathway is unclear. Glycine could modulate the pathway biphasically, enhancing its function through NMDA receptor activation or reducing it through glycine receptor activation. Chronic hyperammonemia impairs the glutamate-NO-cGMP pathway in the cerebellum and induces cognitive impairment. The possible alterations in hyperammonemia of glycinergic neurotransmission and of glutamate-NO-cGMP pathway modulation by glycine remain unknown. The aims were to assess, by in vivo microdialysis in cerebellum: (i) the effects of different glycine concentrations, administered through the microdialysis probe, on the glutamate-NO-cGMP pathway function; (ii) the effects of tonic glycine receptors activation on the pathway function, by blocking them with strychnine; (iii) whether hyperammonemia alters the pathway modulation by glycine; (iv) and whether hyperammonemia alters extracellular glycine concentration and/or glycine receptor membrane expression. In control rats, low glycine levels reduce the pathway function, likely by activating glycine receptors, while 20 μM glycine enhances the pathway function, likely by enhancing NMDA receptor activation. In hyperammonemic rats, glycine did not reduce the pathway function, but enhanced it when administered at 1-20 μM. Hyperammonemia reduces extracellular glycine concentration by approximately 50% and glycine receptor membrane expression. However, tonic glycine receptor activation seems to be enhanced in hyperammonemic rats, as indicated by the larger increase in extracellular cGMP induced by strychnine. These data show that glycine modulates the glutamate-NO-cGMP pathway biphasically and that hyperammonemia strongly alters glycinergic neurotransmission and modulation by glycine of the glutamate-NO-cGMP pathway. These alterations may contribute to the cerebellar aspects of cognitive alterations in hyperammonemia. The findings

  14. Structural deficits in the emotion circuit and cerebellum are associated with depression, anxiety and cognitive dysfunction in methadone maintenance patients: a voxel-based morphometric study.

    Science.gov (United States)

    Lin, Wei-Che; Chou, Kun-Hsien; Chen, Hsiu-Ling; Huang, Chu-Chung; Lu, Cheng-Hsien; Li, Shau-Hsuan; Wang, Ya-Ling; Cheng, Yu-Fan; Lin, Ching-Po; Chen, Chien-Chih

    2012-02-28

    Heroin users on methadone maintenance treatment (MMT) have elevated rates of co-morbid depression and are associated with have higher relapse rates for substance abuse. Structural abnormalities in MMT patients have been reported, but their impact on clinical performance is unknown. We investigated differences in gray matter volume (GMV) between 27 MMT patients and 23 healthy controls with voxel-based morphometry, and we correlated findings in the patients with Beck Depression Inventory scores, Beck Anxiety Inventory scores, and diminished cognitive functioning. MMT patients exhibited higher emotional deficits than healthy subjects. There was significantly smaller GMV in multiple cortices, especially in the left inferior frontal gyrus and left cerebellar vermis in the MMT group. The smaller GMV in the pre-frontal cortices, left sub-callosal cingulate gyrus, left post-central gyrus, left insula, and right cerebellar declive correlated with higher depression scores. The smaller GMV in the pre-frontal cortices, left sub-callosal cingulate gyrus, and left postcentral gyrus also correlated with higher anxiety scores, while smaller GMV in the cerebellum and bilateral insula was associated with impaired performance on tests of executive function. These results reveal that MMT patients have low GMV in brain regions that are hypothesized to influence cognition and emotion, and the GMV findings might be involved comorbid disorders in the MMT group. PMID:22386968

  15. A De Novo Mutation in the β-Tubulin Gene TUBB4A Results in the Leukoencephalopathy Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum

    Science.gov (United States)

    Simons, Cas; Wolf, Nicole I.; McNeil, Nathan; Caldovic, Ljubica; Devaney, Joseph M.; Takanohashi, Asako; Crawford, Joanna; Ru, Kelin; Grimmond, Sean M.; Miller, David; Tonduti, Davide; Schmidt, Johanna L.; Chudnow, Robert S.; van Coster, Rudy; Lagae, Lieven; Kisler, Jill; Sperner, Jürgen; van der Knaap, Marjo S.; Schiffmann, Raphael; Taft, Ryan J.; Vanderver, Adeline

    2013-01-01

    Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare hereditary leukoencephalopathy that was originally identified by MRI pattern analysis, and it has thus far defied all attempts at identifying the causal mutation. Only 22 cases are published in the literature to date. We performed exome sequencing on five family trios, two family quartets, and three single probands, which revealed that all eleven H-ABC-diagnosed individuals carry the same de novo single-nucleotide TUBB4A mutation resulting in nonsynonymous change p.Asp249Asn. Detailed investigation of one of the family quartets with the singular finding of an H-ABC-affected sibling pair revealed maternal mosaicism for the mutation, suggesting that rare de novo mutations that are initially phenotypically neutral in a mosaic individual can be disease causing in the subsequent generation. Modeling of TUBB4A shows that the mutation creates a nonsynonymous change at a highly conserved asparagine that sits at the intradimer interface of α-tubulin and β-tubulin, and this change might affect tubulin dimerization, microtubule polymerization, or microtubule stability. Consistent with H-ABC’s clinical presentation, TUBB4A is highly expressed in neurons, and a recent report has shown that an N-terminal alteration is associated with a heritable dystonia. Together, these data demonstrate that a single de novo mutation in TUBB4A results in H-ABC. PMID:23582646

  16. Modeling Spike-Train Processing in the Cerebellum Granular Layer and Changes in Plasticity Reveal Single Neuron Effects in Neural Ensembles

    Directory of Open Access Journals (Sweden)

    Chaitanya Medini

    2012-01-01

    Full Text Available The cerebellum input stage has been known to perform combinatorial operations on input signals. In this paper, two types of mathematical models were used to reproduce the role of feed-forward inhibition and computation in the granular layer microcircuitry to investigate spike train processing. A simple spiking model and a biophysically-detailed model of the network were used to study signal recoding in the granular layer and to test observations like center-surround organization and time-window hypothesis in addition to effects of induced plasticity. Simulations suggest that simple neuron models may be used to abstract timing phenomenon in large networks, however detailed models were needed to reconstruct population coding via evoked local field potentials (LFP and for simulating changes in synaptic plasticity. Our results also indicated that spatio-temporal code of the granular network is mainly controlled by the feed-forward inhibition from the Golgi cell synapses. Spike amplitude and total number of spikes were modulated by LTP and LTD. Reconstructing granular layer evoked-LFP suggests that granular layer propagates the nonlinearities of individual neurons. Simulations indicate that granular layer network operates a robust population code for a wide range of intervals, controlled by the Golgi cell inhibition and is regulated by the post-synaptic excitability.

  17. Metabolomic method: UPLC-q-ToF polar and non-polar metabolites in the healthy rat cerebellum using an in-vial dual extraction.

    Directory of Open Access Journals (Sweden)

    Amera A Ebshiana

    Full Text Available Unbiased metabolomic analysis of biological samples is a powerful and increasingly commonly utilised tool, especially for the analysis of bio-fluids to identify candidate biomarkers. To date however only a small number of metabolomic studies have been applied to studying the metabolite composition of tissue samples, this is due, in part to a number of technical challenges including scarcity of material and difficulty in extracting metabolites. The aim of this study was to develop a method for maximising the biological information obtained from small tissue samples by optimising sample preparation, LC-MS analysis and metabolite identification. Here we describe an in-vial dual extraction (IVDE method, with reversed phase and hydrophilic liquid interaction chromatography (HILIC which reproducibly measured over 4,000 metabolite features from as little as 3mg of brain tissue. The aqueous phase was analysed in positive and negative modes following HILIC separation in which 2,838 metabolite features were consistently measured including amino acids, sugars and purine bases. The non-aqueous phase was also analysed in positive and negative modes following reversed phase separation gradients respectively from which 1,183 metabolite features were consistently measured representing metabolites such as phosphatidylcholines, sphingolipids and triacylglycerides. The described metabolomics method includes a database for 200 metabolites, retention time, mass and relative intensity, and presents the basal metabolite composition for brain tissue in the healthy rat cerebellum.

  18. Calcium, potassium, iron, copper and zinc concentrations in the white and gray matter of the cerebellum and corpus callosum in brain of four genetic mouse strains

    International Nuclear Information System (INIS)

    In the central nervous system, metallic cations are involved in oligodendrocyte maturation and myelinogenesis. Moreover, the metallic cations have been associated with pathogenesis, particularly multiple sclerosis and malignant gliomas. The brain is vulnerable to either a deficit or an excess of available trace elements. Relationship between trace metals and myelinogenesis is important in understanding a severe human pathology : the multiple sclerosis, which remains without efficient treatment. One approach to understand this disease has used mutant or transgenic mice presenting myelin deficiency or excess. But to date, the concentration of trace metals and mineral elements in white and gray matter areas in wild type brain is unknown. The aim of this study is to establish the reference concentrations of trace metals (iron, copper and zinc) and minerals (potassium and calcium) in the white and gray matter of the mouse cerebellum and corpus callosum. The brains of four different genetic mouse strains (C57Black6/SJL, C57Black6/D2, SJL and C3H) were analyzed. The freeze-dried samples were prepared to allow PIXE (Proton-induced X-ray emission) and RBS (Rutherford backscattering spectrometry) analyses with the nuclear microprobe in Bordeaux. The results obtained give the first reference values. Furthermore, one species out of the fours testes exhibited differences in calcium, iron and zinc concentrations in the white matter

  19. Endurance training effects on 5-HT(1B) receptors mRNA expression in cerebellum, striatum, frontal cortex and hippocampus of rats.

    Science.gov (United States)

    Chennaoui, M; Drogou, C; Gomez-Merino, D; Grimaldi, B; Fillion, G; Guezennec, C Y

    2001-07-01

    The 5-HT(1B) receptors are the predominant auto- and heteroreceptors located on serotonergic and non-serotonergic terminals where they regulate the neuronal release of neurotransmitters. The present study investigated the effects of a 7 week period of physical training on the expression of cerebral 5-HT(1B) receptors by measuring corresponding mRNA levels in rat. Using RNase protection assay technique, we have observed no change in 5-HT(1B) receptor mRNA levels in the striatum and in the hippocampus after moderate as well as after intensive training. In contrast, a significant decrease in 5-HT(1B) receptor mRNA levels was observed in cerebellum of intensively trained rats. Moreover, in frontal cortex, a significant decrease in 5-HT(1B) receptors mRNA level occurred in both groups of trained rats. These data suggest the existence of regional differences in the effect of physical exercise on the expression of 5-HT(1B) receptors. PMID:11516568

  20. Effects of taurine depletion on cell migration and NCAM expression in cultures of dissociated mouse cerebellum and N2A cells

    DEFF Research Database (Denmark)

    Maar, T E; Lund, Trine Meldgaard; Gegelashvili, G;

    1998-01-01

    Cultures of dissociated cerebellum from 5- to 6-day-old mice as well as of the N2A neuronal cell line were exposed to guanidino ethane sulfonate (GES, 2-5 mM) to reduce the cellular taurine content. Control cultures were kept in culture medium or medium containing 2-5 mM GES plus 2-5 mM taurine to...... restore the intracellular taurine content. Taurine depletion led to changes in the expression of certain splice variants of NCAM mRNA such as the AAG and the VASE containing forms, while no differences were seen in the expression of the three forms of NCAM protein. In the N2A cells taurine depletion led...... to a decreased migration rate of the cells. The results suggest that the reduced migration rate of neurons caused by taurine depletion may be correlated to changes in expression of certain adhesion molecules such as NCAM. Moreover, taurine appears to be involved in regulation of transcription...

  1. Chronic hyperammonemia reduces the activity of neuronal nitric oxide synthase in cerebellum by altering its localization and increasing its phosphorylation by calcium-calmodulin kinase II.

    Science.gov (United States)

    El-Mlili, Nisrin; Rodrigo, Regina; Naghizadeh, Bahareh; Cauli, Omar; Felipo, Vicente

    2008-08-01

    Impaired function of the glutamate-nitric oxide-cGMP pathway contributes to cognitive impairment in hyperammonemia and hepatic encephalopathy. The mechanisms by which hyperammonemia impairs this pathway remain unclear. Understanding these mechanisms would allow designing clinical treatments for cognitive deficits in hepatic encephalopathy. The aims of this work were: (i) to assess whether chronic hyperammonemia in vivo alters basal activity of neuronal nitric oxide synthase (nNOS) in cerebellum and/or its activation in response to NMDA receptor activation and (ii) to analyse the molecular mechanisms by which hyperammonemia induces these alterations. It is shown that hyperammonemia reduces both basal activity of nNOS and its activation following NMDA receptor activation. Reduced basal activity is because of increased phosphorylation in Ser847 (by 69%) which reduces basal activity of nNOS by about 40%. Increased phosphorylation of nNOS in Ser847 is because of increased activity of calcium-calmodulin-dependent protein kinases (CaMKII) which in turn is because of increased phosphorylation at Thr286. Inhibiting CaMKII with KN-62 normalizes phosphorylation of Ser847 and basal NOS activity in hyperammonemic rats, returning to values similar to controls. Reduced activation of nNOS in response to NMDA receptor activation in hyperammonemia is because of altered subcellular localization of nNOS, with reduced amount in post-synaptic membranes and increased amount in the cytosol. PMID:18498443

  2. Calcium, potassium, iron, copper and zinc concentrations in the white and gray matter of the cerebellum and corpus callosum in brain of four genetic mouse strains

    Science.gov (United States)

    Sergeant, C.; Vesvres, M. H.; Devès, G.; Guillou, F.

    2005-04-01

    In the central nervous system, metallic cations are involved in oligodendrocyte maturation and myelinogenesis. Moreover, the metallic cations have been associated with pathogenesis, particularly multiple sclerosis and malignant gliomas. The brain is vulnerable to either a deficit or an excess of available trace elements. Relationship between trace metals and myelinogenesis is important in understanding a severe human pathology : the multiple sclerosis, which remains without efficient treatment. One approach to understand this disease has used mutant or transgenic mice presenting myelin deficiency or excess. But to date, the concentration of trace metals and mineral elements in white and gray matter areas in wild type brain is unknown. The aim of this study is to establish the reference concentrations of trace metals (iron, copper and zinc) and minerals (potassium and calcium) in the white and gray matter of the mouse cerebellum and corpus callosum. The brains of four different genetic mouse strains (C57Black6/SJL, C57Black6/D2, SJL and C3H) were analyzed. The freeze-dried samples were prepared to allow PIXE (Proton-induced X-ray emission) and RBS (Rutherford backscattering spectrometry) analyses with the nuclear microprobe in Bordeaux. The results obtained give the first reference values. Furthermore, one species out of the fours testes exhibited differences in calcium, iron and zinc concentrations in the white matter.

  3. Hypomyelination with atrophy of the basal ganglia and cerebellum: case report Hipomielinização com atrofia dos núcleos da base e do cerebelo: relato de caso

    OpenAIRE

    André Palma da Cunha Matta; Márcia Cristina Antunes Ribas

    2007-01-01

    Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare disease that has been recently described. It must be remembered as a possible etiology of leukoencephalopathies in children. We describe a typical case of H-ABC in a 11-month-old boy. He presents with global development delay, oral dyskinesia, and global dystonia and spasticity. Magnetic resonance imaging disclosed typical features of H-ABC and clinical laboratory tests were all negative. A slow neurological de...

  4. Autistic-Like Behaviors, Oxidative Stress Status, and Histopathological Changes in Cerebellum of Valproic Acid Rat Model of Autism Are Improved by the Combined Extract of Purple Rice and Silkworm Pupae

    Directory of Open Access Journals (Sweden)

    Nartnutda Morakotsriwan

    2016-01-01

    Full Text Available Due to the crucial role of oxidative stress on the pathophysiology of autism and the concept of synergistic effect, the benefit of the combined extract of purple rice and silkworm pupae (AP1 for autism disorder was the focus. Therefore, we aimed to determine the effect of AP1 on autistic-like behaviors, oxidative stress status, and histopathological change of cerebellum in valproic acid (VPA rat model of autism. VPA was injected on postnatal day (PND 14 and the animals were orally given AP1 at doses of 50, 100, and 200 mg·kg−1 BW between PND 14 and PND 40. The autism-like behaviors were analyzed via hot-plate, rotarod, elevated plus-maze, learning, memory, and social behavior tests. Oxidative stress and the histological change in the cerebellum were assessed at the end of study. AP1 treated rats improved behaviors in all tests except that in hot-plate test. The improvement of oxidative stress and Purkinje cell loss was also observed in the cerebellum of VPA-treated rats. Our data suggest that AP1 partially reduced autism-like behaviors by improving oxidative stress and Purkinje cell loss. Further research is required to identify the active ingredients in AP1 and gender difference effect.

  5. Autistic-Like Behaviors, Oxidative Stress Status, and Histopathological Changes in Cerebellum of Valproic Acid Rat Model of Autism Are Improved by the Combined Extract of Purple Rice and Silkworm Pupae.

    Science.gov (United States)

    Morakotsriwan, Nartnutda; Wattanathorn, Jintanaporn; Kirisattayakul, Woranan; Chaisiwamongkol, Kowit

    2016-01-01

    Due to the crucial role of oxidative stress on the pathophysiology of autism and the concept of synergistic effect, the benefit of the combined extract of purple rice and silkworm pupae (AP1) for autism disorder was the focus. Therefore, we aimed to determine the effect of AP1 on autistic-like behaviors, oxidative stress status, and histopathological change of cerebellum in valproic acid (VPA) rat model of autism. VPA was injected on postnatal day (PND) 14 and the animals were orally given AP1 at doses of 50, 100, and 200 mg·kg(-1) BW between PND 14 and PND 40. The autism-like behaviors were analyzed via hot-plate, rotarod, elevated plus-maze, learning, memory, and social behavior tests. Oxidative stress and the histological change in the cerebellum were assessed at the end of study. AP1 treated rats improved behaviors in all tests except that in hot-plate test. The improvement of oxidative stress and Purkinje cell loss was also observed in the cerebellum of VPA-treated rats. Our data suggest that AP1 partially reduced autism-like behaviors by improving oxidative stress and Purkinje cell loss. Further research is required to identify the active ingredients in AP1 and gender difference effect. PMID:27034733

  6. Transient elevation of element contents as a result of neuronal death in mutant-mice cerebellum studied by neutron activation analysis

    International Nuclear Information System (INIS)

    Accumulation of some metals, in particular iron or manganese, has long been considered to trigger or accentuate neurodegenerative processes in humans. The two most frequently cited examples are Parkinson's and Alzheimer diseases, where excitotoxic processes lead to neuronal death. However, these neuropathies are somewhat unsuitable for investigating the time course of the metal accumulation because the applied analytical methods such as neutron activation analysis (NAA) are invasive. Hence, only one measurement can be made after the patient's death. Animal models of Parkinson's type neurodegeneration, such as mice mutants, are more suitable as a larger number of animals can be investigated at various postnatal ages. In this study we used one type of mice mutants weaver, where primary neurodegeneration is principally confined to the cerebellum and centred in time around the postnatal age of six days. Elemental composition of brain segments with dry mass as low as 0.5 mg, which were isolated from weaver and wild type (normal) mice were investigated using a combination of INAA and RNAA. Elevated concentration of the following elements Fe, Zn, Cu, K, Na, Rb, and Br that were observed in the weaver's cerebella closely followed the time course of neurodegeneration documented for this type of mutant. The transient elevation of these elements never preceded the onset of neurodegeneration but closely mirrored its time course reaching its peak on the sixth day. The concentration of these elements in the weaver's cerebella declined afterwards to converge on the elemental time course observed in the wild type mice. In conclusion, metal and other elemental elevation observed in the cerebella of these mutants are an expression of neurodegenerative processes rather than its precondition. (author)

  7. Neuropsychiatric aspects of the cerebellum

    OpenAIRE

    Xavier, S.; Ferreira, B

    2012-01-01

    As funções neurológicas do cerebelo na regulação do equilíbrio e do movimento são conhecidas desde há longa data. No entanto, nas últimas décadas, a partir dos estudos seminais de Schmahmann, tem sido progressivamente reconhecida a sua participação em processos cognitivos e emocionais e no comportamento. As autoras pretendem rever de forma sumária os principais aspectos da fisiologia “clássica” do cerebelo. Serão depois revistas mais detalhadamente as funções neu...

  8. Effects of differential postnatal exposure of the rat cerebellum to x-rays on spatial discrimination learning as a function of age and position preference

    International Nuclear Information System (INIS)

    The aim of the present research was to analyze the effects of postnatal exposure of the cerebellum to x-irradiation on the use of proprioceptive feedback in spatial learning. A total of 337 naive male Long-Evans hooded rats were assigned at birth to one of four treatments: 12-15x, 4-5x, 4-15x and control. Subjects assigned to the 12-15x treatment were exposed to 200R at 12 and 13 days of age, and to 150R at 15 days of age. The subjects exposed to the 4-5x schedule received 200R on days 4 and 5. The 4-15x subjects are exposed to 200R on days 4 and 5, and to 150R on days 7, 9, 11, 13, 15. Subjects from each treatment started spatial discrimination testing in a T-shaped water maze at 30 to 31, 60 to 63, or 180 to 185 days of age. A preference effect was evident in the control, 12-15x and 4-5x subjects, but not in the 4-15x subjects during acquisition testing. Those control, 12-15x and 4-5x subjects trained against their preference made more errors and required more trials to attain acquisition criterion than did those subjects trained toward their preference. The absence of a position preference in the 4-15x subjects is attributed to the absence of the mossy fiber channel of input to the Purkinje cells in this preparation. Deficits in spatial learning were evident in both the 12-15x and 4-15x subjects, the former differing significantly from control subjects and the latter from the 4-5x subjects in the number of trials needed to complete reversal testing and/or the number of errors made during this phase of the testing. It is the upper portion of the molecular layer, absent in the 12-15x and 4-15x preparations, which receives afferent input from the spinal cord

  9. Exposure to altered gravity during specific developmental periods differentially affects growth, development, the cerebellum and motor functions in male and female rats

    Science.gov (United States)

    Nguon, K.; Ladd, B.; Sajdel-Sulkowska, E. M.

    2006-01-01

    We previously reported that perinatal exposure to hypergravity affects cerebellar structure and motor coordination in rat neonates. In the present study, we explored the hypothesis that neonatal cerebellar structure and motor coordination may be particularly vulnerable to the effects of hypergravity during specific developmental stages. To test this hypothesis, we compared neurodevelopment, motor behavior and cerebellar structure in rat neonates exposed to 1.65 G on a 24-ft centrifuge during discrete periods of time: the 2nd week of pregnancy [gestational day (G) 8 through G15; group A], the 3rd week of pregnancy (G15 through birth on G22/G23; group B), the 1st week of nursing [birth through postnatal day (P) 6; group C], the 2nd and 3rd weeks of nursing (P6 through P21; group D), the combined 2nd and 3rd weeks of pregnancy and nursing (G8 through P21; group E) and stationary control (SC) neonates (group F). Prenatal exposure to hypergravity resulted in intrauterine growth retardation as reflected by a decrease in the number of pups in a litter and lower average mass at birth. Exposure to hypergravity immediately after birth impaired the righting response on P3, while the startle response in both males and females was most affected by exposure during the 2nd and 3rd weeks after birth. Hypergravity exposure also impaired motor functions, as evidenced by poorer performance on a rotarod; while both males and females exposed to hypergravity during the 2nd and 3rd weeks after birth performed poorly on P21, male neonates were most dramatically affected by exposure to hypergravity during the second week of gestation, when the duration of their recorded stay on the rotarod was one half that of SC males. Cerebellar mass was most reduced by later postnatal exposure. Thus, for the developing rat cerebellum, the postnatal period that overlaps the brain growth spurt is the most vulnerable to hypergravity. However, male motor behavior is also affected by midpregnancy exposure to

  10. Brain perfusion ratios by 99mTc HMPAO SPECT utilizing a mean value of the visual cortex to the cerebellum ratio derived from normal subjects

    International Nuclear Information System (INIS)

    Aim: Previous results shows that the cerebellum (CER) is the best reference to calculate relative indexes of perfusion (IP) by brain SPECT. However, it can not be used on patients with bilateral cerebellar hypoperfusion. In such cases visual cortex (VC) or an average of the whole brain activity is recommended (WB). VC and WB are less reliable than CER, making it difficult to compare SPECT scans that have been normalized with different values. Materials and Methods: To overcome this difficulty, we developed a method to calculate IP utilizing a reference value defined as (VC / ), where is the mean value of the VC/CER ratio derived from a normal database which was assumed to be constant. We called the value VC/ the 'Pseudocerebellum' (PCER). For clinical validation, we first tested statistically the VC/CER ratio on a group of 60 [99mTc]-HMPAO SPECT scans of 20 normal subjects and 40 neurological patients with positive SPECT but without involvement of VC and CER. To demonstrate that IPPCER approx. IPCER, we calculated the mean value of the absolute differences CER - IPPCER vertical bar> on two groups of scans from subjects without involvement of VC and CER: 10 normal subjects (GI); and 40 patients (GII). Finally, using an indirect procedure the method was tested on a third group of SPECT scans of 30 patients with bilateral cerebellar hypoperfusion (G III). Results: The VC/CER ratio was approximately constant with gender and age at a 95% confidence level; CER - IPPCER vertical bar> was 1.22%±0.35 and 1.20%±0.42 for GI and GII, respectively. This is less than the within-subject replicability of the HMPAO SPECT studies; and thus demonstrated by an indirect approach that IPPCER is a valid procedure by which to evaluate relative perfusion on patients with bilateral cerebellar hypoperfusion and quantitatively comparable to using CER as reference region. Conclusion: The VC/CER ratio has very little inter-subject variability in individuals where these regions are not

  11. Maternal exposure of rats to nicotine via infusion during gestation produces neurobehavioral deficits and elevated expression of glial fibrillary acidic protein in the cerebellum and CA1 subfield in the offspring at puberty

    International Nuclear Information System (INIS)

    Maternal smoking during pregnancy is known to be a significant contributor to developmental neurological health problems in the offspring. In animal studies, nicotine treatment via injection during gestation has been shown to produce episodic hypoxia in the developing fetus. Nicotine delivery via mini osmotic pump, while avoiding effects due to hypoxia-ischemia, it also provides a steady level of nicotine in the plasma. In the present study timed-pregnant Sprague-Dawley rats (300-350 g) were treated with nicotine (3.3 mg/kg, in bacteriostatic water via s.c. implantation of mini osmotic pump) from gestational days (GD) 4-20. Control animals were treated with bacteriostatic water via s.c. implantation of mini osmotic pump. Offspring on postnatal day (PND) 30 and 60, were evaluated for changes in the ligand binding for various types of nicotinic acetylcholine receptors and neuropathological alterations. Neurobehavioral evaluations for sensorimotor functions, beam-walk score, beam-walk time, incline plane and grip time response were carried out on PND 60 offspring. Beam-walk time and forepaw grip time showed significant impairments in both male and female offspring. Ligand binding densities for [3H]epibatidine, [3H]cytisine and [3H]α-bungarotoxin did not show any significant changes in nicotinic acetylcholine receptors subtypes in the cortex at PND 30 and 60. Histopathological evaluation using cresyl violet staining showed significant decrease in surviving Purkinje neurons in the cerebellum and a decrease in surviving neurons in the CA1 subfield of hippocampus on PND 30 and 60. An increase in glial fibrillary acidic protein (GFAP) immuno-staining was observed in cerebellum white matter as well as granular cell layer of cerebellum and the CA1 subfield of hippocampus on PND 30 and 60 of both male and female offspring. These results indicate that maternal exposure to nicotine produces significant neurobehavioral deficits, a decrease in the surviving neurons and an

  12. Differential Effects of Ethanol on c-Jun N-Terminal Kinase, 14-3-3 Proteins, and Bax in Postnatal Day 4 and Postnatal Day 7 Rat Cerebellum

    OpenAIRE

    Heaton, Marieta Barrow; Paiva, Michael; Kubovic, Stacey; Kotler, Alexandra; Rogozinski, Jonathan; Swanson, Eric; Madorsky, Vladimir; Posados, Michelle

    2011-01-01

    These studies investigated ethanol effects on upstream cellular elements and interactions which contribute to Bax-related apoptosis in neonatal rat cerebellum at ages of peak ethanol sensitivity (postnatal day 4 [P4]), compared to later ages of relative resistance (P7). Analyses were made of basal levels of the pro-apoptotic c-jun N-termimal kinase (JNK), Bax, and the 14-3-3 anchoring proteins, as well as the responsiveness of these substances to ethanol at P4 versus P7. Dimerization of Bax w...

  13. Studies on improvement of diagnosis of neurosurgical lesions by magnetic resonance imaging (MRI), 3; Quantitative evaluation of atrophy of the brain stem and cerebellum on the sagittal view of MRI: normal change due to aging and usefulness of MRI in the diagnosis of cerebellar atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Kotoyuki (Kagoshima Univ. (Japan). Faculty of Medicine)

    1989-05-01

    Fourteen patients with spinocerebellar degeneration (SCD) and 97 healthy volunteers were examined by magnetic resonance imaging (MRI) using inversion recovery technique. According to clinical symptoms and disease course, SCD was divided into late cortical cerebellar atrophy (LCCA) and olivo-ponto-cerebellar atrophy (OPCA). To evaluate atrophic changes in the cerebellum and brain stem with aging, healthy volunteers were divided into four age groups. Parameters measured were: the cerebellar vermis, hemisphere, peduncle, pons and medulla, and the fourth ventricle. In the control group, atrophied vermis and peduncle of the cerebellum, and dilated fourth ventricle were observed with aging. A statistically significant atrophy in all of the parameters for the brain stem and cerebellum was observed in the group of SCD, as compared with the control group. The atrophy was restricted to the cerebellum for LCCA; and was observed in both the cerebellum and brain stem for OPCA. The size of the cerebellar hemisphere (H), as calculated as the product of the major and minor axes, was useful in the quantitative evaluation of atrophy of the cerebellar hemisphere. The ratio of H value to the anterior-posterior diameter of the pons was useful in the differentiation between LCCA and OPCA. (N.K.).

  14. Evidence for oxidative stress in the developing cerebellum of the rat after chronic mild carbon monoxide exposure (0.0025% in air

    Directory of Open Access Journals (Sweden)

    Lopez Ivan A

    2009-05-01

    Full Text Available Abstract Background The present study was designed to test the hypothesis that chronic very mild prenatal carbon monoxide (CO exposure (25 parts per million subverts the normal development of the rat cerebellar cortex. Studies at this chronic low CO exposure over the earliest periods of mammalian development have not been performed to date. Pregnant rats were exposed chronically to CO from gestational day E5 to E20. In the postnatal period, rat pups were grouped as follows: Group A: prenatal exposure to CO only; group B: prenatal exposure to CO then exposed to CO from postnatal day 5 (P5 to P20; group C: postnatal exposure only, from P5 to P20, and group D, controls (air without CO. At P20, immunocytochemical analyses of oxidative stress markers, and structural and functional proteins were assessed in the cerebellar cortex of the four groups. Quantitative real time PCR assays were performed for inducible (iNOS, neuronal (nNOS, and endothelial (eNOS nitric oxide synthases. Results Superoxide dismutase-1 (SOD1, SOD2, and hemeoxygenase-1 (HO-1 immunoreactivity increased in cells of the cerebellar cortex of CO-exposed pups. INOS and nitrotyrosine immunoreactivity also increased in blood vessels and Purkinje cells (PCs of pups from group-A, B and C. By contrast, nNOS immunoreactivity decreased in PCs from group-B. Endothelial NOS immunoreactivity showed no changes in any CO-exposed group. The mRNA levels for iNOS were significantly up-regulated in the cerebellum of rats from group B; however, mRNA levels for nNOS and eNOS remained relatively unchanged in groups A, B and C. Ferritin-H immunoreactivity increased in group-B. Immunocytochemistry for neurofilaments (structural protein, synapsin-1 (functional protein, and glutamic acid decarboxylase (the enzyme responsible for the synthesis of the inhibitory neurotransmitter GABA, were decreased in groups A and B. Immunoreactivity for two calcium binding proteins, parvalbumin and calbindin, remained

  15. The role of the cerebellum in auditory processing using the SSI test A participação do cerebelo no processamento auditivo com o uso do teste SSI

    Directory of Open Access Journals (Sweden)

    Patricia Maria Sens

    2011-10-01

    Full Text Available The Synthetic Sentence Identification (SSI test assesses central auditory pathways by measuring auditory and visual sensitivity and testing selective attention. Cerebellum activation in auditory attention and sensorial activity modulation have already been described. Assessing patients with cerebellar lesions alone using the SSI test can confirm the role of the cerebellum in auditory processing. AIM: To evaluate the role of the cerebellum in auditory processing in individuals with normal hearing and in those with chronic cerebellum lesions, using the SSI test. MATERIALS AND METHODS: Cross-sectional cohort study. A study group comprising 18 patients with chronic cerebellar lesion and a control group of 20 healthy individuals were assessed. The SSI test was applied in an Ipsilateral Competitive Message (ICM and Contralateral Competitive Message (CCM modes. To compare the results between groups, we used the chi-square test for qualitative variables. RESULTS: A statistically significant difference was found between the study and control groups using the ICM mode of the SSI test (p=0.035, but not in the CCM mode (p=0.083. CONCLUSION: The results on the SSI confirmed cerebellar participation in auditory processing in individuals with chronic cerebellar lesions and in those with normal hearing assessed in this study.O teste de Identificação de Sentenças Sintéticas (SSI avalia as vias centrais da audição utilizando a sensibilidade auditiva e visual e testando a atenção seletiva. A ativação do cerebelo na atenção auditiva, assim como na modulação da atividade sensorial, já é descrita. Avaliar pacientes com lesão exclusiva do cerebelo por meio do teste SSI pode confirmar ou refutar a hipótese da participação do cerebelo no processamento auditivo. OBJETIVO: Avaliar pelo teste SSI a participação do cerebelo no processamento auditivo, em indivíduos com lesão crônica do cerebelo e audição normal. MATERIAL E MÉTODOS: Estudo coorte

  16. Autoradiographic localization of binding sites for [3H] γ-aminobutyrate, [3H] muscimol, (+) [3H] bicuculline methiodide and [3H] flunitrazepam in cultures of rat cerebellum and spinal cord

    International Nuclear Information System (INIS)

    Cultures of rat cerebellum and spinal cord were used to visualize sites for [3H]γ-aminobutyrate, [3H]muscimol, [3H]bicuculline methiodide and [3H] flunitrazepam by autoradiography. In cerebellar cultures, many large neurons (presumably Purkinje cells) and interneurons were labelled. In spinal cord cultures, these compounds were mainly bound to small and medium-sized neurons, whereas the majority of large neurons were unlabelled. No binding sites for these radioligands were found on glial cells. Binding of [3H]γ-aminobutyrate, [3H]muscimol and [3H]bicuculline methiodide was markedly reduced or inhibited by adding unlabelled γ-aminobutyrate, muscimol and bicuculline (10-3M) respectively to the incubation medium. Addition of a thienobenzazepine markedly reduced binding with [3H]flunitrazepam. It is concluded that tissues cultures are an excellent tool to visualize the cellular localization of binding sites for neurotransmitters and drugs using autoradiography. (author)

  17. Differential effects of chronic hyperammonemia on modulation of the glutamate-nitric oxide-cGMP pathway by metabotropic glutamate receptor 5 and low and high affinity AMPA receptors in cerebellum in vivo.

    Science.gov (United States)

    Cabrera-Pastor, Andrea; Llansola, Marta; Reznikov, Vitaliy; Boix, Jordi; Felipo, Vicente

    2012-07-01

    Previous studies show that chronic hyperammonemia impairs learning ability of rats by impairing the glutamate-nitric oxide (NO)-cyclic guanosine mono-phosphate (cGMP) pathway in cerebellum. Three types of glutamate receptors cooperate in modulating the NO-cGMP pathway: metabotropic glutamate receptor 5 (mGluR5), (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartic acid (NMDA) receptors. The aim of this work was to assess whether hyperammonemia alters the modulation of this pathway by mGluR5 and AMPA receptors in cerebellum in vivo. The results support that in control rats: (1) low AMPA concentrations (0.1mM) activate nearly completely Ca(2+)-permeable (glutamate receptor subunit 2 (GluR2)-lacking) AMPA receptors and the NO-cGMP pathway; (2) higher AMPA concentrations (0.3 mM) also activate Ca(2+)-impermeable (GluR2-containing) AMPA receptors, leading to activation of NMDA receptors and of NO-cGMP pathway. Moreover, the data support that chronic hyperammonemia: (1) reduces glutamate release and activation of the glutamate-NO-cGMP pathway by activation of mGluR5; (2) strongly reduces the direct activation by AMPA receptors of the NO-cGMP pathway, likely due to reduced entry of Ca(2+) through GluR2-lacking, high affinity AMPA receptors; (3) strongly increases the indirect activation of the NO-cGMP pathway by high affinity AMPA receptors, likely due to increased entry of Na(+) through GluR2-lacking AMPA receptors and NMDA receptors activation; (4) reduces the indirect activation of the NO-cGMP pathway by low affinity AMPA receptors, likely due to reduced activation of NMDA receptors. PMID:22521775

  18. Roles of the NMDA Receptor and EAAC1 Transporter in the Modulation of Extracellular Glutamate by Low and High Affinity AMPA Receptors in the Cerebellum in Vivo: Differential Alteration in Chronic Hyperammonemia.

    Science.gov (United States)

    Cabrera-Pastor, Andrea; Taoro, Lucas; Llansola, Marta; Felipo, Vicente

    2015-12-16

    The roles of high- and low-affinity AMPA receptors in modulating extracellular glutamate in the cerebellum remain unclear. Altered glutamatergic neurotransmission is involved in neurological alterations in hyperammonemia, which differently affects high- and low-affinity AMPA receptors. The aims were to assess by in vivo microdialysis (a) the effects of high- and low-affinity AMPA receptor activation on extracellular glutamate in the cerebellum; (b) whether chronic hyperammonemia alters extracellular glutamate modulation by high- and/or low-affinity AMPA receptors; and (c) the contribution of NMDA receptors and EAAC1 transporter to AMPA-induced changes in extracellular glutamate. In control rats, high affinity receptor activation does not affect extracellular glutamate but increases glutamate if NMDA receptors are blocked. Low affinity AMPA receptor activation increases transiently extracellular glutamate followed by reduction below basal levels and return to basal values. The reduction is associated with transient increased membrane expression of EAAC1 and is prevented by blocking NMDA receptors. Blocking NMDA receptors with MK-801 induces a transient increase in extracellular glutamate which is associated with reduced membrane expression of EAAC1 followed by increased membrane expression of the glutamate transporter GLT-1. Chronic hyperammonemia does not affect responses to activation of low affinity AMPA receptors. Activation of high affinity AMPA receptors increases extracellular glutamate in hyperammonemic rats by an NMDA receptor-dependent mechanism. In conclusion, these results show that there is a tightly controlled interplay between AMPA and NMDA receptors and an EAAC1 transporter in controlling extracellular glutamate. Hyperammonemia alters high- but not low-affinity AMPA receptors. PMID:26428532

  19. Aplicações da ultra-sonografia tridimensional na avaliação do cerebelo fetal Three-dimensional ultrasonography in the evaluation of the fetal cerebellum

    Directory of Open Access Journals (Sweden)

    Edward Araujo Júnior

    2007-06-01

    Full Text Available Nos últimos anos a ultra-sonografia tridimensional tem-se tornado um método de imagem de grande importância no diagnóstico em obstetrícia. Um de seus benefícios seria a maior sensibilidade, em relação ao ultra-som bidimensional, no diagnóstico de algumas malformações fetais. As potenciais aplicações desse novo método seriam uma maior acurácia na medida do volume de órgãos fetais, a possibilidade de rever volumes na ausência da paciente, a possibilidade de utilizar diferentes planos para avaliar determinada estrutura anatômica e a capacidade de transmissão de volumes para centros de referência. A avaliação ultra-sonográfica do cerebelo fetal é de extrema importância, pois, comprovadamente, alterações no seu desenvolvimento estão correlacionadas com alterações do crescimento fetal e anomalias congênitas. O objetivo desta atualização é demonstrar os métodos VOCAL™ e 3D XI™ na avaliação do cerebelo fetal, seus potenciais benefícios e o que há de mais atual na literatura a respeito deste assunto.For the last years three-dimensional ultrasonography has become an imaging diagnosis method of great importance in obstetrics. One of its advantages would be the higher sensitivity compared with two-dimensional ultrasound in the diagnosis of some fetal malformations. The potential applications of this new method would be an improved accuracy in the measurement of fetal organs, the possibility of reviewing volumes in the absence of the patient, and using different planes to assess specific anatomical structures, as well as the capacity to transfer data files to remote reference centers. Ultrasonographic evaluation of fetal cerebellum is particularly important, since developmental alterations are correlated with the fetal growth alterations and congenital anomalies. The objective of this updating is to demonstrate the VOCAL™ and 3D XI™ methods in the evaluation of the fetal cerebellum, their potential benefits

  20. Observation and Nursing of Microsurgical Treatment for Entity Hemangioblastoma in Cerebellum%显微手术治疗小脑内成血管细胞瘤的观察及护理

    Institute of Scientific and Technical Information of China (English)

    赵欣; 陈静; 曹立

    2012-01-01

    Objective To explore the nursing of microsurgical treatment of the entity hemangioblastoma in cerebellum. Methods The clinical data of 24 cases with microsurgical treatment of the entity hemangioblastoma in cerebellum were retrospectively analyzed to summarize the clinical nursing experience. Results Of the 24 patients,21 developed single tumor:8 in the left cerebellar hemisphere and 13 in right;3 developed multiple tumors:2-4 tumor nodules, in the cerebellar hemisphere and cerebellopontine arm. All patients received microsurgery tumor resection completely and the postoperative symptoms were improved and no death occurred. Conclusion Intensive observation and nursing of such patients in the perioperative period can significantly increase the success rate of surgery, reduce complications, promote the rehabilitation process and improve the life quality.%目的 探讨显微手术治疗小脑内成血管细胞瘤的护理.方法 回顾性分析经显微手术治疗的24例小脑内成血管细胞瘤患者的临床资料,总结临床护理经验.结果 24例患者中,肿瘤单发21例:分布于左侧小脑半球8例,右侧小脑半球13例;小脑内多发3例,有2~4个瘤结节,分布于小脑半球以及桥小脑臂.所有患者均行显微手术完全切除肿瘤,术后症状均完全改善,无一例死亡.结论 加强小脑内成血管细胞瘤患者的围术期观察与护理,对提高手术成功率、减少并发症、促进患者康复、提高患者的生活质量具有重要意义.

  1. Behavior Cognition Computational Model Based on Cerebellum and Basal Ganglia Mechanism%基于小脑-基底神经节机理的行为认知计算模型

    Institute of Scientific and Technical Information of China (English)

    陈静; 阮晓钢; 戴丽珍

    2012-01-01

    针对智能体的行为认知问题,提出一种小脑与基底神经节相互协调的行为认知计算模型.该模型核心为操作条件学习算法,包括评价机制、行为选择机制、取向机制及小脑与基底神经节的协调机制.初期的学习信号来自于下橄榄体和黑质两部分,在熵的意义上说明该算法是收敛的.采用该学习方法为自平衡两轮机器人建立运动神经认知系统,利用RBF网络逼近行为和评价网络.仿真实验表明该方法改善仅有基底神经节作用的行为-评价算法学习速度慢和失败次数多的问题,学习后期通过温度的不断降低,加快学习速度,震荡逐渐消失,改善学习效果.%Aiming at agent' s behavioral cognition problem, a behavior cognition computational model based on the coordination of cerebellum and basal ganglia is proposed. Operant conditioning learning algorithm is the central algorithm including evaluation mechanism, action selection mechanism, tropism mechanism, and the coordination mechanism between cerebellum and basal ganglia. The learning signals come from not only the Inferior Olive but also the Substantia Nigra in the beginning. The convergence of the algorithm can be guaranteed in the sense of entropy. With the proposed method, a motor nerve cognitive system for the self-balancing two-wheeled robot has been built using the RBF neural network as the actor and evaluation function approximator. The simulation results show that the learning speed is increased as well as the failure times are reduced by the proposed method than by the Actor-Critic method with the only Basal Ganglia mechanism. Through decreasing temperature in the late stage, the learning speed is increased and the vibration disappeares eventually, and the learning effect is improved.

  2. Redox Status and Neuro Inflammation Indexes in Cerebellum and Motor Cortex of Wistar Rats Supplemented with Natural Sources of Omega-3 Fatty Acids and Astaxanthin: Fish Oil, Krill Oil, and Algal Biomass.

    Science.gov (United States)

    Polotow, Tatiana G; Poppe, Sandra C; Vardaris, Cristina V; Ganini, Douglas; Guariroba, Maísa; Mattei, Rita; Hatanaka, Elaine; Martins, Maria F; Bondan, Eduardo F; Barros, Marcelo P

    2015-10-01

    Health authorities worldwide have consistently recommended the regular consumption of marine fishes and seafood to preserve memory, sustain cognitive functions, and prevent neurodegenerative processes in humans. Shrimp, crabs, lobster, and salmon are of particular interest in the human diet due to their substantial provision of omega-3 fatty acids (n-3/PUFAs) and the antioxidant carotenoid astaxanthin (ASTA). However, the optimal ratio between these nutraceuticals in natural sources is apparently the key factor for maximum protection against most neuro-motor disorders. Therefore, we aimed here to investigate the effects of a long-term supplementation with (n-3)/PUFAs-rich fish oil, ASTA-rich algal biomass, the combination of them, or krill oil (a natural combination of both nutrients) on baseline redox balance and neuro-inflammation indexes in cerebellum and motor cortex of Wistar rats. Significant changes in redox metabolism were only observed upon ASTA supplementation, which reinforce its antioxidant properties with a putative mitochondrial-centered action in rat brain. Krill oil imposed mild astrocyte activation in motor cortex of Wistar rats, although no redox or inflammatory index was concomitantly altered. In summary, there is no experimental evidence that krill oil, fish oil, oralgal biomass (minor variation), drastically change the baseline oxidative conditions or the neuro-inflammatory scenario in neuromotor-associated rat brain regions. PMID:26426026

  3. Redox Status and Neuro Inflammation Indexes in Cerebellum and Motor Cortex of Wistar Rats Supplemented with Natural Sources of Omega-3 Fatty Acids and Astaxanthin: Fish Oil, Krill Oil, and Algal Biomass

    Directory of Open Access Journals (Sweden)

    Tatiana G. Polotow

    2015-09-01

    Full Text Available Health authorities worldwide have consistently recommended the regular consumption of marine fishes and seafood to preserve memory, sustain cognitive functions, and prevent neurodegenerative processes in humans. Shrimp, crabs, lobster, and salmon are of particular interest in the human diet due to their substantial provision of omega-3 fatty acids (n-3/PUFAs and the antioxidant carotenoid astaxanthin (ASTA. However, the optimal ratio between these nutraceuticals in natural sources is apparently the key factor for maximum protection against most neuro-motor disorders. Therefore, we aimed here to investigate the effects of a long-term supplementation with (n-3/PUFAs-rich fish oil, ASTA-rich algal biomass, the combination of them, or krill oil (a natural combination of both nutrients on baseline redox balance and neuro-inflammation indexes in cerebellum and motor cortex of Wistar rats. Significant changes in redox metabolism were only observed upon ASTA supplementation, which reinforce its antioxidant properties with a putative mitochondrial-centered action in rat brain. Krill oil imposed mild astrocyte activation in motor cortex of Wistar rats, although no redox or inflammatory index was concomitantly altered. In summary, there is no experimental evidence that krill oil, fish oil, oralgal biomass (minor variation, drastically change the baseline oxidative conditions or the neuro-inflammatory scenario in neuromotor-associated rat brain regions.

  4. Modulatory effects of N-acetylcysteine on cerebral cortex and cerebellum regions of ageing rat brain Efectos moduladores de la N-acetilcisteína sobre la corteza cerebral y las regiones cerebelosas sobre la del cerebro senescente de rata

    Directory of Open Access Journals (Sweden)

    S. Singh Kanwar

    2007-02-01

    Full Text Available Oxidative stress has been implicated in brain ageing and in age-related neurodegenerative disorders. Since Nacetylcysteine (NAC has recently been shown to prevent oxidative damage in ageing brain, we have examined the effects of this thiolic antioxidant on the age associated oxidative stress related parameters in rat brain regions. The lipid peroxide formation, reduced glutathione (GSH content along with the activities of superoxide dismutase (SOD and catalase were determined in the cerebral cortex and cerebellum brain regions of the young (4 months and older (14 months female rats. The lipid peroxidation was observed to be increased in the cerebral cortex regions accompanied by simultaneous decrease in the GSH content in both the regions of older rats. The SOD activity was reduced in both the regions while catalase was reduced only in cerebellum region of the older rats. Following NAC supplementation (160 mg/kg. b. wt./ day, lipid peroxidation was observed to be reduced which was accompanied by enhanced GSH levels, along with enhanced SOD and catalase in both the brain regions of older rats. Further, in the younger rats the NAC treatment resulted in the decrease of lipid peroxidation in both the regions that was accompanied by the increase catalase activity in cerebral cortex region along with increase in GSH content and SOD in cerebellum regions. Our result suggests that the normal brain ageing is associated with the decrease in antioxidative defense status and the supplementation of thiol antioxidants like NAC may prove helpful in managing the age related brain disorders characterized by compromised antioxidative defense systems.El estrés oxidativo se ha implicado en el envejecimiento cerebral y en los trastornos neurodegenerativos asociados con la edad. Puesto que recientemente se ha demostrado que la N-acetilcisteína (NAC previene el daño oxidativo en el cerebro senescente, hemos explorado los efectos de este antioxidante tiólico sobre

  5. Cerebellum and motor learning, motor memory and motor integration: morphology and distribution of neuropeptide Y neurons in rat cerebellar cortex%大鼠小脑皮质内神经肽Y能神经元的形态与分布小脑的运动学习、记忆及整合功能

    Institute of Scientific and Technical Information of China (English)

    王省; 孙银平; 蔡新华

    2005-01-01

    BACKGROUND: Neuropeptide Y (NPY) neurons are extensively located in various brain regions such as cerebral cortex, caudate-putamen nucleus, syslimbic system, thalamus and brain stem. They are also involved in various brain activities such as motor learning, motor memory and motor integration. Considering the fact that cerebellum can reorganize through motor learning, we tried to identify the morphology and distribution of NPY neurons in rat's cerebellar cortex to obtain the morphologic knowledge that is related to its cerebellar-cortex-based motor learning.OBJECTIVE: To investigate the morphology and distribution of NPY -immunoreactive neurons in rat's cerebellar cortex, and discuss the relationship between NPY neurons and cerebellum motor learning and motor memory.DESIGN: A single-sample-study based on animal samples.SETTING: Anatomy Department, Pathophysiology Department and Morphology Center in Xinxiang Medical College.MATERIALS: From July to December 2001, the experiment was performed at the Morphology Center in Xinxiang Medical College. Ten Sprague-Dawley (SD) rats, clean grade, regardless of their gender and weighing 100-200 g,were selected.METHODS: After intraperitoneal injection anesthesia and ascending aorta infusion fixation, the cerebellum was taken out by craniosurgery. The cerebellum was immersed in the same fixative fluid for duration of 48 hours, and then was embedded in paraffin. The next step was to make continuous sagittal sections. NPY neurons were identified by SP immunohistochemical staining, using rats cerebral section as the positive control. In the negative control, the first antibody replaced by Bovine Calf Serum(BCS), and the second antibody replaced by 0.01 mol/L PBS. Sequentially the light-microscopic observation and micrography were recorded.MAIN OUTCOME MEASUREMENTS: The Morphology and distribution of NPY neurons in rat's cerebellar cortex were taken as main outcome measurements.RESULTS: NPY-immunoreactive neurons were distributed in

  6. The change of pathology and expression of caspase-3 in cerebral cortex and hippocampus and cerebellum of alcoholism rats%大鼠酒精中毒后大脑皮质、海马、小脑的病理学改变及caspase-3的异常表达

    Institute of Scientific and Technical Information of China (English)

    贾明月; 朱丹; 陈嘉峰

    2012-01-01

    目的 探讨大鼠慢性酒精中毒后大脑皮质、海马、小脑的病理学改变及caspase-3的异常表达.方法 选用健康雄性Wistar大鼠随机分为两组,其中酒精中毒组30只;盐水对照组20只.酒精中毒组每日每只大鼠分别按8ml/kg灌胃2w,随后再按照10ml/kg灌胃1w,按12ml/kg灌胃1w,共灌胃4w.每日灌胃两次,其间隔均为6h,酒精浓度为50%.对照组用等量的生理盐水灌胃.并对两组大鼠进行体重、一般生物学特征、HE染色、TUNEL染色、免疫组化caspase-3的检测.结果 造模成功后,两组大鼠的体重存在的统计学差异;HE染色后酒精组大鼠大脑皮质、海马、小脑锥体细胞数目减少,部分神经元变性、坏死;TUNEL法测定酒精组大鼠凋亡细胞数量明显多于对照组(P<0.05),酒精组大鼠大脑皮质、海马、小脑的caspase-3表达明显高于对照组(P<0.05).结论 慢性酒精中毒可引起大鼠大脑皮质、海马及小脑的病理学改变,出现神经细胞凋亡,引起与凋亡相对应部位caspase-3阳性表达,并参与大鼠酒精中毒后凋亡机制的发生、发展.%Objective To discuse the change of pathology and expression of caspase-3 in cerebral cortex, hippocampus and cerebellum of alcoholism rats. Methods There were 50 male healthy Wistar rats divided into 2 groups randomly, alcoholism group,30 rats,saline control group,20 rats. Alcoholic group;every rat was fed with 8ml/kg50% alcohol twice a day, and two weeks later, increased to 10ml/kg for one week, then 12ml/kg for one week. The interval of time was 6 hours of all. Control group: every rat was fed with the same dosage of 0.9% sodium chloride at the same time for four weeks. During the experiment, we measured their weight, observed their general condition, HE dyes, TUNEL dying and expression of caspase-3 by SP dying method. Results After 4 weeks,the alcoholic group rats appeared malnutrition,emaciated,moreover,some also appeared the performance of

  7. Expression changes of DSCAM in the cerebellum of APPtransgenic mice%唐氏综合征黏附分子(DSCAM)在APP转基因阳性小鼠小脑内的表达变化及其意义

    Institute of Scientific and Technical Information of China (English)

    贾永林; 景黎君; 鲁晶晶; 韩瑞; 王淑阳; 彭涛; 贾延劼

    2011-01-01

    目的 研究唐氏综合征细胞黏附分子(DSCAM)在β-淀粉样蛋白前体蛋白(APP)转基因小鼠脑内的表达变化规律,初步探讨其意义.方法 选择月龄分别为新生、1个月、3个月、6个月和12个月的APP转基因阳性和阴性小鼠,应用免疫组化和免疫荧光法对全脑切片进行染色,观察DSCAM在APP转基因阳性小鼠脑内的表达,特别是在小脑内的表达部位及表达量的变化规律.结果 DSCAM主要在APP转基因阳性模型小鼠小脑中的浦肯野细胞、大脑皮层、海马安蒙氏角(Ammon's horn)的锥体细胞、海马齿状回的颗粒细胞层、丘脑及脑干神经元中表达.新生小鼠和1个月小鼠DSCAM的小脑表达量无明显差异(P>0.05),1月龄小鼠小脑内的表达量较3月龄小鼠低(P<0.05),到达3个月时,其表达量达到高峰,6个月时,DSCAM的表达量和3个月时无明显差异(P>0.05),12月龄的小鼠小脑内的DSCAM的表达量较6月龄低(P<0.05).在3个月和6个月时,DSCAM在APP转基因阳性小鼠小脑中的表达量明显高于同龄阴性小鼠(P<0.05).结论 DSCAM在一定月龄APP转基因阳性小鼠小脑内存在过度表达,推测DSCAM作为一种黏附分子,其过度表达在APP小鼠的学习运动能力和运动协调能力的缺陷中可能起重要作用.%[Objective] To investigate the changing regularity of the Down Syndrome Cell Adhesion Molecule (DSCAM) expression in the brain of amyloid precursor protein (APP) transgenic mice and explore the significance of DSCAM expression. [ Methods ] With immunohistochemistry and immumofluorescence, the expression of DSCAM in the brains of APP positive transgenic mice (neonate, aged lm, 3m, 6m, 12m), especially the expression pattern of location and strength in cerebellum, was detected. The control groups were APP negative mice (neonate, aged lm, 3m, 6m, 12m). [Results] We had found that DSCAM widely expressed in the cerebellar purkinje cell, the cerebral cortex, the hippocampal

  8. Imprints of Dyslexia: Implicit Learning and the Cerebellum

    OpenAIRE

    Goldberg, N

    2014-01-01

    Dyslexia, a learning disability affecting reading and spelling, occurs in 3-10% of the general population. For many people diagnosed early in life the symptoms of dyslexia persist into adulthood causing them difficulties with functioning in the modern society so much reliant on the written word. This dissertation assesses the manifestations of developmental dyslexia in behavior, cognition and neuroanatomy as predicted by the procedural deficit hypothesis. According to the theory, a dysfunctio...

  9. Mathematical Modeling of Neuro-Vascular Coupling in Rat Cerebellum

    DEFF Research Database (Denmark)

    Rasmussen, Tina

    Activity in the neurons called climbing fibers causes blood flow changes. But the physiological mechanisms which mediate the coupling are not well understood. This PhD thesis investigates the mechanisms of neuro-vascular coupling by means of mathematical methods. In experiments, the extracellularly....... Mathematical arguments as well as hypotheses about the physiological system have been used to construct the models....... measured field potential is used as an indicator of neuronal activity, and the cortical blood flow is measured by means of laser-Doppler flowmetry. Using system identification methods, these measurements have been used to construct and validate parametric mathematical models of the neuro-vascular system...

  10. Ethanol Neurotoxicity in the Developing Cerebellum: Underlying Mechanisms and Implications

    OpenAIRE

    Ambrish Kumar; LaVoie, Holly A.; DiPette, Donald J; Singh, Ugra S.

    2013-01-01

    Ethanol is the main constituent of alcoholic beverages that exerts toxicity to neuronal development. Ethanol affects synaptogenesis and prevents proper brain development. In humans, synaptogenesis takes place during the third trimester of pregnancy, and in rodents this period corresponds to the initial few weeks of postnatal development. In this period neuronal maturation and differentiation begin and neuronal cells start migrating to their ultimate destinations. Although the neuronal develop...

  11. The role of the cerebellum in multiple sclerosis

    DEFF Research Database (Denmark)

    Weier, Katrin; Banwell, Brenda; Cerasa, Antonio;

    2015-01-01

    In multiple sclerosis (MS), cerebellar signs and symptoms as well as cognitive dysfunction are frequent and contribute to clinical disability with only poor response to symptomatic treatment. The current consensus paper highlights the broad range of clinical signs and symptoms of MS patients, which...

  12. Modeling neuro-vascular coupling in rat cerebellum

    DEFF Research Database (Denmark)

    Rasmussen, Tina; Holstein-Rathlou, Niels-Henrik; Lauritzen, Martin

    2009-01-01

    linearizability. We exercised the model on data from rat cerebellar cortex. In anesthetized rats, stimulation of the inferior olive caused climbing fiber activity and blood flow changes. Field potential amplitudes were used as an indicator of neuronal activity and blood flow was measured by laser...

  13. Radially expanding transglial calcium waves in the intact cerebellum

    OpenAIRE

    Hoogland, Tycho M; Kuhn, Bernd; Göbel, Werner; Huang, Wenying; Nakai, Junichi; HELMCHEN, Fritjof; Flint, Jane; Wang, Samuel S.-H.

    2009-01-01

    Multicellular glial calcium waves may locally regulate neural activity or brain energetics. Here, we report a diffusion-driven astrocytic signal in the normal, intact brain that spans many astrocytic processes in a confined volume without fully encompassing any one cell. By using 2-photon microscopy in rodent cerebellar cortex labeled with fluorescent indicator dyes or the calcium-sensor protein G-CaMP2, we discovered spontaneous calcium waves that filled approximately ellipsoidal domains of ...

  14. Volumetric Analysis of Regional Variability in the Cerebellum of Children with Dyslexia

    OpenAIRE

    Fernandez, Vindia G.; Stuebing, Karla; Juranek, Jenifer; Fletcher, Jack M.

    2013-01-01

    Cerebellar deficits and subsequent impairment in procedural learning may contribute to both motor difficulties and reading impairment in dyslexia. We used quantitative magnetic resonance imaging to investigate the role of regional variation in cerebellar anatomy in children with single-word decoding impairments (N=23), children with impairment in fluency alone (N=8), and typically developing children (N=16). Children with decoding impairments (dyslexia) demonstrated no statistically significa...

  15. The neurotoxic effects of artemether on the cytoarchitecture of the cerebellum of adult male wistar rats

    International Nuclear Information System (INIS)

    In a 70kg adult man, artemether is given at a total dosage of 480mg for five days in the treatment of malarial. Using t-test analysis technique at 95% confidence interval i.e t < 0.05 and P - value = 2.26, no significant difference was observed between the average brain and cerebellar weight, the average width of cerebellar cortical layers, the density and the average size of Purkinje Cells in the control groups C1 and C2 and the experimental group E. In the present study, there were no gross or morphological differences between the two groups of animals (control and experimental groups) on day 7 at the completion of experimental procedure. A significant statistical increase in average body weight was observed in the control groups C1 (which received only standard diet and water) and C2 (which received 1.23mg/kg body weight of normal saline intramuscularly in addition to standard diet and water) from 140 + 19.65g on day 1 to 146 + 19.90g on day 7 and 151 + 12.0g on day 1 to 156.2 + 12.2g on Day 7 respectively. There was a non-statistically significant apparent reduction in body weight in the experimental group E, (which received intramuscular injection of 1.23mg/kg body weight of artemether), from 160 + 9.0g on day 1 to 157.4 + 8.0g on day 7. The rats in the control groups CI and C2 displayed normal balance and co-ordination, while rats in the experimental group E, showed abnormalities of balance and co-ordination. This study investigated the effects of corresponding 1.23mg/kg body weight of artemether for a period of seven days on the functions of rats after drug administration. (author)

  16. Brain classification reveals the right cerebellum as the best biomarker of dyslexia

    Directory of Open Access Journals (Sweden)

    Demonet Jean

    2009-06-01

    Full Text Available Abstract Background Developmental dyslexia is a specific cognitive disorder in reading acquisition that has genetic and neurological origins. Despite histological evidence for brain differences in dyslexia, we recently demonstrated that in large cohort of subjects, no differences between control and dyslexic readers can be found at the macroscopic level (MRI voxel, because of large variances in brain local volumes. In the present study, we aimed at finding brain areas that most discriminate dyslexic from control normal readers despite the large variance across subjects. After segmenting brain grey matter, normalizing brain size and shape and modulating the voxels' content, normal readers' brains were used to build a 'typical' brain via bootstrapped confidence intervals. Each dyslexic reader's brain was then classified independently at each voxel as being within or outside the normal range. We used this simple strategy to build a brain map showing regional percentages of differences between groups. The significance of this map was then assessed using a randomization technique. Results The right cerebellar declive and the right lentiform nucleus were the two areas that significantly differed the most between groups with 100% of the dyslexic subjects (N = 38 falling outside of the control group (N = 39 95% confidence interval boundaries. The clinical relevance of this result was assessed by inquiring cognitive brain-based differences among dyslexic brain subgroups in comparison to normal readers' performances. The strongest difference between dyslexic subgroups was observed between subjects with lower cerebellar declive (LCD grey matter volumes than controls and subjects with higher cerebellar declive (HCD grey matter volumes than controls. Dyslexic subjects with LCD volumes performed worse than subjects with HCD volumes in phonologically and lexicon related tasks. Furthermore, cerebellar and lentiform grey matter volumes interacted in dyslexic subjects, so that lower and higher lentiform grey matter volumes compared to controls differently modulated the phonological and lexical performances. Best performances (observed in controls corresponded to an optimal value of grey matter and they dropped for higher or lower volumes. Conclusion These results provide evidence for the existence of various subtypes of dyslexia characterized by different brain phenotypes. In addition, behavioural analyses suggest that these brain phenotypes relate to different deficits of automatization of language-based processes such as grapheme/phoneme correspondence and/or rapid access to lexicon entries.

  17. Role of Neurotrophins in Mediating the Effect of Altered Gravity on the Developing Rat Cerebellum.

    Science.gov (United States)

    Sajdel-Sulkowska, Elizabeth

    We previously reported that perinatal exposure to hypergravity resulted in oxidative stress that may contribute to the decrease in Purkinje cell number and the impairment of motor coordination in hypergravity-exposed rat neonates. However, the increase in oxidative stress markers was not uniformly observed in males and females. In the present study we explored the possibility that exposure to hypergravity may result in altered level of neurotrophins, which have been recognized as mediators of both neurodegenerative and neuroprotective mechanisms in the central nervous system. An elevation of neurotrophin-3 (NT-3) has been observed in animal models of hypoxia. To test this hypothesis we compared cerebellar levels of NT-3 between stationary control (SC) and rat neonates exposed perinatally to 1.65 G on a 24-ft centrifuge. The levels of NT-3 were determined by specific ELISA. Preliminary data suggests a 123

  18. Oligodendrocyte ablation affects the coordinated interaction between granule and Purkinje neurons during cerebellum development

    International Nuclear Information System (INIS)

    Oligodendrocytes (OLs) are the glial cells of the central nervous system (CNS) classically known to be devoted to the formation of myelin sheaths around most axons of the vertebrate brain. We have addressed the role of these cells during cerebellar development, by ablating OLs in vivo. Previous analyses had indicated that OL ablation during the first six postnatal days results into a striking cerebellar phenotype, whose major features are a strong reduction of granule neurons and aberrant Purkinje cells development. These two cell types are highly interconnected during cerebellar development through the production of molecules that help their proliferation, differentiation and maintenance. In this article, we present data showing that OL ablation has major effects on the physiology of Purkinje (PC) and granule cells (GC). In particular, OL ablation results into a reduction of sonic hedgehog (Shh), Brain Derived Neurotrophic Factor (BDNF), and Reelin (Rln) expression. These results indicate that absence of OLs profoundly alters the normal cerebellar developmental program

  19. Coenzyme Q10 Levels Are Decreased in the Cerebellum of Multiple-System Atrophy Patients

    OpenAIRE

    Schottlaender, Lucia V.; Bettencourt, Conceição; Kiely, Aoife P.; Chalasani, Annapurna; Neergheen, Viruna; Holton, Janice L.; Hargreaves, Iain; Houlden, Henry

    2016-01-01

    Background The objective of this study was to evaluate whether the levels of coenzyme Q10 (CoQ10) in brain tissue of multiple system atrophy (MSA) patients differ from those in elderly controls and in patients with other neurodegenerative diseases. Methods Flash frozen brain tissue of a series of 20 pathologically confirmed MSA patients [9 olivopontocerebellar atrophy (OPCA) type, 6 striatonigral degeneration (SND) type, and 5 mixed type] was used for this study. Elderly controls (n = 37) as ...

  20. Periconception Maternal Folate Status and Human Embryonic Cerebellum Growth Trajectories : The Rotterdam Predict Study

    NARCIS (Netherlands)

    Koning, Irene V; Groenenberg, Irene A L; Gotink, Anniek W; Willemsen, Sten P; Gijtenbeek, Manon; Dudink, Jeroen; Go, Attie T J I; Reiss, Irwin K M; Steegers, Eric A P; Steegers-Theunissen, Régine P M

    2015-01-01

    We aimed to investigate whether periconceptional maternal folate status affects human embryonic cerebellar size and growth trajectories. In a prospective periconceptional cohort participants filled out questionnaires and received weekly transvaginal 3D-ultrasounds between 7+0 and 12+6 weeks gestatio

  1. Periconception Maternal Folate Status and Human Embryonic Cerebellum Growth Trajectories: The Rotterdam Predict Study.

    Directory of Open Access Journals (Sweden)

    Irene V Koning

    Full Text Available We aimed to investigate whether periconceptional maternal folate status affects human embryonic cerebellar size and growth trajectories. In a prospective periconceptional cohort participants filled out questionnaires and received weekly transvaginal 3D-ultrasounds between 7+0 and 12+6 weeks gestational age (GA. Viable non-malformed singleton pregnancies were selected for cerebellar measurements; transcerebellar diameter, (TCD, left and right cerebellar diameters (LCD, RCD. Linear mixed models were performed to estimate associations between questionnaire data on the timing of maternal folic acid supplement initiation and longitudinal cerebellar measurements as a function of crown-rump length (CRL and GA. Maternal red blood cell folate concentrations were analysed before 8 weeks GA to validate the associations. A total of 263 serial high quality three-dimensional ultrasound scans of 135 pregnancies were studied. Preconceptional compared to postconceptional initiation of folic acid use was associated with slightly larger cerebellar diameters per millimetre increase of CRL (TCD: β = 0.260mm, 95%CI = 0.023-0.491, p<0.05; LCD: β = 0.171mm, 95%CI = 0.038-0.305, p<0.05; RCD: β = 0.156mm, 95%CI = 0.032-0.280, p<0.05 and with proportional cerebellar growth (TCD/CRL:β = 0.015mm/mm, 95%CI = 0.005-0.024, p<0.01; LCD/CRL:β = 0.012mm/mm, 95%CI = 0.005-0.018, p<0.01; RCD/CRL:β = 0.011mm/mm, 95%CI = 0.005-0.017, p<0.01. Cerebellar growth was significantly highest in the third quartile of maternal red blood cell folate levels (1538-1813 nmol/L. These first findings show that periconceptional maternal folate status is associated with human embryonic cerebellar development. Implications of these small but significant variations for fetal cerebellar growth trajectories and the child's neurodevelopmental outcome are yet unknown and warrant further investigation.

  2. Transmembrane AMPA receptor regulatory proteins and AMPA receptor function in the cerebellum.

    OpenAIRE

    Coombs, I. D.; Cull-Candy, S. G.

    2009-01-01

    Heterogeneity among AMPA receptor (AMPAR) subtypes is thought to be one of the key postsynaptic factors giving rise to diversity in excitatory synaptic signaling in the CNS. Recently, compelling evidence has emerged that ancillary AMPAR subunits—the so-called transmembrane AMPA receptor regulatory proteins (TARPs)—also play a vital role in influencing the variety of postsynaptic signaling. This TARP family of molecules controls both trafficking and functional properties of AMPARs at most, if ...

  3. Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum

    Science.gov (United States)

    Lu, Ake T.; Hannon, Eilis; Levine, Morgan E.; Hao, Ke; Crimmins, Eileen M.; Lunnon, Katie; Kozlenkov, Alexey; Mill, Jonathan; Dracheva, Stella; Horvath, Steve

    2016-02-01

    DNA methylation (DNAm) levels lend themselves for defining an epigenetic biomarker of aging known as the `epigenetic clock'. Our genome-wide association study (GWAS) of cerebellar epigenetic age acceleration identifies five significant (Pepigenetic tissue age as endophenotype in GWAS.

  4. Biohybrid control of general linear systems using the adaptive filter model of cerebellum

    Directory of Open Access Journals (Sweden)

    Emma D. Wilson

    2015-07-01

    Full Text Available The adaptive filter model of the cerebellar microcircuit has been successfully applied to biological motor control problems such as the vestibulo-ocular reflex (VOR and to sensory processing problems such as the adaptive cancellation of reafferent noise. It has also been successfully applied to problems in robotics such as adaptive camera stabilisation and sensor noise cancellation. In previous applications to inverse control problems the algorithm was applied to the velocity control of a plant dominated by viscous and elastic elements. Naive application of the adaptive filter model to the displacement (as opposed to velocity control of this plant results in unstable learning and control. To be more generally useful in engineering problems it is essential to remove this restriction to enable the stable control of plants of any order. We address this problem here by developing a biohybrid model reference adaptive control (MRAC scheme, which stabilises the control algorithm for strictly proper plants. We evaluate the performance of this novel cerebellar inspired algorithm with MRAC scheme in the experimental control of a dielectric electroactive polymer, a class of artificial muscle. The results show that the augmented cerebellar algorithm is able to accurately control the displacement response of the artificial muscle. The proposed solution not only greatly extends the practical applicability of the cerebellar-inspired algorithm, but may also shed light on cerebellar involvement in a wider range of biological control tasks.

  5. Development and measurement of the transverse diameter of the fetal cerebellum by MRI

    OpenAIRE

    Farinha, Cristina; Tavares, Oscar

    2014-01-01

    A ressonância magnética fetal é um método eficaz na avaliação pré-natal da morfologia normal do cérebro e no diagnóstico de patologias do sistema nervoso central, sendo um importante complemento clínico à ecografia. O cerebelo é uma das estruturas menos afetadas em casos de restrição de crescimento fetal, tornando-se um bom indicador na avaliação do desenvolvimento fetal e da idade gestacional. Deste modo, a avaliação biométrica fetal é fundamental no diagnóstico pré-natal do desenvolvimento ...

  6. Lipoma do cerebelo: relato de caso Lipoma of the cerebellum: case report

    OpenAIRE

    Gisele A. Nai; Mario R Montenegro

    1997-01-01

    Lipomas intracranianos são raros, geralmente sendo achado de autópsia. Situam-se na linha média, mais frequentemente de localização central. Podem ocorrer desde a infância até a vida adulta. Muitos dos "lipomas", na verdade são associados a lesões hamartomatosas ou, mesmo, a neoplasias como os meduloblastomas do cerebelo. Relatamos e discutimos um caso de lipoma de cerebelo, achado de autópsia de um recém-nascido prematuro.Intracranial lipomas are rare. Usually they are incidental findings at...

  7. Role of cerebellum in motion perception and vestibulo-ocular reflex-similarities and disparities

    OpenAIRE

    Shaikh, A G; Palla, A; Marti, S.; Olasagasti, I.; Optican, L.M.; Zee, D S; Straumann, D.

    2013-01-01

    Vestibular velocity storage enhances the efficacy of the angular vestibulo-ocular reflex (VOR) during relatively low-frequency head rotations. This function is modulated by GABA-mediated inhibitory cerebellar projections. Velocity storage also exists in perceptual pathway and has similar functional principles as VOR. However, it is not known whether the neural substrate for perception and VOR overlap. We propose two possibilities. First, there is the same velocity storage for both VOR and per...

  8. Metabolic mapping of the rat cerebellum during delay and trace eyeblink conditioning

    OpenAIRE

    Plakke, Bethany; Freeman, John H.; Poremba, Amy

    2007-01-01

    The essential neural circuitry for delay eyeblink conditioning has been largely identified, whereas much of the neural circuitry for trace conditioning has not been identified. The major difference between delay and trace conditioning is a time gap between the presentation of the conditioned stimulus (CS) and the unconditioned stimulus (US) during trace conditioning. It is this time gap or trace interval which accounts for an additional memory component in trace conditioning. Additional neura...

  9. Deletion of Atoh1 disrupts Sonic Hedgehog signaling in the developing cerebellum and prevents medulloblastoma

    OpenAIRE

    Flora, Adriano; Klisch, Tiemo J.; Schuster, Gabriele; Zoghbi, Huda Y.

    2009-01-01

    Granule neuron precursors (GNPs) are the most actively proliferating cells in the post-natal nervous system and mutations in pathways controlling their cell cycle can result in medulloblastoma. The transcription factor Atoh1 has been suspected to contribute to GNP proliferation, but its role in normal and neoplastic post-natal cerebellar development remains unexplored. We show that Atoh1 regulates the signal transduction pathway of Sonic Hedgehog, an extracellular factor that is essential for...

  10. Signal processing by T-type calcium channel interactions in the cerebellum

    Science.gov (United States)

    Engbers, Jordan D. T.; Anderson, Dustin; Zamponi, Gerald W.; Turner, Ray W.

    2013-01-01

    T-type calcium channels of the Cav3 family are unique among voltage-gated calcium channels due to their low activation voltage, rapid inactivation, and small single channel conductance. These special properties allow Cav3 calcium channels to regulate neuronal processing in the subthreshold voltage range. Here, we review two different subthreshold ion channel interactions involving Cav3 channels and explore the ability of these interactions to expand the functional roles of Cav3 channels. In cerebellar Purkinje cells, Cav3 and intermediate conductance calcium-activated potassium (IKCa) channels form a novel complex which creates a low voltage-activated, transient outward current capable of suppressing temporal summation of excitatory postsynaptic potentials (EPSPs). In large diameter neurons of the deep cerebellar nuclei, Cav3-mediated calcium current (IT) and hyperpolarization-activated cation current (IH) are activated during trains of inhibitory postsynaptic potentials. These currents have distinct, and yet synergistic, roles in the subthreshold domain with IT generating a rebound burst and IH controlling first spike latency and rebound spike precision. However, by shortening the membrane time constant the membrane returns towards resting value at a faster rate, allowing IH to increase the efficacy of IT and increase the range of burst frequencies that can be generated. The net effect of Cav3 channels thus depends on the channels with which they are paired. When expressed in a complex with a KCa channel, Cav3 channels reduce excitability when processing excitatory inputs. If functionally coupled with an HCN channel, the depolarizing effect of Cav3 channels is accentuated, allowing for efficient inversion of inhibitory inputs to generate a rebound burst output. Therefore, signal processing relies not only on the activity of individual subtypes of channels but also on complex interactions between ion channels whether based on a physical complex or by indirect effects on membrane properties. PMID:24348329

  11. Purkinje cell NMDA receptors assume a key role in synaptic gain control in the mature cerebellum

    NARCIS (Netherlands)

    C. Piochon (Claire); C. Levenes (Carole); G. Ohtsuki (Gen); C.R.W. Hansel (Christian)

    2010-01-01

    textabstractA classic view in cerebellar physiology holds that Purkinje cells do not express functional NMDA receptors and that, therefore, postsynaptic NMDA receptors are not involved in the induction of long-term depression (LTD) at parallel fiber (PF) to Purkinje cell synapses. Recently, it has b

  12. Purkinje cell NMDA receptors assume a key role in synaptic gain control in the mature cerebellum

    OpenAIRE

    Piochon, Claire; Levenes, Carole; Ohtsuki, Gen; Hansel, Christian

    2010-01-01

    textabstractA classic view in cerebellar physiology holds that Purkinje cells do not express functional NMDA receptors and that, therefore, postsynaptic NMDA receptors are not involved in the induction of long-term depression (LTD) at parallel fiber (PF) to Purkinje cell synapses. Recently, it has been demonstrated that functional NMDA receptors are postsynaptically expressed at climbing fiber (CF) to Purkinje cell synapses in mice, reaching full expression levels at ∼2 months after birth. He...

  13. Myosin Va is developmentally regulated and expressed in the human cerebellum from birth to old age

    Directory of Open Access Journals (Sweden)

    C.C.R. Souza

    2013-02-01

    Full Text Available Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL. In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence.

  14. The role of basal ganglia and cerebellum in motor learning. A computational model

    OpenAIRE

    Senatore, Rosa

    2012-01-01

    2010 - 2011 Our research activity investigates the computational processes underlying the execution of complex sequences of movements and aims at understanding how different levels of the nervous system interact and contribute to the gradual improvement of motor performance during learning. Many research areas, from neuroscience to engineering, investigate, from different perspectives and for diverse purposes, the processes that allow humans to efficiently perform skilled movem...

  15. Neuroprotective effect of melatonin against ischemia/reperfusion-induced neuronal apoptosis in mouse cerebellum

    Institute of Scientific and Technical Information of China (English)

    Qiuhong Duan; Tao Lu; Yixiang Han; Zhiqiang Lu; Ximing Wang

    2007-01-01

    BACKGROUND: Some experiments have demonstrated that melatonin (N-aceyl-5-methoxytryptamine, Mel) has antioxidation. However, whether it has neuroprotective effect in the ischemia/reperfusion injury of central nervous system is unclear.OBJECTIVE: To observe the protective effect of Mel on ischemia/reperfusion-induced cerebellar neuronal apoptosis of rats, and the action mechanism. DESIGN: Controlled observation experiment.SETTING: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: Eight Sprague-Dawley rats aged 7-8 days and weighing 10-12 g were provided by Medical Experimental Animal Center, Tongji Medical College, Huazhong University of Science and Technology. Anti-cytochrome C monoclonal antibody was purchased from R & D Company; 7-dichlorodihydrofluorescein diacetate(DCFH-DA), rhodamine 123 and Mel were purchased from Sigma Company (USA). Lactate dehydrogenase (LDH) kit was purchased from Nanjing Jiancheng Bioengineering Institute.METHODS: This experiment was carried out in the laboratory for Department of Biochemistry and Molecule Biology, Tongji Medical College between October 2002 and March 2004. Cerebellar neurons of rats were cultured in vitro. After oxygen-glucose deprivation (OGD) for 90 minutes, 1×10-4, 1×10-6, 1×10-9 mol/L Mel was added, respectively, namely high-, middle-, and low-concentration Mel groups. Cells, which were cultured by OGD, served as model group, and control group, in which OGD intervention was omitted, was set. ①Cytochrome C level of mitochondrial cells in each group was detected by ELISA method. ②LDH activity in the cell culture fluid was measured, and cell membrane permeability change was analyzed. The cells in the Mel group with the lowest LDH activity served as Mel treatment group, I.e. Cells were cultured with OGD, and then Mel was added; Meanwhile, Mel prevention group was set, I.e. Mel was added before OGD. Intervention was not changed in the model group and control group. ③DNA level was analyzed and cell apoptosis was observed by agarose gel electrophoresis(AGE). ④Mitochondrial transmembrane potential of cells, and apoptotic way in each group were analyzed by confocal laser scanning microscopy.MAIN OUTCOME MEASURES: ①Mitochondrial cytochrome C level of cerebellar nerve cells. ②LDH activity of cerebellar nerve cells. ③DNA AGE results. ④Mitochondrial transmembrane potential change.RESULTS: ①Mitochondrial cytochrome C level of cerebellar nerve cells: cytochrome C was obviously released at 6 hours of OGD-reperfusion. Mel inhibited the release of cytochrome C in dose-dependent manner. ②LDH activity of cerebellar nerve cells: LDH activity (A value) was significantly lower in the high- and middle-concentration Mel groups than in the model group (P<0.05). LDH activity (A value) in the low-concentration Mel group was 0.415 0 + 0.012 9, indicating that Mel could decrease LDH activity of OGD-treated cell supernatant and promote membrane stablization in dose-dependent manner.③AGE results of DNA: 1×10-9 mol/L was considered as the best concentration of melatonin. Cell DNA was extracted for AGE. Results presented typical ladder shape, indicating apoptosis appeared, while apoptosis was lessened in the Mel treatment group and Mel prevention group.④Mitochondrial transmembrane potential change: Experimental results showed that green fluorescein was evenly distributed in cerebellar granule cells cultured normally, and the axons of neurons were very clear. The body of neurons was condensed and the axons disappeared after cerebellar granule cells undergoing OGD injury. Mel could compltetly reverse the effect of OGD.CONCLUSION:Mel can enhance crerbellar neuronal membrane stabilization of rats in dose-dependent manner,and suppress OGD-induced apoptosis of cerebellar granule cells by preventing against mitochondrial apoptosis.

  16. Non invasive blood flow measurement in cerebellum detects minimal hepatic encephalopathy earlier than psychometric tests

    OpenAIRE

    Felipo, Vicente; Urios, Amparo; Giménez-Garzó, Carla; Cauli, Omar; Andrés-Costa, Maria-Jesús; González, Olga; Serra, Miguel A; Sánchez-González, Javier; Aliaga, Roberto; Giner-Durán, Remedios; Belloch, Vicente; Montoliu Félix, Carmina

    2014-01-01

    AIM: To assess whether non invasive blood flow measurement by arterial spin labeling in several brain regions detects minimal hepatic encephalopathy.METHODS: Blood flow (BF) was analyzed by arterial spin labeling (ASL) in different brain areas of 14 controls, 24 cirrhotic patients without and 16 cirrhotic patients with minimal hepatic encephalopathy (MHE). Images were collected using a 3 Tesla MR scanner (Achieva 3T-TX, Philips, Netherlands). Pulsed ASL was performed. Patients showing MHE wer...

  17. The prominent role of the cerebellum in the learning, origin and advancement of culture

    OpenAIRE

    Vandervert, Larry

    2016-01-01

    Background Vandervert described how, in collaboration with the cerebral cortex, unconscious learning of cerebellar internal models leads to enhanced executive control in working memory in expert music performance and in scientific discovery. Following Vandervert’s arguments, it is proposed that since music performance and scientific discovery, two pillars of cultural learning and advancement, are learned through in cerebellar internal models, it is reasonable that additional if not all compon...

  18. Persistent Angiogenesis in the Autism Brain: An Immunocytochemical Study of Postmortem Cortex, Brainstem and Cerebellum

    Science.gov (United States)

    Azmitia, E. C.; Saccomano, Z. T.; Alzoobaee, M. F.; Boldrini, M.; Whitaker-Azmitia, P. M.

    2016-01-01

    In the current work, we conducted an immunocytochemical search for markers of ongoing neurogenesis (e.g. nestin) in auditory cortex from postmortem sections of autism spectrum disorder (ASD) and age-matched control donors. We found nestin labeling in cells of the vascular system, indicating blood vessels plasticity. Evidence of angiogenesis was…

  19. Monitoring the native phosphorylation state of plasma membrane proteins from a single mouse cerebellum

    DEFF Research Database (Denmark)

    Schindler, J.; Ye, J. Y.; Jensen, O. N.;

    2013-01-01

    metal affinity chromatography, and TiO2 were combined to a sequential extraction procedure prior to mass spectrometric analyses. This strategy resulted in the identification of 1501 different native phosphorylation sites in 507 different proteins. 765 (51%) of these phosphorylation sites were localized...

  20. The contribution of the cerebellum to cognition in Spinocerebellar Ataxia Type 6

    OpenAIRE

    Cooper, Freya E.; Manon Grube; Elsegood, Kelly J.; Welch, John L.; Kelly, Thomas P.; Chinnery, Patrick F; Griffiths, Timothy D

    2010-01-01

    This study sought evidence for a specific cerebellar contribution to cognition by characterising the cognitive phenotype of Spinocerebellar Ataxia Type 6 (SCA-6); an autosomal dominant genetic disease which causes a highly specific late-onset cerebellar degeneration. A comprehensive neuropsychological assessment was administered to 27 patients with genetically confirmed SCA-6. General intellectual ability, memory and executive function were examined using internationally standardised tests (W...

  1. Massive calcification in basal ganglia, thalamus and cerebellum caused by postoperative hypoparathyroidism

    International Nuclear Information System (INIS)

    The depicted case is of a 65 year old woman, who was admitted to hospital with complaints of excess sweating, dizziness and loss of consciousness. Symptomatic epilepsy was established after examination from a neurologist. A CT scan showed hyperdense symmetrical striation of the hemisphere of the small brain (parasagittal); symmetrical double-sided calcifications in the caudate nucleus, globus pallidus, thalamus and medial to the capsula interna; snake-like calcifications of the sulcus (occipital, parasagittai). Paraclinical tests have found hypocalcemia and hypoparathyroidism. Past illnesses: resection of the thyroid due to a nodose struma 20 years before. Key words: Calcifications in Basal Ganglia. Calcifications in the Cerebrum. Hypoparathyroidism

  2. Radiation induced cerebellum impairments in Swiss albino mice and its modulation by dietary Prunus domestica

    International Nuclear Information System (INIS)

    To study the biochemical, quantitative histopathological and behavioural changes after 5 Gy whole body irradiation and its modulation by supplementation of Prunus domestica extract (PDE) for 15 consecutive days on male Swiss albino. For this study healthy mice from an inbred colony were divided into five groups: (i) Control; (ii) PDE treated - mice in this group were orally supplemented with PDE (400 mg/kg body weight (bw)/day) once daily for 15 consecutive days; (iii) Irradiated-mice were whole body exposed to 5 Gy irradiated; (iv) PDE + irradiated-mice in this group were orally supplemented PDE for 15 days (once a day) prior to irradiation; and (v) irradiated+PDE -mice in this group were administered PDE orally for 15 days (once a day) consequently after irradiation. Marked radiation induced changes in the amount of cerebellar lipid peroxidation (LPO), glutathione (GSH), protein, superoxide dismutase (SOD), catalase and histopathological changes (molecular layer, granular layer and purkinje cell numbers) could be significantly ameliorated supplementation of PDE prior/post irradiation. Radiation induced deficits in learning and memory were also significantly ameliorated. PDE was found to have strong radical scavenging activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and also showed in vitro radioprotective activity. The result of present study showed that prior/post-supplementation of Prunus domestica has radioprotective potential as well as neuroprotective properties against the radiation. (author)

  3. GABAergic Neuron Specification in the Spinal Cord, the Cerebellum, and the Cochlear Nucleus

    OpenAIRE

    Kei Hori; Mikio Hoshino

    2012-01-01

    In the nervous system, there are a wide variety of neuronal cell types that have morphologically, physiologically, and histochemically different characteristics. These various types of neurons can be classified into two groups: excitatory and inhibitory neurons. The elaborate balance of the activities of the two types is very important to elicit higher brain function, because its imbalance may cause neurological disorders, such as epilepsy and hyperalgesia. In the central nervous system, inhi...

  4. Measurement by in vivo brain microdialysis of nitric oxide release in the rat cerebellum.

    OpenAIRE

    Shintani, F; Kanba, S; Nakaki, T; Sato, K.; Yagi, G; Kato, R; Asai, M

    1994-01-01

    Using a new method which combines a brain microdialysis technique and measurement of nitrite/nitrate levels by the Griess reaction, it has been proven that activation of N-methyl-D-aspartate (NMDA) receptors in the cerebelli of rats which had been under non-anesthetic and freely moving conditions induces the release of nitric oxide (NO). Since L-NG-monomethylarginine (L-NMMA), which competitively blocks NO synthesis from L-arginine, significantly inhibited the release of nitrite/nitrate from ...

  5. A novel approach to non-biased systematic random sampling: A stereologic estimate of Purkinje cells in the human cerebellum

    Science.gov (United States)

    Agashiwala, Rajiv M.; Louis, Elan D.; Hof, Patrick R.; Perl, Daniel P.

    2010-01-01

    Non-biased systematic sampling using the principles of stereology provides accurate quantitative estimates of objects within neuroanatomic structures. However, the basic principles of stereology are not optimally suited for counting objects that selectively exist within a limited but complex and convoluted portion of the sample, such as occurs when counting cerebellar Purkinje cells. In an effort to quantify Purkinje cells in association with certain neurodegenerative disorders, we developed a new method for stereologic sampling of the cerebellar cortex, involving calculating the volume of the cerebellar tissues, identifying and isolating the Purkinje cell layer and using this information to extrapolate non-biased systematic sampling data to estimate the total number of Purkinje cells in the tissues. Using this approach, we counted Purkinje cells in the right cerebella of four human male control specimens, aged 41, 67, 70 and 84 years, and estimated the total Purkinje cell number for the four entire cerebella to be 27.03, 19.74, 20.44 and 22.03 million cells, respectively. The precision of the method is seen when comparing the density of the cells within the tissue: 266,274, 173,166, 167,603 and 183,575 cells/cm3, respectively. Prior literature documents Purkinje cell counts ranging from 14.8 to 30.5 million cells. These data demonstrate the accuracy of our approach. Our novel approach, which offers an improvement over previous methodologies, is of value for quantitative work of this nature. This approach could be applied to morphometric studies of other similarly complex tissues as well. PMID:18725208

  6. Modulation of ERK1/2 and p38MAPK by lead in the cerebellum of Brazilian catfish Rhamdia quelen

    International Nuclear Information System (INIS)

    Lead (Pb2+) is a neurotoxic trace metal, widespread in aquatic environment that can change physiologic, biochemical and behavioral parameters in diverse fish species. Chemical exposure may drive modulation of mitogen-activated protein kinases (MAPKs) that are a family of highly conserved enzymes which comprise ubiquitous groups of signaling proteins playing critical regulatory roles in cell physiology. Extracellular signal-regulated kinases (ERK1/2) and p38MAPK control complex programs such as gene expression, embryogenesis, cell differentiation, cell proliferation, cell death and synaptic plasticity. Little information is available about MAPKs in aquatic organisms and their modulation by trace metals. The aim of this work was to determine the modulation of ERK1/2 and p38MAPK phosphorylation by Pb2+ in vivo and in vitro, in cerebellar slices of the catfish, Rhamdia quelen. In the in vitro model, slices were incubated for 3 h with lead acetate (1-10 μM). In the in vivo studies, the animals were exposed for 2 days to lead acetate (1 mg L-1). ERK1/2 and p38MAPK (total and phosphorylated forms) were immunodetected in cerebellar slices by Western blotting. Pb2+ added in vitro at 5 and 10 μM increased significantly the phosphorylation of both MAPKs. The in vivo exposed animals also showed a significant increase of ERK1/2 and p38MAPK phosphorylation without changes in the total content of the enzymes. In conclusion, the present work indicates that it is possible to evaluate the ERK1/2 and p38MAPK activation in the central nervous system (CNS) of a freshwater fish largely distributed in South America. Moreover, Pb2+, an important environmental pollutant may activate in vitro and in vivo ERK1/2 and p38MAPK enzymes. These findings are important considering the functional and ecologic implications associated to Pb2+ exposure of a freshwater fish species, such as R. quelen, and the roles of ERK1/2 and p38MAPK in the control of brain development, neuroplasticity and cell death

  7. Activity-dependent increases in local oxygen consumption correlate with postsynaptic currents in the mouse cerebellum in vivo

    DEFF Research Database (Denmark)

    Mathiesen, Claus; Caesar, Kirsten; Thomsen, Kirsten Engelund;

    2011-01-01

    metabolism via mitochondrial signaling, but whether this also occurs in the intact brain is unknown. Here we applied a pharmacological approach to dissect the effects of ionic currents and cytosolic Ca(2+) rises of neuronal origin on activity-dependent rises in CMRO(2). We used two-photon microscopy and...

  8. Genomic convergence analysis of schizophrenia: mRNA sequencing reveals altered synaptic vesicular transport in post-mortem cerebellum.

    Directory of Open Access Journals (Sweden)

    Joann Mudge

    Full Text Available Schizophrenia (SCZ is a common, disabling mental illness with high heritability but complex, poorly understood genetic etiology. As the first phase of a genomic convergence analysis of SCZ, we generated 16.7 billion nucleotides of short read, shotgun sequences of cDNA from post-mortem cerebellar cortices of 14 patients and six, matched controls. A rigorous analysis pipeline was developed for analysis of digital gene expression studies. Sequences aligned to approximately 33,200 transcripts in each sample, with average coverage of 450 reads per gene. Following adjustments for confounding clinical, sample and experimental sources of variation, 215 genes differed significantly in expression between cases and controls. Golgi apparatus, vesicular transport, membrane association, Zinc binding and regulation of transcription were over-represented among differentially expressed genes. Twenty three genes with altered expression and involvement in presynaptic vesicular transport, Golgi function and GABAergic neurotransmission define a unifying molecular hypothesis for dysfunction in cerebellar cortex in SCZ.

  9. Effects of cyclooxygenase inhibitor pretreatment on nitric oxide production, nNOS and iNOS expression in rat cerebellum

    OpenAIRE

    DiGirolamo, G; Farina, M.; Riberio, M L; Ogando, D; Aisemberg, J; de los Santos, A R; Martí, M L; Franchi, A. M.

    2003-01-01

    The therapeutic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is thought to be due mainly to its inhibition of cyclooxygenase (COX) enzymes, but there is a growing body of research that now demonstrates a variety of NSAIDs effects on cellular signal transduction pathways other than those involving prostaglandins.Nitric oxide (NO) as a free radical and an agent that gives rise to highly toxic oxidants (peroxynitrile, nitric dioxide, nitron ion), becomes a cause of neuronal damage and...

  10. Activity-dependent increases in local oxygen consumption correlate with postsynaptic currents in the mouse cerebellum in vivo

    DEFF Research Database (Denmark)

    Mathiesen, Claus; Caesar, Kirsten; Thomsen, Kirsten Engelund;

    2011-01-01

    Evoked neural activity correlates strongly with rises in cerebral metabolic rate of oxygen (CMRO(2)) and cerebral blood flow (CBF). Activity-dependent rises in CMRO(2) fluctuate with ATP turnover due to ion pumping. In vitro studies suggest that increases in cytosolic Ca(2+) stimulate oxidative...

  11. Activity-dependent increases in local oxygen consumption correlate with post-synaptic currents in the mouse cerebellum in vivo

    DEFF Research Database (Denmark)

    Mathiesen, Claus; Caesar, Kirsten; Thomsen, Kirsten Joan;

    2011-01-01

    Evoked neural activity correlates strongly with rises in cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow. Activity-dependent rises in CMRO2 fluctuate with ATP turnover due to ion pumping. In vitro studies suggest that increases in cytosolic Ca2+ stimulate oxidative metabolism via...

  12. Single session imaging of cerebellum at 7 tesla: Obtaining structure and function of multiple motor subsystems in individual subjects

    OpenAIRE

    Melissa A Batson; Natalia Petridou; Dennis W.J. Klomp; Maarten A Frens; Neggers, Sebastiaan F. W.

    2015-01-01

    textabstractThe recent increase in the use of high field MR systems is accompanied by a demand for acquisition techniques and coil systems that can take advantage of increased power and accuracy without being susceptible to increased noise. Physical location and anatomical complexity of targeted regions must be considered when attempting to image deeper structures with small nuclei and/or complex cytoarchitechtonics (i.e. small microvasculature and deep nuclei), such as the brainstem and the ...

  13. Participação do cerebelo no processamento auditivo Participation of the cerebellum in auditory processing

    OpenAIRE

    Patrícia Maria Sens; Clemente Isnard Ribeiro de Almeida

    2007-01-01

    O cerebelo era tradicionalmente visto como um órgão coordenador da motricidade, entretanto é atualmente considerado como um importante centro de integração de sensibilidades e coordenação de várias fases do processo cognitivo. OBJETIVO: é sistematizar as informações da literatura quanto à participação do cerebelo na percepção auditiva. MÉTODOS: foram selecionados na literatura trabalhos em animais sobre a fisiologia e anatomia das vias auditivas do cerebelo, além de trabalhos em humanos sobre...

  14. Abscesso actinomicótico do cerebelo: relato de caso Actinomycotic abscess of the cerebellum: case report

    OpenAIRE

    Mário H. Tsubouchi; Walter O. Arruda; Ari A. Pedrozo; MURILO S. MENESES; Ricardo Ramina; Luiz F. Bleggi-torres

    1995-01-01

    Acometimento do sistema nervoso central por actinomicetos é extremamente raro. Os autores descrevem um caso de actinomicose de cerebelo, com diagnóstico estabelecido após remoção cirúrgica da lesão e tratamento com sucesso com penicilina endovenosa e oral. Breve revisão da literatura sobre o envolvimento do sistema nervoso na actinomicose é apresentada.A 38 year-old man presented fever and a clinical picture of intracranial hypertension and ataxic syndrome. A CT-scan disclosed an expanding le...

  15. Regional differences in the temporal expression of nonapoptotic caspase-3-positive Bergmann glial cells in the developing rat cerebellum

    Directory of Open Access Journals (Sweden)

    VelvetLee Finckbone

    2009-05-01

    Full Text Available Although caspases have been intimately linked to apoptotic events, some of the pro-apoptotic caspases also may regulate differentiation. We previously demonstrated that active caspase-3 is expressed and has an apparent non-apoptotic function during the development of cerebellar Bergmann glia. The current study seeks to further correlate active/cleaved caspase-3 expression with the developmental phenotype of Bergmann glia by examining regional differences in the temporal pattern of expression of cleaved caspase-3 immunoreactivity in lobules of the cerebellar vermis. In general, we found that the expression pattern of cleaved caspase-3 corresponds to the reported developmental temporal profile of the lobes and that its levels peak at 15 days and declines thereafter. Compared to intermediate or late maturing lobules, early maturing lobules had higher levels of active caspase-3 at earlier postnatal times. This period of postnatal development is precisely the time during which Bergmann glia initiate differentiation.

  16. N-Acetyl-L-Leucine Accelerates Vestibular Compensation after Unilateral Labyrinthectomy by Action in the Cerebellum and Thalamus

    OpenAIRE

    Lisa Günther; Roswitha Beck; Guoming Xiong; Heidrun Potschka; Klaus Jahn; Peter Bartenstein; Thomas Brandt; Mayank Dutia; Marianne Dieterich; Michael Strupp; Christian la Fougère; Andreas Zwergal

    2015-01-01

    An acute unilateral vestibular lesion leads to a vestibular tone imbalance with nystagmus, head roll tilt and postural imbalance. These deficits gradually decrease over days to weeks due to central vestibular compensation (VC). This study investigated the effects of i.v. N-acetyl-DL-leucine, N-acetyl-L-leucine and N-acetyl-D-leucine on VC using behavioural testing and serial [18F]-Fluoro-desoxyglucose ([18F]-FDG)-μPET in a rat model of unilateral chemical labyrinthectomy (UL). Vestibular beha...

  17. N-acetyl-L-leucine accelerates vestibular compensation after unilateral labyrinthectomy by action in the cerebellum and thalamus.

    Science.gov (United States)

    Günther, Lisa; Beck, Roswitha; Xiong, Guoming; Potschka, Heidrun; Jahn, Klaus; Bartenstein, Peter; Brandt, Thomas; Dutia, Mayank; Dieterich, Marianne; Strupp, Michael; la Fougère, Christian; Zwergal, Andreas

    2015-01-01

    An acute unilateral vestibular lesion leads to a vestibular tone imbalance with nystagmus, head roll tilt and postural imbalance. These deficits gradually decrease over days to weeks due to central vestibular compensation (VC). This study investigated the effects of i.v. N-acetyl-DL-leucine, N-acetyl-L-leucine and N-acetyl-D-leucine on VC using behavioural testing and serial [18F]-Fluoro-desoxyglucose ([18F]-FDG)-μPET in a rat model of unilateral chemical labyrinthectomy (UL). Vestibular behavioural testing included measurements of nystagmus, head roll tilt and postural imbalance as well as sequential whole-brain [18F]-FDG-μPET was done before and on days 1,3,7 and 15 after UL. A significant reduction of postural imbalance scores was identified on day 7 in the N-acetyl-DL-leucine (p D-leucine group (comparison for applied dose of 24 mg i.v. per rat, equivalent to 60 mg/kg body weight, in each group). The course of postural compensation in the DL- and L-group was accelerated by about 6 days relative to controls. The effect of N-acetyl-L-leucine on postural compensation depended on the dose: in contrast to 60 mg/kg, doses of 15 mg/kg and 3.75 mg/kg had no significant effect. N-acetyl-L-leucine did not change the compensation of nystagmus or head roll tilt at any dose. Measurements of the regional cerebral glucose metabolism (rCGM) by means of μPET revealed that only N-acetyl-L-leucine but not N-acetyl-D-leucine caused a significant increase of rCGM in the vestibulocerebellum and a decrease in the posterolateral thalamus and subthalamic region on days 3 and 7. A similar pattern was found when comparing the effect of N-acetyl-L-leucine on rCGM in an UL-group and a sham UL-group without vestibular damage. In conclusion, N-acetyl-L-leucine improves compensation of postural symptoms after UL in a dose-dependent and specific manner, most likely by activating the vestibulocerebellum and deactivating the posterolateral thalamus. PMID:25803613

  18. Exome sequencing revealed PMM2 gene mutations in a French-Canadian family with congenital atrophy of the cerebellum.

    Science.gov (United States)

    Noreau, Anne; Beauchemin, Philippe; Dionne-Laporte, Alexandre; Dion, Patrick A; Rouleau, Guy A; Dupré, Nicolas

    2014-01-01

    Two affected and one unaffected siblings from a French-Canadian family were evaluated in our neurogenetic clinic. The oldest brother had intentional and postural hand tremor while his youngest sister presented mild ataxia, a similar hand tremor and global developmental delay. Brain MRIs of the two affected family members further revealed a significant cerebellar atrophy. For this study we conducted a whole exome sequencing (WES) investigation using genomic DNA prepared from the affected brother and sister, alongside DNA prepared from their unaffected mother, and identified two mutations previously reported to cause a rare disorder known as Congenital Disorder of Glycosylation, type Ia (CDG1A) (OMIM #212065). This study emphasizes how the diagnosis of patients presenting a mild tremor phenotype associated with cerebellar atrophy may benefit from WES in establishing genetic defects associated with their conditions. PMID:26331032

  19. Dynamics of Trace Element Concentration During Development and Excitotoxic Cell Death in the Cerebellum of Lurcher Mutant Mice

    Czech Academy of Sciences Publication Activity Database

    Bäurle, J.; Kučera, Jan; Frischmuth, S.; Lambertz, M.; Kranda, Karel

    2009-01-01

    Roč. 19, č. 4 (2009), s. 586-595. ISSN 1015-6305 R&D Projects: GA ČR GA309/09/1189 Institutional research plan: CEZ:AV0Z10480505 Keywords : apoptosis * copper * excitotoxicity Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 5.903, year: 2009

  20. The critical role of Golgi cells in regulating spatio-temporal integration and plasticity at the cerebellum input stage

    Directory of Open Access Journals (Sweden)

    2008-07-01

    Full Text Available After the discovery at the end of the 19th century (Golgi, 1883, the Golgi cell was precisely described by S.R. y Cajal (see Cajal, 1987, 1995 and functionally identified as an inhibitory interneuron 50 years later by J.C. Eccles and colleagues (Eccles e al., 1967. Then, its role has been casted by Marr (1969 within the Motor Learning Theory as a codon size regulator of granule cell activity. It was immediately clear that Golgi cells had to play a critical role, since they are the main inhibitory interneuron of the granular layer and control activity of as many as 100 millions granule cells. In vitro, Golgi cells show pacemaking, resonance, phase-reset and rebound-excitation in the theta-frequency band. These properties are likely to impact on their activity in vivo, which shows irregular spontaneous beating modulated by sensory inputs and burst responses to punctuate stimulation followed by a silent pause. Moreover, investigations have given insight into Golgi cells connectivity within the cerebellar network and on their impact on the spatio-temporal organization of activity. It turns out that Golgi cells can control both the temporal dynamics and the spatial distribution of information transmitted through the cerebellar network. Moreover, Golgi cells regulate the induction of long-term synaptic plasticity at the mossy fiber - granule cell synapse. Thus, the concept is emerging that Golgi cells are of critical importance for regulating granular layer network activity bearing important consequences for cerebellar computation as a whole.

  1. How the credit assignment problems in motor control could be solved after the cerebellum predicts increases in error.

    Science.gov (United States)

    Verduzco-Flores, Sergio O; O'Reilly, Randall C

    2015-01-01

    We present a cerebellar architecture with two main characteristics. The first one is that complex spikes respond to increases in sensory errors. The second one is that cerebellar modules associate particular contexts where errors have increased in the past with corrective commands that stop the increase in error. We analyze our architecture formally and computationally for the case of reaching in a 3D environment. In the case of motor control, we show that there are synergies of this architecture with the Equilibrium-Point hypothesis, leading to novel ways to solve the motor error and distal learning problems. In particular, the presence of desired equilibrium lengths for muscles provides a way to know when the error is increasing, and which corrections to apply. In the context of Threshold Control Theory and Perceptual Control Theory we show how to extend our model so it implements anticipative corrections in cascade control systems that span from muscle contractions to cognitive operations. PMID:25852535

  2. How the credit assignment problems in motor control could be solved after the cerebellum predicts increases in error

    Directory of Open Access Journals (Sweden)

    Sergio Oscar Verduzco-Flores

    2015-03-01

    Full Text Available We present a cerebellar architecture with two main characteristics. The first one is that complex spikes respond to increases in sensory errors. The second one is that cerebellar modules associate particular contexts where errors have increased in the past with corrective commands that stop the increase in error. We analyze our architecture formally and computationally for the case of reaching in a 3D environment. In the case of motor control, we show that there are synergies of this architecture with the Equilibrium-Point hypothesis, leading to novel ways to solve the motor error and distal learning problems. In particular, the presence of desired equilibrium lengths for muscles provides a way to know when the error is increasing, and which corrections to apply. In the context of Threshold Control Theory and Perceptual Control Theory we show how to extend our model so it implements anticipative corrections in cascade control systems that span from muscle contractions to cognitive operations.

  3. Gene expression profiles in the cerebellum and hippocampus following exposure to a neurotoxicant, Aroclor 1254: Developmental effects.

    Science.gov (United States)

    The developmental consequences of exposure to the polychlorinated biphenyls (PCBs) have been widely studied, making PCBs a unique model to understand issues related to environmental mixture of persistent chemicals. PCB exposure in humans adversely affects neurocognitive developm...

  4. Developmental Exposure to A Commercial PBDE Mixture: Effects on Protein Networks in the Cerebellum and Hippocampus of Rats

    Science.gov (United States)

    BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are structurally similar topolychlorinated biphenyls (PCBs) and have both central (learning and memory deficits) and peripheral (motor dysfunction) neurotoxic effects at concentrations/doses similar to those of PCBs. The cellular...

  5. Transient expression of functional serotonin 5-HT3 receptors by glutamatergic granule cells in the early postnatal mouse cerebellum

    NARCIS (Netherlands)

    M. Oostland; J. Sellmeijer; J.A. van Hooft

    2011-01-01

    The serotonin 5-HT3 receptor is the only ligand-gated ion channel activated by serotonin and is expressed by GABAergic interneurons in many brain regions, including the cortex, amygdala and hippocampus. Furthermore, 5-HT3 receptors are expressed by glutamatergic Cajal-Retzius cells in the cerebral c

  6. Levels of glutamate, aspartate, GABA, and taurine in different regions of the cerebellum after x-irradiation-induced neuronal loss

    International Nuclear Information System (INIS)

    The levels of glutamate (Glu), aspartate (Asp), gamma-amino-n-butyric acid (GABA), and taurine (Tau) were determined in the cortex, molecular layer, and deep nuclei of cerebella of adult rats exposed to X-irradiation at 12-15 days following birth (to prevent the acquisition of late-forming granule cells; 12-15x group) and 8-15 days following birth (to prevent the acquisition of granule and stellate cells; 8-15x group). Also, the levels of the four amino acids were measured in the crude synaptosomal fraction (P2) isolated from the whole cerebella of the control, 12-15x, and 8-15x groups. The level of Glu was significantly decreased by (1) 6-20% in the cerebellar cortex; (2) 15-20% in the molecular layer; and (3) 25-50% in the P2 fraction of the X-irradiated groups relative to control values. The content of Glu in the deep nuclei was not changed by X-irradiation treatment. Regional levels of Asp were unchanged by X-irradiation, while its level in P2 decreased by 15-30% after treatment. The levels of GABA and Tau in the molecular layer, deep nuclei, or P2 were not changed in the experimental groups. However, there was a 15% increase in the levels of GABA and Tau in the cerebellar cortex of the 8-15x group relative to control values. The data support the proposed role of glutamate as the excitatory transmitter released from the cerebellar granule cells but are inconclusive regarding a transmitter role for either Tau or GABA from cerebellar stellate cells

  7. Levels of glutamate, aspartate, GABA, and taurine in different regions of the cerebellum after x-irradiation-induced neuronal loss

    International Nuclear Information System (INIS)

    The levels of glutamate (Glu), aspartate (Asp), gamma-amino-n-butyric acid (GABA), and taurine (Tau) were determined in the cortex, molecular layer, and deep nuclei of cerebella of adult rats exposed to x-irradiation at 12 to 15 days following birth (to prevent the acquisition of late-forming granule cells; 12 to 15x group) and 8 to 15 days following birth (to prevent the acquisition of granule and stellate cells; 8 to 15x group). Also, the levels of the four amino acids were measured in the crude synaptosomal fraction (P2) isolated from the whole cerebella of the control, 12 to 15x, and 8 to 15x groups. The level of Glu was significantly decreased by (1) 6 to 20% in the cerebellar cortex; (2) 15 to 20% in the molecular layer; and (3) 25 to 50% in the P2 fraction of the x-irradiated groups relative to control values. The content of Glu in the deep nuclei was not changed by x-irradiation treatment. Regional levels of Asp were unchanged by x-irradiation, while its level in P2 decreased by 15 to 30% after treatment. The levels of GABA and Tau in the molecular layer, deep nuclei, or P2 were not changed in the experimental groups. However, there was a 15% increase in the levels of GABA and Tau in the cerebellar cortex of the 8 to 15x group relative to control values. The data support the proposed role of glutamate as the excitatory transmitter released from the cerebellar granule cells but are inconclusive regarding a transmitter role for either Tau or GBA from cerebellar stellate cells

  8. Up-Regulation of Oligodendrocyte Lineage Markers in the Cerebellum of Autistic Patients: Evidence from Network Analysis of Gene Expression.

    Science.gov (United States)

    Zeidán-Chuliá, Fares; de Oliveira, Ben-Hur Neves; Casanova, Manuel F; Casanova, Emily L; Noda, Mami; Salmina, Alla B; Verkhratsky, Alexei

    2016-08-01

    Autism is a neurodevelopmental disorder manifested by impaired social interaction, deficits in communication skills, restricted interests, and repetitive behaviors. In neurodevelopmental, neurodegenerative, and psychiatric disorders, glial cells undergo morphological, biochemical, and functional rearrangements, which are critical for neuronal development, neurotransmission, and synaptic connectivity. Cerebellar function is not limited to motor coordination but also contributes to cognition and may be affected in autism. Oligodendrocytes and specifically oligodendroglial precursors are highly susceptible to oxidative stress and excitotoxic insult. In the present study, we searched for evidence for developmental oligodendropathy in the context of autism by performing a network analysis of gene expression of cerebellar tissue. We created an in silico network model (OLIGO) showing the landscape of interactions between oligodendrocyte markers and demonstrated that more than 50 % (16 out of 30) of the genes within this model displayed significant changes of expression (corrected p value disorders (ASD). PMID:26189831

  9. An Integrated Approach Identifies Nhlh1 and Insm1 as Sonic Hedgehog-regulated Genes in Developing Cerebellum and Medulloblastoma

    Directory of Open Access Journals (Sweden)

    Enrico De Smaele

    2008-01-01

    Full Text Available Medulloblastoma (MB is the most common malignant brain tumor of childhood arising from deregulated cerebellar development. Sonic Hedgehog (Shh pathway plays a critical role in cerebellar development and its aberrant expression has been identified in MB. Gene expression profiling of cerebella from 1- to 14-day-old mice unveiled a cluster of genes whose expression correlates with the levels of Hedgehog (HH activity. From this cluster, we identified Insm1 and Nhlh1/NSCL1 as novel HH targets induced by Shh treatment in cultured cerebellar granule cell progenitors. Nhlh1 promoter was found to be bound and activated by Gli1 transcription factor. Remarkably, the expression of these genes is also upregulated in mouse and human HH-dependent MBs, suggesting that they may be either a part of the HH-induced tumorigenic process or a specific trait of HH-dependent tumor cells.

  10. The Anatomical, physiological and computational principles of adaptive learning in the cerebellum: the micro and macrocircuits of the brain

    OpenAIRE

    Zucca, Riccardo

    2015-01-01

    The human brain is undoubtedly the most complex product of evolution. Understanding how complex behaviour is generated by the intricacy of hundred billion of neurons and synapses fascinated scientists and philosophers for millennia. The multiscale trait of the central nervous system is a hallmark of its architecture and brain functions emerge from the interaction of its components at di erent temporal and spatial scales. A full understanding cannot be achieved unless we appr...

  11. Role of Cerebellum in Fine Speech Control in Childhood: Persistent Dysarthria after Surgical Treatment for Posterior Fossa Tumour

    Science.gov (United States)

    Morgan, A. T.; Liegeois, F.; Liederkerke, C.; Vogel, A. P.; Hayward, R.; Harkness, W.; Chong, K.; Vargha-Khadem, F.

    2011-01-01

    Dysarthria following surgical resection of childhood posterior fossa tumour (PFT) is most commonly documented in a select group of participants with mutism in the acute recovery phase, thus limiting knowledge of post-operative prognosis for this population of children as a whole. Here we report on the speech characteristics of 13 cases seen…

  12. The volume of Purkinje cells decreases in the cerebellum of acrylamide-intoxicated rats, but no cells are lost

    DEFF Research Database (Denmark)

    Larsen, Jytte Overgaard; Tandrup, T; Braendgaard, H

    1994-01-01

    The effects of acrylamide intoxication on the numbers of granule and Purkinje cells and the volume of Purkinje cell perikarya have been evaluated with stereological methods. The analysis was carried out in the cerebella of rats that had received a dose of 33.3 mg/kg acrylamide, twice a week, for 7...

  13. Disease: H00063 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available [DR:D00354] Disease class: polyglutamine disease Affected region: cerebellum, dentate nucleus, brain stem (SCA1); cerebellum,... brain stem, frontotemporal lobes (frontal lobe and temporal lobe) (SCA2); cerebellum,... basal ganglia, brain stem, spinal cord (SCA3); cerebellum (SCA5); cerebellum, dentat...e nucleus, inferior olive (SCA6); cerebellum, inferior olive, dentate nucleus, pontine nuclei (also the reti...na) (SCA7); cerebral cortex, cerebellum (SCA12); cerebellum, inferior olive (SCA17) Microscopic lesion: neur

  14. Interaction of electrical stimulation and voluntary hand movement in SII and the cerebellum during simulated therapeutic functional electrical stimulation in healthy adults

    DEFF Research Database (Denmark)

    Iftime-Nielsen, Simona Denisia; Christensen, Mark Schram; Vingborg, Rune Jersin; Sinkjær, Thomas; Roepstorff, Andreas; Grey, Michael James

    2012-01-01

    activity may reflect a better match between the internal model and the actual sensory feedback. The greater cerebellar activity coupled with reduced angular gyrus activity in FESVOL compared with FES suggests that the cortex may interpret sensory information during the FES condition as an error-like signal...... due to the lack of a voluntary component in the movement....

  15. [123I]epidepride binding to cerebellar dopamine D2/D3 receptors is displaceable: implications for the use of cerebellum as a reference region

    DEFF Research Database (Denmark)

    Pinborg, Lars H; Videbaek, Charlotte; Ziebell, Morten;

    2007-01-01

    ]epidepride-SPECT was performed in 23 patients with schizophrenia before and after 3 months of antipsychotic treatment with either risperidone (n=14) or zuclopenthixol (n=9). In the unblocked situation and partially blocked situation, the average distribution volumes were 5.2+/-1.3 mL/mL and 4.0+/-0.8 mL/mL, respectively...

  16. An Integrated Approach Identifies Nhlh1 and Insm1 as Sonic Hedgehog-regulated Genes in Developing Cerebellum and Medulloblastoma1,2

    OpenAIRE

    De Smaele, Enrico; Fragomeli, Caterina; Ferretti, Elisabetta; Pelloni, Marianna; Po, Agnese; Canettieri, Gianluca; Coni, Sonia; Di Marcotullio, Lucia; Greco, Azzura; Moretti, Marta; Di Rocco, Concezio; Pazzaglia, Simona; Maroder, Marella; Screpanti, Isabella; Giannini, Giuseppe

    2008-01-01

    Medulloblastoma (MB) is the most common malignant brain tumor of childhood arising from deregulated cerebellar development. Sonic Hedgehog (Shh) pathway plays a critical role in cerebellar development and its aberrant expression has been identified in MB. Gene expression profiling of cerebella from 1- to 14-day-old mice unveiled a cluster of genes whose expression correlates with the levels of Hedgehog (HH) activity. From this cluster, we identified Insm1 and Nhlh1/NSCL1 as novel HH targets i...

  17. Quantitative proteomic profiling of membrane proteins from the mouse brain cortex, hippocampus, and cerebellum using the HysTag reagent: mapping of neurotransmitter receptors and ion channels

    DEFF Research Database (Denmark)

    Olsen, Jesper V; Nielsen, Peter Aa; Andersen, Jens R;

    2007-01-01

    Analysis of the brain proteome and studying brain diseases through clinical biopsies and animal disease models require methods of quantitative proteomics that are sensitive and allow identification and quantification of low abundant membrane proteins from minute amount of tissue. Taking advantage...

  18. Quantitative meta-analysis of fMRI and PET studies reveals consistent activation in fronto-striatal-parietal regions and cerebellum during antisaccades and prosaccades

    Directory of Open Access Journals (Sweden)

    Sharna eJamadar

    2013-10-01

    Full Text Available The antisaccade task is a classic task of oculomotor control that requires participants to inhibit a saccade to a target and instead make a voluntary saccade to the mirror opposite location. By comparison, the prosaccade task requires participants to make a visually-guided saccade to the target. These tasks have been studied extensively using behavioural oculomotor, electrophysiological and neuroimaging in both non-human primates and humans. In humans, the antisaccade task is under active investigation as a potential endophenotype or biomarker for multiple psychiatric and neurological disorders. A large and growing body of literature has used functional magnetic resonance imaging (fMRI and positron emission tomography (PET to study the neural correlates of the antisaccade and prosaccade tasks. We present a quantitative meta-analysis of all published voxel-wise fMRI and PET studies (18 of the antisaccade task and show that consistent activation for antisaccades and prosaccades is obtained in a fronto-subcortical-parietal network encompassing frontal and supplementary eye fields, thalamus, striatum and intraparietal cortex. This network is strongly linked to oculomotor control and was activated to a greater extent for antisaccade than prosaccade trials. Antisaccade but not prosaccade trials additionally activated dorsolateral and ventrolateral prefrontal cortices. We also found that a number of additional regions not classically linked to oculomotor control were activated to a greater extent for antisaccade versus prosaccade trials; these regions are often reported in antisaccade studies but rarely commented upon. While the number of studies eligible to be included in this meta-analysis was small, the results of this systematic review reveal that antisaccade and prosaccade trials consistently activate a distributed network of regions both within and outside the classic definition of the oculomotor network.

  19. Aroclor-1254, a developmental neurotoxicant, alters energy metabolism-and intracellular signaling-associated protein networks in rat cerebellum and hippocampus

    Science.gov (United States)

    The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and l...

  20. Mecp2 deficiency leads to altered Htr2c pre-mRNA editing and HTR2C isoform distribution in mouse hippocampus and cerebellum

    Science.gov (United States)

    Rett Syndrome (RTT) is a neurodevelopmental disorder caused by mutations in MECP2, a methyl-CpG binding protein and transcriptional repressor. CpG methylation plays an important role in genomic imprinting since imprinted genes are regulated by regions of differentially methylated CpGs (or ICs). A ...

  1. Dopamine D4 receptors modulate brain metabolic activity in the prefrontal cortex and cerebellum at rest and in response to methylphenidate

    Energy Technology Data Exchange (ETDEWEB)

    Michaelides, M.; Wang, G.; Michaelides, M.; Pascau, J.; Gispert, J.-D.; Delis, F.; Grandy, D.K.; Wang, G.-J.; Desco, M.; Rubinstein, M.; Volkow, N.D.; Thanos, P.K.

    2010-07-16

    Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D{sub 4}) gene have been implicated in vulnerability to ADHD and the response to MP. Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP. We compared brain glucose metabolism (measured with micro-positron emission tomography and [{sup 18}F]2-fluoro-2-deoxy-D-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D{sub 4}. Images were analyzed using a novel automated image registration procedure. Baseline D{sub 4}{sup -/-} mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice; when given MP, D{sub 4}{sup -/-} mice increased metabolism in the PFC and decreased it in the CBV, whereas in D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice, MP decreased metabolism in the PFC and increased it in the CBV. These findings provide evidence that D4Rs modulate not only the PFC, which may reflect the activation by dopamine of D4Rs located in this region, but also the CBV, which may reflect an indirect modulation as D4Rs are minimally expressed in this region. As individuals with ADHD show structural and/or functional abnormalities in these brain regions, the association of ADHD with D4Rs may reflect its modulation of these brain regions. The differential response to MP as a function of genotype could explain differences in brain functional responses to MP between patients with ADHD and healthy controls and between patients with ADHD with different D{sub 4} polymorphisms.

  2. [123I]epidepride binding to cerebellar dopamine D2/D3 receptors is displaceable: implications for the use of cerebellum as a reference region

    DEFF Research Database (Denmark)

    Pinborg, Lars H; Videbaek, Charlotte; Ziebell, Morten;

    2007-01-01

    ]epidepride-SPECT was performed in 23 patients with schizophrenia before and after 3 months of antipsychotic treatment with either risperidone (n=14) or zuclopenthixol (n=9). In the unblocked situation and partially blocked situation, the average distribution volumes were 5.2+/-1.3 mL/mL and 4.0+/-0.8 m...

  3. Ozone Effects on Protein Carbonyl Content in the Frontal Cortex and Cerebellum of Young-Adult, Middle Age, and Senescent Brown Norway Rats

    Science.gov (United States)

    Oxidative stress (OS) plays an important role in susceptibility and disease in old age. Understanding age-related susceptibility is a critical part of community-based human health risk assessment of chemical exposures. There is growing concern over a common air pollutant, ozone ...

  4. A Functional Magnetic Resonance Imaging Study of Foreign-Language Vocabulary Learning Enhanced by Phonological Rehearsal: The Role of the Right Cerebellum and Left Fusiform Gyrus

    Science.gov (United States)

    Makita, Kai; Yamazaki, Mika; Tanabe, Hiroki C.; Koike, Takahiko; Kochiyama, Takanori; Yokokawa, Hirokazu; Yoshida, Haruyo; Sadato, Norihiro

    2013-01-01

    Psychological research suggests that foreign-language vocabulary acquisition recruits the phonological loop for verbal working memory. To depict the neural underpinnings and shed light on the process of foreign language learning, we conducted functional magnetic resonance imaging of Japanese participants without previous exposure to the Uzbek…

  5. Modulation of ERK1/2 and p38{sup MAPK} by lead in the cerebellum of Brazilian catfish Rhamdia quelen

    Energy Technology Data Exchange (ETDEWEB)

    Leal, Rodrigo B. [Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, SC 88040-900 (Brazil)]. E-mail: bainyle@mbox1.ufsc.br; Ribeiro, Sandro Jose [Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, SC 88040-900 (Brazil); Posser, Thais [Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, SC 88040-900 (Brazil); Cordova, Fabiano M. [Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, SC 88040-900 (Brazil); Escola de Medicina Veterinaria e Zootecnia, Universidade Federal do Tocantins, Araguaina - TO 77804-970 (Brazil); Rigon, Ana Paula [Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, SC 88040-900 (Brazil); Filho, Evoy Zaniboni [Departamento de Aquicultura, Centro de Ciencias Agrarias, Universidade Federal de Santa Catarina, Florianopolis, SC 88040-900 (Brazil); Bainy, Afonso C.D. [Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, SC 88040-900 (Brazil)

    2006-04-20

    Lead (Pb{sup 2+}) is a neurotoxic trace metal, widespread in aquatic environment that can change physiologic, biochemical and behavioral parameters in diverse fish species. Chemical exposure may drive modulation of mitogen-activated protein kinases (MAPKs) that are a family of highly conserved enzymes which comprise ubiquitous groups of signaling proteins playing critical regulatory roles in cell physiology. Extracellular signal-regulated kinases (ERK1/2) and p38{sup MAPK} control complex programs such as gene expression, embryogenesis, cell differentiation, cell proliferation, cell death and synaptic plasticity. Little information is available about MAPKs in aquatic organisms and their modulation by trace metals. The aim of this work was to determine the modulation of ERK1/2 and p38{sup MAPK} phosphorylation by Pb{sup 2+} in vivo and in vitro, in cerebellar slices of the catfish, Rhamdia quelen. In the in vitro model, slices were incubated for 3 h with lead acetate (1-10 {mu}M). In the in vivo studies, the animals were exposed for 2 days to lead acetate (1 mg L{sup -1}). ERK1/2 and p38{sup MAPK} (total and phosphorylated forms) were immunodetected in cerebellar slices by Western blotting. Pb{sup 2+} added in vitro at 5 and 10 {mu}M increased significantly the phosphorylation of both MAPKs. The in vivo exposed animals also showed a significant increase of ERK1/2 and p38{sup MAPK} phosphorylation without changes in the total content of the enzymes. In conclusion, the present work indicates that it is possible to evaluate the ERK1/2 and p38{sup MAPK} activation in the central nervous system (CNS) of a freshwater fish largely distributed in South America. Moreover, Pb{sup 2+}, an important environmental pollutant may activate in vitro and in vivo ERK1/2 and p38{sup MAPK} enzymes. These findings are important considering the functional and ecologic implications associated to Pb{sup 2+} exposure of a freshwater fish species, such as R. quelen, and the roles of ERK1/2 and p38{sup MAPK} in the control of brain development, neuroplasticity and cell death.

  6. Neuromodulatory Adaptive Combination of Correlation-based Learning in Cerebellum and Reward-based Learning in Basal Ganglia for Goal-directed Behavior Control

    DEFF Research Database (Denmark)

    Dasgupta, Sakyasingha; Wörgötter, Florentin; Manoonpong, Poramate

    2014-01-01

    envision that such an interaction is influenced by reward modulated heterosynaptic plasticity (RMHP) rule at the thalamus, guiding the overall goal directed behavior. Using a recurrent neural network actor-critic model of the basal ganglia and a feed-forward correlation-based learning model...

  7. Metabolomic Method UPLC-q-ToF Polar and Non-polar Metabolites in the Healthy Rat Cerebellum Using an In-Vial Dual Extraction

    OpenAIRE

    Ebshiana, Amera A.; Snowden, Stuart G.; Madhav Thambisetty; Richard Parsons; Abdul Hye; Cristina Legido-Quigley

    2015-01-01

    Unbiased metabolomic analysis of biological samples is a powerful and increasingly commonly utilised tool, especially for the analysis of bio-fluids to identify candidate biomarkers. To date however only a small number of metabolomic studies have been applied to studying the metabolite composition of tissue samples, this is due, in part to a number of technical challenges including scarcity of material and difficulty in extracting metabolites. The aim of this study was to develop a method for...

  8. Corticotropin-releasing factor receptor types 1 and 2 are differentially expressed in pre- and post-synaptic elements in the post-natal developing rat cerebellum

    NARCIS (Netherlands)

    Swinny, JD; Kalicharan, D; Blaauw, EH; Ijkema-Paassen, J; Shi, F; Gramsbergen, A; van der Want, JJL

    2003-01-01

    Corticotropin-releasing factor (CRF)-like proteins act via two G-protein-coupled receptors (CRF-R1 and CRF-R2) playing important neuromodulatory roles in stress responses and synaptic plasticity. The cerebellar expression of corticotropin-releasing factor-like ligands has been well documented, but t

  9. The quantification of COMT mRNA in post mortem cerebellum tissue: diagnosis, genotype, methylation and expression

    OpenAIRE

    Craig Ian W; Mill Jonathan; Dempster Emma L; Collier David A

    2006-01-01

    Abstract Background The COMT gene is located on chromosome 22q11, a region strongly implicated in the aetiology of several psychiatric disorders, in particular schizophrenia. Previous research has suggested that activity and expression of COMT is altered in schizophrenia, and is mediated by one or more polymorphisms within the gene, including the functional Val158Met polymorphism. Method In this study we examined the expression levels of COMT mRNA using quantitative RT-PCR in 60 post mortem c...

  10. Redox Status and Neuro Inflammation Indexes in Cerebellum and Motor Cortex of Wistar Rats Supplemented with Natural Sources of Omega-3 Fatty Acids and Astaxanthin: Fish Oil, Krill Oil, and Algal Biomass

    OpenAIRE

    Tatiana G. Polotow; Poppe, Sandra C.; Vardaris, Cristina V.; Douglas Ganini; Maísa Guariroba; Rita Mattei; Elaine Hatanaka; Maria F. Martins; Bondan, Eduardo F.; Barros, Marcelo P.

    2015-01-01

    Health authorities worldwide have consistently recommended the regular consumption of marine fishes and seafood to preserve memory, sustain cognitive functions, and prevent neurodegenerative processes in humans. Shrimp, crabs, lobster, and salmon are of particular interest in the human diet due to their substantial provision of omega-3 fatty acids (n-3/PUFAs) and the antioxidant carotenoid astaxanthin (ASTA). However, the optimal ratio between these nutraceuticals in natural sources is appare...

  11. MATERNAL EXPOSURE TO NICOTINE AND CHLORPYRIFOS, ALONE AND IN COMBINATION LEADS TO PERSISTENTLY ELEVATED EXPRESSION OF GLIAL FIBRILARY ACIDIC PROTEIN IN THE CEREBELLUM OF THE OFFSPRING AT LATE PUBERTY. (R829399)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  12. Aplicações da ultra-sonografia tridimensional na avaliação do cerebelo fetal Three-dimensional ultrasonography in the evaluation of the fetal cerebellum

    OpenAIRE

    Edward Araujo Júnior; Hélio Antonio Guimarães Filho; Cláudio Rodrigues Pires; Luciano Marcondes Machado Nardozza; Antonio Fernandes Moron

    2007-01-01

    Nos últimos anos a ultra-sonografia tridimensional tem-se tornado um método de imagem de grande importância no diagnóstico em obstetrícia. Um de seus benefícios seria a maior sensibilidade, em relação ao ultra-som bidimensional, no diagnóstico de algumas malformações fetais. As potenciais aplicações desse novo método seriam uma maior acurácia na medida do volume de órgãos fetais, a possibilidade de rever volumes na ausência da paciente, a possibilidade de utilizar diferentes planos para avali...

  13. Influence of arsenic trioxide on gene expression profile of oxidation reduction enzyme in the cerebellum of mice%三氧化二砷对小鼠小脑氧化还原相关酶基因表达谱的影响

    Institute of Scientific and Technical Information of China (English)

    洪岩; 朴丰源; 王艳艳; 刘鹏

    2008-01-01

    目的 应用基因芯片技术观察三氧化二砷(As2O3)对小鼠小脑组织氧化还原相关酶基因表达谱的影响.方法 昆明种小鼠30只随机分为3组,即生理盐水对照组、低剂量组(1 mg/L As2O3染毒组)和高剂量组(4 mg/L As2O3)染毒组),连续染毒60 d,断头法处死小鼠,利用基因芯片技术检测基因表达谱的变化.结果 基因芯片筛选结果显示,与对照组比较,染砷组中差异表达2倍及以上的基因有18条,其中表达上调的基因有12条,表达下调的基因有6条.高剂量组与低剂量组及对照组比较,表达上调的基因有Ndufa4、Ndufa6、Gpx3、Adil、Rrm2b,表达下调的基因有Spr、Hsd17b11、Ogfod1、Ndufab1.与对照组比较,染砷组中Cyp51、Phgdh、Dhrs4、Prdx4、Aldh1a、1810063805Rik、Glrx表达上调,Prdx2、1110020P15 Rik表达下调.结论 As2O3对小鼠小脑的氧化还原相关酶基因表达谱具有明显的影响,提示这些小脑氧化还原相关酶基因很可能是砷的神经毒作用的靶点.

  14. Periaqueductal Grey Stimulation Induced Panic-Like Behaviour Is Accompanied by Deactivation of the Deep Cerebellar Nuclei

    OpenAIRE

    Moers-Hornikx, Véronique M. P.; Vles, Johan S. H.; Lim, Lee Wei; AYYILDIZ, Mustafa; Kaplan, Sűleyman; Gavilanes, Antonio W. D.; Hoogland, Govert; STEINBUSCH, Harry W.M.; Temel, Yasin

    2010-01-01

    Until recently, the cerebellum was primarily considered to be a structure involved in motor behaviour. New anatomical and clinical evidence has shown that the cerebellum is also involved in higher cognitive functions and non-motor behavioural changes. Functional imaging in patients with anxiety disorders and in cholecystokinin tetrapeptide-induced panic-attacks shows activation changes in the cerebellum. Deep brain stimulation of the dorsolateral periaqueductal grey (dlPAG) and the ventromedi...

  15. Implications of functional anatomy on information processing in the deep cerebellar nuclei

    OpenAIRE

    Jacobson, Gilad A.; Dana Cohen

    2009-01-01

    The cerebellum has been implicated as a major player in producing temporal acuity. Theories of cerebellar timing typically emphasize the role of the cerebellar cortex while overlooking the role of the deep cerebellar nuclei (DCN) that provide the sole output of the cerebellum. Here we review anatomical and electrophysiological studies to shed light on the DCN’s ability to support temporal pattern generation in the cerebellum. Specifically, we examine data on the structure of the DCN, th...

  16. Implications of Functional Anatomy on Information Processing in the Deep Cerebellar Nuclei

    OpenAIRE

    Baumel, Yuval; Jacobson, Gilad A.; Cohen, Dana

    2009-01-01

    The cerebellum has been implicated as a major player in producing temporal acuity. Theories of cerebellar timing typically emphasize the role of the cerebellar cortex while overlooking the role of the deep cerebellar nuclei (DCN) that provide the sole output of the cerebellum. Here we review anatomical and electrophysiological studies to shed light on the DCN's ability to support temporal pattern generation in the cerebellum. Specifically, we examine data on the structure of the DCN, the biop...

  17. Plasticity in eye movement control

    OpenAIRE

    Luo, Chongde

    2005-01-01

    textabstractThe cerebellum plays an important role in the recalibration and adaptive adjustment of movements, as well as learning new motor skills and motor related associations. In this thesis, we investigated the mechanisms underlying cerebellar motor learning. To obtain a better understanding, in how the cerebellum processes and stores information, we used specific perturbations that affected the information processing of the cerebellum. Signal transduction pathways were affected that were...

  18. Steroids, sex and the cerebellar cortex: implications for human disease

    OpenAIRE

    Dean, Shannon L.; McCarthy, Margaret M.

    2008-01-01

    Neurosteroids play an important role in the development of the cerebellum. In particular, estradiol and progesterone appear capable of inducing increases in dendritic spine density during development, and there is evidence that both are synthesized de novo in the cerebellum during critical developmental periods. In normal neonates and adults, there are few differences in the cerebellum between the sexes and most studies indicate that hormone and receptor levels also do not differ significantl...

  19. Macro- and Microscopic Structural Features of the Cerebellar Dentate Nucleus in Humans

    OpenAIRE

    Shyian, D. M.

    2015-01-01

    Since ancient times the study of one part of the brain - the cerebellum - has attracted the attention of many researchers, however, neither anatomy of the cerebellum, nor its function remain fully studied. The nuclei of the cerebellum, including the dentate nucleus are not sufficiently studied. The structural features of the cerebellar dentate nucleus of human in ontogenesis and its topographic and anatomic location are important not only for anatomists, physiologists, but also for clinicians...

  20. Resting state cortico-cerebellar functional connectivity networks: A comparison of anatomical and self-organizing map approaches

    Directory of Open Access Journals (Sweden)

    Jessica A Bernard

    2012-08-01

    Full Text Available The cerebellum plays a role in a wide variety of complex behaviors. In order to better understand the role of the cerebellum in human behavior, it is important to know how this structure interacts with cortical and other subcortical regions of the brain. To date, several studies have investigated the cerebellum using resting-state functional connectivity magnetic resonance imaging (fcMRI; Buckner et al., 2011; Krienen & Buckner, 2009; O’Reilly et al., 2009. However, none of this work has taken an anatomically-driven approach. Furthermore, though detailed maps of cerebral cortex and cerebellum networks have been proposed using different network solutions based on the cerebral cortex (Buckner et al., 2011, it remains unknown whether or not an anatomical lobular breakdown best encompasses the networks of the cerebellum. Here, we used fcMRI to create an anatomically-driven cerebellar connectivity atlas. Timecourses were extracted from the lobules of the right hemisphere and vermis. We found distinct networks for the individual lobules with a clear division into motor and non-motor regions. We also used a self-organizing map algorithm to parcellate the cerebellum. This allowed us to investigate redundancy and independence of the anatomically identified cerebellar networks. We found that while anatomical boundaries in the anterior cerebellum provide functional subdivisions of a larger motor grouping defined using our self-organizing map algorithm, in the posterior cerebellum, the lobules were made up of sub-regions associated with distinct functional networks. Together, our results indicate that the lobular boundaries of the human cerebellum are not indicative of functional boundaries, though anatomical divisions can be useful, as is the case of the anterior cerebellum. Additionally, driving the analyses from the cerebellum is key to determining the complete picture of functional connectivity within the structure.

  1. Inferior Colliculus Lesions Impair Eyeblink Conditioning in Rats

    Science.gov (United States)

    Freeman, John H.; Halverson, Hunter E.; Hubbard, Erin M.

    2007-01-01

    The neural plasticity necessary for acquisition and retention of eyeblink conditioning has been localized to the cerebellum. However, the sources of sensory input to the cerebellum that are necessary for establishing learning-related plasticity have not been identified completely. The inferior colliculus may be a source of sensory input to the…

  2. Neural Circuitry and Plasticity Mechanisms Underlying Delay Eyeblink Conditioning

    Science.gov (United States)

    Freeman, John H.; Steinmetz, Adam B.

    2011-01-01

    Pavlovian eyeblink conditioning has been used extensively as a model system for examining the neural mechanisms underlying associative learning. Delay eyeblink conditioning depends on the intermediate cerebellum ipsilateral to the conditioned eye. Evidence favors a two-site plasticity model within the cerebellum with long-term depression of…

  3. Reactive hyperemia of rat brain following high altitude hypoxia

    International Nuclear Information System (INIS)

    Radioactive 85Sr microparticles were used to assess the cardiac output and blood flow through medulla oblongata, cerebellum, subcortical portions and cerebral cortex in adult laboratory rats 20 hours after 8-hour exposure to 7000 m high altitude hypoxia. The local blood supply increased in all parts of the brain, in particular in medulla oblongata and cerebellum. (author). 10 figs., 9 refs

  4. Automated cerebellar segmentation: Validation and application to detect smaller volumes in children prenatally exposed to alcohol

    Directory of Open Access Journals (Sweden)

    Valerie A. Cardenas

    2014-01-01

    Discussion: These results demonstrate excellent reliability and validity of automated cerebellar volume and mid-sagittal area measurements, compared to manual measurements. These data also illustrate that this new technology for automatically delineating the cerebellum leads to conclusions regarding the effects of prenatal alcohol exposure on the cerebellum consistent with prior studies that used labor intensive manual delineation, even with a very small sample.

  5. Cerebellar Expression of the Neurotrophin Receptor p75 in Naked-Ataxia Mutant Mouse

    Directory of Open Access Journals (Sweden)

    Maryam Rahimi Balaei

    2016-01-01

    Full Text Available Spontaneous mutation in the lysosomal acid phosphatase 2 (Acp2 mouse (nax—naked-ataxia mutant mouse correlates with severe cerebellar defects including ataxia, reduced size and abnormal lobulation as well as Purkinje cell (Pc degeneration. Loss of Pcs in the nax cerebellum is compartmentalized and harmonized to the classic pattern of gene expression of the cerebellum in the wild type mouse. Usually, degeneration starts in the anterior and posterior zones and continues to the central and nodular zones of cerebellum. Studies have suggested that the p75 neurotrophin receptor (NTR plays a role in Pc degeneration; thus, in this study, we investigated the p75NTR pattern and protein expression in the cerebellum of the nax mutant mouse. Despite massive Pc degeneration that was observed in the nax mouse cerebellum, p75NTR pattern expression was similar to the HSP25 pattern in nax mice and comparable with wild type sibling cerebellum. In addition, immunoblot analysis of p75NTR protein expression did not show any significant difference between nax and wild type sibling (p > 0.5. In comparison with wild type counterparts, p75NTR pattern expression is aligned with the fundamental cytoarchitecture organization of the cerebellum and is unchanged in the nax mouse cerebellum despite the severe neurodevelopmental disorder accompanied with Pc degeneration.

  6. Central nervous system malformations in Mohr's syndrome.

    OpenAIRE

    REARDON, W.; Harbord, M G; Hall-Craggs, M A; Kendall, B; Brett, E. M.; Baraitser, M

    1989-01-01

    A boy with severe developmental delay, bilateral, symmetrical hallucal duplication, and accessory alveolar frenula was found to have radiological evidence of a large arachnoid cyst compressing the cerebellum and brain stem. We review neurological abnormalities in Mohr's syndrome.

  7. MRI of the spinocerebellar degeneration (multiple system atrophy, Holmes type, and Menzel-Joseph type)

    Energy Technology Data Exchange (ETDEWEB)

    Mukai, Eiichiro (National Hospital of Nagoya (Japan)); Makino, Naoki

    1991-06-01

    We have analyzed MRI in 33 patients with several forms of spinocerebellar degeneration; 17 with multiple system atrophy, 10 with Holmes type, and 6 with Menzel-Joseph type. The MRIs were obtained using a 1.5-T GEMR System. Patients with multiple system atrophy demonstrated: atrophy of the brain stem, particularly basis pontis; decreased signal intensity of the white matter of pons; atrophy of the white matter of cerebellum; atrophy and decreased signal intensity of the putamen, particularly along their lateral and posterior portions; and atrophy of the cerebrum. Patients with Holmes type showed: atrophy of the cerebellum; atrophy of the vermis more than hemispheres; and nuclei of the cerebellum with no decreased intensity on T{sub 2}-weighted sequences. Patients with Menzel-Joseph type demonstrated moderate atrophy of the brain stem and mild atrophy of the white matter of cerebellum. MRI is a useful diagnostic tool in the management of the spinocerebellar degeneration. (author).

  8. Brain Basics: Know Your Brain

    Science.gov (United States)

    ... sound, sight, and touch. The Cerebral Cortex Coating the surface of the cerebrum and the cerebellum ... is associated with a shortage of acetylcholine. GABA (gamma-aminobutyric acid) is called an inhibitory neurotransmitter because ...

  9. Medline Plus

    Full Text Available ... the brain are the cerebrum, cerebellum, and brain stem. The cerebrum is divided into left and right ... can make complex movements without thinking. The brain stem connects the brain with the spinal cord and ...

  10. CHRONIC DIETARY EXPOSURE WITH INTERMITTENT SPIKE DOSES OF CHLORPYRIFOS FALLS TO ALTER SOMATOSENSORY EVOKED POTENTIALS, COMPOUND NERVE ACTION POTENTIALS, OR NERVE CONDUCTION VELOCITY IN RATS.

    Science.gov (United States)

    Human exposure to pesticides is often characterized by chronic low level exposure with intermittent spiked higher exposures. Cholinergic transmission is involved in sensory modulation in the cortex and cerebellum, and therefore may be altered following chlorpyrifos (CPF) exposure...

  11. Involvement of the crebellum in sequential finger movement learning: Evidence from functional magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    ZHU Yihong; DI Haibo; YUAN Yi; REN Jin'ge; YU Wei; ZHANG Zhaoqi; GAO Jiahong; WENG Xuchu; CHEN Yizhang

    2005-01-01

    Whether the cerebellum is involved in voluntary motor learning or motor performance is the subject of a new debate. Using functional magnetic resonance imaging (fMRI), we examined cerebellar activation in eight volunteers before and after an extended period of training. Activation volume on both sides of cerebellum after learning was significantly reduced compared to that before learning even under the same motor frequency. Remarkably, while motor frequency for the training sequence was significantly higher than the control sequence after 41 d of learning, activation in the cerebellum for both sequences, with respect to activation loci and volumes, was very similar. These results suggest that the cerebellum was involved in motor learning but not motor performance. Changes of cerebellar activation from training thus appear to be associated with learning but not with improvement on task performance.

  12. Experiment list: SRX062949 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available cerebellar nuclei. Its function is to coordinate voluntary movements, maintain ba...lance, and learn motor skills. 57796523,71.5,23.1,31524 GSM722663: RenLab-CTCF-cerebellum source_name=Mouse

  13. Experiment list: SRX143851 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available cerebellar nuclei. Its function is to coordinate voluntary movements, maintain ba...lance, and learn motor skills. 57796523,71.5,23.1,31516 GSM918759: LICR ChipSeq Cerebellum CTCF adult-8wks s

  14. Experiment list: SRX685871 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available cerebellar nuclei. Its function is to coordinate voluntary movements, maintain ba...lance, and learn motor skills. 160531350,0.0,11.8,0 GSM1486384: P14 Cerebellum DNase-seq Rep 1; Mus musculus

  15. Experiment list: SRX685875 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available cerebellar nuclei. Its function is to coordinate voluntary movements, maintain ba...lance, and learn motor skills. 181337188,0.0,0.0,0 GSM1486388: P60 Cerebellum DNase-seq Rep 2; Mus musculus;

  16. Experiment list: SRX685876 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available cerebellar nuclei. Its function is to coordinate voluntary movements, maintain ba...lance, and learn motor skills. 204608825,0.1,13.2,123 GSM1486389: P60 Cerebellum DNase-seq Rep 3; Mus muscul

  17. Experiment list: SRX685869 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available cerebellar nuclei. Its function is to coordinate voluntary movements, maintain ba...lance, and learn motor skills. 59999511,0.0,67.3,0 GSM1486382: P7 Cerebellum DNase-seq Rep 2; Mus musculus;

  18. Experiment list: SRX685868 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available cerebellar nuclei. Its function is to coordinate voluntary movements, maintain ba...lance, and learn motor skills. 68545959,0.0,55.7,0 GSM1486381: P7 Cerebellum DNase-seq Rep 1; Mus musculus;

  19. Experiment list: SRX191022 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available cerebellar nuclei. Its function is to coordinate voluntary movements, maintain ba...lance, and learn motor skills. 100382126,90.2,25.2,70896 GSM1014164: UW DnaseSeq Cerebellum adult-8wks C57BL

  20. Experiment list: SRX685874 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available cerebellar nuclei. Its function is to coordinate voluntary movements, maintain ba...lance, and learn motor skills. 178723963,0.2,27.3,907 GSM1486387: P60 Cerebellum DNase-seq Rep 1; Mus muscul

  1. Experiment list: SRX685872 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available cerebellar nuclei. Its function is to coordinate voluntary movements, maintain ba...lance, and learn motor skills. 186106893,0.2,27.1,1943 GSM1486385: P14 Cerebellum DNase-seq Rep 2; Mus muscu

  2. Experiment list: SRX685870 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available cerebellar nuclei. Its function is to coordinate voluntary movements, maintain ba...lance, and learn motor skills. 64161152,0.0,70.9,0 GSM1486383: P7 Cerebellum DNase-seq Rep 3; Mus musculus;

  3. Experiment list: SRX019014 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available alance, and learn motor skills. 9282155,68.0,41.3,5377 GSM427095: Sirt1 cerebellum ChIPseq source_name=cereb... cerebellar nuclei. Its function is to coordinate voluntary movements, maintain b

  4. Experiment list: SRX685873 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available cerebellar nuclei. Its function is to coordinate voluntary movements, maintain ba...lance, and learn motor skills. 200858891,0.0,11.0,0 GSM1486386: P14 Cerebellum DNase-seq Rep 3; Mus musculus

  5. Sleep disturbances in chronic progressive external ophthalmoplegia.

    NARCIS (Netherlands)

    Smits, B.W.; Westeneng, H.J.; Hal, M.A. van; Engelen, B.G.M. van; Overeem, S.

    2012-01-01

    BACKGROUND: Chronic progressive external ophthalmoplegia (CPEO) is a relatively common mitochondrial disorder. In addition to extraocular muscle weakness, various other organs can typically be affected, including laryngeal and limb muscles, cerebrum, cerebellum, and peripheral nerves. Given this mul

  6. Bilateral cerebellar activation in unilaterally challenged essential tremor

    Directory of Open Access Journals (Sweden)

    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.

  7. Cerebellar ataxia and functional genomics : Identifying the routes to cerebellar neurodegeneration

    NARCIS (Netherlands)

    Smeets, C J L M; Verbeek, D S

    2014-01-01

    Cerebellar ataxias are progressive neurodegenerative disorders characterized by atrophy of the cerebellum leading to motor dysfunction, balance problems, and limb and gait ataxia. These include among others, the dominantly inherited spinocerebellar ataxias, recessive cerebellar ataxias such as Fried

  8. Cerebellar contribution to feedforward control of locomotion

    Directory of Open Access Journals (Sweden)

    Iolanda Pisotta

    2014-06-01

    Full Text Available 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 of 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.

  9. 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. PMID:25009490

  10. Disease: H00076 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available gion: cerebral cortex, cerebellum, basal ganglia Microscopic lesion: accumulate of DNA lesions, tigroid-type...cision repair cross complementing, group 6 (mutation) [HSA:2074] [KO:K10841] Prodarsan (Phase I) Affected re

  11. Disease: H00060 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available AG repeat expansion) [HSA:1822] [KO:K05626] Disease class: polyglutamine disease Affected region: cerebell...um, cerebral cortex, basal ganglia, Luys body Microscopic lesion: neuronal and glia

  12. Medline Plus

    Full Text Available ... us the capacity to remember numerous pieces of information. The 3 major components of the brain are ... communication between the cortex and lower central nervous system centers. The cerebellum is located near the base ...

  13. cDNA: 53523 [ASTRA[Archive

    Lifescience Database Archive (English)

    Full Text Available M. musculus + Mm.277582 Mus musculus 16 days neonate cerebellum cDNA, RIKEN full-length enriched ... rary, clone:9630053E09 product:hypothetical Serine proteases , subtilase family/Leucine-rich repeat containing p ...

  14. cDNA: 43679 [ASTRA[Archive

    Lifescience Database Archive (English)

    Full Text Available M. musculus + Mm.333219 Mus musculus 10 days neonate cerebellum cDNA, RIKEN full-length enriched ... 0 product:hypothetical Eukaryotic thiol (cysteine) proteases ... active site containing protein, full insert sequen ...

  15. Vanishing White Matter Disease

    Science.gov (United States)

    ... coma. Ovary dysgenesis: defective development of the ovaries. Cerebellar ataxia: loss of muscle coordination as a result of abnormal functioning of the cerebellum (a part of the brain). Optic atrophy (variably ...

  16. Medline Plus

    Full Text Available The brain is composed of more than a thousand billion neurons. Specific groups of them, working in concert, provide ... of information. The 3 major components of the brain are the cerebrum, cerebellum, and brain stem. The ...

  17. Cooperation between the Hic1 and Ptch1 tumor suppressors in medulloblastoma

    OpenAIRE

    Briggs, Kimberly J.; Corcoran-Schwartz, Ian M.; Zhang, Wei; Harcke, Thomas; Devereux, Wendy L.; Baylin, Stephen B.; Eberhart, Charles G.; Watkins, D. Neil

    2008-01-01

    Medulloblastoma is an embryonal tumor thought to arise from the granule cell precursors (GCPs) of the cerebellum. PATCHED (PTCH), an inhibitor of Hedgehog signaling, is the best-characterized tumor suppressor in medulloblastoma. However,

  18. A positron emission tomography study of wind-up pain in chronic postherniotomy pain

    DEFF Research Database (Denmark)

    Kupers, Ron; Lonsdale, Markus Georg; Aasvang, Eske Kvanner; Kehlet, Henrik

    2011-01-01

    and non-painful von Frey stimulation revealed that the former more strongly activated contralateral secondary somatosensorycortex, insula, anterior cingulate cortex, right dorsolateral prefrontal cortex, thalamus and cerebellum. In addition, wind-up pain also activated the sublenticular extended...

  19. A positron emission tomography study of wind-up pain in chronic postherniotomy pain

    DEFF Research Database (Denmark)

    Kupers, Ron; Lonsdale, Markus Georg; Aasvang, Eske Kvanner; Kehlet, Henrik

    2011-01-01

    and non-painful von Frey stimulation revealed that the former more strongly activated contralateral secondary somatosensory cortex, insula, anterior cingulate cortex, right dorsolateral prefrontal cortex, thalamus and cerebellum. In addition, wind-up pain also activated the sublenticular extended...

  20. Cerebellopontine angle pilocytic astrocytoma mimicking acoustic schwannoma

    Energy Technology Data Exchange (ETDEWEB)

    Takada, Y.; Ohno, K.; Tamaki, M.; Hirakawa, K. [Dept. of Neurosurgery, Tokyo Medical and Dental Univ. (Japan)

    1999-12-01

    We describe a case of pilocytic astrocytoma of the cerebellum mimicking an acoustic schwannoma. The tumour protruded into the porus acusticus and enlarged the internal auditory meatus, which is a quite unusual characteristic of glial tumours. (orig.)

  1. Cerebellopontine angle pilocytic astrocytoma mimicking acoustic schwannoma

    International Nuclear Information System (INIS)

    We describe a case of pilocytic astrocytoma of the cerebellum mimicking an acoustic schwannoma. The tumour protruded into the porus acusticus and enlarged the internal auditory meatus, which is a quite unusual characteristic of glial tumours. (orig.)

  2. Disease: H00897 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available been reported. All subtypes share common characteristics, including hypoplasia/atrophy of cerebellum and pons, progressive microceph...aly, and variable cerebral involvement. Mutations in thr

  3. A Cerebellar Deficit in Sensorimotor Prediction Explains Movement Timing Variability

    OpenAIRE

    Bo, Jin; Block, Hannah J.; Jane E. Clark; Bastian, Amy J.

    2008-01-01

    A popular theory is that the cerebellum functions as a timer for clocking motor events (e.g., initiation, termination). Consistent with this idea, cerebellar patients have been reported to show greater deficits during hand movements that repeatedly start and stop (i.e., discontinuous movements) compared with continuous hand movements. Yet, this finding could potentially be explained by an alternate theory in which the cerebellum acts as an internal model of limb mechanics. We tested whether a...

  4. Architecture and development of olivocerebellar circuit topography

    OpenAIRE

    Reeber, Stacey L.; White, Joshua J.; George-Jones, Nicholas A.; Sillitoe, Roy V.

    2013-01-01

    The cerebellum has a simple tri-laminar structure that is comprised of relatively few cell types. Yet, its internal micro-circuitry is anatomically, biochemically, and functionally complex. The most striking feature of cerebellar circuit complexity is its compartmentalized topography. Each cell type within the cerebellar cortex is organized into an exquisite map; molecular expression patterns, dendrite projections, and axon terminal fields divide the medial-lateral axis of the cerebellum into...

  5. Alteration in forward model prediction of sensory outcome of motor action in focal hand dystonia

    OpenAIRE

    André Lee; Matthias Karst

    2013-01-01

    Focal hand dystonia in musicians is a movement disorder affecting highly trained movements. Rather than being a pure motor disorder related to movement execution only, movement planning, error prediction and sensorimotor integration are also impaired. Internal models, of which two types, forward and inverse models have been described and most likely processed in the cerebellum, are known to be involved in these tasks. Recent results indicate that the cerebellum may be involved in the pathophy...

  6. Cerebro-cerebellar circuits in autism spectrum disorder

    OpenAIRE

    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...

  7. Cerebellar Control of Locomotion in Health and Disease

    OpenAIRE

    Vinueza Veloz, Maria

    2015-01-01

    markdownabstract__Abstract__ Modern neuroscience is paving the way for new insight into cerebellar functions including the control of cognitive, autonomic and emotional processes. Yet, how the cerebellum contributes to complex motor behaviors, such as locomotion, is still only partially understood. Here, we have investigated the contribution of the cerebellum to locomotion from the perspective of studies performed on mutant mouse lines generated through genetic engineering techniques. Specifi...

  8. An MRI Study of Cerebellar Volume in Tuberous Sclerosis Complex

    OpenAIRE

    Weisenfeld, Neil I.; Peters, Jurriaan M.; Tsai, Peter T; Prabhu, Sanjay P.; Dies, Kira A.; Sahin, Mustafa; Warfield, Simon K.

    2013-01-01

    The cerebellum plays an important role in motor learning and cognition, and structural cerebellar abnormalities have been associated with cognitive impairment. In tuberous sclerosis complex, neurological outcome is highly variable, and no consistent imaging or pathological determinant of cognition has been firmly established. The cerebellum calls for specific attention as mouse models of tuberous sclerosis complex have demonstrated a loss of cerebellar Purkinje cells and cases of human histol...

  9. A cerebellar model for predictive motor control tested in a brain-based device

    OpenAIRE

    McKinstry, Jeffrey L.; Edelman, Gerald M.; Krichmar, Jeffrey L.

    2006-01-01

    The cerebellum is known to be critical for accurate adaptive control and motor learning. We propose here a mechanism by which the cerebellum may replace reflex control with predictive control. This mechanism is embedded in a learning rule (the delayed eligibility trace rule) in which synapses onto a Purkinje cell or onto a cell in the deep cerebellar nuclei become eligible for plasticity only after a fixed delay from the onset of suprathreshold presynaptic activity. To...

  10. CRBL cells: Establishment, characterization and susceptibility to prion infection

    OpenAIRE

    Mays, Charles E.; Kang, Hae-Eun; Kim, Younghwan; Shim, Sung Han; Bang, Ji-Eun; Woo, Hee-Jong; Cho, Youl-Hee; Kim, Jae-Beom; Ryou, Chongsuk

    2008-01-01

    The cerebellum is involved in complex physiological functions including motor control, sensory perception, cognition, language, and emotion. Humans and animals with prion diseases are characterized clinically by ataxia, postural abnormalities and cognitive decline. Pathology in the cerebellum affected by prions includes spongiform degeneration, neuronal loss, and gliosis. To develop an in vitro model system for studying prion biology in cerebellar cells, we established and characterized an im...

  11. Differential contributions of the superior and inferior parietal cortex to feedback versus feedforward control of tools

    OpenAIRE

    Macuga, Kristen L.; Frey, Scott H.

    2014-01-01

    Damage to the superior and/or inferior parietal lobules (SPL, IPL) (Sirigu et al., 1996) or cerebellum (Grealy and Lee, 2011) can selectively disrupt motor imagery, motivating the hypothesis that these regions participate in predictive (i.e., feedforward) control. If so, then the SPL, IPL, and cerebellum should show greater activity as the demands on feedforward control increase from visually-guided execution (closed-loop) to execution without visual feedback (open-loop) to motor imagery. Usi...

  12. Multiple solid pilocytic astrocytomas in cerebleiium with neurofibromatosis type: A case report

    International Nuclear Information System (INIS)

    Pilocytic astrocytoma usually has a classic imaging manifestation of a solitary, cyst-like mass with a strong contrast-enhancing mural nodule. There is only one published report so far of multiple solid and cyst type pilocytic astrocytomas in the cerebellum in neurofibromatosis type 1 (NF1) patient from the United States in 2007. We report a case of pilocytic astrocytoma presenting with only solid, multiple pilocytic astrocytomas in the cerebellum in NF1 patient.

  13. Cerebellar and Hippocampal Activation During Eyeblink ConditioningDepends on the Experimental Paradigm: A MEG Study

    OpenAIRE

    Peter Kirsch; Caroline Achenbach; Martina Kirsch; Matthias Heinzmann; Anne Schienle; Dieter Vaitl

    2003-01-01

    The cerebellum and the hippocampus are key structures for the acquisition of conditioned eyeblink responses. Whereas the cerebellum seems to be crucial for all types of eyeblink conditioning, the hippocampus appears to be involved only in complex types of learning. We conducted a differential conditioning study to explore the suitability of the design for magnetencephalography (MEG). In addition, we compared cerebellar and hippocampal activation during differential delay and trace conditionin...

  14. Atypical cerebral and cerebellar language organisation: a case study

    OpenAIRE

    Dun, Kim; Witte, Elke; Daele, Wendy Van; Van Hecke, Wim; Manto, Mario; Mariën, Peter

    2015-01-01

    Background In the majority of right-handed subjects, language processing is subserved by a close interplay between the left cerebral hemisphere and right cerebellum. Within this network, the dominant fronto-insular region and the contralateral posterior cerebellum are crucially implicated in oral language production. Case Presentation We report atypical anatomoclinical findings in a right-handed patient with an extensive right cerebellar infarction and an older left fronto-insular stroke. Sta...

  15. Clinical and morphopathological characteristics of an enzootic occurrence of acute coenurosis (Coenurus cerebralis) in a sheep herd

    OpenAIRE

    Farjani Kish, GH.; Khodakaram-Tafti, A.; Hajimohammadi, A.; Ahmadi, N.

    2013-01-01

    In this study, 30 sheep from a flock suddenly showed acute neurological symptoms associated with more than 30 % mortality. At necropsy, thickening associated with congestion and turbidity of meningeal membranes particularly on cerebellum, focal to multifocal necrotic areas and whitish spots measuring 1 to 3 cm in diameter were observed in the cortex of cerebrum and cerebellum. Grossly, numerous white tracts were also observed in the myocardium. Histopathologically, the cross sections of coenu...

  16. Moving, sensing and learning with cerebellar damage

    OpenAIRE

    Bastian, Amy J.

    2011-01-01

    The cerebellum is a subcortical brain structure that is essential for learning and controlling movement. Recent work shows that the cerebellum also plays a role in certain perceptual abilities, beyond what would be expected secondary to poor movement control. This review covers these and other recent advances, focusing on how cerebellar damage affects human abilities ranging from sensory perception to movement control and motor learning.

  17. Von hippel-lindaus disease: Report of three cases and review of the literature Doença de von Hippel-Lindau: relato de três casos e revisão da literatura

    OpenAIRE

    Luiz F. Bleggi-Torres; Lúcia de Noranha; J. Fillus Neto; José E. Queiroz Telles; Luiz E. Madalozzo

    1995-01-01

    The authors present the autopsy findings of two related patients and the biopsy findings of a thrid member of the family. The oldest member was 34 years old at death and on postmortem examination he had haemangioblastomas in the retina, cerebellum, medulla and spinal cord. Other findings were renal cell carcinoma, phaechromocytoma, cysts of kidney and pancreas, hydromyelia and atypical meningiomas. His brother died when 30 years old. The autopsy revealed haemangioblastomas of cerebellum, rena...

  18. Dual task effect on postural control in patients with degenerative cerebellar disorders

    OpenAIRE

    Jacobi, H.; Alfes, J.; Minnerop, Martina; Konczak, J; Klockgether, T; Timmann, D.

    2015-01-01

    Background The cerebellum plays an important role for balance control and the coordination of voluntary movements. Beyond that there is growing evidence that the cerebellum is also involved in cognitive functions. How ataxic motor symptoms are influenced by simultaneous performance of a cognitive task, however, has rarely been assessed and some of the findings are contradictory. We assessed stance in 20 patients with adult onset degenerative almost purely cerebellar disorders and 20 healthy c...

  19. Treadmill exercise improves motor coordination through ameliorating Purkinje cell loss in amyloid beta23-35-induced Alzheimer’s disease rats

    OpenAIRE

    Lee, Jae-Min; Shin, Mal-Soon; Ji, Eun-Sang; Kim, Tae-Woon; Cho, Han-Sam; Kim, Chang-Ju; Jang, Myung-Soo; Kim, Tae-Wook; Kim, Bo-Kyun; Kim, Dong-Hee

    2014-01-01

    Alzheimer’s disease (AD) is a most common age-related neurodegenerative disease. AD is characterized by a progressive loss of neurons causing cognitive dysfunction. The cerebellum is closely associated with integration of movement, including motor coordination, control, and equilibrium. In the present study, we evaluated the effect of tread-mill exercise on the survival of Purkinje neurons in relation with reactive astrocyte in the cerebellum using Aβ25–35–induced AD rats. AD was induced by a...

  20. Imaging Spectrum of Cerebellar Pathologies: A Pictorial Essay

    International Nuclear Information System (INIS)

    The cerebellum is a crucial structure of hindbrain which helps in maintaining motor tone, posture, gait and also coordinates skilled voluntary movements including eye movements. Cerebellar abnormalities have different spectrum, presenting symptoms and prognosis as compared to supratentorial structures and brainstem. This article intends to review the various pathological processes involving the cerebellum along with their imaging features on MR, which are must to know for all radiologists, neurologists and neurosurgeons for their prompt diagnosis and management

  1. Multiple solid pilocytic astrocytomas in cerebleiium with neurofibromatosis type: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seo Young; Kim, Myung Soon; Kim, Young Ju [Dept. of Radiology, Yonsei University Wonju College of Medicine, Wonju Severance Christian Hospital, Wonju (Korea, Republic of)

    2014-02-15

    Pilocytic astrocytoma usually has a classic imaging manifestation of a solitary, cyst-like mass with a strong contrast-enhancing mural nodule. There is only one published report so far of multiple solid and cyst type pilocytic astrocytomas in the cerebellum in neurofibromatosis type 1 (NF1) patient from the United States in 2007. We report a case of pilocytic astrocytoma presenting with only solid, multiple pilocytic astrocytomas in the cerebellum in NF1 patient.

  2. A closer look at visually guided saccades in autism and Asperger’s disorder

    OpenAIRE

    Beth Johnson; Lynette Millist

    2012-01-01

    Motor impairments have been found to be a significant clinical feature associated with autism and Asperger’s disorder (AD) in addition to core symptoms of communication and social cognition deficits. Motor deficits in high-functioning autism (HFA) and AD may differentiate these disorders, particularly with respect to the role of the cerebellum in motor functioning. Current neuroimaging and behavioural evidence suggests greater disruption of the cerebellum in HFA than AD. Investigations of ocu...

  3. High membrane protein oxidation in the human cerebral cortex

    OpenAIRE

    Matthias Granold; Bernd Moosmann; Irina Staib-Lasarzik; Thomas Arendt; Adriana del Rey; Kristin Engelhard; Christian Behl; Parvana Hajieva

    2014-01-01

    Oxidative stress is thought to be one of the main mediators of neuronal damage in human neurodegenerative disease. Still, the dissection of causal relationships has turned out to be remarkably difficult. Here, we have analyzed global protein oxidation in terms of carbonylation of membrane proteins and cytoplasmic proteins in three different mammalian species: aged human cortex and cerebellum from patients with or without Alzheimer's disease, mouse cortex and cerebellum from young and old anim...

  4. MyoD is a tumor suppressor gene in Medulloblastoma

    OpenAIRE

    Dey, Joyoti; Dubuc, Adrian M.; Pedro, Kyle D.; Thirstrup, Derek; Mecham, Brig; Northcott, Paul A.; Wu, Xiaochong; Shih, David; Tapscott, Stephen J.; LeBlanc, Michael; Taylor, Michael D.; Olson, James M.

    2013-01-01

    While medulloblastoma, a pediatric tumor of the cerebellum, is characterized by aberrations in developmental pathways, the majority of genetic determinants remain unknown. An unbiased Sleeping Beauty transposon screen revealed MyoD as a putative medulloblastoma tumor suppressor. This was unexpected, as MyoD is a muscle differentiation factor and not previously known to be expressed in cerebellum or medulloblastoma. In response to deletion of one allele of MyoD, two other Sonic hedgehog-driven...

  5. The role of the membrane cytoskeleton cross-linker ezrin in medulloblastoma cells

    OpenAIRE

    Osawa, Hirokatsu; Smith, Christian A.; Ra, Young Shin; Kongkham, Paul; Rutka, James T.

    2009-01-01

    Medulloblastoma is a highly malignant brain tumor that occurs predominantly in children. The molecular pathogenesis of medulloblastoma is under investigation. Previously, we used complementary DNA micro-array analysis to compare patterns of gene expression in medulloblastoma samples versus normal cerebellum. The cytoskeletal protein ezrin was found to be overexpressed in medulloblastoma compared with normal cerebellum, an observation that was further validated by immunohistochemistry and real...

  6. Somatostatin receptors are expressed by immature cerebellar granule cells: evidence for a direct inhibitory effect of somatostatin on neuroblast activity.

    OpenAIRE

    Gonzalez, B; Leroux, P.; Lamacz, M; Bodenant, C; Balazs, R.; Vaudry, H.

    1992-01-01

    Somatostatin and somatostatin receptors are transiently expressed in the immature rat cerebellar cortex but virtually undetectable in the cerebellum of adults. Although somatostatin binding sites have been visualized during the postnatal period in the external granule cell layer, the type of cell that expresses somatostatin receptors has never been identified; thus, the potential function of somatostatin in the developing cerebellum remains unknown. In the present study, we have taken advanta...

  7. Deficits in reflexive covert attention following cerebellar injury.

    Science.gov (United States)

    Striemer, Christopher L; Cantelmi, David; Cusimano, Michael D; Danckert, James A; Schweizer, Tom A

    2015-01-01

    Traditionally the cerebellum has been known for its important role in coordinating motor output. Over the past 15 years numerous studies have indicated that the cerebellum plays a role in a variety of cognitive functions including working memory, language, perceptual functions, and emotion. In addition, recent work suggests that regions of the cerebellum involved in eye movements also play a role in controlling covert visual attention. Here we investigated whether regions of the cerebellum that are not strictly tied to the control of eye movements might also contribute to covert attention. To address this question we examined the effects of circumscribed cerebellar lesions on reflexive covert attention in a group of patients (n = 11) without any gross motor or oculomotor deficits, and compared their performance to a group of age-matched controls (n = 11). Results indicated that the traditional RT advantage for validly cued targets was significantly smaller at the shortest (50 ms) SOA for cerebellar patients compared to controls. Critically, a lesion overlap analysis indicated that this deficit in the rapid deployment of attention was linked to damage in Crus I and Crus II of the lateral cerebellum. Importantly, both cerebellar regions have connections to non-motor regions of the prefrontal and posterior parietal cortices-regions important for controlling visuospatial attention. Together, these data provide converging evidence that both lateral and midline regions of the cerebellum play an important role in the control of reflexive covert visual attention. PMID:26300756

  8. Deficits in reflexive covert attention following cerebellar injury.

    Directory of Open Access Journals (Sweden)

    Christopher eStriemer

    2015-08-01

    Full Text Available Traditionally the cerebellum has been known for its important role in coordinating motor output. Over the past fifteen years numerous studies have indicated that the cerebellum plays a role in a variety of cognitive functions including working memory, language, perceptual functions, and emotion. In addition, recent work suggests that regions of the cerebellum involved in eye movements also play a role in controlling covert visual attention. Here we investigated whether regions of the cerebellum that are not strictly tied to the control of eye movements might also contribute to covert attention. To address this question we examined the effects of circumscribed cerebellar lesions on reflexive covert attention in a group of patients (n=11 without any gross motor or oculomotor deficits, and compared their performance to a group of age-matched controls (n=11. Results indicated that the traditional RT advantage for validly cued targets was significantly smaller at the shortest (50ms SOA for cerebellar patients compared to controls. Critically, a lesion overlap analysis indicated that this deficit in the rapid deployment of attention was linked to damage in Crus I and Crus II of the lateral cerebellum. Importantly, both cerebellar regions have connections to non-motor regions of the prefrontal and posterior parietal cortices – regions important for controlling visuospatial attention. Together, these data provide converging evidence that both lateral and midline regions of the cerebellum play an important role in the control of reflexive covert visual attention.

  9. Regional cerebral blood flow measured with N-isopropyl-p-[123I]iodoamphetamine single-photon emission tomography in patients with Joseph disease

    International Nuclear Information System (INIS)

    Regional cerebral blood flow (rCBF) was measured in five Japanese patients who were clinically diagnosed as having Joseph disease, also called Machado-Joseph disease or Azorean disease, using N-isopropyl-p-[123I]iodoamphetamine (IMP) and single-photon emission tomography (SPET). Cerebellar atrophy was evaluated by a five-step rating scale as defined on X-ray computed tomography (X-CT). Compared with ten age-matched normal controls (mean cerebellar CBF ± SD: 66.9 ± 6.6 ml/100 g/min), rCBF in patients with Joseph disease was significantly decreased in the cerebellum (mean ± SD: 50.2 ± 7.3 ml/100 g/min). No significant relationship, however, was found between the decrease in rCBF in the cerebellum and the degree of cerebellar atrophy on X-CT. rCBF in the cerebellum was minimally decreased in one patient who had severe cerebellar atrophy and in two patients with moderate atrophy. These data may support the findings that Purkinje cells in the cerebellum are almost normal in Joseph disease, and that the granular and molecular layers remain intact in spite of cortical atrophy of the cerebellum. It is concluded that [123I]-IMP SPET is able to identify pathological and metabolic changes in the cerebellum that do not appear on X-CT or magnetic resonance imaging, and thus is useful for the diagnosis of Joseph disease. (orig.)

  10. Cerebella segmentation on MR images of pediatric patients with medulloblastoma

    Science.gov (United States)

    Shan, Zu Y.; Ji, Qing; Glass, John; Gajjar, Amar; Reddick, Wilburn E.

    2005-04-01

    In this study, an automated method has been developed to identify the cerebellum from T1-weighted MR brain images of patients with medulloblastoma. A new objective function that is similar to Gibbs free energy in classic physics was defined; and the brain structure delineation was viewed as a process of minimizing Gibbs free energy. We used a rigid-body registration and an active contour (snake) method to minimize the Gibbs free energy in this study. The method was applied to 20 patient data sets to generate cerebellum images and volumetric results. The generated cerebellum images were compared with two manually drawn results. Strong correlations were found between the automatically and manually generated volumetric results, the correlation coefficients with each of manual results were 0.971 and 0.974, respectively. The average Jaccard similarities with each of two manual results were 0.89 and 0.88, respectively. The average Kappa indexes with each of two manual results were 0.94 and 0.93, respectively. These results showed this method was both robust and accurate for cerebellum segmentation. The method may be applied to various research and clinical investigation in which cerebellum segmentation and quantitative MR measurement of cerebellum are needed.

  11. Species differences in mGluR5 binding sites in mammalian central nervous system determined using in vitro binding with [18F]F-PEB

    International Nuclear Information System (INIS)

    Binding of [18F]3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ([18F]F-PEB) was evaluated in membranes and tissue sections prepared from rat, rhesus and human brain. Saturation equilibrium binding experiments with frozen brain cortex and caudate-putamen membranes of young adult rhesus and human and with cortex and striatum from rat yielded data indicative of specific high-affinity binding (KD=0.1-0.15 nM, n≥3) to a saturable site previously shown to be metabotropic glutamate receptor 5 (mGluR5; Patel S, Ndubizu O, Hamill T, Chaudhary A, Burns HD, Hargreaves RJ, Gibson RE. Screening cascade and development of potential positron emission tomography radiotracers for mGluR5: in vitro and in vivo characterization. Mol Imaging Biol 2005;7:314-323). High-affinity binding of [18F]F-PEB was also detected in cerebellum membranes from rat, rhesus and human. The density of binding sites (Bmax) measured using [18F]F-PEB followed the rank order cortex∼caudate-putamen/striatum>cerebellum for all three species, with the cerebellum Bmax being significantly lower than that observed in the other regions. Receptor autoradiography studies in tissue sections confirmed that the regional distribution of [18F]F-PEB in mammalian central nervous system is consistent with that of mGluR5 and that a small but specific mGluR5 signal is observed in rhesus and human cerebellum. A small and quantifiable specific signal could also be observed in rat cerebellum using this radiotracer. Immunohistochemical analysis in brain sections revealed a rank order of staining in rhesus and human brain of cortex∼caudate-putamen>cerebellum. Rat brain immunohistochemistry followed the same rank order, although the staining in the cerebellum was significantly lower. Using a 'no-wash' wipe assay, the development of a specific signal within 20 min of incubation of tissue brain sections (>60% in the cortex and striatum; 36-49% in the cerebellum) from all three species confirmed previous in vivo data from rat and

  12. Species differences in mGluR5 binding sites in mammalian central nervous system determined using in vitro binding with [{sup 18}F]F-PEB

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Shil [Department of Research Imaging, Merck Research Laboratories, West Point, PA 19486 (United States)], E-mail: shailendra_patel@merck.com; Hamill, Terence G.; Connolly, Brett; Jagoda, Elaine; Li Wenping; Gibson, Raymond E. [Department of Research Imaging, Merck Research Laboratories, West Point, PA 19486 (United States)

    2007-11-15

    Binding of [{sup 18}F]3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ([{sup 18}F]F-PEB) was evaluated in membranes and tissue sections prepared from rat, rhesus and human brain. Saturation equilibrium binding experiments with frozen brain cortex and caudate-putamen membranes of young adult rhesus and human and with cortex and striatum from rat yielded data indicative of specific high-affinity binding (K{sub D}=0.1-0.15 nM, n{>=}3) to a saturable site previously shown to be metabotropic glutamate receptor 5 (mGluR5; Patel S, Ndubizu O, Hamill T, Chaudhary A, Burns HD, Hargreaves RJ, Gibson RE. Screening cascade and development of potential positron emission tomography radiotracers for mGluR5: in vitro and in vivo characterization. Mol Imaging Biol 2005;7:314-323). High-affinity binding of [{sup 18}F]F-PEB was also detected in cerebellum membranes from rat, rhesus and human. The density of binding sites (B{sub max}) measured using [{sup 18}F]F-PEB followed the rank order cortex{approx}caudate-putamen/striatum>cerebellum for all three species, with the cerebellum B{sub max} being significantly lower than that observed in the other regions. Receptor autoradiography studies in tissue sections confirmed that the regional distribution of [{sup 18}F]F-PEB in mammalian central nervous system is consistent with that of mGluR5 and that a small but specific mGluR5 signal is observed in rhesus and human cerebellum. A small and quantifiable specific signal could also be observed in rat cerebellum using this radiotracer. Immunohistochemical analysis in brain sections revealed a rank order of staining in rhesus and human brain of cortex{approx}caudate-putamen>cerebellum. Rat brain immunohistochemistry followed the same rank order, although the staining in the cerebellum was significantly lower. Using a 'no-wash' wipe assay, the development of a specific signal within 20 min of incubation of tissue brain sections (>60% in the cortex and striatum; 36-49% in the cerebellum

  13. Aberrant cerebellar connectivity in motor and association networks in schizophrenia

    Directory of Open Access Journals (Sweden)

    Ann K. Shinn

    2015-03-01

    Full Text Available Schizophrenia is a devastating illness characterized by disturbances in multiple domains. The cerebellum is involved in both motor and non-motor functions, and the cognitive dysmetria and dysmetria of thought models propose that abnormalities of the cerebellum may contribute to schizophrenia signs and symptoms. The cerebellum and cerebral cortex are reciprocally connected via a modular, closed-loop network architecture, but few schizophrenia neuroimaging studies have taken into account the topographical and functional heterogeneity of the cerebellum. In this study, using a previously defined 17-network cerebral cortical parcellation system as the basis for our functional connectivity seeds, we systematically investigated connectivity abnormalities within the cerebellum of 44 schizophrenia patients and 28 healthy control participants. We found selective alterations in cerebro-cerebellar functional connectivity. Specifically, schizophrenia patients showed decreased cerebro-cerebellar functional connectivity in higher level association networks (ventral attention, salience, control, and default mode networks relative to healthy control participants. Schizophrenia patients also showed increased cerebro-cerebellar connectivity in somatomotor and default mode networks, with the latter showing no overlap with the regions found to be hypoconnected within the same default mode network. Finally, we found evidence to suggest that somatomotor and default mode networks may be inappropriately linked in schizophrenia. The relationship of these dysconnectivities to schizophrenia symptoms, such as neurological soft signs and altered sense of agency, is discussed. We conclude that the cerebellum ought to be considered for analysis in all future studies of network abnormalities in SZ, and further suggest the cerebellum as a potential target for further elucidation, and possibly treatment, of the underlying mechanisms and network abnormalities producing symptoms of

  14. Cerebellar Transcranial Direct Current Stimulation (ctDCS): A Novel Approach to Understanding Cerebellar Function in Health and Disease.

    Science.gov (United States)

    Grimaldi, Giuliana; Argyropoulos, Georgios P; Bastian, Amy; Cortes, Mar; Davis, Nicholas J; Edwards, Dylan J; Ferrucci, Roberta; Fregni, Felipe; Galea, Joseph M; Hamada, Masahi; Manto, Mario; Miall, R Chris; Morales-Quezada, Leon; Pope, Paul A; Priori, Alberto; Rothwell, John; Tomlinson, S Paul; Celnik, Pablo

    2016-02-01

    The cerebellum is critical for both motor and cognitive control. Dysfunction of the cerebellum is a component of multiple neurological disorders. In recent years, interventions have been developed that aim to excite or inhibit the activity and function of the human cerebellum. Transcranial direct current stimulation of the cerebellum (ctDCS) promises to be a powerful tool for the modulation of cerebellar excitability. This technique has gained popularity in recent years as it can be used to investigate human cerebellar function, is easily delivered, is well tolerated, and has not shown serious adverse effects. Importantly, the ability of ctDCS to modify behavior makes it an interesting approach with a potential therapeutic role for neurological patients. Through both electrical and non-electrical effects (vascular, metabolic) ctDCS is thought to modify the activity of the cerebellum and alter the output from cerebellar nuclei. Physiological studies have shown a polarity-specific effect on the modulation of cerebellar-motor cortex connectivity, likely via cerebellar-thalamocortical pathways. Modeling studies that have assessed commonly used electrode montages have shown that the ctDCS-generated electric field reaches the human cerebellum with little diffusion to neighboring structures. The posterior and inferior parts of the cerebellum (i.e., lobules VI-VIII) seem particularly susceptible to modulation by ctDCS. Numerous studies have shown to date that ctDCS can modulate motor learning, and affect cognitive and emotional processes. Importantly, this intervention has a good safety profile; similar to when applied over cerebral areas. Thus, investigations have begun exploring ctDCS as a viable intervention for patients with neurological conditions. PMID:25406224

  15. Transplantation of human induced cerebellar granular-like cells improves motor functions in a novel mouse model of cerebellar ataxia

    Science.gov (United States)

    Zhu, Tongming; Tang, Hailiang; Shen, Yiwen; Tang, Qisheng; Chen, Luping; Wang, Zhifu; Zhou, Ping; Xu, Feng; Zhu, Jianhong

    2016-01-01

    Stem cell-based reparative approaches have been applied to cerebellum-related disorders during the last two decades. Direct lineage reprogramming of human fibroblasts into functional granular neurons holds great promise for biomedical applications such as cerebellum regeneration and cellbased disease modeling. In the present study, we showed that a combination of Ascl1, Sox2 and OCT4, in a culture subsequently treated with secreted factors (BMP4, Wnt3a and FGF8b), was capable of converting human fibroblasts from the scalp tissue of patients with traumatic brain injury (TBI) into functional human induced cerebellar granular-like cells (hiCGCs). Morphological analysis, immunocytochemistry, gene expression and electrophysiological analysis were performed to identify the similarity of induced neuronal cells to human cerebellum granular cells. Our strategy improved the efficiency for hiCGCs induction, which gave the highest conversion efficiency 12.30±0.88%, and Ath1+/Tuj1+ double positive cells to 5.56±0.80%. We transplanted hiCGCs into the cerebellum of NmycTRE/TRE: tTS mice, a novel mouse model of cerebellar ataxia, and demonstrated that the hiCGCs were able to survive, migrate, proliferate and promote mild functional recovery after been grafted into cerebellum.

  16. Regulation of five tubulin isotypes by thyroid hormone during brain development.

    Science.gov (United States)

    Aniello, F; Couchie, D; Gripois, D; Nunez, J

    1991-11-01

    Nucleic acid probes derived from the 3' noncoding region of five tubulin cDNAs were used to study the effects of thyroid hormone deficiency on the expression of the mRNAs encoding two alpha (alpha 1 and alpha 2)- and three beta (beta 2, beta 4, and beta 5)-tubulin isotypes in the developing cerebral hemispheres and cerebellum. The content of alpha 1, which markedly declines during development in both brain regions, is maintained at high levels in the hypothyroid cerebellum, whereas it is decreased in the cerebral hemispheres. The alpha 2 level also declines during development and is decreased in both regions by thyroid hormone deficiency, but only during the two first postnatal weeks. Thyroid hormone deficiency slightly increases at all stages the beta 2 level in the cerebellum, whereas a decrease is observed at early stages in the cerebral hemispheres. The beta 5 level seems to be independent of thyroid hormone in the cerebral hemispheres, whereas it decreases at early stages in the hypothyroid cerebellum. Finally, the expression of the brain-specific beta 4 isotype is markedly depressed by thyroid hormone deficiency, particularly in the cerebellum. These data suggest that the genes encoding the tubulin isotypes are, directly or not, differently regulated by thyroid hormone during brain development. This might contribute to abnormal neurite outgrowth seen in the hypothyroid brain and therefore to impairment in brain functions produced by thyroid hormone deficiency. PMID:1717658

  17. Cerebellar contributions to self-motion perception: evidence from patients with congenital cerebellar agenesis.

    Science.gov (United States)

    Dahlem, Kilian; Valko, Yulia; Schmahmann, Jeremy D; Lewis, Richard F

    2016-05-01

    The cerebellum was historically considered a brain region dedicated to motor control, but it has become clear that it also contributes to sensory processing, particularly when sensory discrimination is required. Prior work, for example, has demonstrated a cerebellar contribution to sensory discrimination in the visual and auditory systems. The cerebellum also receives extensive inputs from the motion and gravity sensors in the vestibular labyrinth, but its role in the perception of head motion and orientation has received little attention. Drawing on the lesion-deficit approach to understanding brain function, we evaluated the contributions of the cerebellum to head motion perception by measuring perceptual thresholds in two subjects with congenital agenesis of the cerebellum. We used a set of passive motion paradigms that activated the semicircular canals or otolith organs in isolation or combination, and compared results of the agenesis patients with healthy control subjects. Perceptual thresholds for head motion were elevated in the agenesis subjects for all motion protocols, most prominently for paradigms that only activated otolith inputs. These results demonstrate that the cerebellum increases the sensitivity of the brain to the motion and orientation signals provided by the labyrinth during passive head movements. PMID:26888100

  18. In vivo characteristics of IBZM in rat brains, an agent for quantitative SPECT imaging of D2 dopamine receptors. A basis for semiquantitative measurement of the receptor density using equilibrium analysis

    International Nuclear Information System (INIS)

    To establish a basis for semiquantitative SPECT measurements of the D2 dopamine receptor density using equilibrium analysis, we evaluated in vivo kinetic properties of 125I-IBZM in rat brains. We measured percent uptakes (% dose/g) of 125I-IBZM in the striatum, frontal cortex, and cerebellum. We made these regional measurements at 15, 30, 45, 60, 90, and 120 minutes after injection, respectively. The specific striatal uptake, which is the uptake difference between striatum and frontal cortex or cerebellum, showed a transient equilibrium phase at 60 min. Theoretically, with these 'reversible' D2 receptor binding ligands, the tracer-uptake ratio of the striatum-to-frontal cortex or cerebellum during the equilibrium phase provides an estimate of binding potential (Bound/Free=Bmax/Kd). Our experiment showed that these ratio increased with time after bolus injection of the tracer. Striatum to frontal cortex or cerebellum ratios which were calculated with pooled data (n=12) at 60 minutes in equilibrium phase showed nearly constant values (C.V.=12.3% and 13.5%, respectively). Although measuring the striatum to frontal cortex or cerebellum ratios near equilibrium phase by bolus injection of the tracer which are widely used in human SPECT study could not exactly signify the binding potential, those ratios at fixed time after injection would be reliable for semiquantitative index. (author)

  19. MRI of spinal cord and brain lesions in subacute combined degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Katsaros, V.K.; Schumacher, M. [Dept. of Neuroradiology, University of Freiburg (Germany); Glocker, F.X.; Hemmer, B. [Department of Neurology, University of Freiburg (Germany)

    1998-11-01

    Subacute combined degeneration is a rare cause of demyelination of the dorsal and lateral columns of the spinal cord and even more rarely of the pyramidal and spinocerebellar tracts and cerebellum. We present the initial and follow-up MRI appearances in a patient with subacute combined degeneration of the spinal cord, brain stem and cerebellum, due to vitamin B{sub 12} deficiency. The lesions in these structures were demonstrated clearly as pathologically high-signal areas on T2-weighted images. These lesions, except those of the brain stem and cerebellum, disappeared 4 months after therapy. MRI 14 months after the patient`s discharge on vitamin B{sub 12} therapy showed the same picture. (orig.) With 4 figs., 11 refs.

  20. Reappraisal of Bergmann glial cells as modulators of cerebellar circuit function

    Directory of Open Access Journals (Sweden)

    Chris I De Zeeuw

    2015-07-01

    Full Text Available Just as there is a huge morphological and functional diversity of neuron types specialized for specific aspects of information processing in the brain, astrocytes have equally distinct morphologies and functions that aid optimal functioning of the circuits in which they are embedded. One type of astrocyte, the Bergmann glial cell of the cerebellum, is a prime example of a highly diversified astrocyte type, the architecture of which is adapted to the cerebellar circuit and facilitates an impressive range of functions that optimize information processing in the adult brain. In this review we expand on the function of the Bergmann glial cell in the cerebellum to highlight the importance of astrocytes not only in housekeeping functions, but also in contributing to plasticity and information processing in the cerebellum.