Cerebellum

Distribution by Scientific Domains
Distribution within Life Sciences

Kinds of Cerebellum

  • developing cerebellum
  • mouse cerebellum
  • neonatal cerebellum
  • rat cerebellum
  • right cerebellum


  • Selected Abstracts


    Venous Infarction of Brainstem and Cerebellum

    JOURNAL OF NEUROIMAGING, Issue 4 2001
    Yakup Krespi MD
    ABSTRACT The authors describe 2 cases of posterior fossa venous infarction. A 56-year-old woman with essential thrombocytemia presented with fluctuating complaints of headache, nausea, vomiting, left-sided numbness-weakness, and dizziness and became progressively stuporous. Cranial magnetic resonance imaging (MRI) showed bilateral parasagittal frontoparietal and left cerebellar contrast-enhancing hemorrhagic lesions. On magnetic resonance venography, the left transverse and sigmoid sinuses were occluded. The second patient, a 39-year-old woman, presented with acute onset of diplopia, numbness of the tongue, vertigo, and right-sided weakness following a gestational age stillbirth. MRI revealed lesions in the right half of midbrain and pons and in the superior part of the right cerebellar hemisphere. Digital subtraction angiography showed right transverse and sigmoid sinus occlusion. The authors suggest that one should investigate the possibility of venous infarction in the presence of posterior fossa lesions that are often hemorrhagic and are not within any arterial territory distribution but respect a known venous drainage pattern. Recognition of the observed clinical and neuroimaging features can lead to earlier diagnosis and, potentially, more effective management. [source]


    Ethanol Acutely Modulates mGluR1-Dependent Long-Term Depression in Cerebellum

    ALCOHOLISM, Issue 7 2010
    Li-Da Su
    Background:, Acute and chronic ethanol exposure produces profound impairments in motor functioning. Individuals with lower sensitivity to the acute motor impairing effects of ethanol have an increased risk of developing alcohol dependence and abuse, and infants with subtle delays in motor coordination development may have an increased risk for subsequently developing alcoholism. Thus, understanding the mechanism by which ethanol disrupts motor functioning is very important. Methods:, Parasagittal slices of the cerebellar vermis (250 ,M thick) were prepared from P17 to 20 Sprague,Dawley rats. Whole-cell recordings of Purkinje cells were obtained with an Axopatch 200B amplifier. Parallel fiber-Purkinje cell synaptic currents were sampled at 1 kHz and digitized at 10 kHz, and synaptic long-term depression (LTD) was observed in either external or internal application of ethanol for comparison. Results:, We determined whether ethanol acutely affects parallel fiber LTD using whole-cell patch-clamp recordings from Purkinje cells. Application of ethanol both externally (50 mM) and internally (17 and 10 mM) significantly suppressed mGluR-mediate slow currents. Short-term external ethanol exposure (50 but not 17 mM) during tetanus blocked mGluR-dependent parallel fiber LTD. Furthermore, internal 17 and 10 mM ethanol completely inhibited this LTD. Conclusions:, The results of the current study demonstrate that ethanol acutely suppresses parallel fiber LTD and may influence the mGluR-mediated slow current intracellularly. This study, plus previous evidence by Carta and colleagues (2006) and Belmeguenai and colleagues (2008), suggests significant actions of ethanol on mGluR-mediated currents and its dependent plasticity in brain. [source]


    Antioxidant Pretreatment Does Not Ameliorate Alcohol-Induced Purkinje Cell Loss in the Developing Rat Cerebellum

    ALCOHOLISM, Issue 7 2005
    Jedidiah J. Grisel
    Background: Recent research has suggested that oxidative stress is a potential mechanism for alcohol-induced injury and that supplementation with antioxidants can ameliorate alcohol-induced damage. In this study, two known antioxidants, melatonin and U83836E, were assessed for their effectiveness in blocking the expected alcohol-induced cerebellar Purkinje cell loss in neonatal rat pups. Methods: Sprague-Dawley rat pups were artificially reared from postnatal days (PDs) 4,9 and were exposed to either alcohol or antioxidants (melatonin or U83836E) individually or in combination. A normal control group (raised by rat dams) was included in this study. On PD 9, the brain from each pup was removed and weighed, and the cerebellar vermis was processed for stereological cell counting. Results: Alcohol exposure during the brain growth spurt produced microencephaly, in addition to significant decreases in the number and density of Purkinje cells in lobule I and the volume of lobule I. The antioxidants did not reduce any of the adverse effects observed from alcohol exposure, and they did not decrease the Purkinje cell number when administered alone. Furthermore, antioxidants did not change the only blood alcohol concentration measured on PD 6. Conclusions: The results confirmed alcohol-induced microencephaly and cerebellar Purkinje cell loss from neonatal alcohol exposure, and they showed that neither antioxidant could attenuate these adverse effects on the developing brain. The inability of antioxidants to reduce Purkinje cell loss from neonatal alcohol exposure suggests the existence of alternative mechanisms for developmental alcohol-induced Purkinje cell loss. [source]


    The Role of Neurotrophic Factors, Apoptosis-Related Proteins, and Endogenous Antioxidants in the Differential Temporal Vulnerability of Neonatal Cerebellum to Ethanol

    ALCOHOLISM, Issue 4 2003
    Marieta Barrow Heaton
    Background: Ethanol produces abnormalities in the developing nervous system, with certain regions being vulnerable during well-defined periods. Neonatal rodent cerebellum is particularly susceptible to ethanol during the early postnatal period [on postnatal days 4-5 (P4-5)], while this region is resistant to ethanol at a slightly later time (P7-9). We assessed basal levels of several substances which may be involved in differential temporal ethanol vulnerability in neonatal cerebellum, and analyzed alterations in these substances after early ethanol exposure. Methods: Assessments were made of neurotrophic factors nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4; apoptosis-related proteins Bcl-2, Bcl-xl, Bax, Bcl-xs, Bad, phosphorylated-Bad, phosphorylated-Akt, and phosphorylated-c-Jun N-terminal kinase; and the antioxidants superoxide dismutase, glutathione reductase, and catalase. These analyses quantified basal levels (in controls), and sequential changes following acute ethanol exposure at the vulnerable and resistant cerebellar periods (P4, P7). Results: Comparisons of basal levels of the molecules assessed between P4 and P7 revealed higher levels of total proapoptotic Bad at p4, higher levels of the protective pAkt kinase at P7, and lower levels of proapoptotic pJNK at P7. Other basal levels did not differ. While ethanol-mediated alterations were found at both ages favoring both apoptosis and survival, the apoptosis-promoting changes produced on P4 exceeded those on P7, and most occurred within the first 2 hr after exposure, a critical survival/death period. The number of alterations favoring survival were similar at the two ages, but at P7 most occurred within the first 2 hr after exposure, possibly acting in a protective manner. Conclusions: Differential temporal vulnerability to ethanol in the neonatal cerebellum appears to be paralleled by cellular alterations in neurotrophic factors, apoptosis-regulatory proteins, and/or antioxidant activities which generally favor apoptosis at the most sensitive age and survival at the resistant age. [source]


    Emotion and the Psychodynamics of the Cerebellum: A Neuro-Psychoanalytic Analysis and Synthesis

    THE INTERNATIONAL JOURNAL OF PSYCHOANALYSIS, Issue 3 2010
    Charles P. Fisher
    First page of article [source]


    Review of animal models for autism: implication of thyroid hormone

    CONGENITAL ANOMALIES, Issue 1 2006
    Miyuki Sadamatsu
    ABSTRACT,, Autism is a behaviorally defined disorder associated with characteristic impairments in social interactions and communication, as well as restricted and repetitive behaviors and interest. Its prevalence was once thought to be 2/10 000, but recently several large autism prevalence reviews revealed that the rate of occurrence was roughly 30/10 000. While it has been considered a developmental disorder, little is certain about its etiology. Neuroanatomical studies at the histological level in the brains of autistic patients provide many arguments in the etiology of autism. Results from postmortem and imaging studies have implicated many major structures of the brain including the limbic system, cerebellum, corpus callosum, basal ganglia and brainstem. There is no single biological or clinical marker for autism. While several promising candidate genes have been presented, the critical loci are yet unknown. Environmental influences such as rubella virus, valproic acid, and thalidomide exposure during pregnancy are also considered important, as concordance in monozygotic twins is less than 100% and the phenotypic expression of the disorder varies widely. It is thus hypothesized that non-genetic mechanisms contribute to the onset of autistic syndrome. In light of these ambiguities, hope is held that an animal model of autism may help elucidate matters. In this article, we overview most of the currently available animal models for autism, and propose the rat with mild and transient neonatal hypothyroidism as a novel model for autism. [source]


    Functions of glutamate transporters in cerebellar Purkinje cell synapses

    ACTA PHYSIOLOGICA, Issue 1 2009
    Y. Takayasu
    Abstract Glutamate transporters play a critical role in the maintenance of low extracellular concentrations of glutamate, which prevents the overactivation of post-synaptic glutamate receptors. Four distinct glutamate transporters, GLAST/EAAT1, GLT-1/EAAT2, EAAC1/EAAT3 and EAAT4, are distributed in the molecular layer of the cerebellum, especially near glutamatergic synapses in Purkinje cells (PCs). This review summarizes the current knowledge about the differential roles of these transporters at excitatory synapses of PCs. Data come predominantly from electrophysiological experiments in mutant mice that are deficient in each of these transporter genes. GLAST expressed in Bergmann glia contributes to the clearing of the majority of glutamate that floods out of the synaptic cleft immediately after transmitter release from the climbing fibre (CF) and parallel fibre (PF) terminals. It is indispensable to maintain a one-to-one relationship in synaptic transmission at the CF synapses by preventing transcellular glutamate spillover. GLT-1 plays a similar but minor role in the uptake of glutamate as GLAST. Although the loss of neither GLAST nor GLT-1 affects cerebellar morphology, the deletion of both GLAST and GLT-1 genes causes the death of the mutant animal and hinders the folium formation of the cerebellum. EAAT4 removes the low concentrations of glutamate that escape from uptake by glial transporters, preventing the transmitter from spilling over into neighbouring synapses. It also regulates the activation of metabotropic glutamate receptor 1 (mGluR1) in perisynaptic regions at PF synapses, which in turn affects mGluR1-mediated events including slow EPSCs and long-term depression. No change in synaptic function is detected in mice that are deficient in EAAC1. [source]


    Physiological functions of glucose-inhibited neurones

    ACTA PHYSIOLOGICA, Issue 1 2009
    D. Burdakov
    Abstract Glucose-inhibited neurones are an integral part of neurocircuits regulating cognitive arousal, body weight and vital adaptive behaviours. Their firing is directly suppressed by extracellular glucose through poorly understood signalling cascades culminating in opening of post-synaptic K+ or possibly Cl, channels. In mammalian brains, two groups of glucose-inhibited neurones are best understood at present: neurones of the hypothalamic arcuate nucleus (ARC) that express peptide transmitters NPY and agouti-related peptide (AgRP) and neurones of the lateral hypothalamus (LH) that express peptide transmitters orexins/hypocretins. The activity of ARC NPY/AgRP neurones promotes food intake and suppresses energy expenditure, and their destruction causes a severe reduction in food intake and body weight. The physiological actions of ARC NPY/AgRP cells are mediated by projections to numerous hypothalamic areas, as well as extrahypothalamic sites such as the thalamus and ventral tegmental area. Orexin/hypocretin neurones of the LH are critical for normal wakefulness, energy expenditure and reward-seeking, and their destruction causes narcolepsy. Orexin actions are mediated by highly widespread central projections to virtually all brain areas except the cerebellum, including monosynaptic innervation of the cerebral cortex and autonomic pre-ganglionic neurones. There, orexins act on two specific G-protein-coupled receptors generally linked to neuronal excitation. In addition to sensing physiological changes in sugar levels, the firing of both NPY/AgRP and orexin neurones is inhibited by the ,satiety' hormone leptin and stimulated by the ,hunger' hormone ghrelin. Glucose-inhibited neurones are thus well placed to coordinate diverse brain states and behaviours based on energy levels. [source]


    Mechanisms of metabotropic glutamate receptor-mediated synaptic signalling in cerebellar Purkinje cells

    ACTA PHYSIOLOGICA, Issue 1 2009
    J. Hartmann
    Abstract The metabotropic glutamate receptors type 1 (mGluR1s) are required for a normal function of the mammalian cerebellum. These G-protein-coupled receptors are abundantly expressed in the principle cerebellar cells, namely the Purkinje neurones. Under physiological conditions, mGluR1s are activated during repetitive activity of both afferent glutamatergic synaptic inputs provided by the climbing and parallel fibres respectively. Unlike the common ionotropic glutamate receptors that underlie rapid synaptic excitation, mGluR1s produce a complex post-synaptic response consisting of a Ca2+ -release signal from intracellular stores and a slow excitatory post-synaptic potential. While it is well established that the mGluR1-dependent Ca2+ -release signal from intracellular stores involves the activation of inositol-trisphosphate receptors, the mechanisms underlying the slow synaptic excitation remained unclear. Here we will review recent evidence indicating an essential role of C-type transient receptor potential (TRPC) cation channels, especially that of the subunit TRPC3, for the generation of the mGluR1-dependent synaptic current. For the signalling pathways underlying both, Ca2+ -release from intracellular stores and the slow synaptic potential, we present current knowledge about the activators, downstream effectors and possible roles for mGluR1-dependent signalling in Purkinje neurones. [source]


    The heterogeneity of causes and courses of attention-deficit/hyperactivity disorder

    ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2009
    H-C. Steinhausen
    Objective:, Attention-deficit / Hyperactivity Disorder (ADHD) is a frequent mental disorder with onset in childhood and persistence into adulthood in a sizeable number of people. Despite a rather simple clinical definition, ADHD has many facets because of frequent co-morbid disorders and varying impact on psychosocial functioning. Thus, there is considerable heterogeneity in various domains. Method:, A review of recent research findings in: i) selected domains of aetiology reflecting the role of genes, brain structures and functioning and the interplay of causal factors and ii) clinical heterogeneity in terms of co-morbidities, gender effects, courses and outcomes. Results:, Molecular genetic studies have identified a number of candidate genes which have a small effect on behavioural variation in ADHD. In the most recent Genome Scan Meta Analysis of seven ADHD linkage studies, genome-wide significant linkage was identified on chromosome 16. The volume of both the total brain and various regions including the prefrontal cortex, the caudate nucleus and the vermis of the cerebellum is smaller in ADHD. Functional MRI has documented a specific deficit of frontostriatal networks in ADHD. Integrative aetiological models have to take the interaction of gene and environment on various dysfunctions into account. Clinical heterogeneity results from frequent associations with various co-morbidities, the impact of the disorder on psychosocial functioning, and gender effects. Partly, these effects are evident also in the course and outcome of ADHD. Conclusion:, ADHD is a chronic mental disorder with a complex aetiology. So far, various neurobiological factors have been identified that need to be studied further to better understand their interaction with environmental factors. The clinical presentation and the long-term course of ADHD are manifold. [source]


    Isthmus organizer for mesencephalon and metencephalon

    DEVELOPMENT GROWTH & DIFFERENTIATION, Issue 2008
    Harukazu Nakamura
    The vertebrate central nervous system is elaborated from a simple neural tube. Brain vesicles formation is the first sign of regionalization. Classical transplantation using quail and chick embryos revealed that the mesencephalon,metencephalon boundary (isthmus) functions as an organizer of the mesencephalon and metencephalon. Fgf8 is accepted as a main organizing molecule of the isthmus. Strong Fgf8 signal activates the Ras-ERK signaling pathway to differentiate the cerebellum. In this review, the historical background of the means of identifying the isthmus organizer and the molecular mechanisms of signal transduction for tectum and cerebellum differentiation is reviewed. [source]


    How does Fgf signaling from the isthmic organizer induce midbrain and cerebellum development?

    DEVELOPMENT GROWTH & DIFFERENTIATION, Issue 6 2004
    Tatsuya Sato
    The mesencephalic/rhombomere 1 border (isthmus) is an organizing center for early development of midbrain and cerebellum. In this review, we summarize recent progress in studies of Fgf signaling in the isthmus and discuss how the isthmus instructs the differentiation of the midbrain versus cerebellum. Fgf8 is shown to play a pivotal role in isthmic organizer activity. Only a strong Fgf signal mediated by Fgf8b activates the Ras-extracellular signal-regulated kinase (ERK) pathway, and this is sufficient to induce cerebellar development. A lower level of signaling transduced by Fgf8a, Fgf17 and Fgf18 induce midbrain development. Numerous feedback loops then maintain appropriate mesencephalon/rhombomere1 and organizer gene expression. [source]


    The use of neuroimaging in the diagnosis of mitochondrial disease

    DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2010
    Seth D. Friedman
    Abstract Mutations in nuclear and mitochondrial DNA impacting mitochondrial function result in disease manifestations ranging from early death to abnormalities in all major organ systems and to symptoms that can be largely confined to muscle fatigue. The definitive diagnosis of a mitochondrial disorder can be difficult to establish. When the constellation of symptoms is suggestive of mitochondrial disease, neuroimaging features may be diagnostic and suggestive, can help direct further workup, and can help to further characterize the underlying brain abnormalities. Magnetic resonance imaging changes may be nonspecific, such as atrophy (both general and involving specific structures, such as cerebellum), more suggestive of particular disorders such as focal and often bilateral lesions confined to deep brain nuclei, or clearly characteristic of a given disorder such as stroke-like lesions that do not respect vascular boundaries in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS). White matter hyperintensities with or without associated gray matter involvement may also be observed. Across patients and discrete disease subtypes (e.g., MELAS, Leigh syndrome, etc.), patterns of these features are helpful for diagnosis. However, it is also true that marked variability in expression occurs in all mitochondrial disease subtypes, illustrative of the complexity of the disease process. The present review summarizes the role of neuroimaging in the diagnosis and characterization of patients with suspected mitochondrial disease. © 2010 Wiley-Liss, Inc. Dev Disabil Res Rev 2010;16:129,135. [source]


    Turner syndrome: Neuroimaging findings: Structural and functional

    DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 4 2009
    Ronan Mullaney
    Abstract Neuroimaging studies of Turner syndrome can advance our understanding of the X chromosome in brain development, and the modulatory influence of endocrine factors. There is increasing evidence from neuroimaging studies that TX individuals have significant differences in the anatomy, function, and metabolism of a number of brain regions; including the parietal lobe; cerebellum, amygdala, hippocampus; and basal ganglia; and perhaps differences in "connectivity" between frontal and parieto-occipital regions. Finally, there is preliminary evidence that genomic imprinting, sex hormones and growth hormone have significant modulatory effects on brain maturation in TS. © 2009 Wiley-Liss, Inc. Dev Disabil Res Rev 2009;15:279,283. [source]


    Enhancer detection in zebrafish permits the identification of neuronal subtypes that express Hox4 paralogs

    DEVELOPMENTAL DYNAMICS, Issue 8 2008
    Beena Punnamoottil
    Abstract Activity of zebrafish hoxb4a in the developing brain was analyzed in comparison to hoxa4a and hoxd4a using unique enhancer detection transgenes. Cytoplasmic YFP revealed shape and axonal projections of neurons in animals with insertions near the Hox4 genes and provided a means for the identification of neuronal subtypes. Despite an early activity of the genes in neuroepithelial cells and later in immature postmitotic neurons, we found reporter expression in distinct neuronal subtypes in the r7,r8-derived hindbrain. Most strikingly, hoxb4a neuronal subtypes projected through the vagus and into the pectoral fin while others formed symmetrically located fiber tracts innervating the cerebellum and the tectum, features that are partially shared by the other two paralogs. Collectively, our expression analysis indicates that hoxb4a in combination with its paralogs may play a significant role in the development of precerebellar, vagal, and pectoral fin neuronal subtypes. Developmental Dynamics 237:2195,2208, 2008. © 2008 Wiley-Liss, Inc. [source]


    Sexual dimorphism of g-protein subunit Gng13 expression in the cortical region of the developing mouse ovary

    DEVELOPMENTAL DYNAMICS, Issue 7 2007
    Akihiro Fujino
    Abstract In our search for genes required for the development and function of mouse gonads, we identified Gng13 (guanine nucleotide binding protein 13, gamma), a gene with an embryonic expression pattern highly restricted to the ovary. Based on reverse transcriptase-polymerase chain reaction (RT-PCR) and whole-mount in situ hybridization, Gng13 is expressed in both XX and XY gonads at embryonic day (E) 11.5, but becomes up-regulated in the XX gonad by E12.5. Expression is retained after treatment with busulfan, a chemical known to eliminate germ cells, pointing to the soma as a site of Gng13 transcription. In situ hybridization of embryonic ovarian tissue sections further localized the expression to the cortex of the developing XX gonad. Gng13 expression in the adult is also highly restricted. Northern blot analyses and Genomic Institute of the Novartis Research Foundation expression profiling of adult tissues detected very high expression in the cerebrum and cerebellum, in addition to, a weaker signal in the ovary. Gng13 belongs to a well-known family of signal transduction molecules with functions in many aspects of development and organ physiology. Here, we report that, in the developing mouse embryo, expression of Gng13 mRNA is highly restricted to the cortex of the XX gonad during sexual differentiation, suggesting a role for this gene during ovarian development. Developmental Dynamics 236:1991,1996, 2007. © 2007 Wiley-Liss, Inc. [source]


    Zic4, a zinc-finger transcription factor, is expressed in the developing mouse nervous system

    DEVELOPMENTAL DYNAMICS, Issue 3 2005
    Carles Gaston-Massuet
    Abstract Zic genes comprise a family of transcription factors, characterized by the presence of a zinc-finger domain containing two cysteines and two histidines (C2-H2). Whereas the embryonic expression patterns of Zic1, 2, 3, and 5 have been described in detail, Zic4 has not yet received close attention. We studied the expression of Zic4 by in situ hybridization during mouse embryogenesis. Zic4 mRNA was first detected at low intensity at embryonic day (E) 9 and, by E10.5, expression was up-regulated in the dorsal midline of the forebrain with a strong, expanded expression domain at the boundary between the diencephalon and telencephalon, the septum, and the lamina terminalis. The choroid plexus of the third ventricle expresses Zic4, as does the dorsal part of the spinal neural tube, excluding the roof plate. The dorsal sclerotome and the dorsomedial lip of the dermomyotome also express Zic4 whereas dorsal root ganglia are negative. At E12.5, Zic4 continues to be expressed in the midline of the forebrain and in the dorsal spinal neural tube. Postnatally, Zic4 is expressed in the granule cells of the postnatal day 2 cerebellum, and in the periventricular thalamus and anterior end of the superior colliculus. We conclude that Zic4 has an expression pattern distinct from, but partly overlapping with, other members of the Zic gene family. Developmental Dynamics 233:1110,1115, 2005. © 2005 Wiley-Liss, Inc. [source]


    Olfactory epithelium influences the orientation of mitral cell dendrites during development

    DEVELOPMENTAL DYNAMICS, Issue 2 2005
    Laura López-Mascaraque
    Abstract We have established previously that, although the olfactory epithelium is absent in the homozygous Pax-6 mutant mouse, an olfactory bulb-like structure (OBLS) does develop. Moreover, this OBLS contains cells that correspond to mitral cells, the primary projection neurons in the olfactory bulb. The current study aimed to address whether the dendrites of mitral cells in the olfactory bulb or in the OBLS mitral-like cells, exhibit a change in orientation in the presence of the olfactory epithelium. The underlying hypothesis is that the olfactory epithelium imparts a trophic signal on mitral and mitral-like cell that influences the growth of their primary dendrites, orientating them toward the surface of the olfactory bulb. Hence, we cultured hemibrains from wild-type and Pax 6 mutant mice from two different embryonic stages (embryonic days 14 and 15) either alone or in coculture with normal olfactory epithelial explants or control tissue (cerebellum). Our results indicate that the final dendritic orientation of mitral and mitral-like cells is directly influenced both by age and indeed by the presence of the olfactory epithelium. Developmental Dynamics 232:325,335, 2005. © 2004 Wiley-Liss, Inc. [source]


    A cognitive and affective pattern in posterior fossa strokes in children: a case series

    DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 7 2010
    MANOELLE KOSSOROTOFF
    Aim, Posterior fossa strokes account for about 10% of ischaemic strokes in children. Although motor and dysautonomic symptoms are common, to our knowledge cognitive and affective deficits have not been described in the paediatric literature. Our aim, therefore, was to describe these symptoms and deficits. Method, In a retrospective study, we included all cases of posterior fossa strokes in children occurring at a single centre between 2005 and 2007, and investigated cognitive and affective deficits. Results, Five males aged 3 to 14 years met the inclusion criteria. They all presented very early with mood disturbances: outbursts of laughter and/or crying and alternating agitation or prostration that disappeared spontaneously within a few days. Persistent cognitive deficits were also diagnosed in all five: initial mutism, then anomia, followed by comprehension deficiency and deficiencies of planning ability, visual,spatial organization, and attention. Despite early and intensive rehabilitation, recovery from these cognitive deficits was slow and sometimes incomplete, and on follow-up they proved to be more disabling than the motor symptoms. Interpretation, These findings are similar to the cerebellar cognitive affective syndrome described in adults, and quite similar to the language and affective deficits observed in children after surgery for posterior fossa tumour. This is consistent with the role of the cerebellum and brainstem in affective and cognitive processes from early development. [source]


    Smooth ocular pursuit in Chiari type II malformation

    DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2007
    Michael S Salman MRCP PhD
    Chiari type II malformation (CII) is a congenital anomaly of the cerebellum and brainstem, both important structures for processing smooth ocular pursuit. CII is associated with myelomeningocele and hydrocephalus. We investigated the effects of CII on smooth pursuit (SP) eye movements, and determined the effects of spinal lesion level, number of shunt revisions, nystagmus, and brain dysmorphology on SP. SP was recorded using an infrared eye tracker in 21 participants with CII (11 males, 10 females; age range 8-19y, mean 14y 3mo [SD 3y 2mo]). Thirty-eight healthy children (21 males, 17 females) constituted the comparison group. Participants followed a visual target moving sinusoidally at ± 10° amplitude, horizontally and vertically at 0.25 or 0.5Hz. SP gains, the ratio of eye to target velocities, were abnormal in the CII group with nystagmus (n= 8). The number of shunt revisions (range 0-10), brain dysmorphology, or spinal lesion level (n= 15 for lower and n= 6 for upper spinal lesion level) did not correlate with SP gains. SP is impaired in children with CII and nystagmus. Abnormal pursuit might be related to the CII dysgenesis or to effects of hydrocephalus. The lack of effect of shunt revisions and abnormal tracking in participants with nystagmus provide evidence that it is related primarily to the cerebellar and brainstem malformation. [source]


    Cerebrospinal fluid insulin-like growth factors IGF-1 and IGF-2 in infantile autism

    DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2006
    Raili Riikonen MD PhD
    There has been little exploration of major biologic regulators of cerebral development in autism. We measured insulin-like growth factors (IGF) -1 and -2 from cerebrospinal fluid (CSF) by radio immunoassay in 25 children with autism (median age 5y 5mo; range 1y 11mo-15y 10mo; 20 males, 5 females), and in 16 age-matched comparison children without disability (median age 7y 4mo; range 1y 1mo-15y 2mo; eight males, eight females). IGF-1 and -2 concentrations were further correlated with age of patients and head size. CSF IGF-1 concentration was significantly lower in patients with autism than in the comparison group. The CSF concentrations of children with autism under 5 years of age were significantly lower than their age-matched comparisons. The head circumferences correlated with CSF IGF-1 in children with autism but no such correlation was found in the comparison group. There was no difference between the two groups in CSF IGF-2 concentrations. No patients with autism had macrocephaly. We conclude that low concentrations of CSF IGF-1 at an early age might be linked with the pathogenesis in autism because IGF-1 is important for the survival of Purkinje cells of the cerebellum. The head growth might be explained by the actions of IGF-1 and -2 reflected in CSF concentrations. [source]


    Ataxia, autism, and the cerebellum: a clinical study of 32 individuals with congenital ataxia

    DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 3 2005
    Ingegerd Åhsgren MD
    The suggested link between autism and cerebellar dysfunction formed the background for a Swedish clinical study in 2001. Thirty-two children (17 females, 15 males; mean age 12y, SD 3y 10mo; range 6 to 21y) with a clinical suspicion of non-progressive congenital ataxia were examined, and parents were interviewed about the presence of neuropsychiatric problems in the child. Twelve children had simple ataxia, eight had ataxic diplegia, and 12 had,borderline'ataxia. All but one of the 32 children had a mild to moderate gross motor disability according to Gross Motor Function Classification System (15 were categorized as level I,16 as level II, and one child as level IV). Neuroimaging and neuropsychological testing were achieved in most cases. There was a strong association between learning disability* and autism spectrum disorder (often combined with hyperactivity disorder) on the one hand, and both simple and borderline,ataxia'on the other, but a weaker link between ataxic diplegia and neuropsychiatric disorders. A correlation between cerebellar macropathology on neuroimaging and neuropsychiatric disorders was not supported. Congenital ataxia might not be a clear-cut syndrome of cerebellar disease, but one of many signs of prenatal events or syndromes, leading to a complex neurodevelopmental disorder including autism and learning disability. [source]


    Evidence for neural stem cells in the medaka optic tectum proliferation zones,

    DEVELOPMENTAL NEUROBIOLOGY, Issue 10 2010
    Alessandro Alunni
    Abstract Few adult neural stem cells have been characterized in vertebrates. Although teleosts continually generate new neurons in many regions of the brain after embryogenesis, only two types of neural stem cells (NSCs) have been reported in zebrafish: glial cells in the forebrain resembling mammalian NSCs, and neuroepithelial cells in the cerebellum. Here, following our previous studies on dividing progenitors (Nguyen et al. [1999]: J Comp Neurol 413:385,404.), we further evidenced NSCs in the optic tectum (OT) of juvenile and adult in the medaka, Oryzias latipes. To detect very slowly cycling progenitors, we did not use the commonly used BrdU/PCNA protocol, in which PCNA may not be present during a transiently quiescent state. Instead, we report the optimizations of several protocols involving long subsequent incubations with two thymidine analogs (IdU and CldU) interspaced with long chase times between incubations. These protocols allowed us to discriminate and localize fast and slow cycling cells in OT of juvenile and adult in the medaka. Furthermore, we showed that adult OT progenitors are not glia, as they express neither brain lipid-binding protein (BLBP) nor glial fibrillary acidic protein (GFAP). We also showed that expression of pluripotency-associated markers (Sox2, Musashi1 and Bmi1) colocalized with OT progenitors. Finally, we described the spatio-temporally ordered population of NSCs and progenitors in the medaka OT. Hence, the medaka appears as an invaluable model for studying neural progenitors that will open the way to further exciting comparative studies of neural stem cells in vertebrates. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 693,713, 2010 [source]


    Differential expression of TrkB isoforms switches climbing fiber-Purkinje cell synaptogenesis to selective synapse elimination

    DEVELOPMENTAL NEUROBIOLOGY, Issue 10 2009
    Rachel M. Sherrard
    Abstract Correct neural function depends on precisely organized connectivity, which is refined from broader projections through synaptic/collateral elimination. In the rat, olivocerebellar topography is refined by regression of multiple climbing fiber (CF) innervation of Purkinje cells (PC) during the first two postnatal weeks. The molecules that initiate this regression are not fully understood. We assessed the role of cerebellar neurotrophins by examining tropomycin receptor kinase (Trk) receptor expression in the inferior olive and cerebellum between postnatal days (P)3-7, when CF-PC innervation changes from synapse formation to selective synapse elimination, and in a denervation-reinnervation model when synaptogenesis is delayed. Trks A, B, and C are expressed in olivary neurons; although TrkA was not transported to the cerebellum and TrkC was unchanged during innervation and reinnervation, suggesting that neither receptor is involved in CF-PC synaptogenesis. In contrast, both total and truncated TrkB (TrkB.T) increased in the olive and cerebellum from P4, whereas full-length and activated phosphorylated TrkB (phospho-TrkB) decreased from P4-5. This reveals less TrkB signaling at the onset of CF regression. This expression pattern was reproduced during CF-PC reinnervation: in the denervated hemicerebellum phospho-TrkB decreased as CF terminals degenerated, then increased in parallel with the delayed neosynaptogenesis as new CFs reinnervated the denervated hemicerebellum. In the absence of this signaling, CF reinnervation did not develop. Our data reveal that olivocerebellar TrkB activity parallels CF-PC synaptic formation and stabilization and is required for neosynaptogenesis. Furthermore, TrkB.T expression rises to reduce TrkB signaling and permit synapse elimination. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009 [source]


    In vivo analysis reveals different apoptotic pathways in pre- and postmigratory cerebellar granule cells of rabbit

    DEVELOPMENTAL NEUROBIOLOGY, Issue 4 2004
    Laura Lossi
    Abstract Naturally occurring neuronal death (NOND) has been described in the postnatal cerebellum of several species, mainly affecting the cerebellar granule cells (CGCs) by an apoptotic mechanism. However, little is known about the cellular pathway(s) of CGC apoptosis in vivo. By immunocytochemistry, in situ detection of fragmented DNA, electron microscopy, and Western blotting, we demonstrate here the existence of two different molecular mechanisms of apoptosis in the rabbit postnatal cerebellum. These two mechanisms affect CGCs at different stages of their maturation and migration. In the external granular layer, premigratory CGCs undergo apoptosis upon phosphorylation of checkpoint kinase 1 (Chk1), and hyperphosphorylation of retinoblastoma protein. In postmigratory CGCs within the internal granular layer, caspase 3 and to a lesser extent 7 and 9 are activated, eventually leading to poly-ADP-ribose polymerase-1 (PARP-1) cleavage and programmed cell death. We conclude that NOND of premigratory CGCs is linked to activation of DNA checkpoint and alteration of normal cell cycle, whereas in postmigratory CGCs apoptosis is, more classically, dependent upon caspase 3 activation. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 437,452, 2004 [source]


    Phosphatidylinositol-3-OH kinase regulatory subunits are differentially expressed during development of the rat cerebellum

    DEVELOPMENTAL NEUROBIOLOGY, Issue 1 2001
    José L. Trejo
    Abstract Recent evidence implicates a central role for PI3K signalling in mediating cell survival during the process of neuronal differentiation. Although PI3K activity is stimulated by a wide range of growth factors and cytokines in different cell lines and tissues, activation of this pathway by insulin-like growth factor I (IGF-I) most likely represents the main survival signal during neuronal differentiation. IGF-I is highly expressed during development of the central nervous system, and thus is a critical factor for the development and maturation of the cerebellum. Upon ligand binding, the IGF-I receptor phosphorylates tyrosine residues in SHC and insulin receptor substrates (IRSs) initiating two main signalling cascades, the MAP kinase and the phosphatidylinositol 3-kinase (PI3K) pathways. Activated PI3K is composed of a catalytic subunit (p110, or ,) associated with one of a large family of regulatory subunits (p85,, p85,, p55,, p55,, and p50,). To evaluate the contributions of these various regulatory subunits to neuronal differentiation, we have used antibodies specific for each of the PI3K subunits. Using these antisera, we now demonstrate that PI3K subunits are differentially regulated in cerebellar development, and that the expression level of the p55, regulatory subunit reaches a maximum during postnatal development, decreasing thereafter to low levels in the adult cerebellum. Furthermore, our studies reveal that the distribution of the various PI3K regulatory subunits varies during development of the cerebellum. Interestingly, p55, is expressed in both glial and neuronal cells; moreover, in Purkinje neurones, this subunit colocalises with the IGF-IR. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 39,50, 2001 [source]


    Eyeblink conditioning using cochlear nucleus stimulation as a conditioned stimulus in developing rats

    DEVELOPMENTAL PSYCHOBIOLOGY, Issue 7 2008
    John H. Freeman
    Abstract Previous studies demonstrated that the development of auditory conditioned stimulus (CS) input to the cerebellum may be a neural mechanism underlying the ontogenetic emergence of eyeblink conditioning in rats. The current study investigated the role of developmental changes in the projections of the cochlear nucleus (CN) in the ontogeny of eyeblink conditioning using electrical stimulation of the CN as a CS. Rat pups were implanted with a bipolar stimulating electrode in the CN and given six 100-trial training sessions with a 300 ms stimulation train in the CN paired with a 10 ms periorbital shock unconditioned stimulus (US) on postnatal days (P) 17,18 or 24,25. Control groups were given unpaired presentations of the CS and US. Rats in both age groups that received paired training showed significant increases in eyeblink conditioned responses across training relative to the unpaired groups. The rats trained on P24,25, however, showed stronger conditioning relative to the group trained on P17,18. Rats with missed electrodes in the inferior cerebellar peduncle or in the cerebellar cortex did not show conditioning. The findings suggest that developmental changes in the CN projections to the pons, inferior colliculus, or medial auditory thalamus may be a neural mechanism underlying the ontogeny of auditory eyeblink conditioning. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 640-646, 2008. [source]


    Cytologic feature by squash preparation of pineal parenchyma tumor of intermediate differentiation

    DIAGNOSTIC CYTOPATHOLOGY, Issue 10 2008
    Keiji Shimada M.D., Ph.D.
    Abstract Pineal parenchyma tumor of intermediate differentiation (PPTID) is a very rare intracranial tumor, and pathological investigation limited to immunohistological and ultrastructural analyses have been published to date. Although intraoperative cytology is one of the important approaches for initial diagnosis in brain tumors, no or little studies on cellular morphology of PPTID have been demonstrated due to its rarity. We report here cytological features of PPTID obtained from stereotactic surgical specimens in a case of 27-year-old female manifested by dizziness and diplopia. Brain MRI revealed an unhomogeneously enhanced, large-sized tumor (56 × 52 × 60 mm) mainly located in the pineal region expanding from the midbrain to superior portion of the cerebellum and the fourth ventricle. Squash cytology showed increased nucleocytoplasmic ratio, hyperchromatic nuclei, and small rosette-like cell cluster but cellular pleomorphism was mild to moderate and necrotic background was not observed. Histology showed high cellularity, moderate nuclear atypia, and small rosette formation but neither bizarre tumor cells nor necrosis was present. Mitotic counts were very low (less than 1 per 10 high-power fields) and the MIB-1 labeling index was relatively high (10.1%). Tumor cells were immunohistochemically positive for neural markers such as synaptophysin, neurospecific enolase but not for glial fibrillary acidic protein or S-100. In some parts, cells were strongly reactive for neurofilament protein. Taken together, we made a final diagnosis of PPTID. This is the first presentation of cytological analysis by squash preparation that gives an important clue to accurate diagnosis of pineal parenchymal tumor and to understand its malignant potential. Diagn. Cytopathol. 2008;36:749,753. © 2008 Wiley-Liss, Inc. [source]


    Atypical teratoid/rhabdoid tumor: Cytology and differential diagnosis in adults

    DIAGNOSTIC CYTOPATHOLOGY, Issue 1 2004
    Jack Raisanen M.D.
    Abstract Atypical teratoid/rhabdoid tumors (AT/RTs) are malignant intracranial neoplasms that usually occur in the posterior fossa of children. They are characterized by cells with paranuclear rhabdoid inclusions, a mesenchymal and epithelial immunohistochemical profile, and 22q deletions with inactivation of the INI1/hSNF5 gene. Although they usually occur in young children, AT/RTs are being recognized in adults with increasing frequency. We report the cytologic features of an AT/RT from the cerebellum of a 45-year-old man and discuss the differential diagnosis in adults. Diagn. Cytopathol. 2004;31:60,63. © 2004 Wiley-Liss, Inc. [source]


    Cloned P2X receptor subunits in cerebellum and hippocampus

    DRUG DEVELOPMENT RESEARCH, Issue 1-2 2001
    Florentina Soto
    Abstract P2X receptor subunits have been found in the brain, with P2X2, P2X4, and P2X6 showing a high level of expression. Here, we review the findings about the distribution of P2X receptor subunits in cerebellum and hippocampus and discuss their implication on the possible roles of ATP as neurotransmitter/neuromodulator in the brain. Drug Dev. Res. 52:133,139, 2001. © 2001 Wiley-Liss, Inc. [source]