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- ItemEmbargoAnálise da expressão diferencial de genes por precursores neuronais e células da glia durante o desenvolvimento cerebelar pós-natal(Universidade Federal de São Paulo (UNIFESP), 2009-01-28) Ribeiro, Maria Emilia de Oliveira Brenha [UNIFESP]; Porcionatto, Marimélia Aparecida [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The role played by glial cells in the development of the central nervous system is not completely understood and the interaction of those cells with neurons is extremely important to the correct development of the brain. The purpose of this thesis was to identify genes differentialy expressed by neuronal precursors and glial cells during postnatal cerebellar development which could be related to the control of axonal outgrowth. Our results show that glial cells release soluble factors that stimulate axonal outgrowth by cerebellar granule cell precursors in an age-dependent manner. In order to identify candidate genes that could have their expression controlled by glial cells and could also be involved in the control of axonal outgrowth during the cerebellar development we used RDA (Representational Differential Analysis) to compare gene expression of neuronal precursors and glial cells from 3 and 9 days-old mice (P3 and P9). RNA extracted from P3 and P9 isolated granule cell precursors were reverse-transcribed into double-strand cDNA [(ds)- cDNAs]. The (ds)-cDNAs were digested using Sau3AI/Bsp143I and the fragments, called "representations", were used to produce subtractive libraries for each cell type. The libraries represented genes more expressed at P3 (forward library) and at P9 (reverse library). Using the cohesive ends generated by the digestion, adaptors were added to each end of the representations and three rounds of subtractive hybridizations were performed (1st round ratio 1:50; 2nd round ratio 1:200, and 3rd round ratio 1:500). By the end of the third round of subtractive hybridization, the differentialy expressed sequences were cloned into a pGEM-T Easy plasmid and DH5 bacteria were transformed with the vectors. The bacterial clones were selected and the inserts (representations) were sequenced. From sequencing we found two candidate genes, stmn1 which codes the protein stathmin1, in the forward library; and sept11 that codes septin11, in the reverse library. To validate the RDA results, we performed the quantification of the differentialy expressed genes by qRT-PCR. As expected, we found higher expression of sept11 in P9 neuronal precursors. On the other hand, there was no difference in stmn1 expression between P3 and P9 neuronal precursors. We also compared the expression of these genes in neuronal precursors treated with and without glial conditioned media. In P3 precursors, the treatment upregulated the expression of stathmin1 and did not change the expression of septin. In P9 neuronal precursors, both genes were downregulated. We also found the endogenous genes, -actin and GAPDH, to be downregulated, suggesting an inhibition of the global gene expression by the treatment. In consequence, it is possible that the downregulation observed for sept11 is a reflex of what is happening to the global gene expression. In conclusion, we have identified two candidate genes that are likely to be regulated in neuronal precursors and that the proteins they code for may participate in the events of early postnatal cerebellar development: stathmin1, involved in the organization of microtubules, and septin11, that plays an important role in cytokinesis and vesicular transport.
- ItemAcesso aberto (Open Access)Aplicações da ultra-sonografia tridimensional na avaliação do cerebelo fetal(Colégio Brasileiro de Radiologia e Diagnóstico por Imagem, 2007-06-01) Araujo Júnior, Edward [UNIFESP]; Guimarães Filho, Hélio Antonio [UNIFESP]; Pires, Claudio Rodrigues [UNIFESP]; Nardozza, Luciano Marcondes Machado [UNIFESP]; Moron, Antonio Fernandes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)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, and the latest information in the literature about this subject.
- ItemAcesso aberto (Open Access)Avaliação dos efeitos da inflamação sistêmica no período neonatal sobre o cerebelo na vida adulta(Universidade Federal de São Paulo (UNIFESP), 2019-08-29) Pires, Jaime Moreira [UNIFESP]; Mello, Luiz Eugenio Araujo De Moraes [UNIFESP]; Foresti, Maira Licia [UNIFESP]; http://lattes.cnpq.br/5451196671533628; http://lattes.cnpq.br/4462750801249231; http://lattes.cnpq.br/2487629230355637; Universidade Federal de São Paulo (UNIFESP)Objectives: To evaluate the chronic effects of a systemic inflammatory process in the cerebellum during the neonatal period. Methodology: Wistar norvegicus (male) rat pups were distributed in the NAIVE, SHAM and LPS groups. Treated animals received either sodium chloride 0.9% or lipopolysaccharide solution intraperitoneally on the first, third, fifth and seventh postnatal days. On the postnatal day 84, the animals were submitted to the open field test to evaluate the locomotor activity. On postnatal day 89, some animals were perfused with fixative, and the cerebellum was processed for Purkinje and microglia cells immunofluorescence, and for ethidine histochemistry for the detection of superoxide anion and evaluation of oxidative stress. Other animals were euthanized by decapitation, to evaluate expression of the inflammatory cytokine TNF-α in the cerebellum and hippocampus. Results: Animals exposed to neonatal systemic inflammation (LPS group) had higher density of microglia cells and greater superoxide anion production in the adult phase when compared to the control groups (NAIVE and SHAM groups). No significant differences were found regarding locomotor activity, Purkinje cell density and TNF-α expression. Conclusion: Exposure to systemic inflammatory processes in the neonatal phase may have chronic effects on the cerebellum. Being an important structure for motor, executive, as well as cognitive and emotional functions, further studies are necessary to understand the mechanisms by which injuries in the neonatal period can result in changes last through life.
- ItemAcesso aberto (Open Access)Avaliação Ultra-Sonográfica do Crescimento Fetal com uso do Diâmetro Transverso do Cerebelo(Federação Brasileira das Sociedades de Ginecologia e Obstetrícia, 2000-06-01) Nery, Luiz; Moron, Antonio Fernandes [UNIFESP]; Kulay Junior, Luiz [UNIFESP]; Universidade Estadual de Maringá Hospital Universitário; Universidade Federal de São Paulo (UNIFESP)Purpose: to evaluate the effectiveness of the transverse cerebellar diameter (TCD), by ultrasonography, in the evolution of the fetal growth, and to relate it to gestational age, biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL). Method: a prospective and longitudinal study was performed on 254 pregnant women considered of low risk, with a gestational age from 20 to 40 weeks. Only 55 pregnant women were included in the study, according to inclusion and exclusion criteria. All the examinations, 217 ultrasonographic evaluations, were done by the author (LN), at least three and at most six examinations for each pregnant woman being accomplished at an interval of one to five weeks. Normality patterns were established between the 10 and 90 percentiles for each gestational age and confirmed postnatally. Results: the transverse cerebellar diameter presented a good correlation with the gestational age either as a dependent variable (R² = 0.90) or as an independent variable (R² = 0.92). A significant relationship was found in the evaluation of the fetal growth between the TCD and the several fetal parameters: BPD and HC (R² = 0.92), FL (R² = 0.90) and AC (R² = 0.89). Conclusions: the transverse cerebellar diameter is a parameter that should be used in the follow-up of development and of fetal growth because of the ascending pattern of its growth curve. Any up- or downward alteration in the growth curve can be useful for the detection of deviations of fetal growth.
- ItemSomente MetadadadosCerebellar Insulin/IGF-1 signaling in diabetic rats: Effects of exercise training(Elsevier Ireland Ltd, 2017) Borges, Mariana Eiras [UNIFESP]; Ribeiro, Alessandra Mussi [UNIFESP]; Pauli, José Rodrigo; Arantes, Luciana Mendonca; Luciano, Eliete; Moura, Leandro Pereira de; Leme, Jose Alexandre Curiacos de Almeida; Medeiros, Alessandra [UNIFESP]; Bertolini, Natalia Oliveira; Sibuya, Clarice Yoshiko; Gomes, Ricardo José [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The Diabetes Mellitus (DM) is a chronic disease associated with loss of brain regions such as the cerebellum, increasing the risk of developing neurodegenerative diseases such as Parkinson's disease (PD). In the brain of diabetic and PD organisms the insulin/IGF-1 signaling is altered. Exercise training is an effective intervention for the prevention of neurodegerative diseases since it release neurotrophic factors and regulating insulin/IGF-1 signaling in the brain. This study aimed to evaluate the proteins involved in the insulin/IGF-1 pathway in the cerebellum of diabetic rats subjected to exercise training protocol. Wistar rats were distributed in four groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD) and trained diabetic (TD). Diabetes was induced by Alloxan (ALX) (32 mg/kg b.w.). The training program consisted in swimming 5 days/week, 1 h/day, during 6 weeks, supporting an overload corresponding to 90% of the anaerobic threshold. At the end, cerebellum was extracted to determinate the protein expression of GSK-3 beta, IR beta and IGF-1R and the phosphorylation of beta-amyloid, Tau, ERK1 + ERK2 by Western Blot analysis. All dependent variables were analyzed by one-way analysis of variance with significance level of 5%. Diabetes causes hyperglycemia in both diabetic groups
- ItemAcesso aberto (Open Access)Cerebellar volume in patients with dementia(Associação Brasileira de Psiquiatria - ABP, 2011-06-01) Baldaçara, Leonardo [UNIFESP]; Borgio, João Guilherme Fiorani [UNIFESP]; Moraes, Walter André dos Santos [UNIFESP]; Lacerda, Acioly Luiz Tavares de [UNIFESP]; Montaño, Maria Beatriz Marcondes Macedo [UNIFESP]; Tufik, Sergio [UNIFESP]; Bressan, Rodrigo Affonseca [UNIFESP]; Ramos, Luiz Roberto [UNIFESP]; Jackowski, Andrea Parolin [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade Federal do Tocantins; Instituto Sinapse de Neurociências ClínicasOBJECTIVE: The aim of this study was to examine the cerebellar volume of subjects at different stages of Alzheimer's disease and to investigate whether volume reductions in this structure are related to cognitive decline. METHOD: Ninety-six subjects from an epidemiological study were submitted to a magnetic resonance imaging scan and evaluated using the Mini-Mental State Examination and the Functional Activities Questionnaire. Subjects were divided into five groups according to the Clinical Dementia Rating scale. Twenty-six subjects from the original group who had no dementia diagnosis at baseline were re-evaluated for the onset of dementia after two years. RESULTS: The volumes of the cerebellar hemispheres, posterior cerebellar lobe, vermis and temporal lobe were found to be reduced as a function of the severity of the disease. There were significant positive correlations between the volume of the temporal lobe and cerebellum and the language, attention, and total scores in the Mini-Mental State Examination and the Functional Activities Questionnaire. A logistic regression analysis demonstrated that reduced temporal lobe, posterior cerebellar lobe and vermal volume at baseline is a risk factor for the onset of dementia. CONCLUSION: This is the first study demonstrating that reduced cerebellar volume is already apparent at the predementia stage. The results of this study support the involvement of the cerebellum in the progression of dementia. Whereas the cerebellum might not be directly associated with the origin of Alzheimer's disease, it may provide useful information related to its prognosis.
- ItemAcesso aberto (Open Access)Cerebellum and psychiatric disorders(Associação Brasileira de Psiquiatria - ABP, 2008-09-01) Baldaçara, Leonardo [UNIFESP]; Borgio, João Guilherme Fiorani [UNIFESP]; Lacerda, Acioly Luiz Tavares de [UNIFESP]; Jackowski, Andrea Parolin [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Irmandade da Santa Casa de São Paulo Centro de Atenção Integrada à Saúde Mental; Universidade Federal do Tocantins; Instituto Sinapse de Neurociências Clínicas; Centro de Pesquisa e Ensaios Clínicos Sinapse-BairralOBJECTIVE: 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.
- ItemSomente MetadadadosCerebelo e psicopatologia na infância e na adolescência(Universidade Federal de São Paulo (UNIFESP), 2021) Verreschi, Otavio Jose Figueira [UNIFESP]; Jackowski, Andrea Parolin [UNIFESP]; Universidade Federal de São PauloSeveral psychiatric disorders such as schizophrenia, bipolar disorder, anxiety, unipolar depression and attention defict hiperactivity disorder have been related to morphological and functional alterations of the cerebellum. Most of the literature refers to adult populations with specific psychopathology of a given disorder. Objective: To evaluate baseline cerebellar volume as a predictor of general psychopathology in a cohort of children and adolescents aged 7 to 14 years, 3 years after the baseline evaluation. Methods: From a high-risk cohort for the development of psychiatric disorders, 609 individuals were selected. Psychiatric diagnoses were done according to DSM-IV in a structured psychiatric interview / DAWBA. MR images were collected with 1.5 T equipment and processed in Free Surfer while CBCL was used to evaluate psychopathology. Values of cerebellar measurements and CBCL were performed in the two-time evaluation: initial and follow-up 3 years later. Results: The cross lagged statistical model demonstrated that measures of cerebellar volume are not predictive of psychopathology 3 years later. Conclusion: Although cerebellar alterations were described in different diagnoses in the literature, no correlation was found between general psychopathology and cerebellar volume.
- ItemSomente MetadadadosConsensus Paper: Radiological Biomarkers of Cerebellar Diseases(Springer, 2015-04-01) Baldarcara, Leonardo [UNIFESP]; Currie, Stuart; Hadjivassiliou, M.; Hoggard, Nigel; Jack, Allison; Jackowski, Andrea P. [UNIFESP]; Mascalchi, Mario; Parazzini, Cecilia; Reetz, Kathrin; Righini, Andrea; Schulz, Joerg B.; Vella, Alessandra; Webb, Sara Jane; Habas, Christophe; Fed Univ Tocantins; Universidade Federal de São Paulo (UNIFESP); Univ Sheffield; Royal Hallamshire Hosp; Yale Univ; Univ Florence; Meyer Children & Careggi Hosp Florence; Childrens Hosp Buzzi; RWTH Aachen Univ Hosp; Forschungszentrum Julich; Julich Aachen Res Alliance JARA; Univ Hosp Siena; Univ Washington; CHNO Quinze VingtsHereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. in the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine.
- ItemSomente MetadadadosCorrelation of the fetal cerebellar volume with other fetal growth indices by three-dimensional ultrasound(Taylor & Francis Ltd, 2007-08-01) Araujo Junior, Edward [UNIFESP]; Pires, Claudio Rodrigues [UNIFESP]; Nardozza, Luciano Marcondes Machado [UNIFESP]; Guimarães Filho, Hélio Antonio [UNIFESP]; Moron, Antonio Fernandes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Objective. To verify the correlation of fetal cerebellar volume by three- dimensional ultrasound ( 3D US) with other indices of fetal growth in normal fetuses.Methods. This was a longitudinal prospective study involving 52 normal pregnant women between 20 and 32 weeks of gestation. the assessments of the fetal cerebellar volume were carried out at intervals of two weeks, and the method used was VOCAL ( virtual organ computer- aided analysis) with a 308 rotation angle. At each assessment, the following biometric indices were evaluated using the two- dimensional method: biparietal diameter, head circumference, transverse cerebellar diameter, femur length, and estimated fetal weight. We used Pearson's correlation coefficient to evaluate the correlation between fetal cerebellar volume and these indices; we also used polynomial regression analysis with fetal cerebellar volume as the dependent variable and the other indices as the independent variable.Results. the fetal cerebellar volume was highly correlated with gestational age ( r 0.94; p < 0.001) and with all other fetal growth indices ( p < 0.001).Conclusions. the assessment of the fetal cerebellar volume by 3D US is an important tool to evaluate fetal growth.
- ItemAcesso aberto (Open Access)Diabetes mellitus, equilíbrio e memória: efeito agudo do exercício físico(Universidade Federal de São Paulo (UNIFESP), 2016-03-21) Borges, Mariana Eiras [UNIFESP]; Gomes, Ricardo José [UNIFESP]; Ribeiro, Alessandra Mussi [UNIFESP]; http://lattes.cnpq.br/7373640456805525; http://lattes.cnpq.br/2738281530091229; Universidade Federal de São Paulo (UNIFESP)Diabetes Mellitus (DM) is controlled deficits associated with the central nervous system. Regular exercise training is effective in reducing cognitive impairment, but little is known about the acute effects of exercise on these aspects. Thus, the aim of this study was to investigate the effect of acute aerobic exercise on memory and balance, as well as the IGF-1R protein, GSK- 3? and tau in the hippocampus and cerebellum of diabetic rats induced by alloxan (32 mg / kg). The study was divided into two experiments. In experiment I, 20 male Wistar rats randomly assigned into groups: control evaluated immediately after exercise (C0), rated control 24 hours after exercise (C24), diabetic evaluated immediately after exercise (D0) and diabetic assessed 24 hours after exercise (D24). In the second experiment (n=20), the animals were divided into sedentary control group (CS), exercise control (EC), sedentary diabetic (SD) and diabetic exercise (DE). Molecular analysis of the hippocampus and cerebellum (pIGF-1R, pGSK-3? and ptau) were performed immediately after exercise in C0 and D0 groups, and 24 hours after exercise in C24 and D24 groups. In the experimental II, behavioral analyzis were performed using body balance testing and object recognition task. Data were expressed as mean ± standard deviation error and analyzed using Student's t test and/or two-way ANOVA, with a significance level of p <0.05. The results showed deficit of short term memory to DS group and increase to the DE group. Furthermore, the DS group showed higher number of errors in crossing the balance beam. In the cerebellum there was increase in GSK-3? phosphorylation and IGF-1R inC24 group when compared to D0 and increase phosphorylation of GSK-3? in comparison D24 to D0. In the hippocampus, acute exercise was able to increase phosphorylation of GSK-3? and IGF-1R in C24 and D24 groups when compared to D0 group. Taken together, results show that DM leads to an impairment in short term memory and balance, and acute exercise is able to improve these parameters accompanied by increase in the phosphorylation of proteins signaling pathway in the hippocampus and cerebellum.
- ItemAcesso aberto (Open Access)Estudo da atividade cerebral na distonia focal idiopática utilizando ressonância magnética funcional(Universidade Federal de São Paulo (UNIFESP), 2020-01-30) Faria, Danilo Donizete de [UNIFESP]; Aguiar, Patricia Maria de Carvalho [UNIFESP]; Balardin, Joana; Silva, Sonia Maria Cesar de Azevedo; http://lattes.cnpq.br/0687940760242933; http://lattes.cnpq.br/5503820245990006; http://lattes.cnpq.br/1353339234022554; http://lattes.cnpq.br/8397606355173155; Universidade Federal de São PauloIntroduction: Dystonia is a neurological syndrome characterized by sustained or intermittent involuntary muscle contractions, leading to repetitive twisting movements and / or abnormal postures with or without tremor. Focal dystonia may also be defined as a network disorder, previously attributed to the basal nuclei and currently to other areas such as the cerebellum, thalamus, and the sensorimotor cortex. Objective: To investigate the brain functional activity of individuals with idiopathic focal upper limb dystonia using finger tapping task functional magnetic resonance imaging. Methods: 27 right-handed patients and 26 controls, matched for sex and age underwent finger tapping task with the right hand, left and both hands interspersed with rest. The functional images were acquired with a 3.0 Tesla equipment (Siemens® PRISMA). Results: The number of finger taps was analyzed under the three conditions of interest. Patients had statistical significance fewer number of taps relative to controls for the right hand, and for both hands. There was no statistically significant difference for the left hand. Patients with focal upper limb dystonia showed a higher BOLD effect in the right cerebellum relative to controls during finger tapping with the right hand (509 voxels). No difference in terms of BOLD effect was found for the remaining conditions. The cerebellar cluster in which patients had a higher activity is ipsilateral to the affected limb, comprising lobes V and VI. Conclusion: This study corroborates the role of the distinct cerebellum activation between patients and controls. These data may form the basis to investigate cerebellar neuromodulation as a treatment strategy for this type of dystonia.
- ItemAcesso aberto (Open Access)The extracellular matrix provides directional cues for neuronal migration during cerebellar development(Associação Brasileira de Divulgação Científica, 2006-03-01) Porcionatto, Marimélia Aparecida [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Normal central nervous system development relies on accurate intrinsic cellular programs as well as on extrinsic informative cues provided by extracellular molecules. Migration of neuronal progenitors from defined proliferative zones to their final location is a key event during embryonic and postnatal development. Extracellular matrix components play important roles in these processes, and interactions between neurons and extracellular matrix are fundamental for the normal development of the central nervous system. Guidance cues are provided by extracellular factors that orient neuronal migration. During cerebellar development, the extracellular matrix molecules laminin and fibronectin give support to neuronal precursor migration, while other molecules such as reelin, tenascin, and netrin orient their migration. Reelin and tenascin are extracellular matrix components that attract or repel neuronal precursors and axons during development through interaction with membrane receptors, and netrin associates with laminin and heparan sulfate proteoglycans, and binds to the extracellular matrix receptor integrins present on the neuronal surface. Altogether, the dynamic changes in the composition and distribution of extracellular matrix components provide external cues that direct neurons leaving their birthplaces to reach their correct final location. Understanding the molecular mechanisms that orient neurons to reach precisely their final location during development is fundamental to understand how neuronal misplacement leads to neurological diseases and eventually to find ways to treat them.
- ItemSomente MetadadadosGlial cells modulate heparan sulfate proteoglycan (HSPG) expression by neuronal precursors during early postnatal cerebellar development(Elsevier B.V., 2010-11-01) Araujo, Ana Paula B. [UNIFESP]; Ribeiro, Maria Emilia de Oliveira Brenha [UNIFESP]; Ricci, Ritchelli [UNIFESP]; Torquato, Ricardo José Soares [UNIFESP]; Toma, Leny [UNIFESP]; Porcionatto, Marimélia Aparecida [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Investiga Inst PesquisaCerebellum controls motor coordination, balance, eye movement, and has been implicated in memory and addiction. As in other parts of the CNS, correct embryonic and postnatal development of the cerebellum is crucial for adequate performance in the adult. Cellular and molecular defects during cerebellar development can lead to severe phenotypes, such as ataxias and tumors. Knowing how the correct development occurs can shed light into the mechanisms of disease. Heparan sulfate proteoglycans are complex molecules present in every higher eukaryotic cells and changes in their level of expression as well as in their structure lead to drastic functional alterations. This work aimed to investigate changes in heparan sulfate proteoglycans expression during cerebellar development that could unveil control mechanisms. Using real time RT-PCR we evaluated the expression of syndecans, glypicans and modifying enzymes by isolated cerebellar granule cell precursors, and studied the influence of soluble glial factors on the expression of those genes. We evaluated the possible involvement of Runx transcription factors in the response of granule cell precursors to glial factors. Our data show for the first time that cerebellar granule cell precursors express members of the Runx family and that the expression of those genes can also be controlled by glial factors. Our results also show that the expression of all genes studied vary during postnatal development and treatment of precursors with glial factors indicate that the expression of heparan sulfate proteoglycan genes as well as genes encoding heparan sulfate modifying enzymes can be modulated by the microenvironment, reflecting the intricate relations between neuron and glia. (C) 2010 ISDN. Published by Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosIs cerebellar volume related to bipolar disorder?(Elsevier B.V., 2011-12-01) Baldacara, Leonardo [UNIFESP]; Nery-Fernandes, F.; Rocha, M.; Quarantini, L. C.; Rocha, G. G. L.; Guimaraes, J. L.; Araujo, C.; Oliveira, I.; Miranda-Scippa, A.; Jackowski, A. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Fed Tocantins; Universidade Federal da Bahia (UFBA); Med DiagnostBackground: Recent data suggest that cerebellum influences emotion modulation in humans. the findings of cerebellar abnormalities in bipolar disorder (BD) are especially intriguing given the link between the cerebellum emotional and behavioral regulation. the purpose of this study was to evaluate cerebellar volume in patients with euthymic BD type I compared to controls. Moreover, we investigated the possible relationship between cerebellar volume and suicidal behavior.Methods: Forty-patients with euthymic BD type I, 20 with and 20 without history of suicide attempt, and 22 healthy controls underwent an MRI scan. the participants were interviewed using the Structured Clinical Interview with the DSM-IV axis I (SCID-I), the Hamilton Depression Rating Scale (HDRS), the Young Mania Rating Scale (YMRS) and the Barratt Impulsiveness Scale (BIS-11).Results: Groups were age, gender and years of schooling-matched. the left cerebellum (p = 0.02), right cerebellum (p = 0.02) and vermis (p<0.01) were significantly smaller in the BD group; however, there were no volumetric differences between the BD subjects with and without suicidal attempt. There was no correlation between cerebellar measurements and clinical variables.Limitations: the main strength is that our sample consisted of patients with euthymic BD type I without any comorbidities, however, these results cannot establish causality as the cross-sectional nature of the study.Conclusions: Our findings suggest that the reduction in cerebellar volumes observed in BD type I might be a trait-related characteristic of this disorder. Additional studies with larger samples and subtypes of this heterogeneous disorder are warranted to determine the possible specificity of this cerebellar finding. (C) 2011 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosNeuroglobin is up-regulated in the cerebellum of pups exposed to maternal epileptic seizures(Elsevier B.V., 2011-12-01) Lima, Daiana Correia [UNIFESP]; Cossa, Ana Carolina [UNIFESP]; Perosa, Sandra Regina [UNIFESP]; Oliveira, Elaine Menezes de [UNIFESP]; Silva Junior, Jose Antonio da; Silva Fernandes, Maria Jose da [UNIFESP]; Silva, Iara Ribeiro da [UNIFESP]; Suemitsu Higa, Elisa Mieko [UNIFESP]; Naffah-Mazzacoratti, Maria da Graca [UNIFESP]; Cavalheiro, Esper Abrao [UNIFESP]; Amado, Debora [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)To evaluate a potential insult in the cerebellum of pups exposed to maternal epileptic seizures during intrauterine life, female rats were subjected to pilocarpine-induced epilepsy. Pups from different litters were sacrificed at 1, 3, 7 and 14 post-natal days (PN) and neuroglobin (Ngb) and gliosis were analyzed in the cerebellum by Western blotting (WB) and RT-PCR. C-14-L-leucine-[C-14-Leu] incorporation was used to analyze protein synthesis at PN1. Nitric Oxide (NO) and thiobarbituric acid-reactive substances (TBARS) levels were also measured. Pups from naive mothers were used as controls. the mRNA level of Ngb was increased in experimental animals at PN1 (**p <= 0.001) and PN3 (**p <= 0.001), at PN7 (***p <= 0.0001) and at PN14 (**p <= 0.001) compared to the respective controls. the protein level of Ngb increased significantly in the experimental pups at PN1 (*p <= 0.05) and at PN3 (**p <= 0.001), when compared to the control pups at PN1 and PN3. At PN7 and PN14 no difference was found. the mRNA level of GFAP increased significantly about two times at PN3 (*p <= 0.05) and PN7 (*p <= 0.05) in the experimental pups when compared to the respective controls, but was unchanged in the other studied ages. Data showed that experimental pups at PN1 exhibited reduced (about 2 times, *p <= 0.05) total protein synthesis in the cerebellum when compared to control. No differences were found in the NO and TBARS levels. Our data support the hypothesis that an up-regulation of Ngb could be a compensatory mechanism in response to the hypoxic-ischemic insults caused by seizures in pups during intrauterine life. (C) 2011 ISDN. Published by Elsevier B.V. All rights reserved.
- ItemAcesso aberto (Open Access)Predição da restrição do crescimento fetal pela biometria do diâmetro transverso do cerebelo(Federação Brasileira das Sociedades de Ginecologia e Obstetrícia, 2004-06-01) Nery, Luiz; Moron, Antonio Fernandes [UNIFESP]; Kulay Junior, Luiz [UNIFESP]; Universidade Estadual de Maringá; Universidade Federal de São Paulo (UNIFESP)OBJECTIVE: to evaluate the accuracy of both the transverse diameter of the cerebellum (TDC) and of the transverse diameter/abdominal circumference (TDC/AC) ratio in the detection of fetal growth restriction (FGR), in high-risk pregnancies. METHOD: a prospective cross-sectional study was carried out in 260 patients with gestational age between 28 and 40 weeks. The TDC and AC of fetuses were measured through ultrasound and the fetuses with TDC below the 10th percentile or TDC/AC ratio above the 90th percentile (>14.6) were classified as FGR suspects. After birth, the accuracy of the TDC and TDC/AC was evaluated using the neonatal diagnosis of FGR as the gold standard (birth weight <10th percentile). RESULTS: after birth, 79 newborns (30.4%) were classified as small for gestational age. The TDC was appropriate in 74 (93.7%) of these fetuses and small in only 5 (6.3%). The sensitivity (SE), specificity (SP), positive (PPV) and negative (NPV) predictive values and accuracy of the TDC in the prediction of FGR were 6.3, 93.4, 29.4, 69.5, and 67%, respectively. The TDC/AC >14.6 correctly identified 59 of the 79 growth-restricted fetuses, with 27 false-positives and 20 false-negatives, SE of 74.5%, SP of 85.1%, PPV of 68.6%, NPV of 88.5% and 81.9% accuracy. CONCLUSION: the TDC is not a good screening parameter for the detection of FGR while the TDC/AC ratio above the 90th percentile is effective in this detection.
- ItemSomente MetadadadosReduced cerebellar left hemisphere and vermal volume in adults with PTSD from a community sample(Elsevier B.V., 2011-12-01) Baldacara, Leonardo [UNIFESP]; Jackowski, Andrea Parolin [UNIFESP]; Schoedl, Aline [UNIFESP]; Pupo, Mariana [UNIFESP]; Andreoli, Sergio Baxter [UNIFESP]; Mello, Marcelo Feijó de [UNIFESP]; Lacerda, Acioly Luiz Tavares de [UNIFESP]; Mari, Jair de Jesus [UNIFESP]; Bressan, Rodrigo Affonseca [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); UFTBackground: Traumatic events exposure is a necessary condition for developing posttraumatic stress disorder (PTSD), but not all individuals exposed to the same trauma will develop PTSD. Human studies have suggested that the cerebellum is involved in human fear perception, anticipation, and recollection. in this context, the current study evaluated whether cerebellar volume is associated with PTSD.Methods: Eighty-four victims of violence, 42 who fulfilled the DSM-IV-TR criteria for PTSD and 42 resilient controls, were identified through an epidemiologic survey conducted in the city of 530 Paulo. Subjects were evaluated using the Clinician-Administered PTSD Scale (CAPS), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and Early Trauma Inventory (ETI). All subjects underwent a magnetic resonance imaging (MRI) scan to evaluate their cerebellar hemispheres and vermis.Results: PTSD subjects had relative smaller left hemisphere (p = 0.04) and vermis (p < 0.01) volumes persisted after controlling for gender, age, and brain volume. in PTSD group, left cerebellar hemisphere volume correlated negatively with PTSD (p = 0.01) and depressive symptoms (p = 0.04). Vermal volume correlated negatively with PTSD symptoms (p < 0.01), early traumatic life events (p < 0.01), depressive symptoms (p = 0.04) and anxiety (p = 0.01).Conclusion: the cerebellum is involved in emotion modulation, and our results suggest that cerebellar volumetric reduction is associated with mood, anxiety and PTSD symptoms. Early traumatic life experiences are related to vermal volume reduction and may be a risk factor for future PTSD development. (C) 2011 Elsevier B.V. All rights reserved.