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1.
Epilepsia Open ; 9(2): 665-678, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38321819

RESUMO

OBJECTIVE: The goal of this research was to evaluate the effect of DM type 2 (DM2) on SE severity, neurodegeneration, and brain oxidative stress (OS) secondary to seizures. METHODS: DM2 was induced in postnatal day (P) 3 male rat pups by injecting streptozocin (STZ) 100 mg/kg; control rats were injected with citrate buffer as vehicle. At P90, SE was induced by the lithium-pilocarpine administration and seizure latency, frequency, and severity were evaluated. Neurodegeneration was assessed 24 h after SE by Fluoro-Jade B (F-JB) staining, whereas OS was estimated by measuring lipid peroxidation and reactive oxygen species (ROS). RESULTS: DM2 rats showed an increase in latency to the first generalized seizure and SE onset, had a higher number and a longer duration of seizures, and displayed a larger neurodegeneration in the hippocampus (CA3, CA1, dentate gyrus, and hilus), the piriform cortex, the dorsomedial nucleus of the thalamus and the cortical amygdala. Our results also show that only SE, neither DM2 nor the combination of DM2 with SE, caused the increase in ROS and brain lipid peroxidation. SIGNIFICANCE: DM2 causes higher seizure severity and neurodegeneration but did not exacerbate SE-induced OS under these conditions. PLAIN LANGUAGE SUMMARY: Our research performed in animal models suggests that type 2 diabetes mellitus (DM2) may be a risk factor for causing higher seizure severity and seizure-induced neuron cell death. However, even when long-term seizures promote an imbalance between brain pro-oxidants and antioxidants, DM2 does not exacerbate that disproportion.


Assuntos
Diabetes Mellitus Tipo 2 , Estado Epiléptico , Ratos , Animais , Masculino , Diabetes Mellitus Tipo 2/complicações , Espécies Reativas de Oxigênio/efeitos adversos , Pilocarpina/efeitos adversos , Convulsões , Estado Epiléptico/induzido quimicamente , Estresse Oxidativo
2.
Pflugers Arch ; 475(1): 101-117, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35066612

RESUMO

Mammalian respiratory rhythm-generating circuits in the brainstem are subject to neuromodulation by multiple peptidergic afferent inputs controlling circuit behavior and outputs. Although functionally important, actions of neuropeptide modulators have not been fully characterized. We analyzed at cellular and circuit levels two inspiratory patterns intrinsically generated by the preBötzinger complex (preBötC) and their modulation by the neuropeptides bombesin and substance P (SP) in neonatal rat medullary slices in vitro. We found that, in recordings of hypoglossal nerve and preBötC neuron inspiratory activity, some inspiratory bursts occurring spontaneously under basal conditions have a biphasic shape with longer duration than normal inspiratory bursts and occur at a lower frequency. This biphasic burst pattern has been proposed to represent inspiratory activity underling periodic sighs. Bath-applied bombesin or SP decreased the period and increased the duration of both normal inspiratory and biphasic bursts and their underlying synaptic drives. The ratio of the biphasic long-duration burst period to the normal inspiratory burst period and the ratio of their burst durations remained the same before and after peptidergic modulation. Bombesin increased the frequency of the inspiratory rhythm in a Ca2+-independent manner and the frequency of long-duration bursts in a Ca2+-dependent manner. This finding suggests that period and burst duration coupling are due to intrinsic mechanisms controlling simultaneously timing and burst termination within the inspiratory rhythm-generating network. We propose a model in which signaling cascades activated by bombesin and SP modulate mechanisms controlling inspiratory burst frequency and duration to coordinate preBötC circuit behavioral outputs.


Assuntos
Bombesina , Mecânica Respiratória , Ratos , Animais , Animais Recém-Nascidos , Bombesina/farmacologia , Ratos Sprague-Dawley , Mecânica Respiratória/fisiologia , Bulbo/fisiologia , Mamíferos
3.
Front Physiol ; 14: 1295632, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38179140

RESUMO

The pre-Bötzinger complex, situated in the ventrolateral medulla, serves as the central generator for the inspiratory phase of the respiratory rhythm. Evidence strongly supports its pivotal role in generating, and, in conjunction with the post-inspiratory complex and the lateral parafacial nucleus, in shaping the respiratory rhythm. While there remains an ongoing debate concerning the mechanisms underlying these nuclei's ability to generate and modulate breathing, transgenic rodent models have significantly contributed to our understanding of these processes. However, there is a significant knowledge gap regarding the spectrum of transgenic rodent lines developed for studying respiratory rhythm, and the methodologies employed in these models. In this study, we conducted a scoping review to identify commonly used transgenic rodent lines and techniques for studying respiratory rhythm generation and modulation. Following PRISMA guidelines, we identified relevant papers in PubMed and EBSCO on 29 March 2023, and transgenic lines in Mouse Genome Informatics and the International Mouse Phenotyping Consortium. With strict inclusion and exclusion criteria, we identified 80 publications spanning 1997-2022 using 107 rodent lines. Our findings revealed 30 lines focusing on rhythm generation, 61 on modulation, and 16 on both. The primary in vivo method was whole-body plethysmography. The main in vitro method was hypoglossal/phrenic nerve recordings using the en bloc preparation. Additionally, we identified 119 transgenic lines with the potential for investigating the intricate mechanisms underlying respiratory rhythm. Through this review, we provide insights needed to design more effective experiments with transgenic animals to unravel the mechanisms governing respiratory rhythm. The identified transgenic rodent lines and methodological approaches compile current knowledge and guide future research towards filling knowledge gaps in respiratory rhythm generation and modulation.

4.
Sleep Sci ; 16(3): e362-e367, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38196764

RESUMO

Neuroglobin (Ngb) is a protein expressed in the central and peripherical nervous systems of the vertebrate. The Ngb has different functions in neurons, including regulating O 2 homeostasis, oxidative stress, and as a neuroprotector after ischemia/hypoxia events. The Ngb is a hemoprotein of the globin family, structurally like myoglobin and hemoglobin. Ngb has higher expression in the cortex, hypothalamus, thalamus, brainstem, and cerebellum in mammals. Interestingly, Ngb immunoreactivity oscillates according to the sleep-wake cycle and decreases after 24 hours of sleep deprivation, suggesting that sleep homeostasis regulates Ngb expression. In addition, Ngb expresses in brain areas related to REM sleep regulation. Therefore, in the present review, we discuss the potential role of the Ngb in the sleep-wake regulation of mammals.

5.
An Acad Bras Cienc ; 94(1): e20191419, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35476059

RESUMO

Several fields of research such as medicine, robotics, sports, informatics, etc., require the analysis of human movement. Traditional systems for acquisition and analysis of human movement data are based on video cameras or active sensors. However, those systems are limited to high-resource settings. Wearable devices allow monitoring subjects outside typical clinical or research environments. Here, we present an open source low-cost wireless sensor system for acquisition of human movement data. Our system consists of two main parts: a server that stores data and, one or more wearable sensor modules that collect movement data through Inertial Measurement Units (IMUs) and transmit them wirelessly to the server. As a proof of concept, we measured human gait activity. Our results show that our system with IMUs can acquire quantifiable movement data. Characteristics such as open source code and its low-cost, make our system a viable alternative for clinical or research.


Assuntos
Movimento , Esportes , Humanos
6.
Behav Processes ; 193: 104539, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34752911

RESUMO

Manual analysis of behavioral tests in rodents involves inspection of video recordings by a researcher that assesses rodent movements to quantify parameters related with a behavior of interest. The assessment of the researcher during the quantification of such parameters can introduce variability among experimental conditions or among sessions of analysis. Here, we introduce Analixity, a video processing software for the elevated plus maze test (EPM), in which quantification of behavioral parameters is automatic, reducing the time spent in analysis and solving the variability problem. Analixity is an adaptable multiplatform open-source system. Analixity generates an Excel file with the quantified behavioral variables, such as time spent in open and closed arms and in the center zone, number of entries to each zone and total distance traveled during the test. For validation, we compared results obtained by Analixity with results obtained by manual analysis. We did not find statistically significant differences. In addition, we compared the results obtained by Analixity with results obtained by the commercial software ANY-maze. We did not find statistically significant differences in the quantification of parameters such as time spent in open arms, time spent in closed arms, time spent in center zone, number of closed arms, open arms entries, and anxiety index. We concluded that Analixity is an open-source software as reliable and effective as a commercial software.


Assuntos
Ansiedade , Teste de Labirinto em Cruz Elevado , Animais , Comportamento Animal , Computadores , Custos e Análise de Custo , Aprendizagem em Labirinto , Gravação em Vídeo
7.
Behav Brain Res ; 413: 113460, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34252502

RESUMO

Evidence suggest that magnesium dietary supplementation has several health benefits including lowering blood pressure, reducing insulin resistance, and improving symptoms of depression, anxiety, and migraine. Here, we aimed to study the effect of chronic magnesium supplementation on anxiety-like behavior in rats by supplementing with magnesium their drinking water for 30 days. Anxiety-like behavior was induced by subcutaneous injection of veratrin 30 min before performing elevated plus maze and open field tests to measure anxiety levels and locomotion, respectively. We quantify the concentration of magnesium in plasma and cerebrospinal fluid. We used diazepam to compare the efficacy of magnesium supplementation as an anxiolytic agent. Our results show that rats supplemented with magnesium had a statistically significant decrease in anxiety levels with not effects on locomotion and a statistically significant increase in concentration of magnesium in plasma and cerebrospinal fluid. However, the anxiolytic effect of magnesium supplementation washes-out in 12 days. We discuss the advantages of using supplemental magnesium as anxiolytic.


Assuntos
Ansiolíticos/farmacologia , Ansiedade , Comportamento Animal/efeitos dos fármacos , Cloreto de Magnésio/farmacologia , Animais , Ansiolíticos/administração & dosagem , Ansiedade/sangue , Ansiedade/líquido cefalorraquidiano , Ansiedade/dietoterapia , Ansiedade/tratamento farmacológico , Diazepam/farmacologia , Modelos Animais de Doenças , Magnésio/sangue , Magnésio/líquido cefalorraquidiano , Cloreto de Magnésio/administração & dosagem , Ratos , Ratos Wistar
8.
An Acad Bras Cienc ; 93(2): e20190861, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33729379

RESUMO

Autism spectrum disorder is associated with alterations in GABAergic and glutamatergic neurotransmission. Here, we aimed to determine the concentration of GABA, glutamate, glutamine, aspartate, taurine, and glycine in brain tissue and plasma of rats prenatally exposed to valproic acid (VPA), a well-characterized experimental model of autism. Pregnant rats were injected with VPA (600mg/Kg) during the twelfth-embryonic-day. Control rats were injected with saline. On the fourteen-postnatal-day, rats from both groups (males and females) were anesthetized, euthanized by decapitation and their brain dissected out. The frontal cortex, hippocampus, amygdala, brain stem and cerebellum were dissected and homogenized. Homogenates were centrifuged and supernatants were used to quantify amino acid concentrations by HPLC coupled with fluorometric detection. Blood samples were obtained by a cardiac puncture; plasma was separated and deproteinized to quantify amino acid concentration by HPLC. We found that, in VPA rats, glutamate and glutamine concentrations were increased in hippocampus and glycine concentration was increased in cortex. We did not find changes in other regions or in plasma amino acid concentration in the VPA group with respect to control group. Our results suggest that VPA exposure in utero may impair inhibitory and excitatory amino acid transmission in the infant brain.


Assuntos
Transtorno do Espectro Autista , Efeitos Tardios da Exposição Pré-Natal , Aminoácidos , Animais , Encéfalo , Feminino , Masculino , Plasma , Gravidez , Ratos , Ácido Valproico/toxicidade
9.
J Neuroimaging ; 31(1): 192-198, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32936994

RESUMO

BACKGROUND AND PURPOSE: Myotonic Dystrophy Type I (DM1) is a neurodegenerative, genetic, and multisystemic disorder with a large variety of symptoms due to a CTG trinucleotide expansion located on Dystrophia Myotonica Protein Kinase (DMPK) gene. Previous reports have shown cognitive deterioration in these patients. Given that white matter (WM) degradation has also been reported in DM1 patients, here we explored if alterations in the cognitive profile of DM1 patients could be related to the deterioration of WM. METHODS: A total of 22 classic DM1 patients with age range (18-56 years) and 22 matched healthy control subjects were neuropsychological evaluated by the Cambridge Neuropsychological Test Automated (CANTAB). Patients were evaluated with the Muscular Impairment Rating Scale (MIRS). We then evaluated the cerebral WM integrity using the Fractional Anisotropy (FA) index obtained from the Diffusion Tensor Imaging (DTI) data acquired with a 3T MR scanner. RESULTS: DM1 patients showed generalized reduction of WM integrity across the brain. Similarly, patients' neuropsychological evaluation showed significant deficits in memory and problem-solving tasks. Correlation analyses showed a significant correlation between FA deterioration at frontal, temporomedial, and parietal lobes and delayed matched to sample deficits. CONCLUSIONS: Our results suggest that despite the pervasive WM integrity loss in DM1 disorder, specific memory impairments can be associated to discreet areas of WM deterioration in these patients.


Assuntos
Disfunção Cognitiva/complicações , Distrofia Miotônica/patologia , Distrofia Miotônica/fisiopatologia , Substância Branca/patologia , Adolescente , Adulto , Anisotropia , Imagem de Tensor de Difusão , Humanos , Masculino , Memória , Pessoa de Meia-Idade , Distrofia Miotônica/complicações , Distrofia Miotônica/diagnóstico por imagem , Testes Neuropsicológicos , Substância Branca/diagnóstico por imagem , Substância Branca/fisiopatologia , Adulto Jovem
10.
Cerebellum ; 20(3): 346-360, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33184781

RESUMO

Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease characterized by progressive ataxia and retinal degeneration. Previous cross-sectional studies show a significant decrease in the gray matter of the cerebral cortex, cerebellum, and brainstem. However, there are no longitudinal studies in SCA7 analyzing whole-brain degeneration and its relation to clinical decline. To perform a 2-year longitudinal characterization of the whole-brain degeneration and clinical decline in SCA7, twenty patients underwent MRI and clinical evaluations at baseline. Fourteen completed the 2-year follow-up study. A healthy-matched control group was also included. Imaging analyses included volumetric and cortical thickness evaluation. We measured the cognitive deterioration in SCA7 patients using MoCA test and the motor deterioration using the SARA score. We found statistically significant differences in the follow-up compared to baseline. Imaging analyses showed that SCA7 patients had severe cerebellar and pontine degeneration compared with the control group. Longitudinal follow-up imaging analyses of SCA7 patients showed the largest atrophy in the medial temporal lobe without signs of a progression of cerebellar and pontine atrophy. Effect size analyses showed that MRI longitudinal analysis has the largest effect size followed by the SARA scale and MoCA test. Here, we report that it is possible to detect significant brain atrophy and motor and cognitive clinical decline in a 2-year follow-up study of SCA7 patients. Our results support the hypothesis that longitudinal analysis of structural MRI and MOCA tests are plausible clinical markers to study the natural history of the disease and to design treatment trials in ecologically valid contexts.


Assuntos
Substância Cinzenta/diagnóstico por imagem , Doenças Neurodegenerativas/diagnóstico por imagem , Ataxias Espinocerebelares/diagnóstico por imagem , Adolescente , Adulto , Atrofia , Encéfalo/patologia , Encéfalo/fisiopatologia , Cerebelo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Progressão da Doença , Feminino , Seguimentos , Substância Cinzenta/fisiopatologia , Humanos , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Doenças Neurodegenerativas/fisiopatologia , Ponte/diagnóstico por imagem , Ataxias Espinocerebelares/fisiopatologia , Aprendizagem Verbal , Adulto Jovem
11.
Artigo em Inglês | MEDLINE | ID: mdl-32351953

RESUMO

Detection, characterization and classification of patterns within time series from electrophysiological signals have been a challenge for neuroscientists due to their complexity and variability. Here, we aimed to use graph theory to characterize and classify waveforms within biological signals using maxcliques as a feature for a deep learning method. We implemented a compact and easy to visualize algorithm and interface in Python. This software uses time series as input. We applied the maxclique graph operator in order to obtain further graph parameters. We extracted features of the time series by processing all graph parameters through K-means, one of the simplest unsupervised machine learning algorithms. As proof of principle, we analyzed integrated electrical activity of XII nerve to identify waveforms. Our results show that the use of maxcliques allows identification of two distinct types of waveforms that match expert classification. We propose that our method can be a useful tool to characterize and classify other electrophysiological signals in a short time and objectively. Reducing the classification time improves efficiency for further analysis in order to compare between treatments or conditions, e.g., pharmacological trials, injuries, or neurodegenerative diseases.

12.
Cerebellum ; 19(1): 48-57, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31656012

RESUMO

Status epilepticus (SE) promotes neuronal proliferation and differentiation in the adult and developing rodent hippocampus. However, the effect of SE on other neurogenic brain regions such as the cerebellum has been less explored. To determine whether SE induced by pentylentetrazole (PTZ-SE) and lithium-pilocarpine (Li-Pilo-SE) increases cell proliferation and neurogenesis in the developing rat cerebellum. SE was induced in 14-day-old (P14) Wistar rat pups (both sexes). One hour after SE and the following day rats were injected intraperitoneally with 5-bromo-2'-deoxyuridine (BrdU, 50 mg/kg). Seven days after SE, immunohistochemistry was performed to detect BrdU-positive (BrdU+) cells or BrdU/NeuN+ cells in the cerebellar vermis. SE induced by PTZ or Li-Pilo statistically significant increased the number of cerebellar BrdU+ cells when compared with the control group (58% and 40%, respectively); maximal cell proliferation occurred in lobules II, III, VIb, VIc, VIII, IXa, and IXb of PTZ-SE group and II, V, VIc, VII, and X of Li-Pilo-SE group. An increased number of BrdU/NeuN+ cells was detected in lobules V (17 ± 1.9), VIc (25.8 ± 2.7), and VII (26.2 ± 3.4) after Li-Pilo-SE compared to their control group (9.8 ± 1.7, 12.8 ± 2.8, and 11 ± 1.7, respectively), while the number of BrdU/NeuN+ cells remained the same after PTZ-induced SE or control conditions. SE induced in the developing rat by different experimental models increases cell proliferation in the granular layer of the cerebellar vermis, but only SE of limbic seizures increases neurogenesis in specific cerebellar lobes.


Assuntos
Proliferação de Células/fisiologia , Cerebelo/crescimento & desenvolvimento , Cerebelo/patologia , Neurogênese/fisiologia , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/patologia , Animais , Proliferação de Células/efeitos dos fármacos , Cerebelo/efeitos dos fármacos , Feminino , Cloreto de Lítio/toxicidade , Masculino , Neurogênese/efeitos dos fármacos , Pentilenotetrazol/toxicidade , Pilocarpina/toxicidade , Ratos , Ratos Wistar
13.
Epilepsy Behav ; 102: 106676, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31756620

RESUMO

Previous research in female rats showed that induction of status epilepticus (SE) during infancy impairs proceptive sexual behavior at the long run in adulthood but temporarily, since full proceptivity is recovered after four mating trials. In male rats, such equivalent effects have not been explored yet. Thus, SE was experimentally induced by injecting lithium chloride (3 mEq/kg, i.p.) in thirteen-day-old (P13) male pups and then, on P14, pilocarpine hydrochloride (100 mg/kg, s.c.). Controls received the same volume of saline. For Experiment 1, at P90, we analyzed c-Fos immunoreactivity (c-Fos-IR) as a measure of unconditioned brain activity after exposing them to sexually receptive females, but without physical contact. For Experiment 2, a different group of males was tested for locomotor activity, and their sexual behavior was assessed during five trials. Then, serum testosterone and corticosterone levels were measured. Our results showed that a lower proportion of SE males performed mounts, intromissions, and ejaculations, and repeated training did not improve their behavior. The levels of testosterone in SE males were reduced, but corticosterone, c-Fos-IR, and locomotion were similar to controls. These results suggest that SE during infancy impairs adult sexual behavior by reducing testosterone.


Assuntos
Encéfalo/metabolismo , Comportamento Sexual Animal/fisiologia , Estado Epiléptico/sangue , Estado Epiléptico/psicologia , Testosterona/sangue , Fatores Etários , Animais , Animais Recém-Nascidos , Encéfalo/efeitos dos fármacos , Corticosterona/sangue , Feminino , Masculino , Pilocarpina/toxicidade , Ratos , Ratos Wistar , Comportamento Sexual Animal/efeitos dos fármacos , Estado Epiléptico/induzido quimicamente
14.
Front Physiol ; 9: 1068, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30233382

RESUMO

The blood labyrinthine barrier (BLB) is critical in the maintenance of inner ear ionic and fluid homeostasis. Recent studies using imaging and histopathology demonstrate loss of integrity of the BLB in the affected inner ear of Meniere's disease (MD) patients. We hypothesized that oxidative stress is involved in the pathogenesis of BLB degeneration, and to date there are no studies of oxidative stress proteins in the human BLB. We investigated the ultrastructural and immunohistochemical changes of the BLB in the vestibular endorgan, the macula utricle, from patients with MD (n = 10), acoustic neuroma (AN) (n = 6) and normative autopsy specimens (n = 3) with no inner ear disease. Each subject had a well-documented clinical history and audiovestibular testing. Utricular maculae were studied using light and transmission electron microscopy and double labeling immunofluorescence. Vascular endothelial cells (VECs) were identified using isolectin B4 (IB4) and glucose-transporter-1 (GLUT-1). Pericytes were identified using alpha smooth muscle actin (αSMA) and phalloidin. IB4 staining of VECS was consistently seen in both AN and normative. In contrast, IB4 was nearly undetectable in all MD specimens, consistent with the significant VEC damage confirmed on transmission electron microscopy. GLUT-1 was present in MD, AN, and normative. αSMA and phalloidin were expressed consistently in the BLB pericytes in normative, AN specimen, and Meniere's specimens. Endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and nitrotyrosine were used as markers of oxidative stress. The VECs of the BLB in Meniere's had significantly higher levels of expression of iNOS and nitrotyrosine compared with normative and AN specimen. eNOS-IF staining showed similar patterns in normative and Meniere's specimens. Microarray-based gene expression profiling confirmed upregulation of iNOS mRNA from the macula utricle of Meniere's patients compared with AN. Nitrotyrosine, a marker recognized as a hallmark of inflammation, especially when seen in association with an upregulation of iNOS, was detected in the epithelial and stromal cells in addition to VECs in MD. Immunohistochemical and ultrastructural degenerative changes of the VEC suggest that these cells are the primary targets of oxidative stress, and pericyte pathology including degeneration and migration, likely also plays a role in the loss of integrity of the BLB and triggering of inflammatory pathways in MD. These studies advance our scientific understanding of oxidative stress in the human inner ear BLB and otopathology.

15.
Eur J Neurosci ; 48(10): 3199-3211, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30255962

RESUMO

Spinocerebellar Ataxia Type 7 (SCA7) is a neurodegenerative disorder caused by cytosine-adenine-guanine (CAG) repeat expansion. It is clinically characterized by ataxia and visual loss. To date, little is known about SCA7 cognitive impairments and its relationship with grey matter volume (GMV) changes. The aim of this study was to explore SCA7 patients' performance in specific components of auditory-verbal neuropsychological tests and to correlate their scores with genetic mutation, severity of ataxia and GMV. We assessed verbal memory and verbal fluency proficiencies in 31 genetically confirmed SCA7 patients, and compared their results with 32 healthy matched volunteers; we also correlated CAG repeats and severity of motor symptoms with performance in the auditory-verbal tests. SCA7 patients exhibited deficiencies in several components of these cognitive tasks, which were independent of motor impairments and showed no relation to CAG repeats. Based on Resonance Images performed in 27 patients we found association between ataxia severity and GMV in "sensoriomotor" cerebellum, as well as correlations of impaired verbal memory and semantic fluency scores with GMV in association cortices, including the right parahippocampal gyrus. To our knowledge, this is the first report of deficits in the organization of semantic information and in the evocation of verbal material, as well as greater susceptibility to proactive interference in SCA7 patients. These findings bring novel information about specific cognitive abilities in SCA7 patients, particularly verbal memory and fluency, and their relation with GMV variations in circumscribed brain regions, including association cortices known to have functional relationships with the cerebellum.


Assuntos
Córtex Cerebelar/patologia , Córtex Cerebral/patologia , Disfunção Cognitiva/fisiopatologia , Ataxias Espinocerebelares/patologia , Ataxias Espinocerebelares/fisiopatologia , Adulto , Córtex Cerebelar/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Memória de Curto Prazo/fisiologia , Rememoração Mental/fisiologia , Pessoa de Meia-Idade , Giro Para-Hipocampal/diagnóstico por imagem , Giro Para-Hipocampal/patologia , Índice de Gravidade de Doença , Ataxias Espinocerebelares/complicações , Ataxias Espinocerebelares/diagnóstico por imagem , Aprendizagem Verbal/fisiologia
16.
J Mol Neurosci ; 64(1): 51-61, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29170997

RESUMO

In mammals, the neural control of breathing is attributed to circuits distributed along the ventral respiratory column (VRC) in the ventrolateral medulla. The VRC contains the kernel for generation of the inspiratory phase of respiratory rhythm and nuclei involved in central chemoreception. During development, the respiratory rhythm, as well as central chemosensitivity, adjusts to meet the changing physiological requirements associated with increased body weight and size. Gene expression in VRC ontogeny is well characterized. However, little is known about gene expression in the VRC during postnatal development. Here, we sought to characterize the changes in gene expression that occur in the VRC of the adult rat (5-6 months of age) in comparison with the VRC of neonate rat (1-4 days old). We isolated total RNA from VRC tissue punches collected from thick transversal slices. We hybridized cDNA to a 5000-oligonucleotide rat microarray. We found that 218 genes (4.4%) of the 5000 genes in the microarray changed their expression in adult VRC with respect to that from neonate. To further analyze the modified expression of specific genes, we quantified the differential expression of 84 genes of neuronal ion channels using a quantitative RT-PCR array. This analysis confirmed the overexpression of 68 genes and the underexpression of 14 genes in the VRC from adult compared with that from neonate. Our findings may help to explain the functional changes in respiratory rhythm and chemosensitivity occurring throughout life.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Canais Iônicos/genética , Centro Respiratório/metabolismo , Animais , Canais Iônicos/metabolismo , Masculino , Ratos , Ratos Wistar , Centro Respiratório/crescimento & desenvolvimento
17.
Adv Exp Med Biol ; 1015: 147-161, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29080026

RESUMO

Breathing is a continuous behavior essential for life in mammals and one of the few behaviors that can be studied in vivo in intact animals awake, anesthetized or decerebrated and in highly reduced in vitro and in situ preparations. The preBötzinger complex (preBötC) is a small nucleus in the brainstem that plays an essential role in normal breathing and is widely accepted as the site necessary and sufficient for generation of the inspiratory phase of the respiratory rhythm. Substantial advances in understanding the anatomical and cellular basis of respiratory rhythmogenesis have arisen from in vitro and in vivo studies in the past 25 years; however, the underlying cellular mechanisms remain unknown.


Assuntos
Geradores de Padrão Central/fisiologia , Respiração , Centro Respiratório/fisiologia , Mecânica Respiratória/fisiologia , Animais , Neurônios/fisiologia
18.
PeerJ ; 4: e2709, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27917314

RESUMO

BACKGROUND: Epidemiological evidence indicates epilepsy is more common in patients with autism spectrum disorders (ASD) (20-25%) than in the general population. The aim of this project was to analyze seizure susceptibility in developing rats prenatally exposed to valproic acid (VPA) as autism model. METHODS: Pregnant females were injected with VPA during the twelfth embryonic day. Seizures were induced in fourteen-days-old rat pups using two models of convulsions: pentylenetetrazole (PTZ) and lithium-pilocarpine (Li-Pilo). RESULTS: Two subgroups with different PTZ-induced seizure susceptibility in rats exposed to VPA were found: a high susceptibility (VPA+) (28/42, seizure severity 5) and a low susceptibility (VPA-) (14/42, seizure severity 2). The VPA+ subgroup exhibited an increased duration of the generalized tonic-clonic seizure (GTCS; 45 ± 2.7 min), a higher number of rats showed several GTCS (14/28) and developed status epilepticus (SE) after PTZ injection (19/27) compared with control animals (36.6 ± 1.9 min; 10/39; 15/39, respectively). No differences in seizure severity, latency or duration of SE induced by Li-Pilo were detected between VPA and control animals. DISCUSSION: Prenatal VPA modifies the susceptibility to PTZ-induced seizures in developing rats, which may be linked to an alteration in the GABAergic transmission. These findings contribute to a better understanding of the comorbidity between autism and epilepsy.

19.
An Acad Bras Cienc ; 88 Suppl 1: 653-63, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27168372

RESUMO

The contribution of Interleukin-1ß (IL-1ß) to neuronal injury induced by status epilepticus (SE) in the immature brain remains unclear. The goal of this study was to determine the hippocampal expression of IL-1ß and its type 1 receptor (IL-1RI) following SE induced by the lithium-pilocarpine model in fourteen-days-old rat pups; control animals were given an equal volume of saline instead of the convulsant. IL-1ß and IL-1RI mRNA hippocampal levels were assessed by qRT-PCR 6 and 24 h after SE or control conditions. IL-1ß and IL-1RI expression was detected in the dorsal hippocampus by immunohistochemical procedures; Fluoro-Jade B staining was carried out in parallel sections in order to detect neuronal cell death. IL-1ß mRNA expression was increased 6 h following SE, but not at 24 h; however IL-1RI mRNA expression was unaffected when comparing with the control group. IL-1ß and IL-1RI immunoreactivity was not detected in control animals. IL-1ß and IL-1RI were expressed in the CA1 pyramidal layer, the dentate gyrus granular layer and the hilus 6 h after SE, whereas injured cells were detected 24 h following seizures. Early expression of IL-1ß and IL-1RI in the hippocampus could be associated with SE-induced neuronal cell death mechanisms in the developing rat.


Assuntos
Hipocampo/metabolismo , Interleucina-1beta/metabolismo , Receptores de Interleucina-1/metabolismo , Estado Epiléptico/metabolismo , Animais , Convulsivantes , Modelos Animais de Doenças , Interleucina-1beta/genética , Lítio , Pilocarpina , RNA Mensageiro/metabolismo , Ratos , Receptores de Interleucina-1/genética , Estado Epiléptico/induzido quimicamente
20.
Brain Res ; 1618: 9-16, 2015 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-26014620

RESUMO

There are different kinds of visuomotor learnings. One of the most studied is error-based learning where the information about the sign and magnitude of the error is used to update the motor commands. However, there are other instances where subjects show visuomotor learning even if the use of error sign and magnitude information is precluded. In those instances subjects could be using strategic instead of procedural adaptation mechanisms. Here, we present the results of the effect of aging on visuomotor strategic learning under a reversed error feedback condition, and its contrast with procedural visuomotor learning within the same participants. A number of measures were obtained from a task consisting of throwing clay balls to a target before, during and after wearing lateral displacing or reversing prisms. The displacing prism results show an age dependent decrease on the learning rate that corroborates previous findings. The reversing prism results also show significant adaptation impairment in the aged population. However, decreased reversing learning in the older group was the result of an increase in the number of subjects that could not adapt to the reversing prism, and not on a reduction of the learning capacity of all the individuals of the group. These results suggest a significant deleterious effect of aging on visuomotor strategic learning implementation.


Assuntos
Envelhecimento/fisiologia , Aprendizagem/fisiologia , Desempenho Psicomotor/fisiologia , Percepção Visual/fisiologia , Adaptação Fisiológica , Adolescente , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Estimulação Luminosa , Adulto Jovem
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