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1.
Proc Natl Acad Sci U S A ; 107(7): 3180-5, 2010 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-20133704

RESUMO

Refractory temporal lobe epilepsy (TLE) is associated with a dysfunction of inhibitory signaling mediated by GABA(A) receptors. In particular, the use-dependent decrease (run-down) of the currents (I(GABA)) evoked by the repetitive activation of GABA(A) receptors is markedly enhanced in hippocampal and cortical neurons of TLE patients. Understanding the role of I(GABA) run-down in the disease, and its mechanisms, may allow development of medical alternatives to surgical resection, but such mechanistic insights are difficult to pursue in surgical human tissue. Therefore, we have used an animal model (pilocarpine-treated rats) to identify when and where the increase in I(GABA) run-down occurs in the natural history of epilepsy. We found: (i) that the increased run-down occurs in the hippocampus at the time of the first spontaneous seizure (i.e., when the diagnosis of epilepsy is made), and then extends to the neocortex and remains constant in the course of the disease; (ii) that the phenomenon is strictly correlated with the occurrence of spontaneous seizures, because it is not observed in animals that do not become epileptic. Furthermore, initial exploration of the molecular mechanism disclosed a relative increase in alpha4-, relative to alpha1-containing GABA(A) receptors, occurring at the same time when the increased run-down appears, suggesting that alterations in the molecular composition of the GABA receptors may be responsible for the occurrence of the increased run-down. These observations disclose research opportunities in the field of epileptogenesis that may lead to a better understanding of the mechanism whereby a previously normal tissue becomes epileptic.


Assuntos
Epilepsia do Lobo Temporal/fisiopatologia , Hipocampo/fisiologia , Neurônios/metabolismo , Receptores de GABA-A/metabolismo , Transdução de Sinais/fisiologia , Análise de Variância , Animais , Eletrofisiologia , Fluoresceínas , Imunofluorescência , Hipocampo/metabolismo , Imuno-Histoquímica , Masculino , Oócitos/metabolismo , Compostos Orgânicos , Pilocarpina , Ratos , Ratos Sprague-Dawley , Receptores de GABA-A/fisiologia , Xenopus
2.
J Neurosci ; 31(45): 16327-35, 2011 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-22072684

RESUMO

The chemokine CX3CL1 and its receptor CX3CR1 are constitutively expressed in the nervous system. In this study, we used in vivo murine models of permanent middle cerebral artery occlusion (pMCAO) to investigate the protective potential of CX3CL1. We report that exogenous CX3CL1 reduced ischemia-induced cerebral infarct size, neurological deficits, and caspase-3 activation. CX3CL1-induced neuroprotective effects were long lasting, being observed up to 50 d after pMCAO in rats. The neuroprotective action of CX3CL1 in different models of brain injuries is mediated by its inhibitory activity on microglia and, in vitro, requires the activation of adenosine receptor 1 (A1R). We show that, in the presence of the A1R antagonist 1,3-dipropyl-8-cyclopentylxanthine and in A1R⁻/⁻ mice, the neuroprotective effect of CX3CL1 on pMCAO was abolished, indicating the critical importance of the adenosine system in CX3CL1 protection also in vivo. In apparent contrast with the above reported data but in agreement with previous findings, cx3cl1⁻/⁻ and cx3cr1(GFP/GFP) mice, respectively, deficient in CX3CL1 or CX3CR1, had less severe brain injury on pMCAO, and the administration of exogenous CX3CL1 increased brain damage in cx3cl1⁻/⁻ ischemic mice. We also report that CX3CL1 induced a different phagocytic activity in wild type and cx3cl1⁻/⁻ microglia in vitro during cotreatment with the medium conditioned by neurons damaged by oxygen-glucose deprivation. Together, these data suggest that acute administration of CX3CL1 reduces ischemic damage via an adenosine-dependent mechanism and that the absence of constitutive CX3CL1-CX3CR1 signaling changes the outcome of microglia-mediated effects during CX3CL1 administration to ischemic brain.


Assuntos
Quimiocina CX3CL1/metabolismo , Quimiocina CX3CL1/uso terapêutico , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/prevenção & controle , Antagonistas do Receptor A1 de Adenosina/uso terapêutico , Análise de Variância , Animais , Animais Geneticamente Modificados , Animais Recém-Nascidos , Infarto Encefálico/etiologia , Infarto Encefálico/prevenção & controle , Receptor 1 de Quimiocina CX3C , Células Cultivadas , Córtex Cerebral/citologia , Quimiocina CX3CL1/deficiência , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática/métodos , Glucose/deficiência , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Hipóxia/prevenção & controle , Infarto da Artéria Cerebral Média/complicações , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/terapia , Neurônios/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Ratos , Receptores de Quimiocinas/deficiência , Receptores Purinérgicos P1/deficiência , Xantinas/uso terapêutico
3.
Proc Natl Acad Sci U S A ; 106(37): 15927-31, 2009 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-19721003

RESUMO

We previously found that the endogenous anticonvulsant adenosine, acting through A(2A) and A(3) adenosine receptors (ARs), alters the stability of currents (I(GABA)) generated by GABA(A) receptors expressed in the epileptic human mesial temporal lobe (MTLE). Here we examined whether ARs alter the stability (desensitization) of I(GABA) expressed in focal cortical dysplasia (FCD) and in periglioma epileptic tissues. The experiments were performed with tissues from 23 patients, using voltage-clamp recordings in Xenopus oocytes microinjected with membranes isolated from human MTLE and FCD tissues or using patch-clamp recordings of pyramidal neurons in epileptic tissue slices. On repetitive activation, the epileptic GABA(A) receptors revealed instability, manifested by a large I(GABA) rundown, which in most of the oocytes (approximately 70%) was obviously impaired by the new A(2A) antagonists ANR82, ANR94, and ANR152. In most MTLE tissue-microtransplanted oocytes, a new A(3) receptor antagonist (ANR235) significantly improved I(GABA) stability. Moreover, patch-clamped pyramidal neurons from human neocortical slices of periglioma epileptic tissues exhibited altered I(GABA) rundown on ANR94 treatment. Our findings indicate that antagonizing A(2A) and A(3) receptors increases the I(GABA) stability in different epileptic tissues and suggest that adenosine derivatives may offer therapeutic opportunities in various forms of human epilepsy.


Assuntos
Receptor A2A de Adenosina/metabolismo , Receptor A3 de Adenosina/metabolismo , Receptores de GABA-A/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Antagonistas do Receptor A2 de Adenosina , Antagonistas do Receptor A3 de Adenosina , Animais , Epilepsia do Lobo Temporal/tratamento farmacológico , Epilepsia do Lobo Temporal/metabolismo , Feminino , Humanos , Técnicas In Vitro , Malformações do Desenvolvimento Cortical/metabolismo , Oócitos/metabolismo , Técnicas de Patch-Clamp , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Xenopus laevis
4.
J Neurosci ; 30(8): 2835-43, 2010 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-20181581

RESUMO

We applied the group-I metabotropic glutamate (mGlu) receptor agonist, 3,5-dihydroxyphenylglycine (DHPG), to neonatal or adult rat hippocampal slices at concentrations (10 microM) that induced a short-term depression (STD) of excitatory synaptic transmission at the Schaffer collateral/CA1 synapses. DHPG-induced STD was entirely mediated by the activation of mGlu5 receptors because it was abrogated by the mGlu5 receptor antagonist, MPEP [2-methyl-6-(phenylethynyl)pyridine], but not by the mGlu1 receptor antagonist, CPCCOEt [7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester]. Knowing that ephrin-Bs functionally interact with group-I mGlu receptors (Calò et al., 2005), we examined whether pharmacological activation of ephrin-Bs could affect DHPG-induced STD. We activated ephrin-Bs using their cognate receptor, EphB1, under the form of a preclustered EphB1/Fc chimera. Addition of clustered EphB1/Fc alone to the slices induced a small but nondecremental depression of excitatory synaptic transmission, which differed from the depression induced by 10 microM DHPG. Surprisingly, EphB1/Fc-induced synaptic depression was abolished by MPEP (but not by CPCCOEt) suggesting that it required the endogenous activation of mGlu5 receptors. In addition, coapplication of DHPG and EphB1/Fc, resulted in a large and nondecremental long-term depression. The effect of clustered EphB1/Fc was specific because it was not mimicked by unclustered EphB1/Fc or clustered EphA1/Fc. These findings raise the intriguing possibility that changes in synaptic efficacy mediated by mGlu5 receptors are under the control of the ephrin/Eph receptor system, and that the neuronal actions of ephrins can be targeted by drugs that attenuate mGlu5 receptor signaling.


Assuntos
Efrinas/metabolismo , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Depressão Sináptica de Longo Prazo/fisiologia , Receptores de Glutamato Metabotrópico/metabolismo , Transmissão Sináptica/fisiologia , Animais , Efrina-B1/agonistas , Efrina-B1/metabolismo , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Hipocampo/citologia , Masculino , Técnicas de Cultura de Órgãos , Técnicas de Patch-Clamp , Piridinas/farmacologia , Ratos , Ratos Wistar , Receptor EphB1/genética , Receptor EphB1/metabolismo , Receptor de Glutamato Metabotrópico 5 , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Transmissão Sináptica/efeitos dos fármacos
5.
Hum Mol Genet ; 18(20): 3997-4006, 2009 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-19628475

RESUMO

Sporadic amyotrophic lateral sclerosis (SALS) is a motor neuron degenerative disease of unknown etiology. Current thinking on SALS is that multiple genetic and environmental factors contribute to disease liability. Since neuronal acetylcholine receptors (nAChRs) are part of the glutamatergic pathway, we searched for sequence variants in CHRNA3, CHRNA4 and CHRNB4 genes, encoding neuronal nicotinic AChR subunits, in 245 SALS patients and in 450 controls. We characterized missense variants by in vitro mutagenesis, cell transfection and electrophysiology. Sequencing the regions encoding the intracellular loop of AChRs subunits disclosed 15 missense variants (6.1%) in 14 patients compared with only six variants (1.3%) in controls (P = 0.001; OR 4.48, 95% CI 1.7-11.8). The frequency of variants in exons encoding extracellular and transmembrane domains and in intronic regions did not differ. NAChRs formed by mutant alpha3 and alpha4 and wild-type (WT) beta4 subunits exhibited altered affinity for nicotine (Nic), reduced use-dependent rundown of Nic-activated currents (I(Nic)) and reduced desensitization leading to sustained intracellular Ca(2+) concentration, in comparison with WT-nAChR. The cellular loop has a crucial importance for receptor trafficking and regulating ion channel properties. Missense variants in this domain are significantly over-represented in SALS patients and alter functional properties of nAChR in vitro, resulting in increased Ca(2+) entry into the cells. We suggest that these gain-of-function variants might contribute to disease liability in a subset of SALS because Ca(2+) signals mediate nAChR's neuromodulatory effects, including regulation of glutamate release and control of cell survival.


Assuntos
Variação Genética , Doença dos Neurônios Motores/metabolismo , Mutação de Sentido Incorreto , Proteínas do Tecido Nervoso/metabolismo , Receptores Nicotínicos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos de Casos e Controles , Linhagem Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença dos Neurônios Motores/genética , Proteínas do Tecido Nervoso/genética , Ratos , Receptores Nicotínicos/genética , Adulto Jovem
6.
Proc Natl Acad Sci U S A ; 105(39): 15118-23, 2008 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-18809912

RESUMO

We examined how the endogenous anticonvulsant adenosine might influence gamma-aminobutyric acid type A (GABA(A)) receptor stability and which adenosine receptors (ARs) were involved. Upon repetitive activation (GABA 500 microM), GABA(A) receptors, microtransplanted into Xenopus oocytes from neurosurgically resected epileptic human nervous tissues, exhibited an obvious GABA(A)-current (I(GABA)) run-down, which was consistently and significantly reduced by treatment with the nonselective adenosine receptor antagonist CGS15943 (100 nM) or with adenosine deaminase (ADA) (1 units/ml), that inactivates adenosine. It was also found that selective antagonists of A2B (MRS1706, 10 nM) or A3 (MRS1334, 30 nM) receptors reduced I(GABA) run-down, whereas treatment with the specific A1 receptor antagonist DPCPX (10 nM) was ineffective. The selective A2A receptor antagonist SCH58261 (10 nM) reduced or potentiated I(GABA) run-down in approximately 40% and approximately 20% of tested oocytes, respectively. The ADA-resistant, AR agonist 2-chloroadenosine (2-CA) (10 microM) potentiated I(GABA) run-down but only in approximately 20% of tested oocytes. CGS15943 administration again decreased I(GABA) run-down in patch-clamped neurons from either human or rat neocortex slices. I(GABA) run-down in pyramidal neurons was equivalent in A1 receptor-deficient and wt neurons but much larger in neurons from A2A receptor-deficient mice, indicating that, in mouse cortex, GABA(A)-receptor stability is tonically influenced by A2A but not by A1 receptors. I(GABA) run-down from wt mice was not affected by 2-CA, suggesting maximal ARs activity by endogenous adenosine. Our findings strongly suggest that cortical A2-A3 receptors alter the stability of GABA(A) receptors, which could offer therapeutic opportunities.


Assuntos
Adenosina/metabolismo , Anticonvulsivantes/metabolismo , Epilepsia/metabolismo , Antagonistas de Receptores Purinérgicos P1 , Receptores de GABA-A/metabolismo , Adenosina/farmacologia , Adenosina Desaminase/farmacologia , Adulto , Animais , Anticonvulsivantes/farmacologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Feminino , Agonistas de Receptores de GABA-A , Humanos , Masculino , Neurônios/metabolismo , Oócitos , Tratos Piramidais/metabolismo , Pirimidinas/farmacologia , Quinazolinas/farmacologia , Ratos , Triazóis/farmacologia , Xantinas/farmacologia , Xenopus , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/farmacologia
7.
J Neurochem ; 114(4): 1231-40, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20533996

RESUMO

Verapamil, a Ca(2+) channel blocker widely used in clinical practice, also affects the properties of frog and mouse muscle acetylcholine receptor (AChR). Here, we examine the mechanism of action of verapamil on human wild-type and slow-channel mutant muscle AChRs harboring in any subunit a valine-to-alanine mutation of 13' residue of the pore-lining M2 transmembrane segment. Verapamil, after a pre-treatment of 0.5-10 s, accelerated the decay of whole-cell or macroscopic outside-out currents within milliseconds of ACh application even at clinically attainable doses. Recordings of unitary events in the cell-attached and outside-out configurations showed that verapamil does not alter single-channel conductance, but reduces channel open probability, by prolonging the dwell time into the closed state for wild-type and all mutant AChR. The duration of channel openings decreased only for the epsilonV265A-AChR, by shortening the longest exponential component of the open-time distribution. These results provide a rationale for the therapeutic use of verapamil in the slow-channel syndrome and emphasize the major role played by epsilon subunit in controlling the functional properties of human muscle AChR, as revealed by the peculiar alterations imparted by mutations in this subunit.


Assuntos
Mutação/genética , Junção Neuromuscular/efeitos dos fármacos , Junção Neuromuscular/genética , Receptores Colinérgicos/efeitos dos fármacos , Receptores Colinérgicos/genética , Verapamil/farmacologia , Alanina/genética , Substituição de Aminoácidos/genética , Bloqueadores dos Canais de Cálcio/farmacologia , Células Cultivadas , Humanos , Ativação do Canal Iônico/efeitos dos fármacos , Ativação do Canal Iônico/genética , Junção Neuromuscular/metabolismo , Mutação Puntual/genética , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/genética , Receptores Colinérgicos/metabolismo , Membranas Sinápticas/efeitos dos fármacos , Membranas Sinápticas/genética , Membranas Sinápticas/metabolismo , Valina/genética
8.
Proc Natl Acad Sci U S A ; 104(52): 20944-8, 2007 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-18083839

RESUMO

A study was made of the "rundown" of GABA(A) receptors, microtransplanted to Xenopus oocytes from surgically resected brain tissues of patients afflicted with drug-resistant human mesial temporal lobe epilepsy (mTLE). Cell membranes, isolated from mTLE neocortex specimens, were injected into frog oocytes that rapidly incorporated functional GABA(A) receptors. Upon repetitive activation with GABA (1 mM), "epileptic" GABA(A) receptors exhibited a GABA(A)-current (I(GABA)) rundown that was significantly enhanced by Zn(2+) (

Assuntos
Epilepsia do Lobo Temporal/metabolismo , Receptores de GABA-A/fisiologia , Ácido gama-Aminobutírico/metabolismo , Animais , Eletrofisiologia/métodos , Humanos , Masculino , Neurônios/metabolismo , Ácido Okadáico/farmacologia , Oócitos/metabolismo , Pilocarpina/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de GABA-A/metabolismo , Sensibilidade e Especificidade , Lobo Temporal/patologia , Xenopus , Zinco/química
9.
Neuroimage ; 45(2): 512-21, 2009 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-19111623

RESUMO

The present study tested the two following hypotheses: (i) compared to non-athletes, elite athletes are characterized by a reduced cortical activation during the judgment of sporting observed actions; (ii) in elite athletes, a good judgment of observed sporting actions is related to a low cortical activation. To address these issues, electroencephalographic (EEG) data were recorded in 15 elite rhythmic gymnasts and 13 non-gymnasts. They observed a series of 120 rhythmic gymnastic videos. At the end of each video, the subjects had to judge the artistic/athletic level of the exercise by a scale from 0 to 10. The mismatch between their judgment and that of the coach indexed the degree of action judgment. The EEG cortical sources were estimated by sLORETA. With reference to a pre-stimulus period, the power decrease of alpha (8-12 Hz) rhythms during the videos indexed the cortical activation (event related desynchronization, ERD). Regarding the hypothesis (i), low- and high-frequency alpha ERD was lower in amplitude in the elite rhythmic gymnasts compared to the non-gymnasts in occipital and temporal areas (ventral pathway) and in dorsal pathway. Regarding the hypothesis (ii), in the elite rhythmic gymnasts high-frequency alpha ERD was higher in amplitude with the videos characterized by a high judgment error than those characterized by a low judgment error; this was true in inferior posterior parietal and ventral premotor areas ("mirror" pathway). These results globally suggest that the judgment of observed sporting actions is related to low amplitude of alpha ERD, as a possible index of spatially selective cortical activation ("neural efficiency").


Assuntos
Encéfalo/fisiologia , Tomada de Decisões/fisiologia , Potenciais Evocados/fisiologia , Prova Pericial/métodos , Ginástica/fisiologia , Destreza Motora/fisiologia , Análise e Desempenho de Tarefas , Percepção Visual/fisiologia , Adolescente , Adulto , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Adulto Jovem
10.
Neuroimage ; 44(1): 123-35, 2009 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-18805495

RESUMO

Atrophy of hippocampus and alteration of resting eyes-closed electroencephalographic (EEG) rhythms represent important features of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Here we evaluated linear and non-linear aspects of the relationship between these features in the continuum along MCI and AD conditions, as a reflection of neurodegenerative processes. Eyes-closed resting EEG data were recorded in 60 healthy elderly (Nold), 88 MCI, and 35 Alzheimer's disease (AD) patients. Hippocampal volume was measured in magnetic resonance imaging of the MCI and AD subjects. Based on the normalized hippocampal volume, selected MCI subjects could be divided into two demographically paired sub-groups: those with larger hippocampal volume (MCI +h; N=40; mini mental state evaluation - MMSE - score=27.5+/-0.26 SE) and those with smaller hippocampal volume (MCI -h; N=40; h; MMSE=26.5+/-0.34 SE); the normalized hippocampal volume was statistically greater in the MCI +h than in the MCI -h and AD subjects (p<0.0001). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). Cortical EEG generators were estimated by LORETA software. Results showed that the power of occipital, parietal, and temporal alpha 1 sources was maximum in MCI +h, intermediate in MCI -h, and low in AD patients. Furthermore, the power of these sources was linearly and non-linearly correlated with the normalized hippocampal volume. These 3 EEG sources were given as input for evaluating correlations (linear, exponential, logarithmic and power) with hippocampal volume. When subjects were considered as a unique group, there was a significant linear correlation of hippocampal volume with the magnitude of alpha 1 sources in the parietal, occipital and temporal areas. In general, the EEG sources showing significant linear correlation with hippocampal volume also supported a non-linear correlation with hippocampal volume strongly for the logarithmic one. The present results suggest that progressive atrophy of hippocampus correlates with decreased cortical alpha power, as estimated by using LORETA source modeling, in the continuum along MCI and AD conditions.


Assuntos
Ritmo alfa , Doença de Alzheimer/patologia , Mapeamento Encefálico , Transtornos Cognitivos/patologia , Hipocampo/patologia , Idoso , Humanos , Imageamento por Ressonância Magnética , Testes Neuropsicológicos
11.
Hum Brain Mapp ; 30(3): 998-1013, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18465752

RESUMO

What is the timing of cortical activation related to consciousness of visuo-spatial executive functions? Electroencephalographic data (128 channels) were recorded in 13 adults. Cue stimulus briefly appeared on right or left (equal probability) monitor side for a period, inducing about 50% of recognitions. It was then masked and followed (2 s) by a central visual go stimulus. Left (right) mouse button had to be clicked after right (left) cue stimulus. This "inverted" response indexed executive processes. Afterward, subjects said "seen" if they had detected the cue stimulus or "not seen" when it was missed. Sources of event-related potentials (ERPs) were estimated by LORETA software. The inverted responses were about 95% in seen trials and about 60% in not seen trials. Cue stimulus evoked frontal-parietooccipital potentials, having the same peak latencies in the seen and not seen data. Maximal difference in amplitude of the seen and not seen ERPs was detected at about +300-ms post-stimulus (P3). P3 sources were higher in amplitude in the seen than not seen trials in dorsolateral prefrontal, premotor and parietooccipital areas. This was true in dorsolateral prefrontal and premotor cortex even when percentage of the inverted responses and reaction time were paired in the seen and not seen trials. These results suggest that, in normal subjects, the primary consciousness enhances the efficacy of visuo-spatial executive processes and is sub-served by a late (100- to 400-ms post-stimulus) enhancement of the neural synchronization in frontal areas.


Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Cognição/fisiologia , Estado de Consciência/fisiologia , Potenciais Evocados Visuais/fisiologia , Percepção Visual/fisiologia , Adulto , Sinais (Psicologia) , Eletroencefalografia , Feminino , Humanos , Masculino , Estimulação Luminosa
12.
Hum Brain Mapp ; 30(1): 138-46, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17999400

RESUMO

What is the neural substrate of our capability to properly react to changes in the environment? It can be hypothesized that the anterior cingulate cortex (ACC) manages repetitive stimuli in routine conditions and alerts the dorsolateral prefrontal cortex (PFC) when stimulation unexpectedly changes. To provide evidence in favor of this hypothesis, intracerebral stereoelectroencephalographic (SEEG) data were recorded from the anterior cingulate and dorsolateral PFC of eight epileptic patients in a standard visual oddball task during presurgical monitoring. Two types of stimuli (200 ms duration) such as the letters O (frequent stimuli; 80% of probability) and X (rare stimuli) were presented in random order, with an interstimulus interval between 2 and 5 s. Subjects had to mentally count the rare (target) stimuli and to press a button with their dominant hand as quickly and accurately as possible. EEG frequency bands of interest were theta (4-8 Hz), alpha (8-12 Hz), beta (14-30 Hz), and gamma (30-45 Hz). The directionality of the information flux within the EEG rhythms was indexed by a directed transfer function (DTF). The results showed that compared with the frequent stimuli, the target stimuli induced a statistically significant increase of DTF values from the anterior cingulate to the dorsolateral PFC at the theta rhythms (P < 0.01). These results provide support to the hypothesis that ACC directly or indirectly affects the oscillatory activity of dorsolateral PFC by a selective frequency code under typical oddball conditions.


Assuntos
Relógios Biológicos/fisiologia , Potenciais Evocados/fisiologia , Giro do Cíngulo/fisiologia , Córtex Pré-Frontal/fisiologia , Potenciais de Ação/fisiologia , Adulto , Mapeamento Encefálico , Cognição/fisiologia , Interpretação Estatística de Dados , Eletroencefalografia/métodos , Feminino , Giro do Cíngulo/anatomia & histologia , Humanos , Masculino , Processos Mentais/fisiologia , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Neurônios/fisiologia , Testes Neuropsicológicos , Estimulação Luminosa , Córtex Pré-Frontal/anatomia & histologia , Processamento de Sinais Assistido por Computador , Adulto Jovem
13.
Hum Brain Mapp ; 30(7): 2077-89, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18819109

RESUMO

It is well known that theta rhythms (3-8 Hz) are the fingerprint of hippocampus, and that neural activity accompanying encoding of words differs according to whether the items are later remembered or forgotten ["subsequent memory effect" (SME)]. Here, we tested the hypothesis that temporal synchronization of theta rhythms among hippocampus, amygdala, and neocortex is related to immediate memorization of repeated words. To address this issue, intracerebral electroencephalographic (EEG) activity was recorded in five subjects with drug-resistant temporal lobe epilepsy (TLE), under presurgical monitoring routine. During the recording of the intracerebral EEG activity, the subjects performed a computerized version of Rey auditory verbal learning test (RAVLT), a popular test for the clinical evaluation of the immediate and delayed memory. They heard the same list of 15 common words for five times. Each time, immediately after listening the list, the subjects were required to repeat as many words as they could recall. Spectral coherence of the intracerebral EEG activity was computed in order to assess the temporal synchronization of the theta (about 3-8 Hz) rhythms among hippocampus, amygdala, and temporal-occipital neocortex. We found that theta coherence values between amygdala and hippocampus, and between hippocampus and occipital-temporal cortex, were higher in amplitude during successful than unsuccessful immediate recall. A control analysis showed that this was true also for a gamma band (40-45 Hz). Furthermore, these theta and gamma effects were not observed in an additional (control) subject with drug-resistant TLE and a wide lesion to hippocampus. In conclusion, a successful immediate recall to the RAVLT was associated to the enhancement of temporal synchronization of the theta (gamma) rhythms within a cerebral network including hippocampus, amygdala, and temporal-occipital neocortex.


Assuntos
Tonsila do Cerebelo/fisiologia , Córtex Cerebral/fisiologia , Sincronização Cortical , Hipocampo/fisiologia , Rememoração Mental/fisiologia , Ritmo Teta , Estimulação Acústica , Adulto , Tonsila do Cerebelo/patologia , Análise de Variância , Córtex Cerebral/patologia , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Hipocampo/patologia , Humanos , Aprendizagem/fisiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fala , Fatores de Tempo
14.
Hum Brain Mapp ; 30(5): 1431-43, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19097164

RESUMO

Does impairment of cholinergic systems represent an important factor in the development of amnesic mild cognitive impairment (aMCI), as a preclinical stage of Alzheimer's disease (AD)? Here we tested the hypothesis that electroencephalographic (EEG) rhythms, known to be modulated by the cholinergic system, may be particularly affected in aMCI patients with lesions along the cholinergic white-matter tracts. Eyes-closed resting EEG data were recorded in 28 healthy elderly (Nold) and 57 aMCI patients. Lesions along the cholinergic white-matter tracts were detected with fluid-attenuated inversion recovery sequences on magnetic resonance imaging. The estimation of the cholinergic lesion was performed with a validated semi-automatic algorithm pipeline after registration to a stereotactic template, image integration with stereotactic masks of the cholinergic tracts, and normalization to intracranial volume. The aMCI patients were divided into two groups of high (MCI Ch+; N = 29; MMSE = 26.2) and low cholinergic damage (MCI Ch-; N = 28; MMSE = 26.6). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). Cortical EEG generators were estimated by LORETA software. As main results, (i) power of occipital, parietal, temporal, and limbic alpha 1 sources was maximum in Nold, intermediate in MCI Ch-, and low in MCI Ch+ patients; (ii) the same trend was true in theta sources. These results are consistent with the hypothesis that damage to the cholinergic system is associated with alterations of EEG sources in aMCI subjects.


Assuntos
Acetilcolina/metabolismo , Ritmo alfa , Amnésia/patologia , Córtex Cerebral , Transtornos Cognitivos/patologia , Idoso , Amnésia/complicações , Análise de Variância , Mapeamento Encefálico , Córtex Cerebral/lesões , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Transtornos Cognitivos/complicações , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/patologia , Testes Neuropsicológicos , Análise Espectral
15.
Hum Brain Mapp ; 30(11): 3527-40, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19350556

RESUMO

This study tested the two following hypotheses: (i) compared with non-athletes, elite athletes are characterized by a reduced cortical activation during the preparation of precise visuo-motor performance; (ii) in elite athletes, an optimal visuo-motor performance is related to a low cortical activation. To this aim, electroencephalographic (EEG; 56 channels; Be Plus EB-Neuro) data were recorded in 18 right-handed elite air pistol shooters and 10 right-handed non-athletes. All subjects performed 120 shots. The EEG data were spatially enhanced by surface Laplacian estimation. With reference to a baseline period, power decrease/increase of alpha rhythms during the preshot period indexed the cortical activation/deactivation (event-related desynchronization/synchronization, ERD/ERS). Regarding the hypothesis (i), low- (about 8-10 Hz) and high-frequency (about 10-12 Hz) alpha ERD was lower in amplitude in the elite athletes than in the non-athletes over the whole scalp. Regarding the hypothesis (ii), the elite athletes showed high-frequency alpha ERS (about 10-12 Hz) larger in amplitude for high score shots (50%) than for low score shots; this was true in right parietal and left central areas. A control analysis confirmed these results with another indicator of cortical activation (beta ERD, about 20 Hz). The control analysis also showed that the amplitude reduction of alpha ERD for the high compared with low score shots was not observed in the non-athletes. The present findings globally suggest that in elite athletes (experts), visuo-motor performance is related to a global decrease of cortical activity, as a possible index of spatially selective cortical processes ("neural efficiency").


Assuntos
Ritmo alfa , Atenção/fisiologia , Mapeamento Encefálico , Córtex Cerebral/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Desempenho Psicomotor/fisiologia , Adulto , Análise de Variância , Atletas , Eletroculografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento/fisiologia , Estimulação Luminosa/métodos , Tempo de Reação/fisiologia , Adulto Jovem
16.
Eur J Appl Physiol ; 107(5): 603-10, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19711097

RESUMO

Breath-by-breath O(2) uptake (VO2, L min(-1)) and blood lactate concentration were measured before, during exercise, and recovery in six kata and six kumite karate Word Champions performing a simulated competition. VO2max, maximal anaerobic alactic, and lactic power were also assessed. The total energy cost (VO2TOT mL kg(-1) above resting) of each simulated competition was calculated and subdivided into aerobic, lactic, and alactic fractions. Results showed that (a) no differences between kata and kumite groups in VO2max, height of vertical jump, and Wingate test were found; (b) VO2TOT were 87.8 +/- 6.6 and 82.3 +/- 12.3 mL kg(-1) in kata male and female with a performance time of 138 +/- 4 and 158 +/- 14 s, respectively; 189.0 +/- 14.6 mL kg(-1) in kumite male and 155.8 +/- 38.4 mL kg(-1) in kumite female with a predetermined performance time of 240 +/- 0 and 180 +/- 0 s, respectively; (c) the metabolic power was significantly higher in kumite than in kata athletes (p < or = 0.05 in both gender); (d) aerobic and anaerobic alactic sources, in percentage of the total, were significantly different between gender and disciplines (p < 0.05), while the lactic source was similar; (e) HR ranged between 174 and 187 b min(-1) during simulated competition. In conclusion, kumite appears to require a much higher metabolic power than kata, being the energy source with the aerobic contribution predominant.


Assuntos
Atletas , Metabolismo Energético/fisiologia , Artes Marciais/fisiologia , Adolescente , Adulto , Desempenho Atlético/fisiologia , Teste de Esforço , Feminino , Humanos , Ácido Láctico/sangue , Ácido Láctico/metabolismo , Masculino , Consumo de Oxigênio/fisiologia , Adulto Jovem
17.
Neuroimage ; 42(4): 1544-53, 2008 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-18602484

RESUMO

"Neural efficiency" hypothesis posits that cortical activity is spatially focused in experts. Here we tested the hypothesis that compared to non-athletes, elite athletes are characterized by a reduced cortical activation during visuo-motor tasks related to the field of expertise, as a function of movement side. EEG data (56 channels; EB-Neuro) were continuously recorded in the following right-handed subjects: 11 non-athletes, 11 elite fencing athletes, and 11 elite karate athletes. During the EEG recordings, they observed pictures with fencing and karate attacks, and had to quickly click a right (left) keyboard button for the attacks at right (left) monitor side. The EEG data were averaged with respect to the movement onset, and were spatially enhanced by surface Laplacian estimation. The potentials related to the preparation (readiness potential) and initiation (motor potential) of the movements were measured. For the right movement, the potentials overlying supplementary motor and contralateral sensorimotor areas were higher in amplitude in the non-athletes than in the elite karate and fencing athletes. Furthermore, the amplitude of the motor potential over ipsilateral sensorimotor area was higher in the elite karate than fencing athletes, and its distribution over bilateral sensorimotor areas was less asymmetrical in the karate than in the other two groups. For the left movement, these potentials showed no difference between the groups. The present results suggest that "neural efficiency" hypothesis does not fully account for the organization of motor systems in elite athletes. "Neural efficiency" would depend on several factors including side of the movement, hemisphere, and kind of athletes.


Assuntos
Encéfalo/fisiologia , Eletroencefalografia/métodos , Destreza Motora/fisiologia , Análise e Desempenho de Tarefas , Percepção Visual/fisiologia , Adulto , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
18.
Hum Brain Mapp ; 29(12): 1355-67, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17979121

RESUMO

Do cerebrovascular and Alzheimer's disease (AD) lesions represent additive factors in the development of mild cognitive impairment (MCI) as a putative preclinical stage of AD? Here we tested the hypothesis that directionality of fronto-parietal functional coupling of electroencephalographic (EEG) rhythms is relatively preserved in amnesic MCI subjects in whom the cognitive decline is mainly explained by white-matter vascular load. Resting EEG was recorded in 40 healthy elderly (Nold) and 78 amnesic MCI. In the MCI subjects, white-matter vascular load was quantified based on magnetic resonance images (0-30 visual rating scale). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), and beta2 (20-30 Hz). Directionality of fronto-parietal functional coupling of EEG rhythms was estimated by directed transfer function software. As main results, (i) fronto-parietal functional coupling of EEG rhythms was higher in magnitude in the Nold than in the MCI subjects; (ii) more interestingly, that coupling was higher at theta, alpha1, alpha2, and beta1 in MCI V+ (high vascular load; N = 42; MMSE = 26) than in MCI V- group (low vascular load; N = 36; MMSE= 26.7). These results are interpreted as supporting the additive model according to which MCI state would result from the combination of cerebrovascular and neurodegenerative lesions.


Assuntos
Cérebro/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Demência Vascular/fisiopatologia , Eletroencefalografia/métodos , Potenciais Evocados/fisiologia , Imageamento por Ressonância Magnética/métodos , Idoso , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Amnésia/patologia , Amnésia/fisiopatologia , Arteríolas/patologia , Biomarcadores/análise , Artérias Cerebrais/patologia , Cérebro/patologia , Transtornos Cognitivos/patologia , Demência Vascular/patologia , Progressão da Doença , Lobo Frontal/patologia , Lobo Frontal/fisiopatologia , Humanos , Modelos Neurológicos , Fibras Nervosas Mielinizadas/patologia , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Lobo Parietal/patologia , Lobo Parietal/fisiopatologia , Valor Preditivo dos Testes
19.
Neuropsychologia ; 46(6): 1707-20, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18440574

RESUMO

It is an open issue if vascular and Alzheimer's disease (AD) lesions represent additive factors in the development of mild cognitive impairment (MCI), as a preclinical stage of Alzheimer's disease (AD) at group level. In the present study, we tested the hypothesis that electroencephalographic (EEG) alpha rhythms, which are affected (i.e. decreased in amplitude) by AD processes, are relatively preserved in MCI subjects in whom the cognitive decline is mainly explained by white-matter vascular load. Resting EEG was recorded in 40 healthy elderly (Nold), 80 MCI, and 40 AD subjects. In the MCI subjects, white-matter vascular load was quantified based on MRI (0-30 Wahlund visual rating scale). EEG rhythms of interest were delta (2-4Hz), theta (4-8Hz), alpha 1 (8-10.5Hz), alpha 2 (10.5-13Hz), beta 1 (13-20Hz), and beta 2 (20-30Hz). Low resolution electromagnetic source tomography (LORETA) was used for EEG source analysis. As expected, we observed that alpha 1 sources in parietal, occipital, and temporal areas were lower in amplitude in the AD and MCI subjects than in the Nold subjects, whereas the amplitude of wide delta sources was higher in the AD than in the Nold and MCI subjects. As novel results, the amplitude of parietal, occipital, and temporal alpha 1 sources was higher in the MCI V+ (high vascular load; N=42; MMSE=26) than MCI V- group (low vascular load; N=37; MMSE=26.7). Furthermore, a weak but significant (p<0.05) positive statistical correlation was found between the parietal alpha 1 sources and the score of Wahlund scale across all MCI subjects (i.e. the more severe white-matter lesions, the higher parietal alpha source power). The present results are in line with the additive model of cognitive impairment postulating that this arises as the sum of neurodegenerative and cerebrovascular lesions.


Assuntos
Ritmo alfa , Mapeamento Encefálico , Córtex Cerebral/patologia , Transtornos Cerebrovasculares/patologia , Transtornos Cognitivos/complicações , Transtornos Cognitivos/patologia , Idoso , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Córtex Cerebral/fisiopatologia , Transtornos Cerebrovasculares/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Entrevista Psiquiátrica Padronizada , Testes Neuropsicológicos , Análise Espectral
20.
J Neuroimmunol ; 198(1-2): 75-81, 2008 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-18508130

RESUMO

The chemokine interleukin 8/CXCL8 induces the phosphorylation of the GluR1 subunit of the AMPA-type glutamate receptor in neurons and transfected HEK cells, on both serine 845 (S845) and 831 (S831) residues. We previously described that CXCL8 receptor CXCR2 and GluR1 co-precipitate and that GluR1/CXCR2 co-expression both in HEK cells and neurons impairs CXCL8-induced cell migration. Here we show that replacement of S845 with Ala (A), but not with Glu (E), strongly reduces GluR1/CXCR2 interaction and abolishes the impairment of CXCL8-induced cell migration. Considered together our findings point to the phosphorylated state of S845GluR1 as a determinant of GluR1-CXCR2 physical coupling.


Assuntos
Interleucina-8/fisiologia , Receptores de AMPA/efeitos dos fármacos , Receptores de AMPA/metabolismo , Animais , Animais Recém-Nascidos , Cálcio/metabolismo , Carbazóis/farmacologia , Células Cultivadas , Cerebelo/citologia , Quelantes/farmacologia , Quimiotaxia/efeitos dos fármacos , AMP Cíclico/metabolismo , Ácido Egtázico/análogos & derivados , Ácido Egtázico/farmacologia , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Hipocampo/citologia , Humanos , Interleucina-8/farmacologia , Mutação , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Fosforilação/efeitos dos fármacos , Pirróis/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de AMPA/genética , Fatores de Tempo , Transfecção
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