Role of morphological changes in newly born granule cells of hippocampus after status epilepticus induced by pilocarpine in hyperexcitability

JT is the recipient of a Post-Doctoral Fellowship from CNPq, Brazil. NGC and ACR are recipients of grants from CNPq, FAPESP, FAPESP-Cinapce, CAPES-PROEX, CNPq-Research Fellowships, Brazil

Morphological Alterations in Newly Born Dentate Gyrus Granule Cells That Emerge after Status Epilepticus Contribute to Make Them Less Excitable

Computer simulations of external current stimulations of dentate gyrus granule cells of rats with Status Epilepticus induced by pilocarpine and control rats were used to evaluate whether morphological differences alone between these cells have an impact on their electrophysiological behavior. The cell models were constructed using morphological information from tridimensional reconstructions with Neurolucida software. To evaluate the effect of morphology differences alone, ion channel conductances, densities and distributions over the dendritic trees of dentate gyrus granule cells were the same for all models. External simulated currents were injected in randomly chosen dendrites belonging to one of three different areas of dentate gyrus granule cell molecular layer: inner molecular layer, medial molecular layer and outer molecular layer. Somatic membrane potentials were recorded to determine firing frequencies and inter-spike intervals. The results show that morphologically altered granule cells from pilocarpine-induced epileptic rats are less excitable than control cells, especially when they are stimulated in the inner molecular layer, which is the target area for mossy fibers that sprout after pilocarpine-induced cell degeneration. This suggests that morphological alterations may act as a protective mechanism to allow dentate gyrus granule cells to cope with the increase of stimulation caused by mossy fiber sprouting.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico National Counsel of Technological and Scientific Development (CNPq) BrazilConselho Nacional de Desenvolvimento Cientifico e Tecnologico - "National Counsel of Technological and Scientific Development" (CNPq) -Brazil [156597/2101-1]CNPq FellowshipCNPq FellowshipCNPqCNPqFundacao de Amparo a Pesquisa do Estado de Sao Paulo Foundation for Research Support of the State of Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - "Foundation for Research Support of the State of Sao Paulo" (FAPESP)Cooperacao Interinstitucional de Apoio a Pesquisas sobre o Cerebro da FAPESP Interinstitutional Cooperation in Support of Brain Research Program of FAPESP (FAPESPCinapce)Cooperacao Interinstitucional de Apoio a Pesquisas sobre o Cerebro da FAPESP "Inter-institutional Cooperation in Support of Brain Research Program of FAPESP" (FAPESP-Cinapce)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior Federal Agency of Support and Evaluation of Postgraduate Education (CAPES)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - "Federal Agency of Support and Evaluation of Postgraduate Education" (CAPES)CAPES program of Academic Excellence (CAPES-PROEX), BrazilCAPES program of Academic Excellence (CAPESPROEX), Brazi

Pathophysiology of mood disorders in temporal lobe epilepsy

Objective: There is accumulating evidence that the limbic system is pathologically involved in cases of psychiatric comorbidities in temporal lobe epilepsy (TLE) patients. Our objective was to develop a conceptual framework describing how neuropathological, neurochemical and electrophysiological aspects might contribute to the development of psychiatric symptoms in TLE and the putative neurobiological mechanisms that cause mood disorders in this patient subgroup. Methods: In this review, clinical, experimental and neuropathological findings, as well as neurochemical features of the limbic system were examined together to enhance our understanding of the association between TLE and psychiatric comorbidities. Finally, the value of animal models in epilepsy and mood disorders was discussed. Conclusions: TLE and psychiatric symptoms coexist more frequently than chance would predict. Alterations and neurotransmission disturbance among critical anatomical networks, and impaired or aberrant plastic changes might predispose patients with TLE to mood disorders. Clinical and experimental studies of the effects of seizures on behavior and electrophysiological patterns may offer a model of how limbic seizures increase the vulnerability of TLE patients to precipitants of psychiatric symptoms.FAPESPPROEXCNPqFAEP

Intoxication by star fruit (Averrhoa carambola) in 32 uraemic patients: treatment and outcome

Abstract Background. Clinical symptoms and outcomes of uraemic patients ingesting star fruit are quite variable and may progress to death. The purpose of the present report was to discuss the neurotoxic effects of star fruit intoxication in uraemic patients and to present the efficacy of different therapeutic approaches. Methods. We studied a total of 32 uraemic patients who had ingested star fruit. Before the intoxication episodes, 20 patients were on regular haemodialysis, eight were on peritoneal dialysis and four were not yet undergoing dialysis. Two patients were analysed retrospectively from their charts, 17 were directly monitored by our clinic and 13 were referred by physicians from many areas throughout the country, allowing us to follow their outcome from a distance. Intoxicated patients were given different therapeutic approaches (haemodialysis, peritoneal dialysis and supportive treatment), and their outcomes were analysed. Results. The most common symptoms were persistent and intractable hiccups in 30 patients (93.75%), vomiting in 22 (68.7%), variable degrees of disturbed consciousness (mental confusion, psychomotor agitation) in 21 (65.6%), decreased muscle power, limb numbness, paresis, insomnia and paresthesias in 13 (40.6%) and seizures in seven (21.8%). Patients who were promptly treated with haemodialysis, including those with severe intoxication, recovered without sequelae. Patients with severe intoxication who were not treated or treated with peritoneal dialysis did not survive. Conclusions. Haemodialysis, especially on a daily basis, is the ideal treatment for star fruit intoxication. In severe cases, continuous methods of replacement therapy may provide a superior initial procedure, since rebound effects are a common event. Peritoneal dialysis is of no use as a treatment, especially when consciousness disorders ensue

Considerações sobre as relações neurais e etológicas na avaliação das alterações do controle motor: I. Substratos neurais da motricidade

O movimento é a expressão final da ativação harmônica de múltiplos sistemas cerebrais e musculares. Na natureza ele medeia respostas primárias de profundo valor adaptativo como a reprodução, predação e fuga, entre outras. A descrição dos movimentos como atos ou padrões motores correspondeu inicialmente à Etologia. Com o avanço nas Neurociências, hoje é proposta abordagem neuroetológica para a pesquisa nesta área. Quando se apresentam disfunções do movimento, praticamente os mesmos sistemas musculares e cerebrais são utilizados, só que de maneira aberrante, tanto no tempo quanto no espaço. Nesta revisão são ilustrados os principais sistemas envolvidos no controle motor normal, particularmente córtex, gânglios basais, cerebelo, tronco cerebral, medula, periferia muscular receptora e efetora

Puzzling challenges in contemporary neuroscience: Insights from complexity and emergence in epileptogenic circuits

The brain is a complex system that, in the normal condition, has emergent properties like those associated with activity-dependent plasticity in learning and memory, and in pathological situations, manifests abnormal long-term phenomena like the epilepsies. Data from our laboratory and from the literature were classified qualitatively as sources of complexity and emergent properties from behavior to electrophysiological, cellular, molecular, and computational levels. We used such models as brainstem-dependent acute audiogenic seizures and forebrain-dependent kindled audiogenic seizures. Additionally we used chemical OF electrical experimental models of temporal lobe epilepsy that induce status epilepticus with behavioral, anatomical, and molecular sequelae such as spontaneous recurrent seizures and long-term plastic changes. Current Computational neuroscience tools will help the interpretation. storage, and sharing of the exponential growth of information derived from those studies. These strategies are considered solutions to deal with the complexity of brain pathologies such as the epilepsies. (C) 2008 Elsevier Inc. All rights reserved.FAPESP-CinapceCNPqPROEX/CAPESFAEP

Combined role of seizure-induced dendritic morphology alterations and spine loss in newborn granule cells with mossy fiber sprouting on the hyperexcitability of a computer model of the dentate gyrus.

Temporal lobe epilepsy strongly affects hippocampal dentate gyrus granule cells morphology. These cells exhibit seizure-induced anatomical alterations including mossy fiber sprouting, changes in the apical and basal dendritic tree and suffer substantial dendritic spine loss. The effect of some of these changes on the hyperexcitability of the dentate gyrus has been widely studied. For example, mossy fiber sprouting increases the excitability of the circuit while dendritic spine loss may have the opposite effect. However, the effect of the interplay of these different morphological alterations on the hyperexcitability of the dentate gyrus is still unknown. Here we adapted an existing computational model of the dentate gyrus by replacing the reduced granule cell models with morphologically detailed models coming from three-dimensional reconstructions of mature cells. The model simulates a network with 10% of the mossy fiber sprouting observed in the pilocarpine (PILO) model of epilepsy. Different fractions of the mature granule cell models were replaced by morphologically reconstructed models of newborn dentate granule cells from animals with PILO-induced Status Epilepticus, which have apical dendritic alterations and spine loss, and control animals, which do not have these alterations. This complex arrangement of cells and processes allowed us to study the combined effect of mossy fiber sprouting, altered apical dendritic tree and dendritic spine loss in newborn granule cells on the excitability of the dentate gyrus model. Our simulations suggest that alterations in the apical dendritic tree and dendritic spine loss in newborn granule cells have opposing effects on the excitability of the dentate gyrus after Status Epilepticus. Apical dendritic alterations potentiate the increase of excitability provoked by mossy fiber sprouting while spine loss curtails this increase