一种与癫痫发作有关的星形胶质细胞
2010-06-06 抗癌健康网
专注健康 关爱生命 意大利帕多瓦神经科学研究所等机构的科学家在新一期美国《科学公共图书馆·生物学》杂志上发表论文说，癫痫发作的典型症状是抽搐，这是神经元活动异常的结果。但他们的研究发现，星形胶质细胞也参与了癫痫的发作。这种细胞会与神经元持续交互作用，这种交互作用使神经元活动异常，从而导致癫痫发作。
科学家的研究还证明，抑制星形胶质细胞的活动可以减轻癫痫发作时的症状，加强其活动则会使癫痫发作更为强烈。
星形胶质细胞普遍存在于哺乳动物大脑中，这种细胞数量相当多。过去认为这种细胞在大脑中的作用很小。
生物谷推荐原文出处：
PLoS Biol. doi:10.1371/journal.pbio.1000352
An Excitatory Loop with Astrocytes Contributes to Drive Neurons to Seizure Threshold
Marta Gómez-Gonzalo1,2#, Gabriele Losi1,2#, Angela Chiavegato1,2, Micaela Zonta1,2, Mario Cammarota1,2, Marco Brondi3,4, Francesco Vetri4, Laura Uva5, Tullio Pozzan1,2,6, Marco de Curtis5, Gian Michele Ratto3,4, Giorgio Carmignoto1,2*
1 Institute of Neuroscience – Consiglio Nazionale delle Ricerche (CNR), University of Padova, Padova, Italy, 2 Department of Experimental Biomedical Sciences, University of Padova, Padova, Italy, 3 National Enterprise for nanoScience and nanoTechnology (NEST), Instituto Nanoscienze CNR, Scuola Normale Superiore, Pisa, Italy, 4 Institute of Neuroscience – CNR, Pisa, Italy, 5 Fondazione Istituto Neurologico Carlo Besta, Milano, Italy, 6 Venetian Institute of Molecular Medicine, Padova, Italy
Seizures in focal epilepsies are sustained by a highly synchronous neuronal discharge that arises at restricted brain sites and subsequently spreads to large portions of the brain. Despite intense experimental research in this field, the earlier cellular events that initiate and sustain a focal seizure are still not well defined. Their identification is central to understand the pathophysiology of focal epilepsies and to develop new pharmacological therapies for drug-resistant forms of epilepsy. The prominent involvement of astrocytes in ictogenesis was recently proposed. We test here whether a cooperation between astrocytes and neurons is a prerequisite to support ictal (seizure-like) and interictal epileptiform events. Simultaneous patch-clamp recording and Ca2+ imaging techniques were performed in a new in vitro model of focal seizures induced by local applications of N-methyl-D-aspartic acid (NMDA) in rat entorhinal cortex slices. We found that a Ca2+ elevation in astrocytes correlates with both the initial development and the maintenance of a focal, seizure-like discharge. A delayed astrocyte activation during ictal discharges was also observed in other models (including the whole in vitro isolated guinea pig brain) in which the site of generation of seizure activity cannot be precisely monitored. In contrast, interictal discharges were not associated with Ca2+ changes in astrocytes. Selective inhibition or stimulation of astrocyte Ca2+ signalling blocked or enhanced, respectively, ictal discharges, but did not affect interictal discharge generation. Our data reveal that neurons engage astrocytes in a recurrent excitatory loop (possibly involving gliotransmission) that promotes seizure ignition and sustains the ictal discharge. This neuron–astrocyte interaction may represent a novel target to develop effective therapeutic strategies to control seizures.
科学家的研究还证明，抑制星形胶质细胞的活动可以减轻癫痫发作时的症状，加强其活动则会使癫痫发作更为强烈。
星形胶质细胞普遍存在于哺乳动物大脑中，这种细胞数量相当多。过去认为这种细胞在大脑中的作用很小。
生物谷推荐原文出处：
PLoS Biol. doi:10.1371/journal.pbio.1000352
An Excitatory Loop with Astrocytes Contributes to Drive Neurons to Seizure Threshold
Marta Gómez-Gonzalo1,2#, Gabriele Losi1,2#, Angela Chiavegato1,2, Micaela Zonta1,2, Mario Cammarota1,2, Marco Brondi3,4, Francesco Vetri4, Laura Uva5, Tullio Pozzan1,2,6, Marco de Curtis5, Gian Michele Ratto3,4, Giorgio Carmignoto1,2*
1 Institute of Neuroscience – Consiglio Nazionale delle Ricerche (CNR), University of Padova, Padova, Italy, 2 Department of Experimental Biomedical Sciences, University of Padova, Padova, Italy, 3 National Enterprise for nanoScience and nanoTechnology (NEST), Instituto Nanoscienze CNR, Scuola Normale Superiore, Pisa, Italy, 4 Institute of Neuroscience – CNR, Pisa, Italy, 5 Fondazione Istituto Neurologico Carlo Besta, Milano, Italy, 6 Venetian Institute of Molecular Medicine, Padova, Italy
Seizures in focal epilepsies are sustained by a highly synchronous neuronal discharge that arises at restricted brain sites and subsequently spreads to large portions of the brain. Despite intense experimental research in this field, the earlier cellular events that initiate and sustain a focal seizure are still not well defined. Their identification is central to understand the pathophysiology of focal epilepsies and to develop new pharmacological therapies for drug-resistant forms of epilepsy. The prominent involvement of astrocytes in ictogenesis was recently proposed. We test here whether a cooperation between astrocytes and neurons is a prerequisite to support ictal (seizure-like) and interictal epileptiform events. Simultaneous patch-clamp recording and Ca2+ imaging techniques were performed in a new in vitro model of focal seizures induced by local applications of N-methyl-D-aspartic acid (NMDA) in rat entorhinal cortex slices. We found that a Ca2+ elevation in astrocytes correlates with both the initial development and the maintenance of a focal, seizure-like discharge. A delayed astrocyte activation during ictal discharges was also observed in other models (including the whole in vitro isolated guinea pig brain) in which the site of generation of seizure activity cannot be precisely monitored. In contrast, interictal discharges were not associated with Ca2+ changes in astrocytes. Selective inhibition or stimulation of astrocyte Ca2+ signalling blocked or enhanced, respectively, ictal discharges, but did not affect interictal discharge generation. Our data reveal that neurons engage astrocytes in a recurrent excitatory loop (possibly involving gliotransmission) that promotes seizure ignition and sustains the ictal discharge. This neuron–astrocyte interaction may represent a novel target to develop effective therapeutic strategies to control seizures.
