Objective Understanding the molecular and cellular mechanisms underlying epileptogenesis yields new in- sights into potential therapies that may ultimately prevent epilepsy. Gap junctions （GJs） create direct interce...Objective Understanding the molecular and cellular mechanisms underlying epileptogenesis yields new in- sights into potential therapies that may ultimately prevent epilepsy. Gap junctions （GJs） create direct intercellular conduits between adjacent cells and are formed by hexameric protein subunits called connexins （Cxs）. Changes in the expression of Cxs affect GJ communication and thereby could modulate the dissemination of electrical discharges. The hippocampus is one of the main regions involved in epileptogenesis and has a wide network of GJs between different cell types where Cx30 is expressed in astrocytes and Cx32 exists in neurons and oligodendrocytes. In the present study, we evaluated the changes of Cx30 and Cx32 expression in rat hippocampus during kindling epileptogenesis. Methods Rats were stereotaxically implanted with stimulating and recording electrodes in the basolateral amygdala, which was electrically stimulated once daily at afterdischarge threshold. Expression of Cx30 and Cx32, at both the mRNA and protein levels, was measured in the hippocampus at the beginning, in the middle （after acquisition of focal seizures）, and at the end （after establishment of generalized seizures） of the kindling process, by real-time PCR and Western blot. Results Cx30 mRNA expression was upregulated at the beginning of kindling and after acquisition of focal seizures. Then it was downregulated when the animals acquired generalized seizures. Overexpression of Cx30 mRNA at the start of kindling was consistent with the respective initial protein increase. Thereafter, no change was found in protein abundance during kindling. Regarding Cx32, mRNA expression decreased after acquisition of generalized seizures and no other significant change was detected in mRNA and protein abundance during kindling. Conclusion We speculate that Cx32 GJ communication in the hip- pocampus does not contribute to kindling epileptogenesis. The Cx30 astrocytic network localized to perivascular regions in the hippocampus is, however, overexpressed at the initiation of kindling to clear excitotoxic molecules from the milieu.展开更多
Neurons and glial cells, particularly astrocytes, are the two main cell populations in the central nervous system. While it is established that brain functions primarily rely on neuronal activity, an active contributi...Neurons and glial cells, particularly astrocytes, are the two main cell populations in the central nervous system. While it is established that brain functions primarily rely on neuronal activity, an active contribution of astrocytes to information processing is only starting to be considered. There is growing evidence that astrocytes, as part of the tripartite synapse, participate in this challenge by receiving and integrating neuronal signals and, in turn, by sending signals that target neurons[1]. The involvement of astrocytes in information processing has mainly been studied at the level of the single astrocyte, often missing the role of astrocyte networks in this process.展开更多
Genetic defects are one of the most important etiologies of severe to profound sensorineural hearing loss and play an important role in determining cochlear implantation outcomes.While the pathogenic mutation types of...Genetic defects are one of the most important etiologies of severe to profound sensorineural hearing loss and play an important role in determining cochlear implantation outcomes.While the pathogenic mutation types of a number of deafness genes have been cloned,the pathogenesis mechanisms and their relationship to the outcomes of cochlear implantation remain a hot research area.The auditory performance is considered to be affected by the etiology of hearing loss and the number of surviving spiral ganglion cells,as well as others.Current research advances in cochlear implantation for hereditary deafness,especially the relationship among clinic-types,genotypes and outcomes of cochlear implantation,will be discussed in this review.展开更多
文摘Objective Understanding the molecular and cellular mechanisms underlying epileptogenesis yields new in- sights into potential therapies that may ultimately prevent epilepsy. Gap junctions （GJs） create direct intercellular conduits between adjacent cells and are formed by hexameric protein subunits called connexins （Cxs）. Changes in the expression of Cxs affect GJ communication and thereby could modulate the dissemination of electrical discharges. The hippocampus is one of the main regions involved in epileptogenesis and has a wide network of GJs between different cell types where Cx30 is expressed in astrocytes and Cx32 exists in neurons and oligodendrocytes. In the present study, we evaluated the changes of Cx30 and Cx32 expression in rat hippocampus during kindling epileptogenesis. Methods Rats were stereotaxically implanted with stimulating and recording electrodes in the basolateral amygdala, which was electrically stimulated once daily at afterdischarge threshold. Expression of Cx30 and Cx32, at both the mRNA and protein levels, was measured in the hippocampus at the beginning, in the middle （after acquisition of focal seizures）, and at the end （after establishment of generalized seizures） of the kindling process, by real-time PCR and Western blot. Results Cx30 mRNA expression was upregulated at the beginning of kindling and after acquisition of focal seizures. Then it was downregulated when the animals acquired generalized seizures. Overexpression of Cx30 mRNA at the start of kindling was consistent with the respective initial protein increase. Thereafter, no change was found in protein abundance during kindling. Regarding Cx32, mRNA expression decreased after acquisition of generalized seizures and no other significant change was detected in mRNA and protein abundance during kindling. Conclusion We speculate that Cx32 GJ communication in the hip- pocampus does not contribute to kindling epileptogenesis. The Cx30 astrocytic network localized to perivascular regions in the hippocampus is, however, overexpressed at the initiation of kindling to clear excitotoxic molecules from the milieu.
文摘Neurons and glial cells, particularly astrocytes, are the two main cell populations in the central nervous system. While it is established that brain functions primarily rely on neuronal activity, an active contribution of astrocytes to information processing is only starting to be considered. There is growing evidence that astrocytes, as part of the tripartite synapse, participate in this challenge by receiving and integrating neuronal signals and, in turn, by sending signals that target neurons[1]. The involvement of astrocytes in information processing has mainly been studied at the level of the single astrocyte, often missing the role of astrocyte networks in this process.
文摘Genetic defects are one of the most important etiologies of severe to profound sensorineural hearing loss and play an important role in determining cochlear implantation outcomes.While the pathogenic mutation types of a number of deafness genes have been cloned,the pathogenesis mechanisms and their relationship to the outcomes of cochlear implantation remain a hot research area.The auditory performance is considered to be affected by the etiology of hearing loss and the number of surviving spiral ganglion cells,as well as others.Current research advances in cochlear implantation for hereditary deafness,especially the relationship among clinic-types,genotypes and outcomes of cochlear implantation,will be discussed in this review.
