Architectural changes in the neuronal nucleus during epileptogenesis
Synaptic plasticity is the ability of neurons to change the strength of their synaptic connections according to the demands of the changing environment. The phenomenon underlies cognitive functions like learning and memory, and, in its aberrant form, plays important pathogenic role in brain disorders, especially in epilepsy. It is now firmly established that long-lasting synaptic plasticity involves dramatic changes in neuronal gene expression. The mechanisms of these changes are quite well understood at the level of cis- and trans-acting regulatory factors. In contrast, the potential role of higher-order nuclear architecture in genetic regulation of synaptic plasticity and epileptogenesis has not been explored. Therefore, we have examined the structure of the nuclei in the neurons of the rat hippocampus at different time points after acute seizures, using high-resolution morphological techniques and three-dimensional quantitative analysis. Our results indicate that there is prominent reorganization of the neuronal nucleus upon seizures, involving movements of highly expressed genes and chromosomal gene clusters. Such reorganization may lead to formation of molecular factories, in which transcription, splicing, and (possibly) quality control/export of pre-mRNA occur in concert.
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