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Vol. 29, No. 1-2, 2007
Issue release date: December 2006
Dev Neurosci 2007;29:168–178
(DOI:10.1159/000096221)

Recurrent Seizures and the Molecular Maturation of Hippocampal and Neocortical Glutamatergic Synapses

Swann J.W. · Le J.T. · Lee C.L.
aThe Cain Foundation Laboratories, Department of Pediatrics, bDepartment of Neuroscience, and cProgram in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Tex., USA

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Abstract

Recurrent seizures in animal models of early-onset epilepsy have been shown to produce deficits in spatial learning and memory. While neuronal loss does not appear to underlie these effects, dendritic spine loss has been shown to occur. In experiments reported here, seizures induced either by tetanus toxin or flurothyl during the second postnatal week were found to reduce the expression of NMDA receptor subunits in both the hippocampus and neocortex. Most experiments focused on alterations in the expression of the NR2A subunit and its associated scaffolding protein, PSD95, since their expression is developmentally regulated. Results suggest that the depression in expression can be delayed by at least 5 days but persists for at least 3–4 weeks. These effects were dependent on the number of seizures experienced, and were not observed when seizures were induced in adult mice. Taken together, the results suggest that recurrent seizures in infancy may interrupt synapse maturation and produce persistent decreases in molecular markers for glutamatergic synapses – particularly components of the NMDA receptor complex implicated in learning and memory.



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