Recurrent Seizures and the Molecular Maturation of Hippocampal and Neocortical Glutamatergic SynapsesSwann 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
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.
John W. Swann, PhD
The Cain Foundation Laboratories
6621 Fannin St., MC3-6365
Houston, TX 77030 (USA)
Tel. +1 832 824 3969, Fax +1 832 825 4217, E-Mail firstname.lastname@example.org
Received: February 6, 2006
Accepted: March 16, 2006
Number of Print Pages : 11
Number of Figures : 6, Number of Tables : 0, Number of References : 40
Vol. 29, No. 1-2, Year 2007 (Cover Date: December 2006)
Journal Editor: Campagnoni, A.T. (Los Angeles, Calif.)
ISSN: 0378–5866 (print), 1421–9859 (Online)
For additional information: http://www.karger.com/DNE