Distinct pro-survival and cell death gene profiles within hippocampal subregions following multiple early life seizures

International Conference on Epilepsy & Treatment

September 21-22, 2015 Baltimore, USA

Friedman L K, Hu S, Wan W Y and Slomko A M

New York Medical College, USA

Posters-Accepted Abstracts: J Neurol Disord

Abstract :

In mature adults, harmful side-effects of recurrent seizures are known to be due to excessive release of glutamate, over-activation of glutamate receptors, and simultaneous alterations of the GABAergic system whereas non-lethal traumas render the brain more resistant to subsequent insults due to activation of certain genes and signaling cascades that raise the threshold for cell death. Multiple neonatal seizures produce spatial preconditioning at juvenile ages. For example, seizures cause robust injury to the CA1 and very little injury to the CA3 hippocampal subfield following a single injection of Kainic Acid (KA) (1Ã?Â?KA) induced on P20, but this damage is attenuated if the P20 rats have a history of two sustained neonatal seizures on P6 and P9 (3Ã?Â?KA). Further, the Dentate Gyrus (DG) is always resistant to injury regardless of age. Underlying mechanisms of age-dependent, spatially distinct neuroprotection and the responsible major signaling cascades remain unknown but are associated with high elevations of [Ca2+] i. Previously we profiled transcriptomes of the isolated CA1 sub-region after 1Ã?Â?KA and 3Ã?Â?KA. Herein we isolated transcriptomes of the CA3 and DG subregions under the same conditions. Autophagy genes were triggered by single or multiple seizures within the CA3, but many protective genes were also differentially upregulated, particularly after 3Ã?Â?KA in both age groups but with different expression profiles. The DG was absent in cell death genes. Instead, immunity, ion transport, and stabilizing genes were upregulated and proliferation and migration cues were down-regulated. Results indicate resistance to insult of the pyramidal fields after neonatal seizures is due to region specific attenuation of glutamate stimulated Ca2+ currents, reduced apoptosis, and induction of survival signaling pathways, whereas cell resistance of the DG is due to axonal vesicular, and energy dependent stabilizers and their vulnerability lies within disrupted proliferation and migratory domains.

Biography :

Email: Linda_Friedman@nymc.edu