Abstracts

There is an increase in the birth of dentate granule neurons (DGNs) after status epilepticus (SE) and concurrent alterations in DGN neurotransmitter receptors that may contribute to the development of spontaneous seizures. In this study, we identify which populations of DGN[apos]s: immature, mature or both, undergo changes in their glutamate receptor (AMPA and Kainate) subunit expression following SE. Rats at postnatal day 19-20 (P19-20) were injected with lithium and pilocarpine to induce a prolonged episode of SE. Fourteen days later (P34) animals were sacrificed and perfused with 4% paraformaldehyde for immunohistochemistry. Individual immature, PSA-NCAM expressing, or mature, NeuN expressing DGNs were dissected from antibody labeled sections. Single cell RNA amplification was performed and a reverse northern was probed for neurotransmitter receptor subunits, AMPA (gluR1, 2, 3, 4) and kainate (gluR5, 6, 7, KA2). In control animals only a single difference in AMPA (glu R1) subunit mRNA levels was identified between the immature and mature DGN and no diffference in the kainate receptor subunit mRNA levels. Mature DGN after SE had multiple alterations in their AMPA (glu R1[darr], R2[uarr], R3[darr], and R4[darr]), and kainate (glu R5[uarr], R6[darr], R7[darr], and KA2[uarr]) receptor subunit mRNA levels. After SE mature DGN had a 50% overall reduction in total AMPA receptor mRNA levels (sum of gluR1,2,3 and 4), and no change in the total kainate receptor subunit (sum glu R5,6,7 and KA2) levels. In contrast, SE had little impact on immature DGN. A decreased expression of the glu R6 subunit was the only difference in immature DGN AMPA and kainate receptor mRNA levels, after SE. Alterations in glutamate receptor transcription after SE are predominantly in the mature population of DGN, those neurons present at the time of SE. Mature DGN had alterations in all AMPA and kainate receptor subunit mRNA levels measured. Specific changes include increases in GluR2 and decreases in GluR1, 3, and 4 suggesting a shift to a Ca ion impermeable AMPA receptor and an overall 50% reduction in AMPA receptor mRNA levels. SE has distinct effects on transcriptional regulation of neurotransmitter receptors in immature and mature population of DGN. Thus, each population of DGN may differentially contribute to DGN physiology during the latent period and to the eventual development of epilepsy. (Supported by NINDS K08 grant to BEP
Child Neurology Foundation grant to ABK)