KAINATE INDUCED STATUS EPILEPTICUS ALTERS GABA MEDIATED NEUROTRANSMISSION IN THE IMMATURE MOUSE HIPPOCAMPUS
Abstract number :
1.073
Submission category :
Year :
2003
Submission ID :
2269
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Moushumi Sehgal, John W. Swann The Cain Foundation Laboratories, Department of Pediatrics, Baylor College of Medicine, Houston, TX
Neuronal and synaptic reorganization of inhibitory circuits within the adult rodent hippocampus after kainate-induced status epilepticus has been previously described. Alterations of GABAergic transmission in the immature mouse brain could contribute to the known resistance of developing hippocampal neurons to seizure-induced damage and a resulting chronic epilepsy.
Intraperitoneal injection of kainic acid in mouse pups on postnatal day (PND) 10 was used to induce pronounced limbic convulsions, progressing to status epilepticus. At two different time points after seizure induction (PNDs 14 and 28), we investigated GABAergic interneurons through immunohistochemical markers (parvalbumin and calbindin D28k) and also, analyzed GAD-67 and the major GABA (A)-receptor subunits expressed in the hippocampus by Western blot.
On postnatal day (PND) 14, a partial loss of parvalbumin-positive interneurons was noted, suggesting either acute degeneration of these cells or a down regulation in the expression of this calcium-binding protein. This was mainly seen in the CA1 region of the hippocampus. Calbindin staining of interneurons was spared throughout the hippocampus. The decreased immunoreactivity of the parvalbumin interneuron population was transient and appeared to have fully recovered by PND 28. This supports the conclusion that changes are more likely due to decreased expression rather than cell loss.
In keeping with this conclusion are results from GAD-67 immunoblotting, which did not show a change in expression between experimental and sham animals at either of the two investigational time points. Thus, a significant loss of GABAergic neurons appears unlikely.
At a post-synaptic level, on PND 14, the expression of the GABA (A)-receptor subunits alpha-1 and gamma-2, were significantly increased though the beta subunit expression remained unaltered. These early changes in GABA (A)-receptor subunit composition also subsided completely by PND 28.
It can be postulated that subunit upregulation produce changes in the GABA(A)-receptor soon after status epilepticus, which, in turn, transiently decreases CNS excitability and mediates a neuroprotective homeostatic process. This may help to explain why status epilepticus does not produce chronic epilepsy in the immature animal.
[Supported by: NIH grants NS18309 and NS37171]