Selective Alterations of GABA-A Receptor Subunit Expression and Function in Hippocampal Dentate Granule Cells after Seizures in the Developing Brain.
Abstract number :
3.015
Submission category :
Year :
2001
Submission ID :
293
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
G. Zhang, M.D., Ph.D., Neurology, Children[ssquote]s Hospital of Philadelphia, Philadelphia, PA; F-C. Hsu, Ph.D., Neurology, Children[ssquote]s Hospital of Philadelphia, Philadelphia, PA; Y.H. Raol, Ph.D., Neurology, Children[ssquote]s Hospital of Philade
RATIONALE: GABA-A receptors (GABARs) are heteromeric protein complexes composed of multiple subunits that are expressed in individual neurons. GABAR subunit expression varies in different cell types and over the course of postnatal development. Long-term alterations in post-synaptic GABAR function and gene expression, including decreases in GABAR subunit [alpha]1-mRNA levels, have been demonstrated in the process of epileptogenesis in adult rat models of epilepsy. Little is known, however, regarding potential changes in GABAR function and subunit expression following seizures in the developing brain.
METHODS: Rat pups of 10 days postnatal age were subjected to lithium-pilocarpine induced status epilepticus (SE). Whole cell patch-clamp recording and single-cell antisense RNA amplification (aRNA) techniques were used to examine the expression of 16 different GABAR subunit mRNAs and associated changes in the pharmacological properties of the receptor in acutely isolated dentate granule cells (DGCs) from adult rats (age 3-5 months) previously subjected to pilocarpine-induced SE at P10 compared to DGCs from age-matched, sham treated littermate control rats.
RESULTS: Relative expression of [alpha]1-subunit mRNA (compared to [beta]-actin) was increased [gt] 2 fold (p [lt] 0.01) and zinc inhibition of GABA-evoked currents was significantly reduced (25%, p [lt] 0.001) in DGCs from adult rats subjected to pilocarpine-induced SE at P10 compared to DGCs from age-matched, sham treated littermate control rats.
CONCLUSIONS: The findings suggest that seizures in the developing brain lead to long-term alterations in GABAR subunit mRNA expression and function in DGCs which are markedly different than those which occur following SE in adulthood. Seizure-induced alterations in GABAR development may contribute to the increased seizure susceptibility seen following early-life seizures in various models.
Support: NIH NS38595, NS01936, and Epilepsy Foundation of America