LONG-TERM CHANGES OF [gamma]-AMINOBUTYRIC ACID (GABA)A RECEPTOR SUBUNIT IN HIPPOCAMPAL DENTATE GRANULE CELLS AFTER PROLONGED SEIZURES IN IMMATURE RATS
Abstract number :
1.074
Submission category :
Year :
2003
Submission ID :
3771
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
Guojun Zhang, Yogendra Sinh H. Raol, Amy R. Brooks-Kayal Neurology, Children[apos]s Hospital of Philadelphia, Philadelphia, PA; Neurology and Pediatrics, University of Pennsylvania, Philadelphia, PA
Previous studies from our laboratory suggest that 70% of rats that had experienced status epilepticus (SE) at postnatal day (P20) goes on to develop spontaneous seizures while 30% do not. The morphological examination of the hippocampus of these rats does not identify any specific changes, which could contribute to the development of spontaneous seizures. Long-term alterations in postsynaptic GABAA receptor (GABAR) function and gene expression has been observed in various animal models following SE. For example, a decrease in [alpha]1-mRNA levels were found in the rats that had experienced SE in adulthood, whereas, adult rats that had experienced SE at P10 had higher [alpha]1 levels. In the present study we determined the effect of SE at P20 on GABAR expression and function.
Rat pups of 20 days postnatal age (P20) were subjected to lithium-pilocarpine induced status epilepticus (SE). Occurrence of staus-epilepticus (SE) was confirmed by EEG and behavioural monitoring. Rats were video-EEG monitored in adulthood ([gt]P90) to identify animals with spontaneous seizures. Whole-cell patch clamp recording and single cell antisense RNA amplification (aRNA) techniques were used to examine the expression of different GABAR subunit mRNAs and associated changes in the pharmacologic properties in single hippocampal dentate granule cells (DGC).
Relative expression of [alpha]1 subunit mRNA of GABAR (compared to total b-actin) were increased (two fold) significantly in all rats that experienced seizures at P20 compared to lithium control rats (p[lt]0.01). Notably expression of [alpha]1 subunit mRNA (compared to total GABA subunit) were significantly elevated (35%) in rats without spontaneous seizures compared to rats with spontaneous seizures (p[lt]0.01). The potentiation of zolpidem on GABA currents was increased in rats that had experienced seizures in P20 compared to lithium control rats.
Prolonged seizures at postnatal day (P20) lead to long-term alterations in GABAR subunit mRNA expression and function in DGCs, and these changes occur differentially in animals that become epileptic and those that do not. These findings suggest that levels of [alpha]1 subunit mRNA may play determining role in development of epilepsy after early seizures.
[Supported by: NIH NS38595 and Epilepsy Foundation of America to ABK]