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Selective changes in single cell GABAA receptor subunit expression and function in temporal lobe epilepsy

Nature Medicine volume 4, pages 1166–1172 (1998)Cite this article

An Erratum to this article was published on 01 May 1999

Abstract

Temporal lobe epilepsy is the most prevalent seizure disorder in adults. Compromised inhibitory neurotransmitter function in the hippocampus contributes to the hyperexcitability generating this condition, but the underlying molecular mechanisms are unknown. Combining patch-clamp recording and single-cell mRNA amplification (aRNA) techniques in single dentate granule cells, we demonstrate that expression of GABAA receptor subunit mRNAs is substantially altered in neurons from epileptic rats. These changes in gene expression precede epilepsy onset by weeks and correlate with profound alterations in receptor function, indicating that aberrant GABAA receptor expression and function has an essential role in the process of epileptogenesis.

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Figure 1: Whole-cell patch-clamp recordings and aRNA expression profiling in a single dentate granule neuron from a rat with temporal lobe epilepsy after pilocarpine injection.
Figure 2: Functional alterations in GABAA receptor response properties of dentate granule neurons isolated from epileptic rats.
Figure 3: Relative expression of GABAR subunit mRNAs in isolated DGCs from control rats (open bars) and chronically epileptic rats in which temporal lobe epilepsy has been elicited by pilocarpine injection (filled bars).
Figure 4: Comparative changes in GABAR expression and function in isolated DGCs from control (open bars), latent-period (hashed bars) and chronically epileptic pilocarpine-treated (solid bars) rats.
Figure 5: Relative expression of GAD67 and GAD65 mRNAs in isolated DGCs from control rats, latent-period rats and chronically epileptic rats in which temporal lobe epilepsy has been elicited by pilocarpine injection.

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Acknowledgements

The authors thank J. Eberwine, M. Dichter, D. Pleasure, M. Robinson, D. Lynch and R. DeLorenzo for their critical review of the manuscript, and M. Ciafre for assistance with manuscript preparation. This work was supported by grants from the National Institutes of Health (K08 NS01936 and HD28815 to ABK, and R01 NS32403 and P01 NS25630 to DAC).

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Authors and Affiliations

  1. Pediatric Regional Epilepsy Program and Joseph Stokes Research Institute of The Children's Hospital of Philadelphia, 34th and Civic Center Boulevard, Philadelphia, 19104, Pennsylvania, USA

    Amy R. Brooks-Kayal & Hong Jin

  2. Departments of Neurology and Pediatrics, University of Pennsylvania, 3400 Spruce Street, Philadelphia , 19104, Pennsylvania, USA

    Amy R. Brooks-Kayal

  3. Departments of Neurology, Physiology and Anatomy, Medical College of Virginia, Virginia Commonwealth University, Richmond , 23298-0599, Virginia, USA

    Melissa D. Shumate, Tatiana Y. Rikhter & Douglas A. Coulter

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  1. Amy R. Brooks-Kayal
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  2. Melissa D. Shumate
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Correspondence to Amy R. Brooks-Kayal.

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Brooks-Kayal, A., Shumate, M., Jin, H. et al. Selective changes in single cell GABAA receptor subunit expression and function in temporal lobe epilepsy. Nat Med 4, 1166–1172 (1998). https://doi.org/10.1038/2661

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