Elsevier

Neuroscience

Volume 138, Issue 2, 2006, Pages 457-474
Neuroscience

Clinical neuroscience
Serial analysis of gene expression in the hippocampus of patients with mesial temporal lobe epilepsy

https://doi.org/10.1016/j.neuroscience.2005.11.043Get rights and content

Abstract

Hippocampal sclerosis constitutes the most frequent neuropathological finding in patients with medically intractable mesial temporal lobe epilepsy. Serial analysis of gene expression was used to get a global view of the gene profile in human hippocampus in control condition and in epileptic condition associated with hippocampal sclerosis. Libraries were generated from control hippocampus, obtained by rapid autopsy, and from hippocampal surgical specimens of patients with mesial temporal lobe epilepsy and the classical pattern of hippocampal sclerosis. More than 50,000 tags were analyzed (28,282, control hippocampus; 25,953, hippocampal sclerosis) resulting in 9206 (control hippocampus) and 9599 (hippocampal sclerosis) unique tags (genes), each representing a specific mRNA transcript. Comparison of the two libraries resulted in the identification of 143 transcripts that were differentially expressed. These genes belong to a variety of functional classes, including basic metabolism, transcription regulation, protein synthesis and degradation, signal transduction, structural proteins, regeneration and synaptic plasticity and genes of unknown identity of function. The database generated by this study provides an extensive inventory of genes expressed in human control hippocampus, identifies new high-abundant genes associated with altered hippocampal morphology in patients with mesial temporal lobe epilepsy and serves as a reference for future studies aimed at detecting hippocampal transcriptional responses under various pathological conditions.

Section snippets

Tissue

In order to make a sensible comparison between control tissue and surgical tissue from patients we needed material from controls with the shortest postmortem interval possible. For obvious reasons this material is very rarely available and therefore we used only one control specimen. Control hippocampus (used to construct the SAGE control library) was obtained from a 48 year old man without history of seizures or other neurological diseases and no brain abnormalities at autopsy and

Results

The main aim of this study was to construct and compare SAGE libraries of control human hippocampus and hippocampus of patients with MTLE and HS.

Discussion

In this study we used SAGE to provide information on the human hippocampal transcriptome. As SAGE is an open system-based gene screening procedure, it provides an unbiased view of the transcriptome, capable of identifying both known and novel hippocampal genes and their relative expression levels under normal and epileptic conditions.

The database generated by this study represents an extensive inventory of approximately 9000 different genes that are most abundantly expressed in the human

Conclusion

In conclusion, identification and assessment of the gene expression profile is a useful first step in understanding molecular mechanisms leading to or representing the neuropathology of HS. The database generated by this study provides an extensive inventory of genes expressed in human control hippocampus, identifies new high-abundant genes associated with altered hippocampal morphology in patients with MTLE and serves as a reference for future studies aimed at detecting hippocampal

Acknowledgments

The work was supported by the National Epilepsy Fund “Power of the Small” and Hersenstichting Nederland (NEF grant 02–10 and 05–11; E. Aronica and K. Boer), the “Christelijke Vereniging voor de Verpleging van Lijders aan Epilepsie” (E. Aronica) and by Hacettepe University Research Fund (project number: 01 02 101 007; M. Özgüç). Filiz Ozbas-Gerceker was supported by European Science Foundation–Integrated Approaches for Functional Genomics Programme Exchange grant. We express gratitude to Prof.

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