Transcriptome analysis suggests a role for the differential expression of cerebral aquaporins and the MAPK signalling pathway in human temporal lobe epilepsy

Mootaz M. Salman, Mariam A. Sheilabi, Dev Bhattacharyya, Philip Kitchen, Alex C. Conner, Roslyn M. Bill, M. Nicola Woodroofe, Matthew T. Conner, Alessandra P. Princivalle*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Epilepsies are common disorders of the central nervous system (CNS), affecting up to 2% of the global population. Pharmaco-resistance is a major clinical challenge affecting about 30% of temporal lobe epilepsy (TLE) patients. Water homeostasis has been shown crucial for regulation of neuronal excitability. The control of water movement is achieved through a family of small integral membrane channel proteins called aquaporins (AQPs). Despite the fact that changes in water homeostasis occur in sclerotic hippocampi of people with TLE, the expression of AQPs in the epileptic brain is not fully characterised. This study uses microarray and ELISA methods to analyse the mRNA and protein expression of the human cerebral AQPs in sclerotic hippocampi (TLE-HS) and adjacent neocortex tissue (TLE-NC) of TLE patients. The expression of AQP1 and AQP4 transcripts was significantly increased, while that of the AQP9 transcript was significantly reduced in TLE-HS compared to TLE-NC. AQP4 protein expression was also increased while expression of AQP1 protein remained unchanged, and AQP9 was undetected. Microarray data analysis identified 3,333 differentially regulated genes and suggested the involvement of the MAPK signalling pathway in TLE pathogenesis. Proteome array data validated the translational profile for 26 genes and within the MAPK pathway (e.g. p38, JNK) that were identified as differentially expressed from microarray analysis. ELISA data showed that p38 and JNK inhibitors decrease AQP4 protein levels in cultured human primary cortical astrocytes. Elucidating the mechanism of selective regulation of different AQPs and associated regulatory proteins may provide a new therapeutic approach to epilepsy treatment. This article is protected by copyright. All rights reserved.

Original languageEnglish
Pages (from-to)2121-2132
Number of pages12
JournalEuropean Journal of Neuroscience
Volume46
Issue number5
Early online date17 Jul 2017
DOIs
Publication statusPublished - 1 Sep 2017

Bibliographical note

This is the peer reviewed version of the following article: Salman, M. M., Sheilabi, M. A., Bhattacharyya, D., Kitchen, P., Conner, A. C., Bill, R. M., ... Princivalle, A. P. (2017). Transcriptome analysis suggests a role for the differential expression of cerebral aquaporins and the MAPK signalling pathway in human temporal lobe epilepsy. European Journal of Neuroscience, 46(5), 2121-2132, which has been published in final form at http://dx.doi.org/10.1111/ejn.13652. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

All relevant data are within the paper and its Supporting Information files were made publicly available at: DOI 10.6084/m9.figshare.5100394.

Keywords

  • aquaporins
  • AQP4
  • TLE
  • epilepsy
  • AQP1
  • microarray

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