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Transcriptome analysis suggests a role for the differential expression of cerebral aquaporins and the MAPK signalling pathway in human temporal lobe epilepsy
Author(s) -
Salman Mootaz M.,
Sheilabi Mariam A.,
Bhattacharyya Dev,
Kitchen Philip,
Conner Alex C.,
Bill Roslyn M.,
Woodroofe M. Nicola,
Conner Matthew T.,
Princivalle Alessandra P.
Publication year - 2017
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13652
Subject(s) - biology , microarray analysis techniques , transcriptome , neocortex , mapk/erk pathway , aquaporin , microarray , gene expression profiling , microbiology and biotechnology , epilepsy , proteome , neuroscience , gene expression , signal transduction , gene , bioinformatics , genetics
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 ( AQP s). Despite the fact that changes in water homeostasis occur in sclerotic hippocampi of people with TLE , the expression of AQP s 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 AQP s in sclerotic hippocampi ( TLE ‐ HS ) and adjacent neocortex tissue ( TLE ‐ NC ) of TLE patients. The expression of AQP 1 and AQP 4 transcripts was significantly increased, while that of the AQP 9 transcript was significantly reduced in TLE ‐ HS compared to TLE ‐ NC . AQP 4 protein expression was also increased while expression of AQP 1 protein remained unchanged, and AQP 9 was undetected. Microarray data analysis identified 3333 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 AQP 4 protein levels in cultured human primary cortical astrocytes. Elucidating the mechanism of selective regulation of different AQP s and associated regulatory proteins may provide a new therapeutic approach to epilepsy treatment.