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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 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 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.

Original publication

DOI

10.1111/ejn.13652

Type

Journal article

Journal

Eur J Neurosci

Publication Date

09/2017

Volume

46

Pages

2121 - 2132

Keywords

AQP1, AQP4, aquaporins, epilepsy, microarray, temporal lobe epilepsy, Adult, Aquaporins, Astrocytes, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Epilepsy, Temporal Lobe, Female, Gene Expression, Gene Expression Profiling, Hippocampus, Humans, MAP Kinase Signaling System, Male, Middle Aged, Neocortex, Proteome, RNA, Messenger, Sclerosis, Transcriptome, Young Adult