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

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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. / 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.

In: European Journal of Neuroscience, Vol. 46, No. 5, 03.09.2017, p. 2121-2132.

Research output: Contribution to journalArticlepeer-review

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Salman, M. M., Sheilabi, M. A., Bhattacharyya, D., Kitchen, P., Conner, A. C., Bill, R. M., Woodroofe, M. N., Conner, M. T., & 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. https://doi.org/10.1111/ejn.13652

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Author

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. / Transcriptome analysis suggests a role for the differential expression of cerebral aquaporins and the MAPK signalling pathway in human temporal lobe epilepsy. In: European Journal of Neuroscience. 2017 ; Vol. 46, No. 5. pp. 2121-2132.

Bibtex

@article{3f365edd93d34299beaf38a44cd503df,
title = "Transcriptome analysis suggests a role for the differential expression of cerebral aquaporins and the MAPK signalling pathway in human temporal lobe epilepsy",
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 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.",
author = "Salman, {Mootaz M} and Sheilabi, {Mariam A} and Dev Bhattacharyya and Philip Kitchen and Conner, {Alex C} and Bill, {Roslyn M} and Woodroofe, {M Nicola} and Conner, {Matthew T} and Princivalle, {Alessandra P}",
note = "{\textcopyright} 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.",
year = "2017",
month = sep,
day = "3",
doi = "10.1111/ejn.13652",
language = "English",
volume = "46",
pages = "2121--2132",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley",
number = "5",

}

RIS

TY - JOUR

T1 - Transcriptome analysis suggests a role for the differential expression of cerebral aquaporins and the MAPK signalling pathway in human temporal lobe epilepsy

AU - Salman, Mootaz M

AU - Sheilabi, Mariam A

AU - Bhattacharyya, Dev

AU - Kitchen, Philip

AU - Conner, Alex C

AU - Bill, Roslyn M

AU - Woodroofe, M Nicola

AU - Conner, Matthew T

AU - Princivalle, Alessandra P

N1 - © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

PY - 2017/9/3

Y1 - 2017/9/3

N2 - 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.

AB - 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.

U2 - 10.1111/ejn.13652

DO - 10.1111/ejn.13652

M3 - Article

C2 - 28715131

VL - 46

SP - 2121

EP - 2132

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 5

ER -