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

5.00
Hdl Handle:
http://hdl.handle.net/2436/620641
Title:
Transcriptome analysis suggests a role for the differential expression of cerebral aquaporins and the MAPK signalling pathway in human temporal lobe epilepsy
Authors:
Salman, Mootaz M. ( 0000-0002-5683-1706 ) ; Sheilabi, Mariam A.; Bhattacharyya, Dev; Kitchen, Philip; Conner, Alex C.; Bill, Roslyn M.; Woodroofe, M. Nicola; Conner, Matthew T. ( 0000-0001-5662-9121 ) ; Princivalle, Alessandra P. ( 0000-0001-5375-0604 )
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.
Citation:
Transcriptome analysis suggests a role for the differential expression of cerebral aquaporins and the MAPK signalling pathway in human temporal lobe epilepsy 2017 European Journal of Neuroscience
Publisher:
Federation of European Neuroscience Societies (FENS)
Journal:
European Journal of Neuroscience
Issue Date:
21-Aug-2017
URI:
http://hdl.handle.net/2436/620641
DOI:
10.1111/ejn.13652
Additional Links:
http://doi.wiley.com/10.1111/ejn.13652
Type:
Article
Language:
en
ISSN:
0953-816X
Sponsors:
BMRC Sheffield Hallam University, RIHS University of Wolverhampton and the HCED grant number GD-13-3 (MMS), LMHESR.
Appears in Collections:
FSE

Full metadata record

DC FieldValue Language
dc.contributor.authorSalman, Mootaz M.en
dc.contributor.authorSheilabi, Mariam A.en
dc.contributor.authorBhattacharyya, Deven
dc.contributor.authorKitchen, Philipen
dc.contributor.authorConner, Alex C.en
dc.contributor.authorBill, Roslyn M.en
dc.contributor.authorWoodroofe, M. Nicolaen
dc.contributor.authorConner, Matthew T.en
dc.contributor.authorPrincivalle, Alessandra P.en
dc.date.accessioned2017-08-31T13:40:20Z-
dc.date.available2017-08-31T13:40:20Z-
dc.date.issued2017-08-21-
dc.identifier.citationTranscriptome analysis suggests a role for the differential expression of cerebral aquaporins and the MAPK signalling pathway in human temporal lobe epilepsy 2017 European Journal of Neuroscienceen
dc.identifier.issn0953-816Xen
dc.identifier.doi10.1111/ejn.13652-
dc.identifier.urihttp://hdl.handle.net/2436/620641-
dc.description.abstractEpilepsies 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.en
dc.description.sponsorshipBMRC Sheffield Hallam University, RIHS University of Wolverhampton and the HCED grant number GD-13-3 (MMS), LMHESR.en
dc.language.isoenen
dc.publisherFederation of European Neuroscience Societies (FENS)en
dc.relation.urlhttp://doi.wiley.com/10.1111/ejn.13652en
dc.rightsArchived with thanks to European Journal of Neuroscienceen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectaquaporinsen
dc.subjectAQP1en
dc.subjectAQP4en
dc.subjectepilepsyen
dc.subjectmicroarrayen
dc.subjecttemporal lobe epilepsyen
dc.titleTranscriptome analysis suggests a role for the differential expression of cerebral aquaporins and the MAPK signalling pathway in human temporal lobe epilepsyen
dc.typeArticleen
dc.identifier.journalEuropean Journal of Neuroscienceen
dc.contributor.institutionBiomolecular Sciences Research Centre (BMRC); Sheffield Hallam University; Howard Street Sheffield S1 1WB UK-
dc.contributor.institutionBiomolecular Sciences Research Centre (BMRC); Sheffield Hallam University; Howard Street Sheffield S1 1WB UK-
dc.contributor.institutionNeurosurgery Department; Royal Hallamshire Hospital; Sheffield UK-
dc.contributor.institutionSchool of Clinical and Experimental Medicine; University of Birmingham; Birmingham UK-
dc.contributor.institutionSchool of Clinical and Experimental Medicine; University of Birmingham; Birmingham UK-
dc.contributor.institutionSchool of Life and Health Sciences; Aston University; Birmingham UK-
dc.contributor.institutionBiomolecular Sciences Research Centre (BMRC); Sheffield Hallam University; Howard Street Sheffield S1 1WB UK-
dc.contributor.institutionBiomolecular Sciences Research Centre (BMRC); Sheffield Hallam University; Howard Street Sheffield S1 1WB UK-
dc.contributor.institutionBiomolecular Sciences Research Centre (BMRC); Sheffield Hallam University; Howard Street Sheffield S1 1WB UK-
dc.date.accepted2017-07-
rioxxterms.funderBMRC Sheffield Hallam University, RIHS University of Wolverhampton and the HCED grant number GD-13-3 (MMS), LMHESRen
rioxxterms.identifier.projectUoW310817MCen
rioxxterms.versionAMen
rioxxterms.licenseref.urihttps://creativecommons.org/CC BY-NC-ND 4.0en
rioxxterms.licenseref.startdate2018-08-21en
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