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dc.contributor.authorSalman, Mootaz M.
dc.contributor.authorSheilabi, Mariam A.
dc.contributor.authorBhattacharyya, Dev
dc.contributor.authorKitchen, Philip
dc.contributor.authorConner, Alex C.
dc.contributor.authorBill, Roslyn M.
dc.contributor.authorWoodroofe, M. Nicola
dc.contributor.authorConner, Matthew T.
dc.contributor.authorPrincivalle, Alessandra P.
dc.date.accessioned2017-08-31T13:40:20Z
dc.date.available2017-08-31T13:40:20Z
dc.date.issued2017-08-21
dc.identifier.citationSalman, MM., Sheilabi, MA., Bhattacharyya, D., Kitchen, P., Conner, AC., Bill, RM., Woodroofe, M., Conner, MT., Princivalle, AP. (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), pp. 2121-2132 doi: 10.1111/ejn.13652
dc.identifier.issn0953-816X
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.
dc.description.sponsorshipBMRC Sheffield Hallam University, RIHS University of Wolverhampton and the HCED grant number GD-13-3 (MMS), LMHESR.
dc.language.isoen
dc.publisherFederation of European Neuroscience Societies (FENS)
dc.relation.urlhttp://doi.wiley.com/10.1111/ejn.13652
dc.subjectaquaporins
dc.subjectAQP1
dc.subjectAQP4
dc.subjectepilepsy
dc.subjectmicroarray
dc.subjecttemporal lobe epilepsy
dc.titleTranscriptome analysis suggests a role for the differential expression of cerebral aquaporins and the MAPK signalling pathway in human temporal lobe epilepsy
dc.typeJournal article
dc.identifier.journalEuropean Journal of Neuroscience
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.accepted2017-07-31
rioxxterms.funderUniversity of Wolverhampton
rioxxterms.identifier.projectUoW310817MC
rioxxterms.versionAM
rioxxterms.licenseref.urihttps://creativecommons.org/CC BY-NC-ND 4.0
rioxxterms.licenseref.startdate2018-08-21
dc.source.volume46
dc.source.issue5
dc.source.beginpage2121
dc.source.endpage2132
refterms.dateFCD2018-10-19T09:24:43Z
refterms.versionFCDAM
html.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.


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