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dc.contributor.authorEngmann, O.
dc.contributor.authorHortobágyi, T.
dc.contributor.authorPidsley, R.
dc.contributor.authorTroakes, C.
dc.contributor.authorBernstein, H.-G.
dc.contributor.authorKreutz, M.R.
dc.contributor.authorMill, J.
dc.contributor.authorNikolic, M.
dc.contributor.authorGiese, K.P.
dc.date.accessioned2013-09-17T11:00:17Z
dc.date.available2013-09-17T11:00:17Z
dc.date.issued2011-08
dc.identifier.citationEngmann , O , Hortobágyi , T , Pidsley , R , Troakes , C , Bernstein , H-G , Kreutz , M R , Mill , J , Nikolic , M & Giese , K P 2011 , ' Schizophrenia is associated with dysregulation of a Cdk5 activator that regulates synaptic protein expression and cognition ' , Brain , vol. 134 , no. 8 , pp. 2408-2421 . https://doi.org/10.1093/brain/awr155
dc.identifier.issn0006-8950
dc.identifier.otherPURE: 1795801
dc.identifier.otherPURE UUID: 7b83615f-adda-458c-8f50-a0f9bf335061
dc.identifier.otherScopus: 80051966439
dc.identifier.urihttp://hdl.handle.net/2299/11611
dc.description.abstractCyclin-dependent kinase 5 is activated by small subunits, of which p35 is the most abundant. The functions of cyclin-dependent kinase 5 signalling in cognition and cognitive disorders remains unclear. Here, we show that in schizophrenia, a disorder associated with impaired cognition, p35 expression is reduced in relevant brain regions. Additionally, the expression of septin 7 and OPA1, proteins downstream of truncated p35, is decreased in schizophrenia. Mimicking a reduction of p35 in heterozygous knockout mice is associated with cognitive endophenotypes. Furthermore, a reduction of p35 in mice results in protein changes similar to schizophrenia post-mortem brain. Hence, heterozygous p35 knockout mice model both cognitive endophenotypes and molecular changes reminiscent of schizophrenia. These changes correlate with reduced acetylation of the histone deacetylase 1 target site H3K18 in mice. This site has previously been shown to be affected by truncated p35. By restoring H3K18 acetylation with the clinically used specific histone deacetylase 1 inhibitor MS-275 both cognitive and molecular endophenotypes of schizophrenia can be rescued in p35 heterozygous knockout mice. In summary, we suggest that reduced p35 expression in schizophrenia has an impact on synaptic protein expression and cognition and that these deficits can be rescued, at least in part, by the inhibition of histone deacetylase 1.en
dc.format.extent14
dc.language.isoeng
dc.relation.ispartofBrain
dc.titleSchizophrenia is associated with dysregulation of a Cdk5 activator that regulates synaptic protein expression and cognitionen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.contributor.institutionPharmacology and Clinical Science Research
dc.contributor.institutionAgriculture, Food and Veterinary Sciences
dc.contributor.institutionBiochemistry and Bioinformatics
dc.description.statusPeer reviewed
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=80051966439&partnerID=8YFLogxK
dc.relation.schoolSchool of Life and Medical Sciences
dcterms.dateAccepted2011-08
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.1093/brain/awr155
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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