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dc.contributor.authorMalekizadeh, Yasaman
dc.contributor.authorHoliday, Alison
dc.contributor.authorRedfearn, Devon
dc.contributor.authorAinge, James A.
dc.contributor.authorDoherty, Gayle
dc.contributor.authorHarvey, Jenni
dc.date.accessioned2017-09-06T23:32:24Z
dc.date.available2017-09-06T23:32:24Z
dc.date.issued2017-10
dc.identifier.citationMalekizadeh , Y , Holiday , A , Redfearn , D , Ainge , J A , Doherty , G & Harvey , J 2017 , ' A leptin fragment mirrors the cognitive enhancing and neuroprotective actions of leptin ' , Cerebral Cortex , vol. 27 , no. 10 , pp. 4769–4782 . https://doi.org/10.1093/cercor/bhw272en
dc.identifier.issn1047-3211
dc.identifier.otherPURE: 245137292
dc.identifier.otherPURE UUID: 811b17b1-4606-43ed-822b-bfb1c5d100a5
dc.identifier.otherScopus: 85030789536
dc.identifier.otherORCID: /0000-0003-3494-5857/work/60427293
dc.identifier.otherORCID: /0000-0002-0007-1533/work/60428113
dc.identifier.otherWOS: 000410394400008
dc.identifier.urihttps://hdl.handle.net/10023/11617
dc.descriptionJ.H. is funded by The Anonymous Trust and Cunningham Trust. GD is funded by ARUK, DR received a University of St Andrews Research Internship. JAA is funded by the Carnegie Trust.en
dc.description.abstractA key pathology of Alzheimer’s disease (AD) is amyloid β (Aβ) accumulation which triggers synaptic impairments and neuronal death. Metabolic disruption is common in AD and recent evidence implicates impaired leptin function in AD. Thus the leptin system may be a novel therapeutic target in AD. Indeed, leptin has cognitive enhancing properties and it prevents the aberrant effects of Aβ on hippocampal synaptic function and neuronal viability. However as leptin is a large peptide, development of smaller leptin-mimetics may be the best therapeutic approach. Thus, we have examined the cognitive enhancing and neuroprotective properties of known bioactive leptin fragments. Here we show that the leptin (116-130) fragment, but not leptin (22-56), mirrored the ability of leptin to promote AMPA receptor trafficking to synapses and facilitate activity-dependent hippocampal synaptic plasticity. Administration of leptin (116-130) also mirrored the cognitive enhancing effects of leptin as it enhanced performance in episodic-like memory tests. Moreover, leptin (116-130) prevented hippocampal synaptic disruption and neuronal cell death in models of amyloid toxicity. These findings establish further the importance of the leptin system as a therapeutic target in AD.
dc.language.isoeng
dc.relation.ispartofCerebral Cortexen
dc.rights© The Author 2016. Published by Oxford University Press. This work is made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://dx.doi.org/10.1093/cercor/bhw272en
dc.subjectHippocampusen
dc.subjectSynaptic plasticityen
dc.subjectAmyloid betaen
dc.subjectAMPA receptor traffickingen
dc.subjectEpisodic memoryen
dc.subjectAlzheimer’s diseaseen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectNDASen
dc.subjectBDCen
dc.subjectR2Cen
dc.subject.lccRC0321en
dc.titleA leptin fragment mirrors the cognitive enhancing and neuroprotective actions of leptinen
dc.typeJournal articleen
dc.contributor.sponsorBBSRCen
dc.description.versionPostprinten
dc.contributor.institutionUniversity of St Andrews. School of Psychology and Neuroscienceen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.identifier.doihttps://doi.org/10.1093/cercor/bhw272
dc.description.statusPeer revieweden
dc.date.embargoedUntil2017-09-06
dc.identifier.grantnumberBB/I019367/1en


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