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A leptin fragment mirrors the cognitive enhancing and neuroprotective actions of leptin
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dc.contributor.author | Malekizadeh, Yasaman | |
dc.contributor.author | Holiday, Alison | |
dc.contributor.author | Redfearn, Devon | |
dc.contributor.author | Ainge, James A. | |
dc.contributor.author | Doherty, Gayle | |
dc.contributor.author | Harvey, Jenni | |
dc.date.accessioned | 2017-09-06T23:32:24Z | |
dc.date.available | 2017-09-06T23:32:24Z | |
dc.date.issued | 2017-10 | |
dc.identifier | 245137292 | |
dc.identifier | 811b17b1-4606-43ed-822b-bfb1c5d100a5 | |
dc.identifier | 85030789536 | |
dc.identifier | 000410394400008 | |
dc.identifier.citation | Malekizadeh , 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/bhw272 | en |
dc.identifier.issn | 1047-3211 | |
dc.identifier.other | ORCID: /0000-0003-3494-5857/work/60427293 | |
dc.identifier.other | ORCID: /0000-0002-0007-1533/work/60428113 | |
dc.identifier.uri | https://hdl.handle.net/10023/11617 | |
dc.description | J.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.abstract | A 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.format.extent | 2368350 | |
dc.language.iso | eng | |
dc.relation.ispartof | Cerebral Cortex | en |
dc.subject | Hippocampus | en |
dc.subject | Synaptic plasticity | en |
dc.subject | Amyloid beta | en |
dc.subject | AMPA receptor trafficking | en |
dc.subject | Episodic memory | en |
dc.subject | Alzheimer’s disease | en |
dc.subject | RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry | en |
dc.subject | NDAS | en |
dc.subject | BDC | en |
dc.subject | R2C | en |
dc.subject.lcc | RC0321 | en |
dc.title | A leptin fragment mirrors the cognitive enhancing and neuroprotective actions of leptin | en |
dc.type | Journal article | en |
dc.contributor.sponsor | BBSRC | en |
dc.contributor.institution | University of St Andrews. School of Psychology and Neuroscience | en |
dc.contributor.institution | University of St Andrews. Institute of Behavioural and Neural Sciences | en |
dc.identifier.doi | https://doi.org/10.1093/cercor/bhw272 | |
dc.description.status | Peer reviewed | en |
dc.date.embargoedUntil | 2017-09-06 | |
dc.identifier.grantnumber | BB/I019367/1 | en |
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