Show simple item record

Files in this item

Thumbnail

Item metadata

dc.contributor.authorCheng, Ying
dc.contributor.authorBuchan, Matthew
dc.contributor.authorVitanova, Karina
dc.contributor.authorAitken, Laura
dc.contributor.authorGunn-Moore, Frank J
dc.contributor.authorRamsay, Rona R.
dc.contributor.authorDoherty, Gayle
dc.date.accessioned2020-04-09T15:30:01Z
dc.date.available2020-04-09T15:30:01Z
dc.date.issued2020-10-13
dc.identifier.citationCheng , Y , Buchan , M , Vitanova , K , Aitken , L , Gunn-Moore , F J , Ramsay , R R & Doherty , G 2020 , ' Neuroprotective actions of leptin facilitated through balancing mitochondrial morphology and improving mitochondrial function ' , Journal of Neurochemistry , vol. 155 , no. 2 , e15003 , pp. 191-206 . https://doi.org/10.1111/jnc.15003en
dc.identifier.issn0022-3042
dc.identifier.otherPURE: 266884705
dc.identifier.otherPURE UUID: 6e1e06df-cd5f-45dc-ad87-fedbb699edd9
dc.identifier.otherRIS: urn:3D5B72EC44371A30DB4C6EC0B978EA3D
dc.identifier.otherORCID: /0000-0003-1535-4904/work/71954811
dc.identifier.otherORCID: /0000-0003-3422-3387/work/71954844
dc.identifier.otherORCID: /0000-0003-3494-5857/work/71954983
dc.identifier.otherORCID: /0000-0001-7259-4491/work/71955028
dc.identifier.otherScopus: 85082929284
dc.identifier.otherWOS: 000559593600001
dc.identifier.urihttp://hdl.handle.net/10023/19774
dc.descriptionAuthors would like to acknowledge ARUK for supporting this research. YC is Chinese Scholarship recipient. The University of St Andrews is a charity registered in Scotland: No SC013532en
dc.description.abstractMitochondrial dysfunction has a recognised role in the progression of Alzheimer's disease (AD) pathophysiology. Cerebral perfusion becomes increasingly inefficient throughout ageing, leading to unbalanced mitochondrial dynamics. This effect is exaggerated by amyloid β (Aβ) and phosphorylated tau, two hallmark proteins of AD pathology. A neuroprotective role for the adipose‐derived hormone, leptin, has been demonstrated in neuronal cells. However, its effects with relation to mitochondrial function in AD remain largely unknown. To address this question, we have used both a glucose‐serum deprived (CGSD) model of ischaemic stroke in SH‐SY5Y cells and a Aβ1‐42‐treatment model of AD in differentiated hippocampal cells. Using a combination of JC‐1 and MitoRed staining techniques, we show that leptin prevents depolarisation of the mitochondrial membrane and excessive mitochondrial fragmentation induced by both CGSD and Aβ1‐42. Thereafter, we used ELISAs and a number of activity assays to reveal the biochemical underpinnings of these processes. Specifically, leptin was seen to inhibit upregulation of the mitochondrial fission protein Fis1 and downregulation of the mitochondrial fusion protein, Mfn2. Furthermore, leptin was seen to upregulate the expression and activity of the antioxidant enzyme, monoamine oxidase B. Herein we provide the first demonstration that leptin is sufficient to protect against aberrant mitochondrial dynamics and resulting loss of function induced by both CGSD and Aβ1‐42. We conclude that the established neuroprotective actions of leptin may be facilitated through regulation of mitochondrial dynamics.
dc.language.isoeng
dc.relation.ispartofJournal of Neurochemistryen
dc.rightsCopyright © 2020 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en
dc.subjectHippocampalen
dc.subjectLeptinen
dc.subjectMitochondrial fissionen
dc.subjectMitochondrial fusionen
dc.subjectMitochondrionen
dc.subjectMonoamine oxidaseen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectDASen
dc.subject.lccRC0321en
dc.titleNeuroprotective actions of leptin facilitated through balancing mitochondrial morphology and improving mitochondrial functionen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Psychology and Neuroscienceen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews.Sir James Mackenzie Institute for Early Diagnosisen
dc.contributor.institutionUniversity of St Andrews.Centre for Biophotonicsen
dc.contributor.institutionUniversity of St Andrews.Institute of Behavioural and Neural Sciencesen
dc.identifier.doihttps://doi.org/10.1111/jnc.15003
dc.description.statusPeer revieweden


This item appears in the following Collection(s)

Show simple item record