Trehalose Improves Cognition in the Transgenic Tg2576 Mouse Model of Alzheimer's Disease.
- Publisher:
- IOS PRESS
- Publication Type:
- Journal Article
- Citation:
- J Alzheimers Dis, 2017, 60, (2), pp. 549-560
- Issue Date:
- 2017
Closed Access
Filename | Description | Size | |||
---|---|---|---|---|---|
Trehalose Improves Cognition in the Transgenic Tg2576 Mouse Model of Alzheimers Disease.pdf | Published version | 1.69 MB | Adobe PDF |
Copyright Clearance Process
- Recently Added
- In Progress
- Closed Access
This item is closed access and not available.
Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Portbury, SD | |
dc.contributor.author | Hare, DJ | |
dc.contributor.author | Sgambelloni, C | |
dc.contributor.author | Perronnes, K | |
dc.contributor.author | Portbury, AJ | |
dc.contributor.author | Finkelstein, DI | |
dc.contributor.author | Adlard, PA | |
dc.date.accessioned | 2022-08-07T03:29:02Z | |
dc.date.available | 2022-08-07T03:29:02Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | J Alzheimers Dis, 2017, 60, (2), pp. 549-560 | |
dc.identifier.issn | 1387-2877 | |
dc.identifier.issn | 1875-8908 | |
dc.identifier.uri | http://hdl.handle.net/10453/159718 | |
dc.description.abstract | This study assessed the therapeutic utility of the autophagy enhancing stable disaccharide trehalose in the Tg2576 transgenic mouse model of Alzheimer's disease (AD) via an oral gavage of a 2% trehalose solution for 31 days. Furthermore, as AD is a neurodegenerative condition in which the transition metals, iron, copper, and zinc, are understood to be intricately involved in the cellular cascades leading to the defining pathologies of the disease, we sought to determine any parallel impact of trehalose treatment on metal levels. Trehalose treatment significantly improved performance in the Morris water maze, consistent with enhanced learning and memory. The improvement was not associated with significant modulation of full length amyloid-β protein precursor or other amyloid-β fragments. Trehalose had no effect on autophagy as assessed by western blot of the LC3-1 to LC3-2 protein ratio, and no alteration in biometals that might account for the improved cognition was observed. Biochemical analysis revealed a significant increase in the hippocampus of both synaptophysin, a synaptic vesicle protein and surrogate marker of synapses, and doublecortin, a reliable marker of neurogenesis. The growth factor progranulin was also significantly increased in the hippocampus and cortex with trehalose treatment. This study suggests that trehalose might invoke a suite of neuroprotective mechanisms that can contribute to improved cognitive performance in AD that are independent of more classical trehalose-mediated pathways, such as Aβ reduction and activation of autophagy. Thus, trehalose may have utility as a potential AD therapeutic, with conceivable implications for the treatment of other neurodegenerative disorders. | |
dc.format | ||
dc.language | eng | |
dc.publisher | IOS PRESS | |
dc.relation | http://purl.org/au-research/grants/arc/LP140100095 | |
dc.relation.ispartof | J Alzheimers Dis | |
dc.relation.isbasedon | 10.3233/JAD-170322 | |
dc.rights | info:eu-repo/semantics/closedAccess | |
dc.subject | 1103 Clinical Sciences, 1109 Neurosciences, 1702 Cognitive Sciences | |
dc.subject.classification | Neurology & Neurosurgery | |
dc.subject.mesh | Alzheimer Disease | |
dc.subject.mesh | Amyloid beta-Protein Precursor | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Brain | |
dc.subject.mesh | Cognition Disorders | |
dc.subject.mesh | Disease Models, Animal | |
dc.subject.mesh | Green Fluorescent Proteins | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Laser Therapy | |
dc.subject.mesh | Mass Spectrometry | |
dc.subject.mesh | Maze Learning | |
dc.subject.mesh | Metals | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Mice, Transgenic | |
dc.subject.mesh | Microtubule-Associated Proteins | |
dc.subject.mesh | Neuroprotective Agents | |
dc.subject.mesh | Presenilin-1 | |
dc.subject.mesh | Recombinant Fusion Proteins | |
dc.subject.mesh | Trehalose | |
dc.subject.mesh | Brain | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Mice, Transgenic | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Alzheimer Disease | |
dc.subject.mesh | Disease Models, Animal | |
dc.subject.mesh | Metals | |
dc.subject.mesh | Trehalose | |
dc.subject.mesh | Amyloid beta-Protein Precursor | |
dc.subject.mesh | Microtubule-Associated Proteins | |
dc.subject.mesh | Green Fluorescent Proteins | |
dc.subject.mesh | Recombinant Fusion Proteins | |
dc.subject.mesh | Neuroprotective Agents | |
dc.subject.mesh | Maze Learning | |
dc.subject.mesh | Cognition Disorders | |
dc.subject.mesh | Mass Spectrometry | |
dc.subject.mesh | Presenilin-1 | |
dc.subject.mesh | Laser Therapy | |
dc.title | Trehalose Improves Cognition in the Transgenic Tg2576 Mouse Model of Alzheimer's Disease. | |
dc.type | Journal Article | |
utslib.citation.volume | 60 | |
utslib.location.activity | Netherlands | |
utslib.for | 1103 Clinical Sciences | |
utslib.for | 1702 Cognitive Sciences | |
utslib.for | 1109 Neurosciences | |
utslib.for | 1103 Clinical Sciences | |
utslib.for | 1109 Neurosciences | |
utslib.for | 1702 Cognitive Sciences | |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences | |
utslib.copyright.status | closed_access | * |
dc.date.updated | 2022-08-07T03:28:54Z | |
pubs.issue | 2 | |
pubs.publication-status | Published | |
pubs.volume | 60 | |
utslib.citation.issue | 2 |
Abstract:
This study assessed the therapeutic utility of the autophagy enhancing stable disaccharide trehalose in the Tg2576 transgenic mouse model of Alzheimer's disease (AD) via an oral gavage of a 2% trehalose solution for 31 days. Furthermore, as AD is a neurodegenerative condition in which the transition metals, iron, copper, and zinc, are understood to be intricately involved in the cellular cascades leading to the defining pathologies of the disease, we sought to determine any parallel impact of trehalose treatment on metal levels. Trehalose treatment significantly improved performance in the Morris water maze, consistent with enhanced learning and memory. The improvement was not associated with significant modulation of full length amyloid-β protein precursor or other amyloid-β fragments. Trehalose had no effect on autophagy as assessed by western blot of the LC3-1 to LC3-2 protein ratio, and no alteration in biometals that might account for the improved cognition was observed. Biochemical analysis revealed a significant increase in the hippocampus of both synaptophysin, a synaptic vesicle protein and surrogate marker of synapses, and doublecortin, a reliable marker of neurogenesis. The growth factor progranulin was also significantly increased in the hippocampus and cortex with trehalose treatment. This study suggests that trehalose might invoke a suite of neuroprotective mechanisms that can contribute to improved cognitive performance in AD that are independent of more classical trehalose-mediated pathways, such as Aβ reduction and activation of autophagy. Thus, trehalose may have utility as a potential AD therapeutic, with conceivable implications for the treatment of other neurodegenerative disorders.
Please use this identifier to cite or link to this item:
Download statistics for the last 12 months
Not enough data to produce graph