A novel approach to rapidly prevent age-related cognitive decline

Adlard, PA; Sedjahtera, A; Gunawan, L; Bray, L; Hare, D; Lear, J; Doble, P; Bush, AI; Finkelstein, DI; Cherny, RA

A novel approach to rapidly prevent age-related cognitive decline

Adlard, PA Sedjahtera, A Gunawan, L Bray, L Hare, D

Lear, J Doble, P

Bush, AI Finkelstein, DI Cherny, RA

Permalink

Publication Type:: Journal Article
Citation:: Aging Cell, 2014, 13 (2), pp. 351 - 359
Issue Date:: 2014-01-01

Closed Access

	Filename	Description	Size
	2013001762OK.pdf		999.01 kB	Adobe PDF	View/Open

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	Adlard, PA	en_US
dc.contributor.author	Sedjahtera, A	en_US
dc.contributor.author	Gunawan, L	en_US
dc.contributor.author	Bray, L	en_US
dc.contributor.author	Hare, D https://orcid.org/0000-0002-5922-7643	en_US
dc.contributor.author	Lear, J	en_US
dc.contributor.author	Doble, P https://orcid.org/0000-0002-8472-1301	en_US
dc.contributor.author	Bush, AI	en_US
dc.contributor.author	Finkelstein, DI	en_US
dc.contributor.author	Cherny, RA	en_US
dc.date.available	2013-10-21	en_US
dc.date.issued	2014-01-01	en_US
dc.identifier.citation	Aging Cell, 2014, 13 (2), pp. 351 - 359	en_US
dc.identifier.issn	1474-9718	en_US
dc.identifier.uri	http://hdl.handle.net/10453/29544
dc.identifier.uri	http://hdl.handle.net/10453/32800
dc.description.abstract	Summary: The loss of cognitive function is a pervasive and often debilitating feature of the aging process for which there are no effective therapeutics. We hypothesized that a novel metal chaperone (PBT2; Prana Biotechnology, Parkville, Victoria, Australia) would enhance cognition in aged rodents. We show here that PBT2 rapidly improves the performance of aged C57Bl/6 mice in the Morris water maze, concomitant with increases in dendritic spine density, hippocampal neuron number and markers of neurogenesis. There were also increased levels of specific glutamate receptors (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-d-aspartate), the glutamate transporter (VGLUT1) and glutamate itself. Markers of synaptic plasticity [calmodulin-dependent protein kinase II (CaMKII) and phosphorylated CaMKII, CREB, synaptophysin] were also increased following PBT2 treatment. We also demonstrate that PBT2 treatment results in a subregion-specific increase in hippocampal zinc, which is increasingly recognized as a potent neuromodulator. These data demonstrate that metal chaperones are a novel approach to the treatment of age-related cognitive decline. © 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.	en_US
dc.relation	http://purl.org/au-research/grants/arc/LP120200081
dc.relation.ispartof	Aging Cell	en_US
dc.relation.isbasedon	10.1111/acel.12178	en_US
dc.subject.classification	Developmental Biology	en_US
dc.subject.mesh	Hippocampus	en_US
dc.subject.mesh	Dendritic Spines	en_US
dc.subject.mesh	Synapses	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Zinc	en_US
dc.subject.mesh	Clioquinol	en_US
dc.subject.mesh	Glutamic Acid	en_US
dc.subject.mesh	Receptors, Glutamate	en_US
dc.subject.mesh	Biological Markers	en_US
dc.subject.mesh	Cell Count	en_US
dc.subject.mesh	Behavior, Animal	en_US
dc.subject.mesh	Maze Learning	en_US
dc.subject.mesh	Cognition Disorders	en_US
dc.subject.mesh	Aging	en_US
dc.subject.mesh	Neuronal Plasticity	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Vesicular Glutamate Transport Protein 1	en_US
dc.subject.mesh	Protein Phosphatase 2	en_US
dc.subject.mesh	Neurogenesis	en_US
dc.subject.mesh	Biomarkers	en_US
dc.title	A novel approach to rapidly prevent age-related cognitive decline	en_US
dc.type	Journal Article
utslib.citation.volume	2	en_US
utslib.citation.volume	13	en_US
utslib.for	1109 Neurosciences	en_US
utslib.for	0301 Analytical Chemistry	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
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
pubs.organisational-group	/University of Technology Sydney/Strength - CFS - Centre for Forensic Science
utslib.copyright.status	closed_access
pubs.issue	2	en_US
pubs.publication-status	Published	en_US
pubs.volume	13	en_US

Abstract:

Summary: The loss of cognitive function is a pervasive and often debilitating feature of the aging process for which there are no effective therapeutics. We hypothesized that a novel metal chaperone (PBT2; Prana Biotechnology, Parkville, Victoria, Australia) would enhance cognition in aged rodents. We show here that PBT2 rapidly improves the performance of aged C57Bl/6 mice in the Morris water maze, concomitant with increases in dendritic spine density, hippocampal neuron number and markers of neurogenesis. There were also increased levels of specific glutamate receptors (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-d-aspartate), the glutamate transporter (VGLUT1) and glutamate itself. Markers of synaptic plasticity [calmodulin-dependent protein kinase II (CaMKII) and phosphorylated CaMKII, CREB, synaptophysin] were also increased following PBT2 treatment. We also demonstrate that PBT2 treatment results in a subregion-specific increase in hippocampal zinc, which is increasingly recognized as a potent neuromodulator. These data demonstrate that metal chaperones are a novel approach to the treatment of age-related cognitive decline. © 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/29544