A novel approach to rapidly prevent age‐related cognitive decline. Issue 2 (4th December 2013)

• Record Type: Journal Article
• Authors: Adlard, Paul A.; Sedjahtera, Amelia; Gunawan, Lydia; Bray, Lisa; Hare, Dominic; Lear, Jessica; Doble, Philip; Bush, Ashley I.; Finkelstein, David I.; Cherny, Robert A.
• Is Part Of: Aging cell. Volume 13:Issue 2(2014:Apr.)
• Page Start: 351
• Page End: 359
• Publication Date: 2013-12-04
• Subjects: Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.12178
• Languages: English
• ISSNs: 1474-9718

Abstract

<abstract abstract-type="main" id="acel12178-abs-0001"> <title>Summary</title> <p>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 <italic>N</italic>‐methyl‐<sc>d</sc>‐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.</p> </abstract>