A novel approach to rapidly prevent age‐related cognitive decline

Aging Cell

Paul A. Adlard¹  Amelia Sedjahtera¹  Lydia Gunawan¹  Lisa Bray¹  Dominic Hare²  Jessica Lear²  Philip Doble²  Ashley I. Bush¹  David I. Finkelstein¹ 

[1] The Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, At Genetics Lane on Royal Parade, The University of Melbourne, Melbourne, Vic., Australia;Elemental Bio-imaging Facility, University of Technology, Sydney, NSW, Australia

关键词: aging;    anti‐aging;    cognition;    PBT2;    zinc;   

DOI  :  10.1111/acel.12178

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.