Journal
JOURNAL OF NEUROSCIENCE
Volume 38, Issue 3, Pages 648-658Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0628-17.2017
Keywords
aging; intrinsic properties; memory enhancement; PERK; translation regulation
Categories
Funding
- Israeli Ministry of Science, Technology, and Space [MOST 3-12080]
- Israel Science Foundation [ISF 1003/12, ISF-IDRC 2395/2015]
- Wolfson Charitable Trust
- Ministry of Science and Technology
- Tauber Foundation
- Israeli Planning and Budgeting Committee Program Fellowships for Outstanding Post-Doctoral Fellows from China and India
Ask authors/readers for more resources
Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is one of four known kinases that respond to cellular stress by deactivating the eukaryotic initiation factor 2 alpha (eIF2 alpha) or other signal transduction cascades. Recently, both eIF2 alpha and its kinases were found to play a role in normal and pathological brain function. Here, we show that reduction of either the amount or the activity of PERK, specifically in the CA1 region of the hippocampus in young adult male mice, enhances neuronal excitability and improves cognitive function. In addition, this manipulation rescues the age-dependent cellular phenotype of reduced excitability and memory decline. Specifically, the reduction of PERK expression in the CA1 region of the hippocampus of middle-aged male mice using a viral vector rejuvenates hippocampal function and improves hippocampal-dependent learning. These results delineate a mechanism for behavior and neuronal aging and position PERK as a promising therapeutic target for age-dependent brain malfunction.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available