Repression of eEF2 kinase improves deficits in novel object recognition memory in aged mice

Saahj P. Gosrani, Hannah M. Jester, Xueyan Zhou, Alexey G. Ryazanov, Tao Ma

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


The normal aging process is commonly associated with mild cognitive deficits including memory decline. Previous studies indicate a role of dysregulated messenger ribonucleic acid translation capacity in cognitive defects associated with aging and aging-related diseases, including hyperphosphorylation of eukaryotic elongation factor 2 (eEF2). Phosphorylation of eEF2 by the kinase eEF2K inhibits its activity, hindering general protein synthesis. Here, we sought to determine whether cognitive deficits in aged mice can be improved by genetically deleting eEF2K (eEF2K KO) and consequently reduction of eEF2 phosphorylation. We found that suppression of eEF2K prevented aging-related deficits in novel object recognition memory. Interestingly, deletion of eEF2K did not alter overall protein synthesis in the hippocampus. Ultrastructural analysis revealed increase size and larger active zone lengths of postsynaptic densities in the hippocampus of aged eEF2K KO mice. Biochemical assays showed hippocampal eIF2α hyperphosphorylation in aged eEF2K KO mice, indicating inhibition of translation initiation. Our findings may provide insight into mechanistic understanding and thus development of novel therapeutic strategies for aging-related cognitive decline.

Original languageEnglish (US)
Pages (from-to)154-160
Number of pages7
JournalNeurobiology of Aging
StatePublished - Nov 2020

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • Aging
  • Developmental Biology
  • Clinical Neurology
  • Geriatrics and Gerontology


  • Aging
  • Elongation factor 2
  • Memory
  • Protein synthesis
  • Signaling
  • Synapse


Dive into the research topics of 'Repression of eEF2 kinase improves deficits in novel object recognition memory in aged mice'. Together they form a unique fingerprint.

Cite this