Pharmacological activation of Nr4a rescues age-associated memory decline

Snehajyoti Chatterjee, Emily N. Walsh, Amy L. Yan, K. Peter Giese, Stephen Safe, Ted Abel

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Age-associated cognitive impairments affect an individual's quality of life and are a growing problem in society. Therefore, therapeutic strategies to treat age-related cognitive decline are needed to enhance the quality of life among the elderly. Activation of the Nr4a family of transcription factors has been closely linked to memory formation and dysregulation of these transcription factors is thought to be associated with age-related cognitive decline. Previously, we have shown that Nr4a transcription can be activated by synthetic bisindole-derived compounds (C-DIM). C-DIM compounds enhance synaptic plasticity and long-term contextual fear memory in young healthy mice. In this study, we show that activation of Nr4a2 by 1,1-bis(3′-Indolyl)-1-(p-chlorophenyl) methane (C-DIM12), enhances long-term spatial memory in young mice and rescues memory deficits in aged mice. These findings suggest that C-DIM activators of Nr4a transcription may be suitable to prevent memory deficits associated with aging.

Original languageEnglish (US)
Pages (from-to)140-144
Number of pages5
JournalNeurobiology of Aging
Volume85
DOIs
StatePublished - Jan 2020

Keywords

  • Aging
  • C-DIM drugs
  • Nr4a
  • Spatial memory
  • Mice, Inbred C57BL
  • Male
  • Indoles/pharmacology
  • Animals
  • Memory Disorders/etiology
  • Nuclear Receptor Subfamily 4, Group A, Member 1/genetics
  • Spatial Memory/drug effects
  • Transcription, Genetic/drug effects
  • Cognitive Aging

ASJC Scopus subject areas

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

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