Pharmacological activation of Nr4a rescues age-associated memory decline

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

doi:10.1016/j.neurobiolaging.2019.10.001

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Pharmacological activation of Nr4a rescues age-associated memory decline

Journal article

Peer reviewed

Pharmacological activation of Nr4a rescues age-associated memory decline

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

Neurobiology of aging, Vol.85, pp.140-144

01/2020

DOI: 10.1016/j.neurobiolaging.2019.10.001

PMID: 31732218

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https://www.ncbi.nlm.nih.gov/pmc/articles/6917472View

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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.\n•Pharmacological activation of Nr4a using C-DIM drugs enhances long-term memory in young mice.•C-DIM drug reverses long-term memory deficits in aged mice.•Nr4a could be a potential therapeutic target to treat age-related cognitive impairment.

Aging

C-DIM drugs

Nr4a

Spatial memory

Details

Title: Subtitle: Pharmacological activation of Nr4a rescues age-associated memory decline
Creators: Snehajyoti Chatterjee - Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Emily N Walsh - Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Amy L Yan - Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute Carver College of Medicine, University of Iowa, Iowa City, IA, USA
K. Peter Giese - Department of Basic and Clinical Neuroscience, King's College London, London, UK
Stephen Safe - Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA
Ted Abel - Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Neurobiology of aging, Vol.85, pp.140-144
DOI: 10.1016/j.neurobiolaging.2019.10.001
PMID: 31732218
NLM abbreviation: Neurobiol Aging
ISSN: 0197-4580
eISSN: 1558-1497
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health; DOI: 10.13039/100012138, name: Nellie Ball Trust
Language: English
Date published: 01/2020
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984070877402771

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