Abstract
The molecular mechanisms underlying age-related cognitive deficits are not yet fully elucidated. In aged animals, a decrease in the intrinsic excitability of CA1 pyramidal neurons is believed to contribute to age-related cognitive impairments. Increasing activity of the transcription factor cAMP response element-binding protein (CREB) in young adult rodents facilitates cognition, and increases intrinsic excitability. However, it has yet to be tested if increasing CREB expression also ameliorates age-related behavioral and biophysical deficits. To test this hypothesis, we virally overexpressed CREB in CA1 of dorsal hippocampus. Rats received CREB or control virus, before undergoing water maze training. CREB overexpression in aged animals ameliorated the long-term memory deficits observed in control animals. Concurrently, cells overexpressing CREB in aged animals had reduced post-burst afterhyperpolarizations, indicative of increased intrinsic excitability. These results identify CREB modulation as a potential therapy to treat age-related cognitive decline.
| Original language | English (US) |
|---|---|
| Article number | e19358 |
| Journal | eLife |
| Volume | 6 |
| DOIs | |
| State | Published - Jan 4 2017 |
Funding
American Federation for Aging Research Glenn/AFAR Scholarship for Research in the Biology of Aging Xiao-Wen Yu National Institutes of Health T32 AG020506 Xiao-Wen Yu Daniel M Curlik II National Institutes of Health P30 AG13854 Daniel M Curlik II National Institutes of Health R01 NS063245 Jerry CP Yin National Institutes of Health R37 AG008796 John F Disterhoft National Institutes of Health RF1 AG017139 John F Disterhoft The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
ASJC Scopus subject areas
- General Immunology and Microbiology
- General Biochemistry, Genetics and Molecular Biology
- General Neuroscience