title: CREB overexpression in dorsal CA1 ameliorates long-term memory deficits in aged rats.
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.
authors.affiliation: Department of Physiology, Northwestern University,Feinberg School of Medicine, Chicago, United States.
authors.forename: Xiao-Wen
authors.identifier: 0000-0002-8974-0085
authors.initials: XW
authors.lastname: Yu
authors.affiliation: Department of Physiology, Northwestern University,Feinberg School of Medicine, Chicago, United States.|Department of Behavioral Sciences, Psychology Program, York College of Pennsylvania, York, United States.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Curlik
authors.affiliation: Department of Physiology, Northwestern University,Feinberg School of Medicine, Chicago, United States.
authors.forename: M Matthew
authors.identifier: 0000-0002-6702-5785
authors.initials: MM
authors.lastname: Oh
authors.affiliation: Departments of Genetics and Neurology, University of Wisconsin-Madison, Madison, United States.
authors.forename: Jerry Cp
authors.initials: JC
authors.lastname: Yin
authors.affiliation: Department of Physiology, Northwestern University,Feinberg School of Medicine, Chicago, United States.
authors.forename: John F
authors.identifier: 0000-0002-8817-7913
authors.initials: JF
authors.lastname: Disterhoft
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis*; D015870:Gene Expression; D057567:Memory, Long-Term; D051381:Rats
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein
keywords: CREB; aging; cognition; memory; neuroscience; rat