title: Diminished CRE-Induced Plasticity is Linked to Memory Deficits in Familial Alzheimer's Disease Mice.
abstract: The mechanism underlying impaired learning and memory in Alzheimer's disease is not fully elucidated. The phosphorylation of cyclic-AMP response element binding protein (pCREB) in the hippocampus is thought to be a critical initiating step in the formation of long-term memories. Here, we tested CRE-driven gene expression following learning in mice harboring the familial Alzheimer's disease-linked APPswe/PS1ΔE9 mutations using CRE-β galactosidase reporter. We show that young adult APPswe/PS1ΔE9 mice exhibit impaired recognition memory and reduced levels of pCREB, and its cofactors CREB binding protein (CBP) and p-300 following a learning task, compared to their wild type littermate counterparts. Impairments in learning-induced activation of CREB in these mice are manifested by reduced CRE-driven gene transcription. Importantly, expression of the CRE-driven immediate early gene, Egr-1 (Zif268) is decreased in the CA1 region of the hippocampus. These studies implicate defective CREB-dependent plasticity in the mechanism underlying learning and memory deficits in Alzheimer's disease.
authors.forename: Nancy
authors.initials: N
authors.lastname: Bartolotti
authors.forename: Laura
authors.initials: L
authors.lastname: Segura
authors.forename: Orly
authors.initials: O
authors.lastname: Lazarov
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism*; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein
keywords: Alzheimer’s disease; CBP; CRE; CREB; hippocampal plasticity; learning and memory