title: Presenilin-1 familial Alzheimer's disease mutation alters hippocampal neurogenesis and memory function in CCL2 null mice.
abstract: Aberrations in hippocampal neurogenesis are associated with learning and memory, synaptic plasticity and neurodegeneration in Alzheimer's disease (AD). However, the linkage between them, β-amyloidosis and neuroinflammation is not well understood. To this end, we generated a mouse overexpressing familial AD (FAD) mutant human presenilin-1 (PS1) crossed with a knockout (KO) of the CC-chemokine ligand 2 (CCL2) gene. The PS1/CCL2KO mice developed robust age-dependent deficits in hippocampal neurogenesis associated with impairments in learning and memory, synaptic plasticity and long-term potentiation. Neurogliogenesis gene profiling supported β-amyloid independent pathways for FAD-associated deficits in hippocampal neurogenesis. We conclude that these PS1/CCL2KO mice are suitable for studies linking host genetics, immunity and hippocampal function.
authors.affiliation: Center for Neurodegenerative Disorders, Departments of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: tkiyota@unmc.edu.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kiyota
authors.affiliation: Center for Neurodegenerative Disorders, Departments of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Morrison
authors.affiliation: Center for Neurodegenerative Disorders, Departments of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Guihua
authors.initials: G
authors.lastname: Tu
authors.affiliation: Center for Neurodegenerative Disorders, Departments of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Bhagyalaxmi
authors.initials: B
authors.lastname: Dyavarshetty
authors.affiliation: Center for Neurodegenerative Disorders, Departments of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Weir
authors.affiliation: Center for Neurodegenerative Disorders, Departments of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Center for Neurodegenerative Disorders, Departments of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Huangui
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Center for Neurodegenerative Disorders, Departments of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D017774:Long-Term Potentiation / Q000235:genetics; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C508853:PSEN1 protein, human; D053764:Presenilin-1
keywords: Chemokine; Hippocampus; Long-term potentiation; Morris water maze; Neurogliogenesis