title: Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus.
abstract: Alzheimer's disease is a neurodegenerative disease affecting the aging population. A key neuropathological feature of the disease is the over-production of amyloid-beta and the deposition of amyloid-beta plaques in brain regions of the afflicted individuals. Throughout the years scientists have generated numerous Alzheimer's disease mouse models that attempt to replicate the amyloid-beta pathology. Unfortunately, the mouse models only selectively mimic the disease features. Neuronal death, a prominent effect in the brains of Alzheimer's disease patients, is noticeably lacking in these mice. Hence, we and others have employed a method of directly infusing soluble oligomeric species of amyloid-beta - forms of amyloid-beta that have been proven to be most toxic to neurons - stereotaxically into the brain. In this report we utilize male C57BL/6J mice to document this surgical technique of increasing amyloid-beta levels in a select brain region. The infusion target is the dentate gyrus of the hippocampus because this brain structure, along with the basal forebrain that is connected by the cholinergic circuit, represents one of the areas of degeneration in the disease. The results of elevating amyloid-beta in the dentate gyrus via stereotaxic infusion reveal increases in neuron loss in the dentate gyrus within 1 week, while there is a concomitant increase in cell death and cholinergic neuron loss in the vertical limb of the diagonal band of Broca of the basal forebrain. These effects are observed up to 2 weeks. Our data suggests that the current amyloid-beta infusion model provides an alternative mouse model to address region specific neuron death in a short-term basis. The advantage of this model is that amyloid-beta can be elevated in a spatial and temporal manner.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center; yyj2103@cumc.columbia.edu.
authors.forename: Ying Y
authors.initials: YY
authors.lastname: Jean
authors.affiliation: The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center.
authors.forename: Jimena
authors.initials: J
authors.lastname: Baleriola
authors.affiliation: The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center.
authors.forename: Mauro
authors.initials: M
authors.lastname: Fà
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hengst
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center; Department of Neurology, Columbia University Medical Center.
authors.forename: Carol M
authors.initials: CM
authors.lastname: Troy
mesh_terms: D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000818:Animals; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000008:administration & dosage*; D013238:Stereotaxic Techniques
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)