title: Amyloid-beta1-42 reduces neuronal excitability in mouse dentate gyrus.
abstract: Amyloid-beta (Abeta) is causally implicated in Alzheimer's disease and neuroplasticity failure has acquired validity as a possible mechanism of early AD pathogenesis. We have previously demonstrated that oligomeric Abeta(1-42) inhibits LTP in the dentate gyrus of rat hippocampal slices. We now show, using whole cell recordings in hippocampal granule cells, that oligomeric Abeta(1-42) decreases neuronal excitability. In particular, Abeta(1-42) application was associated with a decrease in the number of action potentials fired in response to current injection, and with an increase in the amplitude of the afterhyperpolarization. Reduced excitability may underlie the Abeta-mediated impairment in neuroplasticity, and ultimately may contribute to the memory loss in Alzheimer disease.
authors.affiliation: Department of Pediatrics and Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60614, USA.
authors.forename: Sung Hwan
authors.initials: SH
authors.lastname: Yun
authors.forename: Georgi
authors.initials: G
authors.lastname: Gamkrelidze
authors.forename: W Blaine
authors.initials: WB
authors.lastname: Stine
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Sullivan
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Pasternak
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Ladu
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Trommer
mesh_terms: D000200:Action Potentials; D016229:Amyloid beta-Peptides / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001704:Biopolymers; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D001704:Biopolymers; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)