title: Beta-amyloid protein (25-35) disrupts hippocampal network activity: role of Fyn-kinase.
abstract: Early cognitive deficit characteristic of early Alzheimer's disease seems to be produced by the soluble forms of beta-amyloid protein. Such cognitive deficit correlates with neuronal network dysfunction that is reflected as alterations in the electroencephalogram of both Alzheimer patients and transgenic murine models of such disease. Correspondingly, recent studies have demonstrated that chronic exposure to betaAP affects hippocampal oscillatory properties. However, it is still unclear if such neuronal network dysfunction results from a direct action of betaAP on the hippocampal circuit or it is secondary to the chronic presence of the protein in the brain. Therefore, we aimed to explore the effect of acute exposure to betaAP(25-35) on hippocampal network activity both in vitro and in vivo, as well as on intrinsic and synaptic properties of hippocampal neurons. We found that betaAP(25-35), reversibly, affects spontaneous hippocampal population activity in vitro. Such effect is not produced by the inverse sequence betaAP(35-25) and is reproduced by the full-length peptide betaAP(1-42). Correspondingly betaAP(25-35), but not the inverse sequence betaAP(35-25), reduces theta-like activity recorded from the hippocampus in vivo. The betaAP(25-35)-induced disruption in hippocampal network activity correlates with a reduction in spontaneous neuronal activity and synaptic transmission, as well as with an inhibition in the subthreshold oscillations produced by pyramidal neurons in vitro. Finally, we studied the involvement of Fyn-kinase on the betaAP(25-35)-induced disruption in hippocampal network activity in vitro. Interestingly, we found that such phenomenon is not observed in slices obtained from Fyn-knockout mice. In conclusion, our data suggest that betaAP acutely affects proper hippocampal function through a Fyn-dependent mechanism. We propose that such alteration might be related to the cognitive impairment observed, at least, during the early phases of Alzheimer's disease.
authors.affiliation: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados Sede Sur, México, D.F., México. jfpena@cinvestav.mx
authors.forename: Fernando
authors.initials: F
authors.lastname: Peña
authors.forename: Benito
authors.initials: B
authors.lastname: Ordaz
authors.forename: Hugo
authors.initials: H
authors.lastname: Balleza-Tapia
authors.forename: Ramón
authors.initials: R
authors.lastname: Bernal-Pedraza
authors.forename: Abraham
authors.initials: A
authors.lastname: Márquez-Ramos
authors.forename: Liliana
authors.initials: L
authors.lastname: Carmona-Aparicio
authors.forename: Magda
authors.initials: M
authors.lastname: Giordano
mesh_terms: D000200:Action Potentials / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000201:enzymology / Q000502:physiology; D005071:Evoked Potentials / Q000502:physiology; D006624:Hippocampus / Q000201:enzymology / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000201:enzymology / Q000502:physiology; D009457:Neuroglia / Q000201:enzymology / Q000502:physiology; D009474:Neurons / Q000201:enzymology / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism*; D010507:Periodicity; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000378:metabolism*; D017966:Pyramidal Cells / Q000201:enzymology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); C113041:amyloid beta-protein (35-25); C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn