Beta-amyloid protein (25-35) disrupts hippocampal network activity: Role of Fyn-kinase
Por:
Pena, F, Ordaz B., Balleza-Tapia H., Bernal-Pedraza R., Márquez-Ramos A., Carmona-Aparicio L., Giordano M.
Publicada:
1 ene 2010
Categoría:
Cognitive Neuroscience
Resumen:
Early cognitive deficit characteristic of early Alzheimer's disease seems to be produced by the soluble forms of ß-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 ßAP affects hippocampal oscillatory properties. However, it is still unclear if such neuronal network dysfunction results from a direct action of ßAP 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 ßAP 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 ßAP 25-35 , reversibly, affects spontaneous hippocampal population activity in vitro. Such effect is not produced by the inverse sequence ßAP 35-25 and is reproduced by the full-length peptide ßAP 1-42 . Correspondingly ßAP 25-35 , but not the inverse sequence ßAP 35-25 , reduces theta-like activity recorded from the hippocampus in vivo. The ßAP 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 ßAP 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 ßAP 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. © 2009 Wiley-Liss, Inc.
Filiaciones:
Ordaz B.:
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados Sede Sur, México, D.F., Mexico
Balleza-Tapia H.:
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados Sede Sur, México, D.F., Mexico
Bernal-Pedraza R.:
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados Sede Sur, México, D.F., Mexico
Márquez-Ramos A.:
Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Conductual & Cognit, Queretaro 76230, Qro, Mexico
Carmona-Aparicio L.:
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados Sede Sur, México, D.F., Mexico
Giordano M.:
Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Conductual & Cognit, Queretaro 76230, Qro, Mexico
|