Article
MOLECULAR AND CELLULAR NEUROSCIENCE  (2009)

Alzheimer ?-amyloid blocks epileptiform activity in hippocampal neurons

Sepúlveda F.J.; Aguayo, L. G.; Opazo C.

Keywords: stimulation, acid, electron, proteins, neurons, rat, membrane, survival, modulation, amyloid, distribution, animals, phosphorylation, transmission, antagonists, binding, culture, brain, rats, protein, cell, clamp, pregnancy, channel, disease, pathogenesis, gaba, peptide, calcium, plasticity, beta, immunoprecipitation, viability, embryo, microscopy, receptor, patch-clamp, fragments, sodium, time, glycoproteins, nerve, tissue, hippocampus, female, immunocytochemistry, beta-protein, element, tetrodotoxin, article, mammalian, variance, blocking, alzheimer, discharge, blockers, analysis, amplitude, cellular, bicuculline, transfection, techniques, controlled, animal, factors, study, 4, western, amino, priority, cyclic, of, nonhuman, journal, AMP, blotting, a, aminobutyric, Electric, patch, Microscopy,, Electron,, Microtubule-Associated, epileptic, Embryo,, Synaptic, biophysics, excitatory, 6-Cyano-7-nitroquinoxaline-2,3-dione, luciferase, protein[1-40], responsive, CREB-Binding

Abstract

Several studies showed that hippocampal neurons respond with an increase in synaptic transmission after chronic blockade of GABAA receptors with bicuculline, a neuroplastic phenomenon likely associated to epileptiform states. Here, we tested the effect of A?1-40 oligomers/aggregates, believed to be involved in Alzheimer's Disease (AD) genesis, on this type of synaptic plasticity. In the presence of bicuculline, the frequency of miniature currents increased from 1.2 ± 0.4 Hz to 3.1 ± 0.6 Hz (n = 6, *p < 0.05). Similarly, current amplitude increased from 45 ± 3 pA to 81 ± 11 pA (n = 5, *p < 0.05). These effects were completely inhibited in the presence of A?1-40 aggregates. Data suggest that A? aggregates exert their influence principally by blocking synaptic transmission and altering the transcriptional pathway associated with CREB-p. In conclusion, neurons exposed to aggregated A?1-40 showed a reduced level of neuronal plasticity and this suggests that they might be acting as anti-epileptiform modulators. © 2009 Elsevier Inc. All rights reserved.

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Título de la Revista: MOLECULAR AND CELLULAR NEUROSCIENCE
Volumen: 41
Número: 4
Editorial: ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS
Fecha de publicación: 2009
Página de inicio: 420
Página final: 428
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-67449102266&partnerID=q2rCbXpz