Alzheimer beta-amyloid blocks epileptiform activity in hippocampal neurons.
Several studies showed that hippocampal neurons respond with an increase in synaptic transmission after chronic blockade of GABA(A) receptors with bicuculline, a neuroplastic phenomenon likely associated to epileptiform states. Here, we tested the effect of Abeta(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 Abeta(1-40) aggregates. Data suggest that Abeta aggregates exert their influence principally by blocking synaptic transmission and altering the transcriptional pathway associated with CREB-p. In conclusion, neurons exposed to aggregated Abeta(1-40) showed a reduced level of neuronal plasticity and this suggests that they might be acting as anti-epileptiform modulators.
Sepúlveda
Fernando J
FJ
Laboratory of Neurophysiology, Department of Physiology, University of Concepción, Chile.
Opazo
Carlos
C
Aguayo
Luis G
LG
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001703:Biophysics; D050882:CREB-Binding Protein / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D047468:Immunoprecipitation / Q000379:methods; D008562:Membrane Glycoproteins / Q000378:metabolism; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques / Q000379:methods; D010446:Peptide Fragments / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D026941:Sodium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection / Q000379:methods
D016229:Amyloid beta-Peptides; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D008562:Membrane Glycoproteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D026941:Sodium Channel Blockers; C489618:Sv2a protein, rat; C078592:amyloid beta-protein (1-40); C085284:microtubule-associated protein 1B; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D050882:CREB-Binding Protein; D002118:Calcium; D001640:Bicuculline