Picomolar amyloid-beta positively modulates synaptic plasticity and memory in hippocampus.
Amyloid-beta (Abeta) peptides are produced in high amounts during Alzheimer's disease, causing synaptic and memory dysfunction. However, they are also released in lower amounts in normal brains throughout life during synaptic activity. Here we show that low picomolar concentrations of a preparation containing both Abeta(42) monomers and oligomers cause a marked increase of hippocampal long-term potentiation, whereas high nanomolar concentrations lead to the well established reduction of potentiation. Picomolar levels of Abeta(42) also produce a pronounced enhancement of both reference and contextual fear memory. The mechanism of action of picomolar Abeta(42) on both synaptic plasticity and memory involves alpha7-containing nicotinic acetylcholine receptors. These findings strongly support a model for Abeta effects in which low concentrations play a novel positive, modulatory role on neurotransmission and memory, whereas high concentrations play the well known detrimental effect culminating in dementia.
Puzzo
Daniela
D
Department of Pathology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York 10032, USA.
Privitera
Lucia
L
Leznik
Elena
E
Fà
Mauro
M
Staniszewski
Agnieszka
A
Palmeri
Agostino
A
Arancio
Ottavio
O
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008464:Mecamylamine / Q000494:pharmacology; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000235:genetics; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000172:deficiency; D013569:Synapses / Q000187:drug effects*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D016229:Amyloid beta-Peptides; D002038:Bungarotoxins; C579167:Chrna7 protein, human; C579166:Chrna7 protein, mouse; D018691:Excitatory Amino Acid Antagonists; D018733:Nicotinic Antagonists; D010446:Peptide Fragments; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C075222:amyloid beta-protein (1-42); D008464:Mecamylamine; D015763:2-Amino-5-phosphonovalerate