title: Rapamycin protects against Aβ-induced synaptotoxicity by increasing presynaptic activity in hippocampal neurons.
abstract: The mammalian target of rapamycin (mTOR) is involved in the regulation of learning and memory. Recently, rapamycin has been shown to be neuroprotective in models for Alzheimer's disease in an autophagy-dependent manner. Here we show that rapamycin exerts neuroprotection via a novel mechanism that involves presynaptic activation. Rapamycin increases the frequency of miniature excitatory postsynaptic currents and calcium transients of rat hippocampal primary neurons by a mechanism that involves the up regulation of SV2, a presynaptic vesicular protein linked to neurotransmitter release. Under these conditions, rapamycin-treated hippocampal neurons are resistant to the synaptotoxic effect induced by Aβ oligomers, suggesting that enhancers of presynaptic activity can be therapeutic agents for Alzheimer's disease.
authors.affiliation: Department of Physiology, University of Concepción, P. O. Box 160-C, Concepcion, Chile.
authors.forename: A E
authors.initials: AE
authors.lastname: Ramírez
authors.affiliation: Department of Physiology, University of Concepción, P. O. Box 160-C, Concepcion, Chile.
authors.forename: C R
authors.initials: CR
authors.lastname: Pacheco
authors.affiliation: Department of Physiology, University of Concepción, P. O. Box 160-C, Concepcion, Chile. Electronic address: laguayo@udec.cl.
authors.forename: L G
authors.initials: LG
authors.lastname: Aguayo
authors.affiliation: Oxidation Biology Laboratory, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010, Australia. Electronic address: carlos.opazo@florey.edu.au.
authors.forename: C M
authors.initials: CM
authors.lastname: Opazo
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents; D002118:Calcium; D020123:Sirolimus
keywords: Alzheimer's disease; Aβ oligomer; Rapamycin; SV2; Synaptic activity; Synaptotoxicity