Rapamycin protects against Aβ-induced synaptotoxicity by increasing presynaptic activity in hippocampal neurons

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1842

Article

Ramirez, A. E.¹  Pacheco, C. R.¹  Aguayo, L. G.¹  Opazo, C. M.² 

[1] Univ Concepcion, Dept Physiol, Concepcion, Chile

[2] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Oxidat Biol Lab, Melbourne, Vic 3010, Australia

关键词: Rapamycin;    A beta oligomer;    Alzheimer's disease;    SV2;    Synaptotoxicity;    Synaptic activity;   

DOI  :  10.1016/j.bbadis.2014.04.019

来源: Elsevier

【 摘 要 】

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 autophagydependent 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 A43 oligomers, suggesting that enhancers of presynaptic activity can be therapeutic agents for Alzheimer's disease. (C) 2014 Elsevier B.V. All rights reserved.

【 授权许可】

Free