Rapamycin increases neurotransmission of hippocampal neurons.
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Up regulation of the presynaptic protein SV2 is promoted by rapamycin.
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Rapamycin protects against synaptotoxic effect induced by Aβ oligomers.
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We propose that enhancers of neurotransmission can be therapeutic agents for Alzheimer's disease.
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.
