Soluble Aβ1–42 increases the heterogeneity in synaptic vesicle pool size among synapses by suppressing intersynaptic vesicle sharing

Cited 4 time in Web of Science Cited 4 time in Scopus

Park, Daehun; Chang, Sunghoe

Issue Date
BioMed Central
Molecular Brain, 11(1):10
Growing evidence has indicated that prefibrillar form of soluble amyloid beta (sAβ1–42) is the major causative factor in the synaptic dysfunction associated with AD. The molecular changes leading to presynaptic dysfunction caused by sAβ1–42, however, still remains elusive. Recently, we found that sAβ1–42 inhibits chemically induced long-term potentiation-induced synaptogenesis by suppressing the intersynaptic vesicle trafficking through calcium (Ca2+) dependent hyperphosphorylation of synapsin and CaMKIV. However, it is still unclear how sAβ1–42 increases intracellular Ca2+ that induces hyperphosphorylation of CaMKIV and synapsin, and what is the functional consequences of sAβ1–42-induced defects in intersynaptic vesicle trafficking in physiological conditions. In this study, we showed that sAβ1–42elevated intracellular Ca2+ through not only extracellular Ca2+ influx but also Ca2+ release from mitochondria. Surprisingly, without Ca2+ release from mitochondria, sAβ1–42 failed to increase intracellular Ca2+ even in the presence of normal extracellular Ca2+. We further found that sAβ1–42-induced mitochondria Ca2+ release alone sufficiently increased Serine 9 phosphorylation of synapsin. By blocking synaptic vesicle reallocation, sAβ1–42 significantly increased heterogeneity of total synaptic vesicle pool size among synapses. Together, our results suggested that by disrupting the axonal vesicle trafficking, sAβ1–42 disabled neurons to adjust synaptic pool sizes among synapses, which might prevent homeostatic rescaling in synaptic strength of individual neurons.
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Physiology (생리학교실)Journal Papers (저널논문_생리학교실)
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Journal Papers (저널논문_의과학과)
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