Alpha-synuclein is associated with the synaptic vesicle apparatus in the human and rat enteric nervous system

Abstract

Background and aims: Aggregation of alpha-synuclein (a-syn) has been implicated in the development of neurodegenerative diseases including its spread from the enteric nervous system (ENS) to the brain. Physiologically, a-syn is located at the presynapse and might be involved in regulating of neurotransmission. Therefore, the aim of the study was to characterize the physiological ontogenetic and locoregional expression pattern of a-syn in the ENS and its association with the synaptic vesicle apparatus.

Material and methods: Ontogenetic mRNA expression of a-syn and synaptophysin was determined in the rat intestine. Myenteric plexus cultures treated with glial cell line-derived neurotrophic factor (GDNF) were assessed for mRNA expression of a-syn, co-localization of a-syn with the pan-neuronal marker PGP 9.5 and the synaptic vesicle marker synaptophysin and studied by scanning electron microscopy (SEM). Human colonic specimens were subjected to co-localization studies of a-syn with synaptophysin.

Results: a-syn and synaptophysin intestinal gene expression levels were highest during early postnatal life and also detectable at adult age. a-syn was co-localized with PGP 9.5 and synaptophysin in myenteric plexus cultures and up-regulated after GDNF treatment. SEM confirmed the presence of neuronal varicosities to which a-syn was associated. Consistently, a-syn and synaptophysin showed partial co-localization in the human ENS.

Conclusions: The ontogenetic and cellular expression pattern as well as the regulation by GNDF give evidence that a-syn is physiologically associated to the synaptic vesicle apparatus. The data suggest that a-syn is involved in the regulation of synaptic plasticity in the ENS during early postnatal life and adult age.

Keywords: Alpha synuclein; Enteric nerve cell culture; Enteric nervous system; Human colon; Synaptic vesicles.