Acute inflammation downregulates alpha-synuclein expression in enteric neurons.

07:00 EST 27th December 2018 | BioPortfolio

Summary of "Acute inflammation downregulates alpha-synuclein expression in enteric neurons."

The protein alpha-synuclein whose expression is strongly implicated in Parkinson's disease (PD) is not only expressed in the central nervous system (CNS) but also in the enteric nervous system (ENS). The growing body of evidence suggesting that gastrointestinal inflammation is involved in the development of PD led us to investigate the effects of inflammation on alpha-synuclein expression in primary culture of rat ENS and in mice with dextran sulfate sodium (DSS)-induced colitis. Using western blot and qPCR, we found that both LPS and a combination of TNF-α and IL1-β (TNF-α/IL1-β) decreased the expression levels of alpha-synuclein in primary culture of rat ENS, an effect that was prevented in the presence of the p38 inhibitors SB203580 and BIRB 796. LPS and TNF-α/IL1-β had no effect on alpha-synuclein expression in primary culture of rat CNS and in HEL cells. In mice, acute but not chronic DSS-induced colitis was associated with a decreased expression of colonic alpha-synuclein. As a whole, our findings indicate that acute inflammatory insults downregulate alpha-synuclein expression in the ENS via a p38 pathway. They provide new insights into the widely discussed concepts of alpha-synuclein expression and aggregation in the ENS in PD and raise issues about the possible role of gastrointestinal inflammation in the development of PD. This article is protected by copyright. All rights reserved.


Journal Details

This article was published in the following journal.

Name: Journal of neurochemistry
ISSN: 1471-4159


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Medical and Biotech [MESH] Definitions

A synuclein that is closely related to ALPHA-SYNUCLEIN. It may play a neuroprotective role against some of the toxic effects of aggregated ALPHA-SYNUCLEIN.

A homolog of ALPHA-SYNUCLEIN that plays a role in neurofilament network integrity. It is overexpressed in a variety of human NEOPLASMS and may be involved in modulating AXON architecture during EMBRYONIC DEVELOPMENT and in the adult. Gamma-Synuclein may also activate SIGNAL TRANSDUCTION PATHWAYS associated with ETS-DOMAIN PROTEIN ELK-1.

A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.

Two ganglionated neural plexuses in the gut wall which form one of the three major divisions of the autonomic nervous system. The enteric nervous system innervates the gastrointestinal tract, the pancreas, and the gallbladder. It contains sensory neurons, interneurons, and motor neurons. Thus the circuitry can autonomously sense the tension and the chemical environment in the gut and regulate blood vessel tone, motility, secretions, and fluid transport. The system is itself governed by the central nervous system and receives both parasympathetic and sympathetic innervation. (From Kandel, Schwartz, and Jessel, Principles of Neural Science, 3d ed, p766)

Motor neurons which activate the contractile regions of intrafusal SKELETAL MUSCLE FIBERS, thus adjusting the sensitivity of the MUSCLE SPINDLES to stretch. Gamma motor neurons may be "static" or "dynamic" according to which aspect of responsiveness (or which fiber types) they regulate. The alpha and gamma motor neurons are often activated together (alpha gamma coactivation) which allows the spindles to contribute to the control of movement trajectories despite changes in muscle length.

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