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Plant Polyphenols and Exendin-4 Prevent Hyperactivity and TNF-alpha Release in LPS-Treated In vitro Neuron/Astrocyte/Microglial Networks

Gullo, F; Ceriani, M; D'Aloia, A; Wanke, E; Constanti, A; Costa, B; Lecchi, M; (2017) Plant Polyphenols and Exendin-4 Prevent Hyperactivity and TNF-alpha Release in LPS-Treated In vitro Neuron/Astrocyte/Microglial Networks. Frontiers in Neuroscience , 11 , Article 500. 10.3389/fnins.2017.00500. Green open access

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Abstract

Increasing evidence supports a decisive role for neuroinflammation in the neurodegenerative process of several central nervous system (CNS) disorders. Microglia are essential mediators of neuroinflammation and can regulate a broad spectrum of cellular responses by releasing reactive oxygen intermediates, nitric oxide, proteases, excitatory amino acids, and cytokines. We have recently shown that also in ex-vivo cortical networks of neurons, astrocytes and microglia, an increased level of tumor necrosis factor-alpha (TNF-α) was detected a few hours after exposure to the bacterial endotoxin lipopolysaccharide (LPS). Simultaneously, an atypical “seizure-like” neuronal network activity was recorded by multi-electrode array (MEA) electrophysiology. These effects were prevented by minocycline, an established anti-inflammatory antibiotic. We show here that the same inhibitory effect against LPS-induced neuroinflammation is exerted also by natural plant compounds, polyphenols, such as curcumin (CU, curcuma longa), crocin (CR, saffron), and resveratrol (RE, grape), as well as by the glucagon like peptide-1 receptor (GLP-1R) agonist exendin-4 (EX-4). The drugs tested also caused per-se early transient (variable) changes of network activity. Since it has been reported that LPS-induced neuroinflammation causes rearrangements of glutamate transporters in astrocytes and microglia, we suggest that neural activity could be putatively increased by an imbalance of glial glutamate transporter activity, leading to prolonged synaptic glutamatergic dysregulation.

Type: Article
Title: Plant Polyphenols and Exendin-4 Prevent Hyperactivity and TNF-alpha Release in LPS-Treated In vitro Neuron/Astrocyte/Microglial Networks
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fnins.2017.00500
Publisher version: http://dx.doi.org/10.3389/fnins.2017.00500
Language: English
Additional information: © 2017 Gullo, Ceriani, D'Aloia, Wanke, Constanti, Costa and Lecchi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, sterile inflammation, LPS, TNF-alpha, GLP-1, plant polyphenols, exendin-4 (EX-4), neocortical cultures, multi-electrode array (MEA), INHIBITS GLUTAMATE RELEASE, PARKINSONS-DISEASE, MICROGLIAL ACTIVATION, NERVE-TERMINALS, DENTATE GYRUS, ION CHANNELS, NEURONS, RESVERATROL, RECEPTOR, LIPOPOLYSACCHARIDE
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/1575419
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