• Tássia Limana da Silveira, Marina Lopes Machado, Leticia Priscilla Arantes, Daniele Coradini Zamberlan, Larissa Marafiga Cordeiro, Fabiane Bicca Baptista Obetine, Aline Franzen da Silva, Cintia Letícia Tassi, and Felix Alexandre Antunes Soares.
• Universidade Federal de Santa Maria, Centro de Ciências Naturais e Exatas, Departamento de Bioquímica e Biologia Molecular, Programa de Pós-graduação em Ciências Biológicas, Bioquímica Toxicológica, Camobi, 97105-900, Santa Maria, RS, Brazil.
• Neuroscience. 2019 Aug 21; 414: 265-272.

AbstractGlutamatergic neurotransmission is present in most mammalian excitatory synapses and plays a key role in central nervous system homeostasis. When over-activated, it can induce excitotoxicity, which is present in several neuropathologies. The nucleoside guanosine (GUO) is a guanine-based purine known to have neuroprotective effects by modulating glutamatergic system during glutamate excitotoxicity in mammals. However, GUO action in Caenorhabditis elegans, as well as on C. elegans glutamatergic excitotoxicity model, is not known. The GUO effects on behavioral parameters in Wild Type (WT) and knockouts worms for glutamate transporters (GLT-3, GLT-1), glutamate vesicular transporter (EAT-4), and NMDA and non-NMDA receptors were used to evaluate the GUO modulatory effects. The GUO tested concentrations did not alter the animals' development, but GUO reduced pharyngeal pumps in WT animals in a dose-dependent manner. The same effect was observed in pharyngeal pumps, when the animals were treated with 4 mM of GUO in glr-1, nmr-1 and eat-4, but not in glt-3 and glt-3;glt-1 knockouts. The double mutant glt-3; glt-1 for GluTs had decreased body bends and an increased number of reversions. This effect was reverted after treatment with GUO. Furthermore, GUO did not alter the sensory response in worms with altered glutamatergic signaling. Thus, GUO seems to modulate the worm's glutamatergic system in situations of exacerbated glutamatergic signaling, which are represented by knockout strains to glutamate transporters. However, in WT animals, GUO appears to reinforce glutamatergic signaling in specific neurons. Our findings indicate that C. elegans strains are useful models to study new compounds that could be used in glutamate-associated neurodegenerative diseases.Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

35 keywords...

hide…