Guanosine enhances glutamate uptake and oxidation, preventing oxidative stress in mouse hippocampal slices submitted to high glutamate levels

Nonose, Yasmine; Pieper, Leandro Zafalon; Silva, J.S. da; Longoni, Aline; Apel, Rodrigo Vieira; Meira-Martins, Leo Anderson; Grings, Mateus; Leipnitz, Guilhian; Souza, Diogo Onofre Gomes de; Assis, Adriano Martimbianco de

doi:10.1016/j.brainres.2020.147080

Cited by 5 publications

(1 citation statement)

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“…During hypoxia/ischemia, a rapid increase of glutamate occurs mainly due to impairment of the glutamate uptake system, the release of excessive glutamate, the reversal of glutamate transporters activity (reverse uptake), and decreased activity of glutamine synthetase (GS) [115][116][117]. Using the model of hippocampal slices subjected to OGD with subsequent reoxygenation, it was demonstrated that guanosine administration promoted glutamate uptake by increasing the uptake Vmax and prevented the reversal of uptake induced by excessive glutamate [27,99,111,118]. No-tably, the stimulatory effect of guanosine on glutamate uptake was predominantly observed in the reoxygenation but not in the hypoxic period, even when administered up to 3 h in the reoxygenation period [27,97].…”

Section: Guanosine Acts Against Glutamate Excitotoxicitymentioning

confidence: 99%

Neuroprotective Effects of Guanosine in Ischemic Stroke—Small Steps towards Effective Therapy

Chojnowski

Opiełka

Nazar

et al. 2021

IJMS

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Guanosine (Guo) is a nucleotide metabolite that acts as a potent neuromodulator with neurotrophic and regenerative properties in neurological disorders. Under brain ischemia or trauma, Guo is released to the extracellular milieu and its concentration substantially raises. In vitro studies on brain tissue slices or cell lines subjected to ischemic conditions demonstrated that Guo counteracts destructive events that occur during ischemic conditions, e.g., glutaminergic excitotoxicity, reactive oxygen and nitrogen species production. Moreover, Guo mitigates neuroinflammation and regulates post-translational processing. Guo asserts its neuroprotective effects via interplay with adenosine receptors, potassium channels, and excitatory amino acid transporters. Subsequently, guanosine activates several prosurvival molecular pathways including PI3K/Akt (PI3K) and MEK/ERK. Due to systemic degradation, the half-life of exogenous Guo is relatively low, thus creating difficulty regarding adequate exogenous Guo distribution. Nevertheless, in vivo studies performed on ischemic stroke rodent models provide promising results presenting a sustained decrease in infarct volume, improved neurological outcome, decrease in proinflammatory events, and stimulation of neuroregeneration through the release of neurotrophic factors. In this comprehensive review, we discuss molecular signaling related to Guo protection against brain ischemia. We present recent advances, limitations, and prospects in exogenous guanosine therapy in the context of ischemic stroke.

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