Modulatory effects of inosine, guanosine and uridine on lipopolysaccharide-evoked increase in spike-wave discharge activity in Wistar Albino Glaxo/Rijswijk rats

Kovács, Zsolt; Kékesi, Katalin A.; Juhász, Gábor; Dobolyi, Árpád

doi:10.1016/j.brainresbull.2015.09.003

Cited by 8 publications

(7 citation statements)

References 65 publications

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“…Guanosine was able to prevent the increase in TNF-α and IL-1β levels through the HO-1 pathway, and, for the first time, we demonstrated the anti-inflammatory effect of guanosine in the aging process. In addition, our findings are in accordance with recent publications that suggest an anti-epileptic activity of guanosine partly via astrocyte modulation in a cross talk between inflammation and glutamatergic system [57][58][59].…”

Section: Discussionsupporting

confidence: 82%

Anti-aging effects of guanosine in glial cells

Souza

Bellaver

Bobermin

et al. 2016

Purinergic Signalling

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Guanosine, a guanine-based purine, has been shown to exert beneficial roles in in vitro and in vivo injury models of neural cells. Guanosine is released from astrocytes and modulates important astroglial functions, including glutamatergic metabolism, antioxidant, and anti-inflammatory activities. Astrocytes are crucial for regulating the neurotransmitter system and synaptic information processes, ionic homeostasis, energy metabolism, antioxidant defenses, and the inflammatory response. Aging is a natural process that induces numerous changes in the astrocyte functionality. Thus, the search for molecules able to reduce the glial dysfunction associated with aging may represent an approach for avoiding the onset of agerelated neurological diseases. Hence, the aim of this study was to evaluate the anti-aging effects of guanosine, using primary astrocyte cultures from newborn, adult, and aged Wistar rats. Concomitantly, we evaluated the role of heme oxygenase 1 (HO-1) in guanosine-mediated glioprotection. We observed age-dependent changes in glutamate uptake, glutamine synthetase (GS) activity, the glutathione (GSH) system, proinflammatory cytokine (tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)) release, and the transcriptional activity of nuclear factor kB (NFkB), which were prevented by guanosine in an HO-1-dependent manner. Our findings suggest guanosine to be a promising therapeutic agent able to provide glioprotection during the aging process. Thus, this study contributes to the understanding of the cellular and molecular mechanisms of guanosine in the aging process.

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Section: Discussionsupporting

confidence: 82%

Anti-aging effects of guanosine in glial cells

Souza

Bellaver

Bobermin

et al. 2016

Purinergic Signalling

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“…Another research group has proposed a pro-epileptic activity for inosine. Kovács et al (2015a , b) used Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats, a genetically absent epileptic WAG/Rij rat model that spontaneously generates absence-like seizures. The absence-like seizures in WAG/Rij rats, especially those older than 3 months, can be evidenced in electroencephalographic recordings by bilateral synchronous and spontaneously occurring spike-wave discharges (SWDs) ( Kovács et al, 2015a ).…”

Section: Inosine and Epilepsymentioning

confidence: 99%

“…It has been demonstrated that intraperitoneal inosine injection (500 or 1000 mg/kg) significantly increased SWD in WAG/Rij rats. Furthermore, a combined injection of inosine (500 or 1000 mg/kg) and LPS increased the SWD number and the total time of SWD to a more significant extent than LPS or inosine alone, suggesting that inosine potentiated LPS-induced SWD ( Kovács et al, 2015b ). Interestingly, muscimol (a GABAa receptor agonist)-induced increase in SWD number was potentiated by inosine (500 mg/kg) ( Kovács et al, 2015b ).…”

Section: Inosine and Epilepsymentioning

confidence: 99%

Inosine as a Tool to Understand and Treat Central Nervous System Disorders: A Neglected Actor?

Nascimento

Macedo-Júnior²,

Lapa-Costa

et al. 2021

Front. Neurosci.

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Since the 1970s, when ATP was identified as a co-transmitter in sympathetic and parasympathetic nerves, it and its active metabolite adenosine have been considered relevant signaling molecules in biological and pathological processes in the central nervous system (CNS). Meanwhile, inosine, a naturally occurring purine nucleoside formed by adenosine breakdown, was considered an inert adenosine metabolite and remained a neglected actor on the purinergic signaling scene in the CNS. However, this scenario began to change in the 1980s. In the last four decades, an extensive group of shreds of evidence has supported the importance of mediated effects by inosine in the CNS. Also, inosine was identified as a natural trigger of adenosine receptors. This evidence has shed light on the therapeutic potential of inosine on disease processes involved in neurological and psychiatric disorders. Here, we highlight the clinical and preclinical studies investigating the involvement of inosine in chronic pain, schizophrenia, epilepsy, depression, anxiety, and in neural regeneration and neurodegenerative diseases, such as Parkinson and Alzheimer. Thus, we hope that this review will strengthen the knowledge and stimulate more studies about the effects promoted by inosine in neurological and psychiatric disorders.

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“…Finally, GUO shows marked anticonvulsant/antiepileptic effects in several models of epilepsy ( Kovacs et al, 2015a ). For example, GUO and other GBPs attenuate the lipopolysaccharide-evoked increase in spike-wave discharges number in rats ( Kovacs et al, 2015a , b ). Also, GBPs are able to prevent seizures ( de Oliveira et al, 2004 ; Schmidt et al, 2005 ) or to counteract electrophysiological spectral changes, including glutamate store into synaptic vesicles, in a quinolinic acid-induced seizure model ( Tavares et al, 2005 , 2008 ; Torres et al, 2010 ).…”

Section: Gbps and Neuroprotectionmentioning

confidence: 99%

“…These effects suggest that GBPs may exert a competitive inhibitory mechanism, acting as antagonists of ionotropic glutamate receptors, thus antagonizing glutamatergic neurotoxicicity, as already discussed in a previous section. Furthermore, GBPs show anti-epileptic activity not only by inhibiting lipopolysaccharide-evoked increase in spike-wave discharges ( Kovacs et al, 2015a , b ) but also by counteracting electrophysiological spectral changes, including glutamate storage into synaptic vesicles ( Tavares et al, 2005 , 2008 ; Torres et al, 2010 ), and by preventing seizures ( de Oliveira et al, 2004 ; Schmidt et al, 2005 ).…”

Section: Neuronal Plasticity Mediated By Gbpsmentioning

confidence: 99%

The Guanine-Based Purinergic System: The Tale of An Orphan Neuromodulation

et al. 2016

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Guanine-based purines (GBPs) have been recently proposed to be not only metabolic agents but also extracellular signaling molecules that regulate important functions in the central nervous system. In such way, GBPs-mediated neuroprotection, behavioral responses and neuronal plasticity have been broadly described in the literature. However, while a number of these functions (i.e., GBPs neurothophic effects) have been well-established, the molecular mechanisms behind these GBPs-dependent effects are still unknown. Furthermore, no plasma membrane receptors for GBPs have been described so far, thus GBPs are still considered orphan neuromodulators. Interestingly, an intricate and controversial functional interplay between GBPs effects and adenosine receptors activity has been recently described, thus triggering the hypothesis that GBPs mechanism of action might somehow involve adenosine receptors. Here, we review recent data describing the GBPs role in the brain. We focus on the involvement of GBPs regulating neuronal plasticity, and on the new hypothesis based on putative GBPs receptors. Overall, we expect to shed some light on the GBPs world since although these molecules might represent excellent candidates for certain neurological diseases management, the lack of putative GBPs receptors precludes any high throughput screening intent for the search of effective GBPs-based drugs.

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Modulatory effects of inosine, guanosine and uridine on lipopolysaccharide-evoked increase in spike-wave discharge activity in Wistar Albino Glaxo/Rijswijk rats

Cited by 8 publications

References 65 publications

Anti-aging effects of guanosine in glial cells

Anti-aging effects of guanosine in glial cells

Inosine as a Tool to Understand and Treat Central Nervous System Disorders: A Neglected Actor?

The Guanine-Based Purinergic System: The Tale of An Orphan Neuromodulation

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