Intranasal guanosine administration presents a wide therapeutic time window to reduce brain damage induced by permanent ischemia in rats

Ramos, Denise Barbosa; Müller, G; Rocha, Guilherme Botter Maio; Dellavia, Gustavo Hirata; Almeida, Roberto Farina de; Pettenuzzo, Letícia Ferreira; Loureiro, Samanta Oliveira; Hansel, Gisele; Horn, Ângelo Cássio Magalhães; Souza, Diogo O.; Ganzella, Marcelo

doi:10.1007/s11302-015-9489-9

Cited by 18 publications

(25 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Guanosine has been studied in a variety of experimental models, including seizures, hypoxia, glucose deprivation, oxidative injury, and inflammatory conditions [4,5,[37][38][39][40]. Because guanosine may be released from glial cells, modulating important glial functions, astrocytes emerge as central players in the protective actions of guanosine [12,14].…”

Section: Discussionmentioning

confidence: 99%

Anti-aging effects of guanosine in glial cells

Souza

Bellaver

Bobermin

et al. 2016

Purinergic Signalling

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Anti-aging effects of guanosine in glial cells

Souza

Bellaver

Bobermin

et al. 2016

Purinergic Signalling

Self Cite

View full text Add to dashboard Cite

show abstract

“…et al, 2015 ). Intranasal administration of guanosine reduced ischaemic brain damage in rats ( Ramos et al, 2016 ). Ambiguously, both A 2A R agonists and antagonists may protect against ischaemic brain injury ( Pedata et al, 2014 ).…”

Section: Disorders Of the Central Nervous System (Cns)mentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

View full text Add to dashboard Cite

Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

show abstract

“…P2X7 antagonists or blockade of pannexin-1 channels attenuates post-ischaemic brain damage [62,63]. Intranasal administration of guanosine reduced brain damage induced by ischaemia in rats [64].…”

Section: Ischaemiamentioning

confidence: 99%

Purinergic Signalling and Neurological Diseases: An Update

Burnstock

2017

CNSNDDT

104

View full text Add to dashboard Cite

Purinergic signalling, i.e. ATP as an extracellular signalling molecule and cotransmitter in both peripheral and central neurons, is involved in the physiology of neurotransmission and neuromodulation. Receptors for purines have been cloned and characterised, including 4 subtypes of the P1(adenosine) receptor family, 7 subtypes of the P2X ion channel nucleotide receptor family and 8 subtypes of the P2Y G protein-coupled nucleotide receptor family. The roles of purinergic signalling in diseases of the central nervous system and the potential use of purinergic compounds for their treatment are attracting increasing attention. In this review, the focus is on the findings reported in recent papers and reviews to update knowledge in this field about the involvement of purinergic signalling in Alzheimer's, Parkinson's and Huntington's diseases, multiple sclerosis, amyotrophic lateral sclerosis, degeneration and regeneration after brain injury, stroke, ischaemia, inflammation, migraine, epilepsy, psychiatric disorders, schizophrenia, bipolar disorder, autism, addiction, sleep disorders and brain tumours. The use in particular of P2X7 receptor antagonists for the treatment of neurodegenerative diseases, cancer, depression, stroke and ischaemia, A2A receptor antagonists for Parkinson's disease and agonists for brain injury and depression and P2X3 receptor antagonists for migraine and seizures has been recommended. P2Y receptors have also been claimed to be involved in some central nervous disorders.

show abstract

Intranasal guanosine administration presents a wide therapeutic time window to reduce brain damage induced by permanent ischemia in rats

Cited by 18 publications

References 42 publications

Anti-aging effects of guanosine in glial cells

Anti-aging effects of guanosine in glial cells

Purinergic Signalling: Therapeutic Developments

Purinergic Signalling and Neurological Diseases: An Update

Contact Info

Product

Resources

About