Behavioral changes induced through adenosine A2A receptor ligands in a rat depression model induced by olfactory bulbectomy

Padilla, Karla; Quintanar-Setephano, Andres; López‐Vallejo, Fabian; Berumen, Laura C.; Miledi, Ricardo; Garcı́a-Alcocer, Guadalupe

doi:10.1002/brb3.952

Cited by 31 publications

(20 citation statements)

References 40 publications

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“…Consistently, selective A2A antagonists have attracted attention for their possible role in the treatment of depression. Preclinical studies highlighted that A2A antagonists have antidepressant effects [39][40][41][42] and may potentiate responses to antidepressant treatment [43], whereas A1 antagonists do not [44]. The A2A selective antagonist istradefylline (KW6002), recently approved by the FDA as an add-on therapy for off episodes in adults with Parkinson's disease [45], may also be effective in treating depressive-like symptoms, with an effect that is independent from monoaminergic transmission in the brain [46].…”

Section: Adenosine and Depressionmentioning

confidence: 99%

Purinergic Signaling and Related Biomarkers in Depression

et al. 2020

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It is established that purinergic signaling can shape a wide range of physiological functions, including neurotransmission and neuromodulation. The purinergic system may play a role in the pathophysiology of mood disorders, influencing neurotransmitter systems and hormonal pathways of the hypothalamic-pituitary-adrenal axis. Treatment with mood stabilizers and antidepressants can lead to changes in purinergic signaling. In this overview, we describe the biological background on the possible link between the purinergic system and depression, possibly involving changes in adenosine- and ATP-mediated signaling at P1 and P2 receptors, respectively. Furthermore, evidence on the possible antidepressive effects of non-selective adenosine antagonist caffeine and other purinergic modulators is reviewed. In particular, A2A and P2X7 receptors have been identified as potential targets for depression treatment. Preclinical studies highlight that both selective A2A and P2X7 antagonists may have antidepressant effects and potentiate responses to antidepressant treatments. Consistently, recent studies feature the possible role of the purinergic system peripheral metabolites as possible biomarkers of depression. In particular, variations of serum uric acid, as the end product of purinergic metabolism, have been found in depression. Although several open questions remain, the purinergic system represents a promising research area for insights into the molecular basis of depression.

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Section: Adenosine and Depressionmentioning

confidence: 99%

Purinergic Signaling and Related Biomarkers in Depression

et al. 2020

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“…Authors also evidenced that A2A receptor is a major regulator of GR function since its inhibition reduces GR hippocampal levels, and acts on GR nuclear translocation and GR-dependent transcriptional regulation ( Batalha et al, 2016 ). Interestingly, some studies showed an anti-depressive effect of A2A receptor antagonists in MDD models ( López-Cruz et al, 2018 ; Padilla et al, 2018 ). A2A receptor is an example among others.…”

Section: Gr a Potential Therapeutic Targetmentioning

confidence: 99%

Central Role of Glucocorticoid Receptors in Alzheimer’s Disease and Depression

et al. 2018

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Alzheimer’s disease (AD) is the principal neurodegenerative pathology in the world displaying negative impacts on both the health and social ability of patients and inducing considerable economic costs. In the case of sporadic forms of AD (more than 95% of patients), even if mechanisms are unknown, some risk factors were identified. The principal risk is aging, but there is growing evidence that lifetime events like chronic stress or stress-related disorders may increase the probability to develop AD. This mini-review reinforces the rationale to consider major depressive disorder (MDD) as an important risk factor to develop AD and points the central role played by the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoids (GC) and their receptors (GR) in the etiology of MDD and AD. Several strategies directly targeting GR were tested to neutralize the HPA axis dysregulation and GC overproduction. Given the ubiquitous expression of GR, antagonists have many undesired side effects, limiting their therapeutic potential. However, a new class of molecules was developed, highly selective and acting as modulators. They present the advantage to selectively abrogate pathogenic GR-dependent processes, while retaining beneficial aspects of GR signaling. In fact, these “selective GR modulators” induce a receptor conformation that allows activation of only a subset of downstream signaling pathways, explaining their capacity to combine agonistic and antagonistic properties. Thus, targeting GR with selective modulators, alone or in association with current strategies, becomes particularly attractive and relevant to develop novel preventive and/or therapeutic strategies to tackle disorders associated with a dysregulation of the HPA axis.

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“…Administration of ZM 241385, an inhibitor of A 2A receptor, decreases the immobility and isolation time in a rat depression model, indicating that activation of A 2A receptor contributes to depressive behaviour. 189 Consistently, rats overexpressing A 2A receptor demonstrate depressive phenotypes. 190 In contrast, stimulation of A 1 receptor exhibits antidepressant effects.…”

Section: Purinergic Neurotransmission In Neurodevelopment and The Pathogenesis Of Brain Diseasesmentioning

confidence: 93%

From purines to purinergic signalling: molecular functions and human diseases

Huang

Xie

Illéš

et al. 2021

Sig Transduct Target Ther

235

151

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Purines and their derivatives, most notably adenosine and ATP, are the key molecules controlling intracellular energy homoeostasis and nucleotide synthesis. Besides, these purines support, as chemical messengers, purinergic transmission throughout tissues and species. Purines act as endogenous ligands that bind to and activate plasmalemmal purinoceptors, which mediate extracellular communication referred to as “purinergic signalling”. Purinergic signalling is cross-linked with other transmitter networks to coordinate numerous aspects of cell behaviour such as proliferation, differentiation, migration, apoptosis and other physiological processes critical for the proper function of organisms. Pathological deregulation of purinergic signalling contributes to various diseases including neurodegeneration, rheumatic immune diseases, inflammation, and cancer. Particularly, gout is one of the most prevalent purine-related disease caused by purine metabolism disorder and consequent hyperuricemia. Compelling evidence indicates that purinoceptors are potential therapeutic targets, with specific purinergic agonists and antagonists demonstrating prominent therapeutic potential. Furthermore, dietary and herbal interventions help to restore and balance purine metabolism, thus addressing the importance of a healthy lifestyle in the prevention and relief of human disorders. Profound understanding of molecular mechanisms of purinergic signalling provides new and exciting insights into the treatment of human diseases.

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Behavioral changes induced through adenosine A2A receptor ligands in a rat depression model induced by olfactory bulbectomy

Cited by 31 publications

References 40 publications

Purinergic Signaling and Related Biomarkers in Depression

Purinergic Signaling and Related Biomarkers in Depression

Central Role of Glucocorticoid Receptors in Alzheimer’s Disease and Depression

From purines to purinergic signalling: molecular functions and human diseases

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