Adenosine A2A receptor and ERK-driven impulsivity potentiates hippocampal neuroblast proliferation

Oliveros, Alfredo; Ch, Cho; A, Cui; Choi, Sun Hee; Lindberg, Daniel M.; Hinton, David J.; Mh, Jang; Ds, Choi

doi:10.1038/tp.2017.64

Cited by 26 publications

(17 citation statements)

References 81 publications

(98 reference statements)

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“…Finally, possible interconnections between adenosine receptors and suicide-related behaviors, often occurring in depression, have been hypothesized, although there is no direct evidence purposively exploring this link. It has been shown that impulsive behaviors might be driven by the inhibition of A2A receptors, accompanied by an increased neuroblast proliferation in the hippocampus [52]. Thus, opposite effects of A2A receptors and related adenosine metabolism have been hypothesized to explain depression-related suicidal ideation and impulsive suicide attempts, respectively [53].…”

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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“…Interestingly, Parrott and colleagues show that peripheral LPS administration primarily promotes kynurenine metabolism in the dorsal hippocampus when compared to the vHip (Parrott et al, 2016). This suggests that the dorsal hippocampus and mPFC may be directly synchronized to regulate neuroimmunological responses and behaviors (O'Leary and Cryan, 2014; Oliveros et al, 2017). …”

Section: Discussionmentioning

confidence: 99%

LPS-induced cortical kynurenic acid and neurogranin-NFAT signaling is associated with deficits in stimulus processing during Pavlovian conditioning

Oliveros

Wininger

Larsson

et al. 2017

Journal of Neuroimmunology

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The N-Methyl-D-Aspartate receptor (NMDAR) antagonist kynurenic acid (KYNA) and the post-synaptic calmodulin binding protein neurogranin (Nrgn) have been implicated in neurological and neuropsychiatric conditions including Alzheimer's disease and schizophrenia. This study indicates that systemic dual-lipopolysaccharide (LPS) injections increases KYNA in the medial prefrontal cortex (mPFC), which is accompanied with increased phosphorylation of nuclear factor kappa chain of activated B cells (NFκB) and activation of the nuclear factor of activated T- cells (NFAT). Our results also indicate that dual-LPS increases Nrgn phosphorylation and concomitantly reduces phosphorylation of calmodulin kinase-I I (CaMKII). We confirmed that systemic blockade of kynurenine-3 monooxygenase in conjunction with kynurenine administration results in significant increases in Nrgn phosphorylation and a significant reduction of CaMKII phosphorylation in the mPFC. Consequently dual-LPS administration induced significant impairments in stimulus processing during Pavlovian conditioning. Taken together, our study indicates that elevations in KYNA in the mPFC can directly regulate NMDA-Nrgn-CaMKII signaling, suggesting that neuroinflammatory conditions affecting this pathway may be associated with cognitive dysfunction.

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“…52 Oliveros et al observed that the pharmacological blockade of A 2A R promoted impulsive behavior, and that in these conditions there was a potentiation of neuroblast proliferation, and likely of adult neurogenesis, in the dorsal hippocampus. 56 Still, A 2A R knockout mice were reported to have cognitive impairments and decreased proliferation of newborn hippocampal cells. 57 Indeed, a gene-based association analysis identified adenosine A 2A R gene ADORA2A as significantly associated with a larger hippocampal volume and better memory.…”

Section: Adenosine Receptors In Postnatal Neurogenesismentioning

confidence: 99%

Neurogenesis and Gliogenesis: Relevance of Adenosine for Neuroregeneration in Brain Disorders

Mateus

Ribeiro

Alonso-Gomes

et al. 2019

Journal of Caffeine and Adenosine Research

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The processes of neural genesis, namely neurogenesis, astrogliogenesis, and oligodendrogenesis, that is, the formation of new neurons, astrocytes, and oligodendrocytes start with embryonic development. Of importance, it continues throughout adulthood, not only in the neurogenic niches where neural stem cells (NSCs) are present, but also from glial precursor cells in the brain parenchyma. Therefore, NSCs can be considered a potential therapeutic option in conditions of neural loss and tissue degeneration, as in neurodegenerative diseases. Specifically, stem cell therapy represents a personalized, localized, and probably fruitful alternative in patient care, and is the subject of ongoing research. Nevertheless, many mechanisms of this regenerative therapy remain elusive: if transplantation is required, not only is it necessary to successfully deliver these NSCs to the brain, but they also need to survive, proliferate, and replace the lost neural cells. In line with this, finding ways to manipulate the endogenous sources of NSCs is also very appealing. In particular, adenosine and caffeine (a nonselective antagonist of adenosine receptors), widely studied modulators of neuronal activity, have emerged as potential targets of neurogenesis and oligodendrogenesis. In this article, we review the present concepts on the role of adenosine in embryonic and postnatal neural cell genesis, together with its relevance in the context of brain regeneration.

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Adenosine A2A receptor and ERK-driven impulsivity potentiates hippocampal neuroblast proliferation

Cited by 26 publications

References 81 publications

Purinergic Signaling and Related Biomarkers in Depression

Purinergic Signaling and Related Biomarkers in Depression

LPS-induced cortical kynurenic acid and neurogranin-NFAT signaling is associated with deficits in stimulus processing during Pavlovian conditioning

Neurogenesis and Gliogenesis: Relevance of Adenosine for Neuroregeneration in Brain Disorders

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