Adenosine A 2A receptor blockade attenuates spatial memory deficit and extent of demyelination areas in lyolecithin-induced demyelination model

Akbari, Atefeh; Khalili-Fomeshi, Mohsen; Ashrafpour, Manouchehr; Moghadamnia, Ali Akbar; Ghasemi-Kasman, Maryam

doi:10.1016/j.lfs.2018.05.007

Cited by 15 publications

(4 citation statements)

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“…It has been suggested that overexpression and overactivity of A 2A R may accelerate neurodegeneration [ 63 ]. Moreover, A 2A R deserves special attention in numerous neurological disorders since its pharmacological inhibition prevents memory deficits [ 17 , 20 , 64 , 65 , 66 ]. Intake of HFD is associated with cognitive dysfunction, as recently reviewed in rodents [ 67 ], and recapitulates some AD-like features in mice [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

High-Fat and Resveratrol Supplemented Diets Modulate Adenosine Receptors in the Cerebral Cortex of C57BL/6J and SAMP8 Mice

et al. 2021

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Neurodegenerative disorders are devastating diseases in which aging is a major risk factor. High-fat diet (HFD) seems to contribute to cognition deterioration, but the underlying mechanisms are poorly understood. Moreover, resveratrol (RSV) has been reported to counteract the loss of cognition associated with age. Our study aimed to investigate whether the adeno-synergic system and plasma membrane cholesterol are modulated by HFD and RSV in the cerebral cortex of C57BL/6J and SAMP8 mice. Results show that HFD induced increased A1R and A2AR densities in C57BL/6J, whereas this remained unchanged in SAMP8. Higher activity of 5′-Nucleotidase was found as a common effect induced by HFD in both mice strains. Furthermore, the effect of HFD and RSV on A2BR density was different depending on the mouse strain. RSV did not clearly counteract the HFD-induced effects on the adeno-synergic system. Besides, no changes in free-cholesterol levels were detected in the plasma membrane of cerebral cortex in both strains. Taken together, our data suggest a different modulation of adenosine receptors depending on the mouse strain, not related to changes in plasma membrane cholesterol content.

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Section: Discussionmentioning

confidence: 99%

High-Fat and Resveratrol Supplemented Diets Modulate Adenosine Receptors in the Cerebral Cortex of C57BL/6J and SAMP8 Mice

et al. 2021

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“…In fact, intra-NAc administration of MSX-3 increased cocaine seeking (5–20 μg/side; O'Neill et al 2012) or enhanced locomotor activity in an open field after intra-NAc (5 μg; Nagel et al 2003), or intra-striatal (9 μg; Hauber et al 1998) MSX-3 administration. The recent paper indicated that SCH 58261 in a dose range of 20–40 μg/side repeatedly injected intracerebroventricularly exerted inhibitory effect on astrocytes activation and prevented the spatial memory impairment in rats (Akbari et al 2018). …”

Section: Methodsmentioning

confidence: 99%

Effects of intra-accumbal or intra-prefrontal cortex microinjections of adenosine 2A receptor ligands on responses to cocaine reward and seeking in rats

et al. 2018

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Rationale and objectivesMany studies indicated that adenosine via its A2A receptors influences the behavioral effects of cocaine by modulating dopamine neurotransmission. The hypothesis was tested that A2A receptors in the nucleus accumbens (NAc) or the prefrontral cortex (PFc) may modulate cocaine reward and/or cocaine seeking behavior in rats.MethodsThe effects of local bilateral microinjections of the selective A2A receptor agonist CGS 21680 or the A2A receptor antagonists KW 6002 and SCH 58261 were investigated on cocaine self-administration on reinstatement of cocaine seeking.ResultsThe intra-NAc shell, but not intra-infralimbic PFc, administration of CGS 21680 significantly reduced the number of active lever presses and the number of cocaine (0.25 mg/kg) infusions. However, tonic activation of A2A receptors located in the NAc or PFc did not play a role in modulating the rewarding actions of cocaine since neither KW 6002 nor SCH 58261 microinjections altered the cocaine (0.5 mg/kg) infusions. The intra-NAc but not intra-PFc microinjections of CGS 21680 dose- dependently attenuated the reinstatement of active lever presses induced by cocaine (10 mg/kg, i.p.) and the drug-associated combined conditioned stimuli using the subthreshold dose of cocaine (2.5 mg/kg, i.p.). On the other hand, the intra-NAc pretreatment with SCH 58261, but not with KW 6002, given alone evoked reinstatement of cocaine seeking behavior.ConclusionThe results strongly support the involvement of accumbal shell A2A receptors as a target, the activation of which exerts an inhibitory control over cocaine reward and cocaine seeking.

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“…The pharmacological or the genetic blockade of A 2A ARs prevents memory deficits in different animal models of Alzheimer’s disease ( Canas et al, 2009 ; Laurent et al, 2016 ; Viana da Silva et al, 2016 ). A 2A AR antagonism also prevents memory dysfunction associated with other conditions, such as convulsions ( Cognato et al, 2010 ), diabetes ( Duarte et al, 2012 ), hypoxia ( Chen et al, 2018 ), traumatic brain injury ( Zhao et al, 2017 ), demyelination conditions ( Akbari et al, 2018 ), repeated stress or depression ( Batalha et al, 2013 ; Kaster et al, 2015 ; Machado et al, 2017 ), PD ( Hu et al, 2016 ; Carmo et al, 2019 ), or cannabis exposure ( Mouro et al, 2019 ). A 2A ARs are not only necessary but actually sufficient to impair memory since their increased activity driven by genetic ( Temido-Ferreira et al, 2020 ), optogenetic ( Li et al, 2015 ), or pharmacological strategies ( Pagnussat et al, 2015 ) impairs memory in normal animals.…”

Section: Pharmacology – Novel Developmentsmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. CXII: Adenosine Receptors: A Further Update

et al. 2022

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Our previous International Union of Basic and Clinical Pharmacology report on the nomenclature and classification of adenosine receptors (2011) contained a number of emerging developments with respect to this G protein-coupled receptor subfamily, including protein structure, protein oligomerization, protein diversity, and allosteric modulation by small molecules. Since then, a wealth of new data and results has been added, allowing us to explore novel concepts such as target binding kinetics and biased signaling of adenosine receptors, to examine a multitude of receptor structures and novel ligands, to gauge new pharmacology, and to evaluate clinical trials with adenosine receptor ligands. This review should therefore be considered a further update of our previous reports from 2001 and 2011. Significance Statement Adenosine receptors (ARs) are of continuing interest for future treatment of chronic and acute disease conditions, including inflammatory diseases, neurodegenerative afflictions, and cancer. The design of AR agonists (“biased” or not) and antagonists is largely structure based now, thanks to the tremendous progress in AR structural biology. The A 2A - and A 2B AR appear to modulate the immune response in tumor biology. Many clinical trials for this indication are ongoing, whereas an A 2A AR antagonist (istradefylline) has been approved as an anti-Parkinson agent.

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Adenosine A 2A receptor blockade attenuates spatial memory deficit and extent of demyelination areas in lyolecithin-induced demyelination model

Cited by 15 publications

References 59 publications

High-Fat and Resveratrol Supplemented Diets Modulate Adenosine Receptors in the Cerebral Cortex of C57BL/6J and SAMP8 Mice

High-Fat and Resveratrol Supplemented Diets Modulate Adenosine Receptors in the Cerebral Cortex of C57BL/6J and SAMP8 Mice

Effects of intra-accumbal or intra-prefrontal cortex microinjections of adenosine 2A receptor ligands on responses to cocaine reward and seeking in rats

International Union of Basic and Clinical Pharmacology. CXII: Adenosine Receptors: A Further Update

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