Adenosine receptors co-operate with NMDA preconditioning to protect cerebellar granule cells against glutamate neurotoxicity

Boeck, Carina Rodrigues; Kroth, E. H.; Bronzatto, Mauro Jesus; Vendite, Deusa

doi:10.1016/j.neuropharm.2005.01.024

Cited by 43 publications

(34 citation statements)

References 41 publications

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“…A 2A receptor activation is also in accordance with the literature, as Boeck and colleagues (Boeck et al, 2005) have described previously that adenosine resulting from ectonucleotidase activity has a preference for A 2A receptors, whereas released adenosine prefers A 1 receptors. Moreover, genetic silencing of A 2A receptors in neurons confirmed their key roles in the CO paracrine effect (Fig.…”

Section: Discussionsupporting

confidence: 91%

Paracrine effect of carbon monoxide: astrocytes promote neuroprotection via purinergic signaling

Queiroga

Alves

Conde

et al. 2016

Journal of Cell Science

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The neuroprotective role of carbon monoxide (CO) has been studied in a cell-autonomous mode. Herein, a new concept is disclosed -CO affects astrocyte-neuron communication in a paracrine manner to promote neuroprotection. Neuronal survival was assessed when co-cultured with astrocytes that had been pre-treated or not with CO. The CO-pre-treated astrocytes reduced neuronal cell death, and the cellular mechanisms were investigated, focusing on purinergic signaling. CO modulates astrocytic metabolism and extracellular ATP content in the co-culture medium. Moreover, several antagonists of P1 adenosine and P2 ATP receptors partially reverted CO-induced neuroprotection through astrocytes. Likewise, knocking down expression of the neuronal P1 adenosine receptor A 2A -R (encoded by Adora2a) reverted the neuroprotective effects of CO-exposed astrocytes. The neuroprotection of CO-treated astrocytes also decreased following prevention of ATP or adenosine release from astrocytic cells and inhibition of extracellular ATP metabolism into adenosine. Finally, the neuronal downstream event involves TrkB (also known as NTRK2) receptors and BDNF. Pharmacological and genetic inhibition of TrkB receptors reverts neuroprotection triggered by CO-treated astrocytes. Furthermore, the neuronal ratio of BDNF to pro-BDNF increased in the presence of CO-treated astrocytes and decreased whenever A 2A -R expression was silenced. In summary, CO prevents neuronal cell death in a paracrine manner by targeting astrocytic metabolism through purinergic signaling.

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Section: Discussionsupporting

confidence: 91%

Paracrine effect of carbon monoxide: astrocytes promote neuroprotection via purinergic signaling

Queiroga

Alves

Conde

et al. 2016

Journal of Cell Science

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“…The doses of the A1R ligands used were not lethal, but they are expected to cause transient hemodynamic, cardiac, and thermogenic alterations [64], which were not measured, and can indirectly affect the measured impact of I/R on the liver. However, although we did not directly ruled out the possible involvement of other adenosine receptors in the liver or indirectly affecting liver function, we favor the contention that the effects observed upon administration of A1R ligands mostly result from direct effects mediated by liver A1R [30], since preconditioning studies in different organs in vivo and in vitro agreed on a direct effect of A1R in the affected cells [27,[31][32][33]. Since ATP content declines substantially during I/R, which is associated with hepatocellular injury and higher mortality, prevention of defective energy production plays an important role in the resistance to I/R injury.…”

Section: Discussionmentioning

confidence: 68%

“…Accumulated evidence suggests that A1R play a role in the protection from I/R injury in several organs such as heart, brain, and lung [12][13][14][26][27][28][29][30][31][32][33][34][35][36][37] through mechanisms that remain to be defined. The present study suggests that A1R activation prevents I/R injury through the control of OXPHOS efficiency.…”

Section: Discussionmentioning

confidence: 99%

Adenosine receptors: regulatory players in the preservation of mitochondrial function induced by ischemic preconditioning of rat liver

Duarte

Amorim

Varela

et al. 2016

Purinergic Signalling

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Although adenosine A 1 receptors (A1R) have been associated to ischemic preconditioning (IPC), direct evidence for their ability to preserve mitochondrial function upon hepatic preconditioning is still missing and could represent a novel strategy to boost the quality of liver transplants. We tested if the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) prevented IPC in the liver and if the A1R agonist 2-chloro-N 6 -cyclopentyladenosine (CCPA) might afford a pharmacological preconditioning. Livers underwent a 120 min of 70% warm ischemia and 16 h of reperfusion (I/R), and the IPC group underwent a 5-min ischemic episode followed by a 10-min period of reperfusion before I/R. DPCPX or CCPA was administered intraperitoneally 2 h before IPC or I/R. The control of mitochondrial function emerged as the central element affected by IPC and controlled by endogenous A1R activation. Thus, livers from IPC-or CCPA-treated rats displayed an improved oxidative phosphorylation with higher state 3 respiratory rate, higher respiratory control ratio, increased ATP content, and decreased lag phase. IPC and CCPA also prevented the I/Rinduced susceptibility to calcium-induced mitochondrial permeability transition, the rate of reactive oxygen species (ROS) generation, and the decreased mitochondrial content of phospho-Ser 9 GSK-3β. DPCPX abrogated these effects of IPC. These implicate the control of GSK-3β activity by Aktmediated Ser 9 -GSK-3β phosphorylation preserving the efficiency of oxidative phosphorylation and ROS-mediated cell death in the ability of A1R activation to mimic IPC in the liver. In conclusion, the parallel between IPC and A1R-mediated preconditioning also paves the way to consider a putative therapeutic use of the later in liver transplants.

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“…Boeck et al [40] have described that A1 receptors antagonists protect cells, but CPA alone had no effect on glutamate-induced damage, glutamate neurotoxicity, and cellular death in cerebellar granulare cells.…”

Section: H]-ccpa and [ 3 H]-mk 801 Bindingmentioning

confidence: 99%

Differential Expression of Cerebellar Metabotropic Glutamate Receptors mGLUR2/3 and mGLUR4a after the Administration of a Convulsant Drug and the Adenosine Analogue Cyclopentyladenosine

et al. 2007

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Metabotropic glutamate receptors (mGluR) play a role in synaptic transmission, neuronal modulation and plasticity but their action in epileptic activity is still controversial. On the other hand adenosine acts as a neuromodulator with endogenous anticonvulsive properties. Since cerebellum from epileptic patients has shown neuronal damage, sometimes associated with Purkinje cells loss, we have explored the effect of repetitive seizures on two types of mGluR in the cerebellum. Seizures were induced by the convulsant drug 3-mercaptopropionic acid (MP) and the effect of the adenosine analogue cyclopentyladenosine (CPA) alone or before MP administration (CPA+MP) were also evaluated. The expression of the receptors subtypes 2/3 (mGluR2/3) and 4a (mGluR4a) was assessed by immunocitochemistry. Granular cell layer was labeled with mGluR2/3 antibody and increased immunoreactivity was observed after MP (60%), CPA (53%) and CPA + MP (85%) treatments. Control cerebellum slices showed mGluR4a reactivity around Purkinje cells, while MP, CPA and CPA+MP treatment decreased this immunostaining. Repetitive administration of MP and CPA induces an increased cerebellar mGluR2/3 and a decreased mGluR4a immunostaining, suggesting a distinct participation of both receptors that may be related to the type of cell involved. A protective action and /or an apoptotic effect may not be discarded. CPA repetitive administration although increase seizure latency, cannot prevent seizure activity.

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Adenosine receptors co-operate with NMDA preconditioning to protect cerebellar granule cells against glutamate neurotoxicity

Cited by 43 publications

References 41 publications

Paracrine effect of carbon monoxide: astrocytes promote neuroprotection via purinergic signaling

Paracrine effect of carbon monoxide: astrocytes promote neuroprotection via purinergic signaling

Adenosine receptors: regulatory players in the preservation of mitochondrial function induced by ischemic preconditioning of rat liver

Differential Expression of Cerebellar Metabotropic Glutamate Receptors mGLUR2/3 and mGLUR4a after the Administration of a Convulsant Drug and the Adenosine Analogue Cyclopentyladenosine

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