Up-regulation of striatal adenosine A2A receptors in schizophrenia

Deckert, Jürgen; Brenner, Markus; Durany, Núria; Zöchling, Robert; Paulus, W.; Ransmayr, Gerhard; Tatschner, Thomas; Danielczyk, W; Jellinger, K.; Riederer, Peter

doi:10.1097/00001756-200303030-00003

Cited by 57 publications

(43 citation statements)

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“…This increase in A 2A R density and efficiency is also observed in other cell models systems, like PC12 cells (see [121,218]) or activated lymphoid cells [219Y223]. Finally, an up-regulation of A 2A Rs was also reported in schizophrenic patients [224].…”

Section: Modification Of Adenosine Metabolism On Stressful Conditionssupporting

confidence: 67%

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Cunha

2005

Purinergic Signalling

482

432

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Adenosine is a neuromodulator that operates via the most abundant inhibitory adenosine A 1 receptors (A 1 Rs) and the less abundant, but widespread, facilitatory A 2A Rs. It is commonly assumed that A 1 Rs play a key role in neuroprotection since they decrease glutamate release and hyperpolarize neurons. In fact, A 1 R activation at the onset of neuronal injury attenuates brain damage, whereas its blockade exacerbates damage in adult animals. However, there is a down-regulation of central A 1 Rs in chronic noxious situations. In contrast, A 2A Rs are up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection in adult animals. The brain neuroprotective effect of A 2A R antagonists is maintained in chronic noxious brain conditions without observable peripheral effects, thus justifying the interest of A 2A R antagonists as novel protective agents in neurodegenerative diseases such as Parkinson's and Alzheimer's disease, ischemic brain damage and epilepsy. The greater interest of A 2A R blockade compared to A 1 R activation does not mean that A 1 R activation is irrelevant for a neuroprotective strategy. In fact, it is proposed that coupling A 2A R antagonists with strategies aimed at bursting the levels of extracellular adenosine (by inhibiting adenosine kinase) to activate A 1 Rs might constitute the more robust brain neuroprotective strategy based on the adenosine neuromodulatory system. This strategy should be useful in adult animals and especially in the elderly (where brain pathologies are prevalent) but is not valid for fetus or newborns where the impact of adenosine receptors on brain damage is different.Abbreviations: Ab -b-amyloid peptide; A 1 Rs -A 1 receptors; A 2A Rs -A 2A

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Section: Modification Of Adenosine Metabolism On Stressful Conditionssupporting

confidence: 67%

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Cunha

2005

Purinergic Signalling

482

432

View full text Add to dashboard Cite

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“…Also, the subtype of adenosine receptor (A 1 or A 2A ) eventually involved in schizophrenia remains undefined. The only postmortem study of adenosine receptors in schizophrenia reported an increase in striatal A 2A receptors [241,242], with no difference between patients on and off medication before death. Also, the A 2A receptor gene, located in the 22q12-13 region, is a candidate gene for susceptibility to schizophrenia [243][244][245].…”

Section: Adenosine a 2a Receptors And Schizophreniamentioning

confidence: 98%

Potential Therapeutic Interest of Adenosine A2A Receptors in Psychiatric Disorders

Cunha¹,

Ferré²,

Vaugeois³

et al. 2008

CPD

176

149

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The interest on targeting adenosine A 2A receptors in the realm of psychiatric diseases first arose based on its tight physical and functional interaction with dopamine D 2 receptors. However, the role of central A 2A receptors is now viewed as much broader than just controlling D 2 receptor function. Thus, there is currently a major interest in the ability of A 2A receptors to control synaptic plasticity at glutamatergic synapses. This is due to a combined ability of A 2A receptors to facilitate the release of glutamate and the activation of NMDA. Therefore, A 2A receptors are now conceived as a normalizing device promoting adequate adaptive responses in neuronal circuits, a role similar to that fulfilled, in essence, by dopamine. This makes A 2A receptors a particularly attractive target to manage psychiatric disorders since adenosine may act as go-between glutamate and dopamine, two of the key players in mood processing. Furthermore, A 2A receptors also control glia function and brain metabolic adaptation, two other emerging mechanisms to understand abnormal processing of mood, and A 2A receptors are an important player in controlling the demise of neurodegeneration, considered an amplificatory loop in psychiatric disorders. Current data only provide an indirect confirmation of this putative role of A 2A receptors, based on the effects of caffeine (an antagonist of both A 1 and A 2A receptors) in psychiatric disorders. However, the introduction of A 2A receptors in clinics as antiparkinsonian agents is hoped to bolster our knowledge on the role of A 2A receptors in mood disorders in the near future.

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“…Using a rat model of focal ischaemia, it has been demonstrated that increases in A 2A AR density may contribute to A 2A AR-mediated neuron death [11]. In addition, an increase in A 2A AR density and/or functionality has also been detected in psychiatric diseases such as schizophrenia [12] and bipolar disorders [13]: in these pathologies, alterations in A 2A AR parameters have been related to the chronic use of antipsychotic drugs, D 2 dopamine receptor (DR) antagonists [14][15][16], and also the functional crosstalk between the adenosine and dopamine systems.…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Receptor crosstalk: haloperidol treatment enhances A2A adenosine receptor functioning in a transfected cell model

Trincavelli

Cuboni

Dell’Osso

et al. 2010

Purinergic Signalling

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A 2A adenosine receptors are considered an excellent target for drug development in several neurological and psychiatric disorders. It is noteworthy that the responses evoked by A 2A adenosine receptors are regulated by D 2 dopamine receptor ligands. These two receptors are coexpressed at the level of the basal ganglia and interact to form functional heterodimers. In this context, possible changes in A 2A adenosine receptor functional responses caused by the chronic blockade/activation of D 2 dopamine receptors should be considered to optimise the therapeutic effectiveness of dopaminergic agents and to reduce any possible side effects. In the present paper, we investigated the regulation of A 2A adenosine receptors induced by antipsychotic drugs, commonly acting as D 2 dopamine receptor antagonists, in a cellular model co-expressing both A 2A and D 2 receptors. Our data suggest that the treatment of cells with the classical antipsychotic haloperidol increased both the affinity and responsiveness of the A 2A receptor and also affected the degree of A 2A -D 2 receptor heterodimerisation. In contrast, an atypical antipsychotic, clozapine, had no effect on A 2A adenosine receptor parameters, suggesting that the two classes of drugs have different effects on adenosinedopamine receptor interaction. Modifications to A 2A adenosine receptors may play a significant role in determining cerebral adenosine effects during the chronic administration of antipsychotics in psychiatric diseases and may account for the efficacy of A 2A adenosine receptor ligands in pathologies associated with dopaminergic system dysfunction.

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Up-regulation of striatal adenosine A2A receptors in schizophrenia

Cited by 57 publications

References 0 publications

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Potential Therapeutic Interest of Adenosine A2A Receptors in Psychiatric Disorders

Receptor crosstalk: haloperidol treatment enhances A2A adenosine receptor functioning in a transfected cell model

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