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Rodrigo Cunha "Does the neuroprotection afforded by adenosine A2A receptors involve a control of neuroinflammation?"

Abstract :


In recent years, epidemiological and animal studies have converged to conclude that the continuous consumption of moderate doses of caffeine affords decreases the incidence of some brain disorders, namely Parkinson's or Alzheimer's disease or depression.
Animal studies have shown that the effects of chronic caffeine consumption are mimicked by antagonists of adenosine A2A receptors (A2AR).
Adenosine is released in an activity-dependent manner and its receptors adjust synaptic properties to the intensity of synaptic recruitment; thus adenosine receptors, namely A2ARs, play a fine-tuning role in assisting synaptic plasticity and to sharpen salience of information in neuronal circuits.
In most pathological brain conditions, there is an early dysfunction of synapses coupled to a recruitment and activation of microglia. Interestingly, pathological conditions trigger an up-regulation and gain of function of A2AR in synapses, but also in glial cells. This paves the way for a double role of A2AR in controlling abnormal synaptic plasticity as well as microglia activation, both contributing for synaptotoxicity. A2AR also control the release of ATP, a major danger signal and an important activator of microglia. On-going work is addressing this emerging role of purines as candidates to mediate the communication between synapses and microglia in the early phases of neurodegenerative conditions. 

Selected publications

Enhanced role of adenosine A(2A) receptors in the modulation of LTP in the rat hippocampus upon ageing.
Costenla AR, Diógenes MJ, Canas PM, Rodrigues RJ, Nogueira C, Maroco J, Agostinho PM, Ribeiro JA, Cunha RA, de Mendonça A.
Eur J Neurosci. 2011 May 25. doi: 10.1111/j.1460-9568.2011.07719.x. [Epub ahead of print]
Chronic caffeine consumption prevents memory disturbance in different animal models of memory decline. Rodrigo A Cunha. Center for Neurosciences of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. J Alzheimers Dis 2010
Adenosine A2A receptors control neuroinflammation and consequent hippocampal neuronal dysfunction.
Rebola N, Simões AP, Canas PM, Tomé AR, Andrade GM, Barry CE, Agostinho PM, Lynch MA, Cunha RA.
J Neurochem. 2011 Apr;117(1):100-11. doi: 10.1111/j.1471-4159.2011.07178.x. Epub 2011 Feb 9.

Scientific focus :

Rodrigo A. Cunha did his PhD at the University of Lisbon with Alex Ribeiro and spent 2 pos-doctoral training periods at the Karolinska Institutet with Bertil Fredholm and at the University of Cambridge with Peter Richardson. He is now a Professor at the Faculty of Medicine of the University of Coimbra and currently serves as Director of the Department of Neuropharmacology of the Center for Neurosciences and Cell Biology. He heads the group 'Purines at CNC' composed by 5 staff PhD researchers, 1 technician, 5 pos-docs, 8 PhD students and sponsored mainly by US and Portuguese grants. The group focuses on the purine-based modulation systems in brain circuits, exploiting the neuroprotective potential of caffeine and has an h-factor of 34.

Christophe Mulle de l'IINS