Overview
Adequate brain function depends on a balanced excitatory and inhibitory transmission fine-tuned by modulation systems. Inspired by the impact of coffee, which bolsters attention, normalizes mood and increases healthspan on ageing with a striking ability to prevent the onset of different neurodegenerative disorders (Alzheimer’s, Parkinson’s diseases), the aim of the group is to study modulation systems operated by purines (adenosine and ATP), known to be targeted by caffeine, to interfere with the evolution of neurodegenerative diseases. We have identified adenosine A2A receptors (A2AR) as the main targets of caffeine to control of brain disorders, using a combination of pharmacological, genetic and opto-genetic tools. We have established that A2AR are necessary and sufficient to trigger symptoms in different animal models of Alzheimer’s or Parkinson’s diseases, depression, epilepsy or diabetic encephalopathy, through a combined ability to restore synaptic plasticity, control neuroinflammation and bolster the metabolic support by astrocytes.
We have in-house different transgenic mice and pharmacologically-induced models of brain disease, as well as a toolbox to interfere with A2AR (cell-specific transgenic mice and viral mediated systems to bolster or decrease A2AR function) and access to human brain tissue. We follow an holistic approach to scientific questions, integrating our expertise in: i) behavior studies assessing learning and memory, motor performance, mood alterations and fear processing; ii) stereotaxic brain surgery; iii) ex-vivo (brain slices) electrophysiological studies to assess the function of brain circuits (extracellular recordings) and ionic currents (patch-clamp); iv) imaging of functional (live cell Ca2+), morphological (histochemistry) and neurochemical alterations (receptor expression binding and trafficking), combining PCR, radioligands, FRET, proximity ligation assay and Western-blot techniques); v) subcellular fractionation of synaptosomes and gliosomes and use of cell cultures (neurons and astrocytes) to study neurotransmitters release and uptake.
The group has a track record of over 250 publications in high-impact factor journals with more than 12,000 citations and an h-factor of 62, based on numerous worldwide collaborations. The group has a large experience in post-graduate training (over 15 post-doc, 40 PhD and 25 Master students), with research funds obtained from American and European agencies and private corporations and pharma.
