Neuroscience and Disease

Brain development and Disease

Brain development


Neuronal migration

Purinergic receptors

Glutamate receptors

Research lines

Role of purinergic receptors in the migration of cortical projection neurons

Role of purinergic receptors in the tangential migration of cortical interneurons

P2Y1R-NMDAR-axonal degeneration as a common neurodegenerative mechanism in different neurodegenerative disorders

Role of purinergic receptors in epileptogenesis

Functional interaction between P2X and NMDA receptors


Brain development is achieved through a tightly controlled sequence of events from neurogenesis, cell migration, differentiation, neuritogenesis, to synapse formation and stabilization, in order to establish a normal neuronal network. The impairment of any of these critical stages of brain development can lead to long-term deleterious effects ranging from mild cognitive impairment, to severe neurological and psychiatric conditions. Moreover, several brain pathologies present developmental-like events in their aetiology, perhaps in an attempt to get a functional recover, but due to the inadequate context become deleterious. Hence, our group explores brain disorders from the perspective of brain development, either using the ground-breaking rationale of the existence of a reactivation of developmental-related mechanisms in brain pathogenesis or evaluating the long-term impact in adulthood of defects in neuronal migration and synaptogenesis during development. In this realm, we are particularly interested in the role of extracellular ATP, a proposed danger signal in the brain, and glutamate, the major excitatory neurotransmitter in the brain, and the interaction between these two receptor signalling systems both in brain development and disease. This is approached using a vast array of techniques from genomics and proteomics to electrophysiology, functional imaging, morphological and histological analysis, and behavior, using primary cell cultures, cell lines, explant cultures and small laboratory animals.


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Information about journal articles, updated at 05-12-2021, from platform CIÊNCIAVITAE.

Adenosine A2A Receptors Contribute to the Radial Migration of Cortical Projection Neurons through the Regulation of Neuronal Polarization and Axon Formation.

Rodrigues, Ricardo J., 2021. Cerebral cortex (New York, N.Y. : 1991). 2021. . 10.1093/cercor/bhab188 . Cerebral cortex (New York, N.Y. : 1991)

Neurogenesis and Gliogenesis: Relevance of Adenosine for Neuroregeneration in Brain Disorders

Joana M. Mateus; Filipa F. Ribeiro; Marta Alonso-Gomes; Rui S. Rodrigues; Joana M. Marques; Ana M. Sebastião; Ricardo J. Rodrigues; Sara Xapelli, 2019. Journal of Caffeine and Adenosine Research. 129 - 144. 4. 9. 2019. . 10.1089/caff.2019.0010 . Journal of Caffeine and Adenosine Research

Purinergic signalling and brain development.

Rodrigues RJ; Marques JM; Cunha RA, 2018. Seminars in cell & developmental biology. 2018. . 10.1016/j.semcdb.2018.12.001 . Seminars in cell & developmental biology

Glutamate-induced and NMDA receptor-mediated neurodegeneration entails P2Y1 receptor activation

Simões, A.P.; Silva, C.G.; Marques, J.M.; Pochmann, D.; Porciúncula, L.O.; Ferreira, S.; Oses, J.P.; et al, 2018. Cell Death and Disease. 3. 9. 2018. . 10.1038/s41419-018-0351-1 . Cell Death and Disease

P2 receptors control the migration of medial ganglionic eminence-derived interneurons

Ferreira, S.; Marques, J. M.; Alcada-Morais, S.; Leyva-Diaz, E.; Lopez-Bendito, G.; Cunha, R. A.; Rodrigues, R. J., 2017. Journal of Neurochemistry. 2017. . Journal of Neurochemistry

Antimicrobial peptide-gold nanoscale therapeutic formulation with high skin regenerative potential

Comune, M.; Rai, A.; Chereddy, K.K.; Pinto, S.; Aday, S.; Ferreira, A.F.; Zonari, A.; et al, 2017. Journal of Controlled Release. 58 - 71. 262. 2017. . 10.1016/j.jconrel.2017.07.007 . Journal of Controlled Release

Presynaptic P2X1-3 and a3-containing nicotinic receptors assemble into functionally interacting ion channels in the rat hippocampus

Rodrigues, R.J.; Almeida, T.; Díaz-Hernández, M.; Marques, J.M.; Franco, R.; Solsona, C.; Miras-Portugal, M.T.; Ciruela, F.; Cunha, R.A., 2016. Neuropharmacology. 241 - 257. 105. 2016. . 10.1016/j.neuropharm.2016.01.022 . Neuropharmacology

Stimulation of brain glucose uptake by cannabinoid CB<inf>2</inf> receptors and its therapeutic potential in Alzheimer's disease

Köfalvi, A.; Lemos, C.; Martín-Moreno, A.M.; Pinheiro, B.S.; García-García, L.; Pozo, M.A.; Valério-Fernandes, Â.; et al, 2016. Neuropharmacology. 519 - 529. 110. 2016. . 10.1016/j.neuropharm.2016.03.015 . Neuropharmacology

High sucrose consumption induces memory impairment in rats associated with electrophysiological modifications but not with metabolic changes in the hippocampus

Lemos, C.; Rial, D.; Gonçalves, F.Q.; Pires, J.; Silva, H.B.; Matheus, F.C.; da Silva, A.C.; et al, 2016. Neuroscience. 196 - 205. 315. 2016. . 10.1016/j.neuroscience.2015.12.018 . Neuroscience

Hierarchical glucocorticoid-endocannabinoid interplay regulates the activation of the nucleus accumbens by insulin

Pinheiro, B.S.; Lemos, C.; Neutzling Kaufmann, F.; Marques, J.M.; da Silva-Santos, C.S.; Carvalho, E.; Mackie, K.; et al, 2016. Brain Research Bulletin. 222 - 230. 124. 2016. . 10.1016/j.brainresbull.2016.05.009 . Brain Research Bulletin

Presynaptic adenosine a2A receptors dampen cannabinoid CB1 receptor-mediated inhibition of corticostriatal glutamatergic transmission

Ferreira, S.G.; Gonc¸alves, F.Q.; Marques, J.M.; Tomé, Â.R.; Rodrigues, R.J.; Nunes-Correia, I.; Ledent, C.; et al, 2015. British Journal of Pharmacology. 1074 - 1086. 4. 172. 2015. . 10.1111/bph.12970 . British Journal of Pharmacology

Adenosine A<inf>2b</inf> receptors control A<inf>1</inf> receptor-mediated inhibition of synaptic transmission in the mouse hippocampus

Gonçalves, F.Q.; Pires, J.; Pliassova, A.; Beleza, R.; Lemos, C.; Marques, J.M.; Rodrigues, R.J.; et al, 2015. European Journal of Neuroscience. 876 - 886. 7. 41. 2015. . 10.1111/ejn.12851 . European Journal of Neuroscience

Adenosine A<inf>2B</inf> receptor activation stimulates glucose uptake in the mouse forebrain

Lemos, C.; Pinheiro, B.S.; Beleza, R.O.; Marques, J.M.; Rodrigues, R.J.; Cunha, R.A.; Rial, D.; Köfalvi, A., 2015. Purinergic Signalling. 561 - 569. 4. 11. 2015. . 10.1007/s11302-015-9474-3 . Purinergic Signalling

ATP as a multi-target danger signal in the brain

Rodrigues, R.J.; Tomé, A.R.; Cunha, R.A., 2015. Frontiers in Neuroscience. APR. 9. 2015. . 10.3389/fnins.2015.00148 . Frontiers in Neuroscience

Predominant loss of glutamatergic terminal markers in a ß-amyloid peptide model of Alzheimer's disease

Canas, P.M.; Simões, A.P.; Rodrigues, R.J.; Cunha, R.A., 2014. Neuropharmacology. 51 - 56. PART A. 76. 2014. . 10.1016/j.neuropharm.2013.08.026 . Neuropharmacology

Synaptic and glia involvement in the purinergic control of neurodegenerative diseases

Canas, Paula M.; Rial, Daniel; Simoes, Ana Patricia; Lopes, Joao Pedro; Silva, Henrique B.; Machado, Nuno J.; Queiroz, Francisco; et al, 2014. Purinergic Signalling. 2014. . Purinergic Signalling

CRMP2 tethers kainate receptor activity to cytoskeleton dynamics during neuronal maturation

Marques, J.M.; Rodrigues, R.J.; Valbuena, S.; Rozas, J.L.; Selak, S.; Marin, P.; Aller, M.I.; Lerma, J., 2013. Journal of Neuroscience. 18298 - 18310. 46. 33. 2013. . 10.1523/JNEUROSCI.3136-13.2013 . Journal of Neuroscience

Metabotropic signaling by kainate receptors

Rodrigues, R.J.; Lerma, J., 2012. Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. 399 - 410. 4. 1. 2012. . 10.1002/wmts.35 . Wiley Interdisciplinary Reviews: Membrane Transport and Signaling

Enhanced role of adenosine A 2A receptors in the modulation of LTP in the rat hippocampus upon ageing

Costenla, A.R.; Diógenes, M.J.; Canas, P.M.; Rodrigues, R.J.; Nogueira, C.; Maroco, J.; Agostinho, P.M.; et al, 2011. European Journal of Neuroscience. 12 - 21. 1. 34. 2011. . 10.1111/j.1460-9568.2011.07719.x . European Journal of Neuroscience

Modification upon aging of the density of presynaptic modulation systems in the hippocampus

Canas, P.M.; Duarte, J.M.N.; Rodrigues, R.J.; Köfalvi, A.; Cunha, R.A., 2009. Neurobiology of Aging. 1877 - 1884. 11. 30. 2009. . 10.1016/j.neurobiolaging.2008.01.003 . Neurobiology of Aging


Cunha, Rodrigo A.; Almeida, Teresa; Rodrigues, Ricardo J.; Diaz-Hernandez, Miguel; Aleu, Jordi; Franco, Rafael; Solsona, Carles; Miras-Portugal, Maria-Teresa; Ciruela, Francisco, 2009. Journal of Physiological Sciences. 2009. . Journal of Physiological Sciences

GABA release by basket cells onto Purkinje cells, in rat cerebellar slices, is directly controlled by presynaptic purinergic receptors, modulating Ca2+ influx

Donato, R.; Rodrigues, R.J.; Takahashi, M.; Tsai, M.C.; Soto, D.; Miyagi, K.; Villafuertes, R.G.; Cunha, R.A.; Edwards, F.A., 2008. Cell Calcium. 521 - 532. 6. 44. 2008. . 10.1016/j.ceca.2008.03.006 . Cell Calcium

Modification of adenosine modulation of acetylcholine release in the hippocampus of aged rats

Rodrigues, R.J.; Canas, P.M.; Lopes, L.V.; Oliveira, C.R.; Cunha, R.A., 2008. Neurobiology of Aging. 1597 - 1601. 10. 29. 2008. . 10.1016/j.neurobiolaging.2007.03.025 . Neurobiology of Aging

Electrophysiological and immunocytochemical evidence for P2X purinergic receptors in pancreatic ß cells

Silva, A.M.; Rodrigues, R.J.; Tomé, Â.R.; Cunha, R.A.; Misler, S.; Rosário, L.M.; Santos, R.M., 2008. Pancreas. 279 - 283. 3. 36. 2008. . 10.1097/MPA.0b013e31815a8473 . Pancreas

Anandamide and NADA bi-directionally modulate presynaptic Ca 2+ levels and transmitter release in the hippocampus

Köfalvi, A.; Pereira, M.F.; Rebola, N.; Rodrigues, R.J.; Oliveira, C.R.; Cunha, R.A., 2007. British Journal of Pharmacology. 551 - 563. 4. 151. 2007. . 10.1038/sj.bjp.0707252 . British Journal of Pharmacology

Modification of purinergic signaling in the hippocampus of streptozotocin-induced diabetic rats

Duarte, J.M.N.; Oses, J.P.; Rodrigues, R.J.; Cunha, R.A., 2007. Neuroscience. 382 - 391. 2. 149. 2007. . 10.1016/j.neuroscience.2007.08.005 . Neuroscience

Differential glutamate-dependent and glutamate-independent adenosine A 1 receptor-mediated modulation of dopamine release in different striatal compartments

Borycz, J.; Pereira, M.F.; Melani, A.; Rodrigues, R.J.; Köfalvi, A.; Panlilio, L.; Pedata, F.; et al, 2007. Journal of Neurochemistry. 355 - 363. 2. 101. 2007. . 10.1111/j.1471-4159.2006.04386.x . Journal of Neurochemistry

Saccharomyces cerevisiae Hog1 protein phosphorylation upon exposure to bacterial endotoxin

Marques, J.M.; Rodrigues, R.J.; De Magalhães-Sant'Ana, A.C.; Gonçalves, T., 2006. Journal of Biological Chemistry. 24687 - 24694. 34. 281. 2006. . 10.1074/jbc.M603753200 . Journal of Biological Chemistry

Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers

Ciruela, F.; Casadó, V.; Rodrigues, R.J.; Luján, R.; Burgueño, J.; Canals, M.; Borycz, J.; et al, 2006. Journal of Neuroscience. 2080 - 2087. 7. 26. 2006. . 10.1523/JNEUROSCI.3574-05.2006 . Journal of Neuroscience

Interaction between P2X and nicotinic acetylcholine receptors in glutamate nerve terminals of the rat hippocampus

Rodrigues, R.J.; Almeida, T.; De Mendonça, A.; Cunha, R.A., 2006. Journal of Molecular Neuroscience. 173 - 176. 1-2. 30. 2006. . 10.1385/JMN:30:1:173 . Journal of Molecular Neuroscience

CB1 receptor antagonism increases hippocampal acetylcholine release: Site and mechanism of action

Degroot, A.; Köfalvi, A.; Wade, M.R.; Davis, R.J.; Rodrigues, R.J.; Rebola, N.; Cunha, R.A.; Nomikos, G.G., 2006. Molecular Pharmacology. 1236 - 1245. 4. 70. 2006. . 10.1124/mol.106.024661 . Molecular Pharmacology

TrkB receptors modulation of glutamate release is limited to a subset of nerve terminals in the adult rat hippocampus

Pereira, D.B.; Rebola, N.; Rodrigues, R.J.; Cunha, R.A.; Carvalho, A.P.; Duarte, C.B., 2006. Journal of Neuroscience Research. 832 - 844. 5. 83. 2006. . 10.1002/jnr.20784 . Journal of Neuroscience Research

Adenosine A1 and A2A receptors are co-expressed in pyramidal neurons and co-localized in glutamatergic nerve terminals of the rat hippocampus

Rebola, N.; Rodrigues, R.J.; Lopes, L.V.; Richardson, P.J.; Oliveira, C.R.; Cunha, R.A., 2005. Neuroscience. 79 - 83. 1. 133. 2005. . 10.1016/j.neuroscience.2005.01.054 . Neuroscience

Co-localization and functional interaction between adenosine A2A and metabotropic group 5 receptors in glutamatergic nerve terminals of the rat striatum

Rodrigues, R.J.; Alfaro, T.M.; Rebola, N.; Oliveira, C.R.; Cunha, R.A., 2005. Journal of Neurochemistry. 433 - 441. 3. 92. 2005. . 10.1111/j.1471-4159.2004.02887.x . Journal of Neurochemistry

Dual presynaptic control by ATP of glutamate release via facilitatory P2X1, P2X2/3, and P2X3 and inhibitory P2Y 1, P2Y2, and/or P2Y4 receptors in the rat hippocampus

Rodrigues, R.J.; Almeida, T.; Richardson, P.J.; Oliveira, C.R.; Cunha, R.A., 2005. Journal of Neuroscience. 6286 - 6295. 27. 25. 2005. . 10.1523/JNEUROSCI.0628-05.2005 . Journal of Neuroscience

Involvement of cannabinoid receptors in the regulation of neurotransmitter release in the rodent striatum: A combined immunochemical and pharmacological analysis

Köfalvi, A.; Rodrigues, R.J.; Ledent, C.; Mackie, K.; Vizi, E.S.; Cunha, R.A.; Sperlágh, B., 2005. Journal of Neuroscience. 2874 - 2884. 11. 25. 2005. . 10.1523/JNEUROSCI.4232-04.2005 . Journal of Neuroscience

Presynaptic kainate receptors are localized close to release sites in rat hippocampal synapses

Pinheiro, P.S.; Rodrigues, R.J.; Rebola, N.; Xapelli, S.; Oliveira, C.R.; Malva, J.O., 2005. Neurochemistry International. 309 - 316. 5. 47. 2005. . 10.1016/j.neuint.2005.05.007 . Neurochemistry International

Different roles of adenosine A1, A2A and A 3 receptors in controlling kainate-induced toxicity in cortical cultured neurons

Rebola, N.; Rodrigues, R.J.; Oliveira, C.R.; Cunha, R.A., 2005. Neurochemistry International. 317 - 325. 5. 47. 2005. . 10.1016/j.neuint.2005.05.009 . Neurochemistry International

Purinergic control of GABA release

Donato, R; Rodrigues, RJ; Cunha, R; Edwards, FA, 2005. Journal of Neurochemistry. 2005. . Journal of Neurochemistry

Comparative immunochemical and pharmacological investigation of the functional CB1 receptors in the Rodent striatum

Koefalvi, A.; Rodrigues, R. J.; Cunha, R. A.; Ledent, C.; Vizi, E. S.; Sperlagh, B., 2004. Fundamental & Clinical Pharmacology. 2004. . Fundamental & Clinical Pharmacology

Release and neuromodulatory role of ATP in hippocampal synapses

Rodrigues, R. J.; Oliveira, C. R.; Cunha, R. A., 2004. Fundamental & Clinical Pharmacology. 2004. . Fundamental & Clinical Pharmacology

Solubilization and immunological identification of presynaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in the rat hippocampus

Pinheiro, P.S.; Rodrigues, R.J.; Silva, A.P.; Cunha, R.A.; Oliveira, C.R.; Malva, J.O., 2003. Neuroscience Letters. 97 - 100. 2. 336. 2003. . 10.1016/S0304-3940(02)01217-X . Neuroscience Letters

Purinergic P2 receptors trigger adenosine release leading to adenosine A2A receptor activation and facilitation of long-term potentiation in rat hippocampal slices

Almeida, T.; Rodrigues, R.J.; De Mendonça, A.; Ribeiro, J.A.; Cunha, R.A., 2003. Neuroscience. 111 - 121. 1. 122. 2003. . 10.1016/S0306-4522(03)00523-2 . Neuroscience



Best paper in Cellular and Molecular Neurobiology section by the Portuguese Society for Neuroscience, Portugal.

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