Neuroscience and Disease

Neuromodulation and Metabolism






Research lines

Changes in Neuromodulation of Corticostriatal Terminals in a Rat Model of Willis-Ekbom Disease

Investigating the role of Adenosine A2ARs in Brain Glucoregulation

The Novel Endocannabinoid Receptor, GPR55 Stimulates Glycolysis in Astrocytes

Fed-State-Dependent Modulation of Hippocampal Synaptic Plasticity by Insulin


Brain glucose metabolism is tightly coupled to neural activity. My lab investigates how modulators of neural activity regulate cerebral energy metabolism. The neuromodulators we are currently interested in and show promising therapeutic potential are adenosine, endocannabinoids and insulin-like peptides. Why is this research important? All neurological and psychiatric disorders are linked with persistent changes in glucose metabolism in very specific regions in the human brain. 18F-deoxyglucose and functional MRI imaging help neurologists detect these alterations. These metabolic dysregulations often precede the loss of brain cells by years. Hence, understanding the selective early markers of brain disorders can help the physicians to categorize the illness and select the appropriate treatments as early as possible. Many times, early recognition of the disease and swift decision on the treatment make the difference. Hence, we also would like to know if the restoration of the impaired brain glucoregulation could improve the outcome of the given brain disease, or even, prevent the onset of it. We are studying basic signalling systems, both in vitro and in vivo in animal models with the future aim of re-testing the promising ideas in humans. We mostly use neurochemistry, flow citometry, microscopy, electrophysiology in brain slices and cell cultures and in vivo behaviour in rodent disease models.


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Information about journal articles, updated at 28-05-2023, from platform CIÊNCIAVITAE.

Brain Iron Deficiency Changes the Stoichiometry of Adenosine Receptor Subtypes in Cortico-Striatal Terminals: Implications for Restless Legs Syndrome

Matilde S. Rodrigues; Samira G. Ferreira; César Quiroz; Christopher J. Earley; Diego García-Borreguero; Rodrigo A. Cunha; Francisco Ciruela; Attila Köfalvi; Sergi Ferré, 2022. Molecules. 2022. . 10.3390/molecules27051489 . Molecules

Diabetes and Cannabinoid CB1 receptor deficiency promote similar early onset aging-like changes in the skin.

Leal, EC; Moura, LI; Pirzgalska, RM; Dorinda Marques-da-Silva; Catherine Ledent; Attila Köfalvi; Carvalho, Eugenia, 2021. Experimental gerontology. 154. 2021. . 10.1016/j.exger.2021.111528 . published Experimental gerontology

Transient gain of function of cannabinoid CB1 receptors in the control of frontocortical glucose consumption in a rat model of Type-1 diabetes

Pedro, Joana Reis; Moura, Liane I.F.; Valério-Fernandes, Ângela; Baptista, Filipa I.; Gaspar, Joana M.; Pinheiro, Bárbara S.; Lemos, Cristina; et al, 2020. Brain Research Bulletin. 106 - 115. 161. 2020. . 10.1016/j.brainresbull.2020.05.004 . Brain Research Bulletin

An optimized spectrophotometric assay reveals increased activity of enzymes involved in 2-arachidonoyl glycerol turnover in the cerebral cortex of a rat model of Alzheimer’s disease

Rodrigues, Matilde S.; Ferreira, Cláudia; Dias, Cândida; Pliássova, Anna; Souza, Lisiane; Ledo, Ana; Laranjinha, João; Cunha, Rodrigo A.; Köfalvi, Attila, 2020. European Journal of Neuroscience. 2020. . 10.1111/ejn.14944 . European Journal of Neuroscience

The Yin and Yang of Adenosine Receptors: A Piquant Story

Köfalvi, Attila, 2020. Journal of Caffeine and Adenosine Research. 2020. . 10.1089/caff.2020.0004 . Journal of Caffeine and Adenosine Research

Control of glutamate release by complexes of adenosine and cannabinoid receptors

Köfalvi, Attila; Moreno, Estefanía; Cordomí, Arnau; Cai, Ning-Sheng; Fernández-Dueñas, Victor; Ferreira, Samira G.; Guixà-González, Ramón; et al, 2020. BMC Biology. 1. 18. 2020. . 10.1186/s12915-020-0739-0 . BMC Biology

Chronic insulinopenia/hyperglycemia decreases cannabinoid CB1 receptor density and impairs glucose uptake in the mouse forebrain

Moura, Liane I.F.; Lemos, Cristina; Ledent, Catherine; Carvalho, Eugénia; Köfalvi, Attila, 2019. Brain Research Bulletin. 101 - 109. 147. 2019. . 10.1016/j.brainresbull.2019.01.024 . Brain Research Bulletin

Memory deficits induced by chronic cannabinoid exposure are prevented by adenosine A2AR receptor antagonism

Mouro, Francisco M.; Köfalvi, Attila; André, Luís A.; Baqi, Younis; Müller, Christa E.; Ribeiro, Joaquim A.; Sebastião, Ana M., 2019. Neuropharmacology. 10 - 21. 155. 2019. . 10.1016/j.neuropharm.2019.05.003 . Neuropharmacology

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

Simões AP; Silva CG; Marques JM; Pochmann D; Porciúncula LO; Ferreira S; Oses JP; et al, 2018. Cell death & disease. 2018. . 10.1038/s41419-018-0351-1 . Cell death & disease

Adenosine A2A Receptors in the Rat Prelimbic Medial Prefrontal Cortex Control Delay-Based Cost-Benefit Decision Making

Douglas T. Leffa; Pablo Pandolfo; Nélio Gonçalves; Nuno J. Machado; Carolina M. de Souza; Joana I. Real; António C. Silva; et al, 2018. Frontiers in Molecular Neuroscience. 11. 2018. . 10.3389/fnmol.2018.00475 . Frontiers in Molecular Neuroscience

Neuronal Adenosine A2A Receptors Are Critical Mediators of Neurodegeneration Triggered by Convulsions

Paula M. Canas; Lisiane O. Porciúncula; Ana Patrícia Simões; Elisabete Augusto; Henrique B. Silva; Nuno J. Machado; Nélio Gonçalves; et al, 2018. eneuro. ENEURO.0385 - 18.2018. 6. 5. 2018. . 10.1523/eneuro.0385-18.2018 . eneuro

Boosting brain glucose metabolism to fight neurodegeneration?

de Ceballos ML; Köfalvi A, 2017. 2017. . 10.18632/oncotarget.15131 .

Cannabis: A Treasure Trove or Pandora's Box?

Katalin Solymosi; Köfalvi, Attila, 2017. Mini-Reviews in Medicinal Chemistry. 13. 17. 2017. . 10.2174/1389557516666161004162133 . Mini-Reviews in Medicinal Chemistry

Stimulation of brain glucose uptake by cannabinoid CB2 receptors and its therapeutic potential in Alzheimer's disease

Attila Köfalvi; Cristina Lemos; Ana M. Martín-Moreno; Bárbara S. Pinheiro; Luis García-García; Miguel A. Pozo; Ângela Valério-Fernandes; et al, 2016. Neuropharmacology. 519 - 529. 110. 2016. . 10.1016/j.neuropharm.2016.03.015 . Neuropharmacology

Methamphetamine Induces Anhedonic-Like Behavior and Impairs Frontal Cortical Energetics in Mice.

Fonseca R; Carvalho RA; Lemos C; Sequeira AC; Pita IR; Carvalho F; Silva CD; et al, 2016. 2016. . 10.1111/cns.12649 .

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

Bárbara S. Pinheiro; Cristina Lemos; Fernanda Neutzling Kaufmann; Joana M. Marques; Carla S. da Silva-Santos; Eugénia Carvalho; Ken Mackie; et al, 2016. Brain Research Bulletin. 222 - 230. 124. 2016. . 10.1016/j.brainresbull.2016.05.009 . Brain Research Bulletin

Caffeine Reverts Memory But Not Mood Impairment in a Depression-Prone Mouse Strain with Up-Regulated Adenosine A2A Receptor in Hippocampal Glutamate Synapses

Nuno J. Machado; Ana Patrícia Simões; Henrique B. Silva; Ana Paula Ardais; Manuella P. Kaster; Pedro Garção; Diana I. Rodrigues; et al, 2016. Molecular Neurobiology. 1552 - 1563. 2. 54. 2016. . 10.1007/s12035-016-9774-9 . Molecular Neurobiology

Adenosine A2B receptor activation stimulates glucose uptake in the mouse forebrain

Lemos, Cristina; Pinheiro, Bárbara S.; Beleza, Rui O.; Marques, Joana M.; Rodrigues, Ricardo J.; Cunha, Rodrigo A.; Rial, Daniel; Köfalvi, Attila, 2015. Purinergic Signalling. 561 - 569. 4. 11. 2015. . 10.1007/s11302-015-9474-3 . Purinergic Signalling

Ketone bodies effectively compete with glucose for neuronal acetyl-CoA generation in rat hippocampal slices

Paula Valente-Silva; Cristina Lemos; Attila Köfalvi; Rodrigo A. Cunha; John G. Jones, 2015. NMR Biomed.. 1111 - 1116. 9. 28. 2015. . 10.1002/nbm.3355 . NMR Biomed.

Lack of presynaptic interaction between glucocorticoid and CB1 cannabinoid receptors in GABA- and glutamatergic terminals in the frontal cortex of laboratory rodents

Rafael M. Bitencourt; Alán Alpár; Valentina Cinquina; Samira G. Ferreira; Bárbara S. Pinheiro; Cristina Lemos; Catherine Ledent; et al, 2015. Neurochemistry International. 2015. . 10.1016/j.neuint.2015.07.014 . Neurochemistry International

Adenosine A2b receptors control A1 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. 2015. . 10.1111/ejn.12851 . European Journal of Neuroscience

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

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

Behavioral Phenotyping of Parkin-Deficient Mice: Looking for Early Preclinical Features of Parkinson's Disease

Rial, Daniel; Castro, Adalberto A.; Machado, Nuno; Garção, Pedro; Gonçalves, Francisco Q.; Silva, Henrique B.; Tomé, Ângelo R.; et al, 2014. PLoS ONE. 12. 9. 2014. . 10.1371/journal.pone.0114216 . PLoS ONE

Functional interaction between pre-synaptic a6ß2-containing nicotinic and adenosine A2A receptors in the control of dopamine release in the rat striatum

Garção, P.; Szabõ, E.C.; Wopereis, S.; Castro, A.A.; Tomé, A.R.; Prediger, R.D.; Cunha, R.A.; Agostinho, P.; Köfalvi, A., 2013. British Journal of Pharmacology. 1600 - 1611. 7. 169. 2013. . 10.1111/bph.12234 . British Journal of Pharmacology

Presynaptic TRPV1 vanilloid receptor function is age- but not CB1 cannabinoid receptor-dependent in the rodent forebrain

Köles, L.; Garção, P.; Zádori, Z.S.; Ferreira, S.G.; Pinheiro, B.S.; da Silva-Santos, C.S.; Ledent, C.; Köfalvi, A., 2013. Brain Research Bulletin. 126 - 135. 97. 2013. . 10.1016/j.brainresbull.2013.06.007 . Brain Research Bulletin

Caffeine regulates frontocorticostriatal dopamine transporter density and improves attention and cognitive deficits in an animal model of attention deficit hyperactivity disorder

Pandolfo, P.; Machado, N.J.; Köfalvi, A.; Takahashi, R.N.; Cunha, R.A., 2013. European Neuropsychopharmacology. 317 - 328. 4. 23. 2013. . 10.1016/j.euroneuro.2012.04.011 . European Neuropsychopharmacology

CB 1 receptor activation inhibits neuronal and astrocytic intermediary metabolism in the rat hippocampus

Duarte, J.M.N.; Ferreira, S.G.; Carvalho, R.A.; Cunha, R.A.; Köfalvi, A., 2012. Neurochemistry International. 1 - 8. 1. 60. 2012. . 10.1016/j.neuint.2011.10.019 . Neurochemistry International

Impaired hippocampal glucoregulation in the cannabinoid CB 1 receptor knockout mice as revealed by an optimized in vitro experimental approach

Lemos, C.; Valério-Fernandes, Â.; Ghisleni, G.C.; Ferreira, S.G.; Ledent, C.; de Ceballos, M.L.; Köfalvi, A., 2012. Journal of Neuroscience Methods. 366 - 373. 2. 204. 2012. . 10.1016/j.jneumeth.2011.11.028 . Journal of Neuroscience Methods

Presynaptic CB1 cannabinoid receptors control frontocortical serotonin and glutamate release - Species differences

Ferreira, S.G.; Teixeira, F.M.; Garção, P.; Agostinho, P.; Ledent, C.; Cortes, L.; MacKie, K.; Köfalvi, A., 2012. Neurochemistry International. 219 - 226. 2. 61. 2012. . 10.1016/j.neuint.2012.05.009 . Neurochemistry International

Presynaptic a2-adrenoceptors control the inhibitory action of presynaptic CB1 cannabinoid receptors on prefrontocortical norepinephrine release in the rat

Richter, H.; Teixeira, F.M.; Ferreira, S.G.; Kittel, Á.; Köfalvi, A.; Sperlágh, B., 2012. Neuropharmacology. 784 - 797. 5. 63. 2012. . 10.1016/j.neuropharm.2012.06.003 . Neuropharmacology

Pre-synaptic adenosine A2A receptors control cannabinoid CB 1 receptor-mediated inhibition of striatal glutamatergic neurotransmission

Martire, A.; Tebano, M.T.; Chiodi, V.; Ferreira, S.G.; Cunha, R.A.; Köfalvi, A.; Popoli, P., 2011. Journal of Neurochemistry. 273 - 280. 2. 116. 2011. . 10.1111/j.1471-4159.2010.07101.x . Journal of Neurochemistry

Diabetes induces early transient changes in the content of vesicular transporters and no major effects in neurotransmitter release in hippocampus and retina

Baptista, F.I.; Gaspar, J.M.; Cristóvão, A.; Santos, P.F.; Köfalvi, A.; Ambrósio, A.F., 2011. Brain Research. 257 - 269. 1383. 2011. . 10.1016/j.brainres.2011.01.071 . Brain Research

Functional Identification of Cell Phenotypes Differentiating from Mice Retinal Neurospheres Using Single Cell Calcium Imaging

De Melo Reis, R.A.; Schitine, C.S.; Köfalvi, A.; Grade, S.; Cortes, L.; Gardino, P.F.; Malva, J.O.; de Mello, F.G., 2011. Cellular and Molecular Neurobiology. 1 - 12. 2011. . 10.1007/s10571-011-9673-6 . Cellular and Molecular Neurobiology

Molecular reorganization of endocannabinoid signalling in Alzheimer's disease

Mulder, J.; Zilberter, M.; Pasquaré, S.J.; Alpár, A.; Schulte, G.; Ferreira, S.G.; Köfalvi, A.; et al, 2011. Brain. 1041 - 1060. 4. 134. 2011. . 10.1093/brain/awr046 . Brain

Cannabinoids inhibit the synaptic uptake of adenosine and dopamine in the rat and mouse striatum

Pandolfo, Pablo; Silveirinha, Vasco; Santos-Rodrigues, Alexandre dos; Venance, Laurent; Ledent, Catherine; Takahashi, Reinaldo N.; Cunha, Rodrigo A.; Köfalvi, Attila, 2011. European Journal of Pharmacology. 38 - 45. 1-3. 655. 2011. . 10.1016/j.ejphar.2011.01.013 . European Journal of Pharmacology

Synthetic cannabinoids inhibit the dopamine transporter whereby increasing stimulated presynaptic net dopamine release in the rat striatum

Attila, Kofalvi, 2009. Frontiers in Neuroscience. 3. 2009. . 10.3389/conf.neuro.01.2009.11.128 . Frontiers in 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

N-acyldopamines control striatal input terminals via novel ligand-gated cation channels

Ferreira, S.G.; Lomaglio, T.; Avelino, A.; Cruz, F.; Oliveira, C.R.; Cunha, R.A.; Köfalvi, A., 2009. Neuropharmacology. 676 - 683. 3. 56. 2009. . 10.1016/j.neuropharm.2008.12.001 . Neuropharmacology

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

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

Increase of cannabinoid CB1 receptor density in the hippocampus of streptozotocin-induced diabetic rats

Duarte, J.M.N.; Nogueira, C.; Mackie, K.; Oliveira, C.R.; Cunha, R.A.; Köfalvi, A., 2007. Experimental Neurology. 479 - 484. 1. 204. 2007. . 10.1016/j.expneurol.2006.11.013 . Experimental Neurology

Regulation of neurotransmitter release by presynaptic P2X receptors

Sperlágh, B.; Köfalvi, A.; Papp, L.; Balázsa, T.; Heinrich, A.; Vizi, E.S., 2006. Autonomic and Autacoid Pharmacology. 1. 26. 2006. . Autonomic and Autacoid Pharmacology

Lack of evidence for functional TRPV1 vanilloid receptors in rat hippocampal nerve terminals

Köfalvi, A.; Oliveira, C.R.; Cunha, R.A., 2006. Neuroscience Letters. 151 - 156. 1-2. 403. 2006. . 10.1016/j.neulet.2006.04.030 . Neuroscience Letters

Erratum: Presynaptically Located CB1 Cannabinoid Receptors Regulate GABA Release from Axon Terminals of Specific Hippocampal Interneurons (Journal of Neuroscience (June 1, 1999) (4544-4558))

Katona, I.; Sperlágh, B.; Sík, A.; Köfalvi, A.; Vizi, E.S.; Mackie, K.; Freund, T.F., 2006. Journal of Neuroscience. 47. 26. 2006. . Journal of 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

Supersensitivity of P2X7 receptors in cerebrocortical cell cultures after in vitro ischemia

Wirkner, K.; Köfalvi, A.; Fischer, W.; Günther, A.; Franke, H.; Gröger-Arndt, H.; Nörenberg, W.; et al, 2005. Journal of Neurochemistry. 1421 - 1437. 5. 95. 2005. . 10.1111/j.1471-4159.2005.03465.x . Journal of Neurochemistry

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

P2X receptor activation elicits transporter-mediated noradrenaline release from rat hippocampal slices

Papp, L.; Balázsa, T.; Köfalvi, A.; Erdélyi, F.; Szabó, G.; Vizi, E.S.; Sperlágh, B., 2004. Journal of Pharmacology and Experimental Therapeutics. 973 - 980. 3. 310. 2004. . 10.1124/jpet.104.066712 . Journal of Pharmacology and Experimental Therapeutics

Cannabinoids inhibit the release of [3H]glutamate from rodent hippocampal synaptosomes via a novel CB1 receptor-independent action

Köfalvi, A.; Vizi, E.S.; Ledent, C.; Sperlágh, B., 2003. European Journal of Neuroscience. 1973 - 1978. 7. 18. 2003. . 10.1046/j.1460-9568.2003.02897.x . European Journal of Neuroscience

Involvement of P2X7 receptors in the regulation of neurotransmitter release in the rat hippocampus

Sperlágh, Beáta; Köfalvi, Attila; Deuchars, Jim; Atkinson, Lucy; J. Milligan, Carol; Buckley, Noel J.; Vizi, E. Sylvester, 2002. Journal of Neurochemistry. 1196 - 1211. 6. 81. 2002. . 10.1046/j.1471-4159.2002.00920.x . Journal of Neurochemistry

Distinct mechanisms underlying a1-adrenoceptor and P2x purinoceptor operated ATP release and contraction in the guinea-pig vas deferens

Sperlágh, B.; Illes, P.; Gerevich, Z.; Köfalvi, A., 2001. Neurochemical Research. 951 - 957. 8-9. 26. 2001. . 10.1023/A:1012336601854 . Neurochemical Research

Excessive release of [3H]noradrenaline by veratridine and ischemia in spinal cord

Sumiya, Y.; Torigoe, K.; Gerevich, Z.; Köfalvi, A.; Vizi, E.S., 2001. Neurochemistry International. 59 - 63. 1. 39. 2001. . 10.1016/S0197-0186(00)00124-8 . Neurochemistry International

GABAergic interneurons are the targets of cannabinoid actions in the human hippocampus

Katona, I.; Sperlágh, B.; Maglóczky, Z.; Sántha, E.; Köfalvi, A.; Czirják, S.; Mackie, K.; Vizi, E.S.; Freund, T.F., 2000. Neuroscience. 797 - 804. 4. 100. 2000. . 10.1016/S0306-4522(00)00286-4 . Neuroscience

Long-lasting facilitation of 4-amino-n-[2,3-3H]butyric acid ([3H]GABA) release from rat hippocampal slices by nicotinic receptor activation

Köfalvi, A.; Sperlagh, B.; Zelles, T.; Vizi, E.S., 2000. Journal of Pharmacology and Experimental Therapeutics. 453 - 462. 2. 295. 2000. . Journal of Pharmacology and Experimental Therapeutics

Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons

Katona, I.; Sperlágh, B.; Sík, A.; Köfalvi, A.; Vizi, E.S.; Mackie, K.; Freund, T.F., 1999. Journal of Neuroscience. 4544 - 4558. 11. 19. 1999. . Journal of Neuroscience

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