Institute of Pharmacology and Neurosciences
Faculty of Medicine and Institute of Molecular Medicine,
Neurosciences
at the
Institute of Pharmacology and Neurosciences
Faculty of Medicine and Institute of Molecular Medicine,
University of Lisbon
The Institute of Pharmacology and Neurosciences pursues research on the neurobiology of purines (adenosine and ATP) and of neuropeptides, namely neurotrophic factores. These are endogenous substances able to fine tuning central nervous system activity, namely by presynaptic modulation of neurotransmitter release and by postsynaptic modification of neurotransmitter actions. The final goal is to understand how to protect neurons and to promote neuronal regeneration. The research groups actively employ integrated approaches involving:
1) electrophysiology (recordings of synaptic currents and potentials),
2) neurochemistry (neurotransmitter release and uptake, molecular visualization at synapses), and
3) behaviour (learning, memory and anxiety tests in laboratory animals).
Research Groups
1. Neuromodulation, molecular mechanisms involved in the fine tuning of the neurosecretion
Principal Investigator (PI): J. Alexandre Ribeiro, MD, PhD
E-mail: jaribeiro @ fm.ul.pt
Funded: FCT - Portugal, EU, IBRO
Ongoing research projects:
2008/11 – Membrane receptors and mediators involved in
plastic changes induced by neuronal insults: implications for neuroprotection.
(PTDC
2005/09 - Role of TrkB receptors in ageing (FCG).
2005/08 -
Interaction between endocannabinoids and adenosine in the hippocampus (FCT -
POCTI/SAU-FCF/57973/2004). With Univ Glasgow.
2. Neuroprotection, neuropeptides, neurothrophic factors, ischaemia/hypoxia models
Principal Investigator (PI): Ana M. Sebastião, PhD
E-mail: anaseb @ fm.ul.pt
Funded: FCT - Portugal and EU
Ongoing research projects:
2007/10 –
Trophic actions of neurotrophic factors: dependency of co-activation of A2A
adenosine receptors. FCT, PTDC/SAU-NEU/64126/2006.
2007/10 –
COST B30 ESF Concerted Action on Neural Regeneration and Plasticity
(NEREPLAS).
2005/08 –
Neurotrophins and neuronal communication: fine tuning by adenosine. (FCT
POCTI/SAU/56332/2004).
3. Synaptic plasticity, ageing, memory and Alzheimer's disease
Principal Investigator (PI): Alexandre de Mendonça, MD, PhD
E-mail: mendonca @ fm.ul.pt
Funded: FCT - Portugal, Portuguese Society for Neurosciences, Portuguese Neurological Society
Ongoing research projects and clinical trials:
Staff Scientist
Luísa Lopes
E-mail: lvlopes @ netc.pt
Project: Chronic stress and function of hippocampal adenosine A2A receptors
Teaching
1st
cycle:
2nd
cycle:
PhD
programmes
Alexandra
Marçal
E-mail: alexandracorreia@fm.ul.pt
Post-doctoral
Diana Cunha-Reis
E-mail: diana-reis @ fm.ul.pt
Project: Role of Vasoactive intestinal peptide (VIP) containing neurons in the control of the rat hippocampal circuits during locomotion, exploration and epilepsy
Cláudia Valente
E-mail:cvalente.castro@gmail.com
Project:The role of glycine receptors in hippocampal neurons
PhD Students
Ana Rita Costenla
E-mail: arcostenla @ fm.ul.pt
Project: Neuroprotective effects of adenosine and caffeine in synaptic plasticity of the rat hippocampus
António Pinto-Duarte
E-mail: pintoduarte @ netcabo.pt
Project: Cross-talk between TrkB-T1 and P2Y receptors in astrocyte-to-astrocyte signalling and effects on neuronal function
Catarina C. Fernandes
E-mail: cfernandes @ fm.ul.pt
Project: Mossy-fiber long-term potentiation (MF-LTP) modulation by purines
Catarina Gomes
E-mail: cvgomes @ fm.ul.pt
Project: Influence of glial-derived neurotrophic factor (GDNF) on striatal dopamine release
Frederico Couto
Email:
Project: Interactions between adenosine receptors and dopamine receptors
Maria José Diógenes
E-mail: diogenes @ fm.ul.pt
Project: Modulation of synaptic transmission by neurotrophic factors
Natália
Assaife Lopes
E-mail: nlopes @ fm.ul.pt
Project: Cross-talk between neurotrophins and adenosine receptors: alterations at the plasma membrane level
Paula Luís
E-mail: luis_paula @ sapo.pt
Project: Role of adenosine A2A receptors in the BDNF effects at the rat diaphragm neuromuscular junction
Sandra
Vaz
E-mail: svaz @ fm.ul.pt
Project: Regulation of GABA transporters in neuronal cells: role of adenosine and neurotrophins
Vasco Sousa
Project: Cross-talk mechanisms between adenosine and endocannabonoids
Raquel Dias
Project: Modulation of glutamate AMPA receptors in hypoxia
Ana Sofia Ferreira
E-mail: aferreira @ fm.ul.pt
Project: Modulation of astrocytic GABA transporters by adenosine
MSc Students
André
Santos
Diogo
Rombo
Fátima
Aidil Carvalho
Joana
Vital
Raquel
Tomé
Rita
Aroeira
Vânia Batalha
Technicians
Elvira Duarte
João Baião
Administrative Support
Alexandra Botelho
Cristina Varandas
TEAM
PICTURE
Left to right:
Top: Ana M.
Sebasião; Alexandra Botelho; Maria Helena Sequeira; Elvira Duarte;
Alexandra Marçal ; Vânia Batalha; Rita Aroeira; Paula Pousinha; Fernando Vale;
Cristina Varandas; Diogo Rombo; Natália Assaife-Lopes; Sandra Vaz; Vasco Sousa;
Sofia Ferreira; João Baião; J. Alexandre Ribeiro
Bottom: Ana Rita
Costenla; Luísa V. Lopes; Maria José Diógenes; Cláudia Valente; Diana
Cunha-Reis; Fátima Aidil Carvalho; Raquel Dias; Raquel
Tomé
Recent Publications
(1998-2008)
Fernandes
C, Pinto-Duarte A, Ribeiro JA, Sebastião AM (2008) Postsynaptic action of
brain-derived neurotrophic factor attenuates alpha7 nicotinic acetylcholine
receptor-mediated responses in hippocampal interneurons. J Neurosci 28,
5611-5618 (TC: 0; IF: 7.490)
Biber K*,
Pinto-Duarte A*, Wittendorp MC, Dolga AM, Fernandes CC, Kunzel JVFD, Keijser JN,
Devries R, Ijzerman AP, Ribeiro JA, Eisel U, Sebastião AM, Boddeke, GM. (2008).
Interleukin-6 upregulates neuronal adenosine A1 receptors: implications for
neuromodulation and neuroprotection. Neuropsychopharmacology 33, 2237–2250
(*co-first authors)(TC: 0; IF: 6.157)
Vaz S,
Rodrigues
RJ, Canas PM, Lopes LV, Oliveira CR, Cunha RA (2008) Modification of adenosine
modulation of acetylcholine release in the hippocampus of aged rats. Neurobiol
Aging, 29, 1597-1601 (TC 0: IF: 5.607)
Fontinha
BM, Ribeiro JA, Sebastião AM (2008) Enhancement of long –term potentiation by
BDNF requires adenosine A2A receptor activation by endogenous adenosine
Neuropharmacology 54, 924-933 (TC: 1; IF:3.215)
Cunha-Reis
D, Ribeiro JA, Sebastião AM (2008) A1 and A2A receptor activation by endogenous
adenosine is required for VIP enhancement of K+-evoked [3H]GABA release from rat
hippocampal nerve terminals. Neurosci Letts 430, 207-212. (TC: 0; IF:
2.085)
Ribeiro,
J. A. (2008). Fine tuning neuromodulation by adenosine and neuroprotection. An
R. Acad. Nac. Farm., 74, 387-408 (2008). (TC: 0; IF:
0.245)
Cunha-Reis D, Ribeiro JA, Sebastião AM.A(1) and A(2A) receptor activation by endogenous adenosine is required for VIP enhancement of K(+)-evoked [(3)H]-GABA release from rat hippocampal nerve terminals. (2008) Neurosci Lett. 430:207-12.
Diógenes MJ, Assaife-Lopes N, Pinto-Duarte A, Ribeiro JA, Sebastião AM.Influence of age on BDNF modulation of hippocampal synaptic transmission: interplay with adenosine A2A receptors. (2007) Hippocampus. 17:577-85.
Chen JF, Sonsalla PK, Pedata F, Melani A, Domenici MR, Popoli P, Geiger J, Lopes LV, de Mendonça A. Adenosine A2A receptors and brain injury: broad spectrum of neuroprotection, multifaceted actions and "fine tuning" modulation.(2007) Prog Neurobiol. 83:310-31.
Ritchie K, Carrière I, de Mendonca A, Portet F, Dartigues JF, Rouaud O, Barberger-Gateau P, Ancelin ML.The neuroprotective effects of caffeine: a prospective population study (the Three City Study). (2007) Neurology. 69:536-45.
Ribeiro F, Guerreiro M, De Mendonça A.Verbal learning and memory deficits in Mild Cognitive Impairment.(2007) J Clin Exp Neuropsychol. 29:187-97.
Rodrigues
RJ, Almeida T, de Mendonça A, Cunha RA.Interaction between P2X and nicotinic
acetylcholine receptors in glutamate nerve terminals of the rat hippocampus.
(2006)
J Mol Neurosci. 30:173-6.
Cerqueira V, de Mendonça A, Minez A, Dias AR, de Carvalho M.Does caffeine modify corticomotor excitability? (2006) Neurophysiol Clin. 36:219-26.
Pereira AF, Simões do Couto F, de Mendonça A.The use of laboratory tests in patients with mild cognitive impairment. (2006) J Alzheimers Dis. 10:53-8.
Ribeiro F, de Mendonça A, Guerreiro M.Mild cognitive impairment: deficits in cognitive domains other than memory. (2006) Dement Geriatr Cogn Disord. 21(5-6):284-90.
Quiroz C,
Gomes C, Pak AC, Ribeiro JA, Goldberg SR, Hope BT, Ferre S. (2006). Blockade of
adenosine A2A receptors prevents protein phosphorylation in the striatum induced
by cortical stimulation. J
Neurosci.
26:10808-12
Cunha-Reis
D, Fontinha BM, Ribeiro JA, Sebastiao AM. (2006). Tonic
adenosine A(1) and A(2A) receptor activation is required for the excitatory
action of VIP on synaptic transmission in the CA1 area of the hippocampus.
Neuropharmacology.
in press
Gomes
CA, Vaz SH, Ribeiro JA, Sebastiao AM. (2006). Glial cell
line-derived neurotrophic factor (GDNF) enhances dopamine release from striatal
nerve endings in an adenosine A2A receptor-dependent manner. Brain Res.
1113:129-36.
Cunha-Reis
D, Ribeiro JA, Sebastiao AM. (2006). VPAC2 receptor activation mediates VIP
enhancement of population spikes in the CA1 area of the hippocampus.
Ann
N Y Acad Sci.
1070:210-4
Fragata
IR, Ribeiro JA, Sebastiao AM. (2006). Nitric
oxide mediates interactions between GABAA receptors and adenosine A1 receptors
in the rat hippocampus. Eur
J Pharmacol.
543:32-9.
Pousinha
PA, Diogenes MJ, Ribeiro JA, Sebastiao AM. (2006). Triggering
of BDNF facilitatory action on neuromuscular transmission by adenosine A2A
receptors. Neurosci
Lett.
40:143-7.
Coelho
JE, Rebola N, Fragata I, Ribeiro JA, de Mendonca A, Cunha RA. (2006).
Hypoxia-induced desensitization and internalization of adenosine A1 receptors in
the rat hippocampus. Neuroscience. 138:1195-203.
RIBEIRO
JA. (2005). What can adenosine neuromodulation do for neuroprotection?
Curr
Drug Targets CNS Neurol Disord.
4:325-329.
CUNHA-REIS
D, RIBEIRO JA, SEBASTIÃO AM. (2005). VIP
enhances synaptic transmission to hippocampal CA1 pyramidal cells through
activation of both VPAC1 and VPAC2 receptors. Brain
Res.
1049:52-60.
da
Silva BM, de Mendonca A, Ribeiro JA. (2005). Long-term
depression is not modulated by ATP receptors in the rat CA1 hippocampal region.
Neurosci Lett. 383:345-9.
Biber K,
Pinto-Duarte A, Wittendorp MC, Dolga AM, Fernandes CC, Kunzel JVFD, Keijser JN,
de Vries R, Ijzerman AP, Ribeiro JA, Eisel U, Sebastião AM and Boddeke GM.
(2005). Interleukin-6 regulates the expression and function of neuronal A1
adenosine receptors: implications for neuroprotection (under
revision).
Pinto-Duarte A,
Coelho JE, Cunha RA, Ribeiro JA, Sebastiao AM (2005) Adenosine A2A
receptors control the extracellular levels of adenosine through modulation of
nucleoside transporters activity in the rat hippocampus. J
Neurochem.
93(3):595-604
de
MENDONÇA A, RIBEIRO F, GUERREIRO M, PALMA T, GARCIA C. (2005). Clinical
significance of subcortical vascular disease in patients with mild cognitive
impairment. Eur
J Neurol.
12:125-30
20 Most Cited Papers
1. Ribeiro JA, Sebastião AM. Adenosine receptors and
calcium – basis for proposing a 3rd (A3) adenosine
receptor. Progress in Neurobiology 26: 179-209, 1986 - Times Cited:
252
2. Sebastião AM, Ribeiro JA. Adenosine A2
receptor-mediated excitatory actions on the nervous system. Progress in
Neurobiology 48: 167-189, 1996 - Times
Cited: 173
3. Ribeiro JA, Walker J. Effects of
adenosine-triphosphate and adenosine-diphosphate on transmission at rat and frog
neuromuscular junctions. British Journal of Pharmacology 54: 213-218,
1975 - Times Cited:
142
4. Cunha RA, Johansson B, van der Ploeg I, Sebastião
AM, Ribeiro JA, Fredholm BB. Evidence for functionally important adenosine
A2A receptors in the rat hippocampus. Brain Research 649: 208-216,
1994 - Times Cited:
130
5. Cunha RA, Johansson B, Constantino MD, Sebastião
AM, Fredholm BB. Evidence for high
affinity binding sites for the adenosine A2A receptor agonist
[3H]CGS 21680 in the rat hippocampus and cerebral cortex that are
different from striatal A2A receptors. Naunyn-Schmiedebergs
Archives of Pharmacology 353: 261-271, 1996 -
Times Cited: 112
6. Sebastião AM, Ribeiro JA. Fine-tuning
neuromodulation by adenosine. Trends in Pharmacological Sciences 21:
341-346, 2000 - Times Cited:
110
7. Cunha RA, Sebastiao AM, Ribeiro JA. Inhibition by ATP
of hippocampal synaptic transmission requires localized extracellular catabolism
by ecto-nucleotidases into adenosine and channeling to adenosine A1
receptors. Journal
of Neuroscience
18: 1987-1995, 1998 - Times Cited:
107
8. Cunha RA, Vizi ES, Ribeiro JA, Sebastião AM.
Preferential
release of ATP and its extracellular catabolism as a source of adenosine upon
high- but not low-frequency stimulation of rat hippocampal slices. Journal of
Neurochemistry 67: 2180-2187, 1996 - Times Cited: 105
9. Ribeiro JA, Sebastião AM. On the role, inactivation
and origin of endogenous adenosine at the frog neuromuscular junction.
Journal of Physiology 384: 571-585, 1987 - Times Cited: 103
10. Ribeiro JA, Sá-Almeida AM, Namorado JM.
Adenosine and
adenosine triphosphate decrease 45Ca uptake by synaptosomes
stimulated by potassium. Biochemical Pharmacology 28: 1297-1300, 1979 -
Times Cited:
100
11. Cunha RA, Milusheva E, Vizi ES, Ribeiro JA,
Sebastiao AM. Excitatory and
inhibitory effects of A1 and A2A adenosine receptor activation on the
electrically evoked [3H]acetylcholine release. Journal of Neurochemistry
63: 207-214, 1994 - Times Cited: 100
12. McQueen DS, Ribeiro JA. Effect of adenosine on
carotid chemoreceptor activity in the cat. British Journal of
Pharmacology 74: 129-136, 1981 - Times
Cited: 100
13. de
Mendonça A, Sebastião AM and Ribeiro JA. Adenosine: does it
have a neuroprotective role after all?. Brain Res
Brain Res Rev.
33:258-74, 2000 Times Cited:
92
14. Cunha RA, Ribeiro JA. ATP as a presynaptic
modulator. Life Sci. 80: 68(2):119-37, 2000- Times Cited: 90
15. Sebastião AM, Ribeiro JA. Evidence for the
presence of excitatory A2 adenosine receptors in the rat hippocampus.
Neuroscience Letters 138: 41-44, 1992 - Times Cited: 87
16. Monteiro EC, Ribeiro JA. Ventilatory effects of
adenosine mediated by carotid body chemoreceptors in the rat.
Naunyn-Schmiedebergs Archives of Pharmacology 335: 143-148, 1987
- Times Cited:
81
17.
McQueen DS, Ribeiro JA. Pharmacological characterization of the
receptor involved in chemoexcitation induced by adenosine. British Journal of
Pharmacology 88: 615-620, 1986 - Times
Cited: 74
18. de Mendonça A, Sebastião AM, Ribeiro JA.
Inhibition of NMDA
receptor-mediated currents in isolated rat hippocampal neurones by adenosine
A1 receptor activation. Neuroreport
6: 1097-1100, 1995 - Times Cited:
74
19. Correia-de-Sá P, Sebastião AM, Ribeiro JA.
Inhibitory and
excitatory effects of adenosine receptor agonists on evoked transmitter release
from phrenic nerve ending of the rat. British Journal of Pharmacology
103: 1614-1620, 1991 - Times Cited:
73
20. Ribeiro JA. Purinergic modulation of transmitter
release. Journal of Theoretical Biology 80: 259-270, 1979 - Times Cited: 65
Instititute
of Molecular Medicine (IMM)
Portuguese
Society for Neurosciences
Federation of European Neuroscience Societies
CostB10
Action on Brain repair
Portuguese
Pharmacological Society
Institute of Pharmacology and Neurosciences
IMM, Faculty of Medicine of Lisbon
Av. Prof. Egas Moniz
1649-028 Lisbon
Portugal
Tel: + 351 217985183
Fax: + 351 217999454