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| Neuroendocrinology and Neurogenesis Group |
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Cláudia Cavadas’s Group
“Neuropeptide Y, a player of neuroendocrinology team”
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| Research Interests |
| In our group we have been interested on the study of the conditions that negatively regulate healthy lifespan, namely high food intake/obesity, stress, and neuronal death focusing on the role of Neuropeptide Y (NPY) on adrenal-hypothalamic-axis and adipose tissue as a promising target system. |
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| Research Highlights and Ongoing Projects |
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Neuropeptide Y in the adrenal gland: a regulatory peptide in stress and inflammation
Adrenal chromaffin cells synthesize and secrete catecholamines and neuropeptides that may regulate hormonal and paracrine signaling in stress and also during inflammation. In this context, we observed that IL-1beta increases the release of catecholamines, norepinephrine and epinephrine, from human and mice chromaffin cells by a MAPK-dependent mechanism, and by NOS activation. Interestingly, IL-1beta also induces NPY release from adrenal chromaffin cells, and this peptide stimulates an additional increase in catecholamine release. Therefore, our study strongly suggests that in some pathophysiological conditions when an increase of plasmatic IL-1beta occurs, like in stress or in inflammation, the NPY is a key element in the regulatory loop between the immune and the adrenal system. Collaborator: Eric. Grouzmann (Division of Clinical Pharmacology and Toxicology, CHUV, Lausanne, Switzerland.
Cavadas C et al (2006) PNAS 103, 10497-10502; Rosmaninho-Salgado J et al (2007) J Neurochem 103, 896-903. Rosmaninho-Salgado J et al. (2009) J Neurochem. 109:911-922.
Support : FCT (POCI/SAU-FCF/60399/2004) and Fonds pour la Recherche des Maladies Cardio Vasculaires et de Nephrologie (Switzerland).
Neuropeptide Y in the adipose tissue: a target to explore
We have been investigating the role of NPY cleaved by the peptidase DPPIV on the regulation of pre-adipocyte proliferation and differentiation of the pre-adipocyte murine cell line (3T3-L1). The results obtained suggest that endogenous NPY Y2 agonist, obtained by NPY cleavage by DPPIV, increases pre-adipocytes proliferation and differentiation. And this adipogenic effect was inhibited by a DPPIV inhibitor, vildagliptin. These results give an explanation to the absence of weight gain in diabetic type 2 patients treated with DPPIV inhibitors, the gliptins used as antidiabetic drugs, and also suggest that these drugs are a putative strategy to inhibit the increase of adipose tissue observed in overweighed diabetic patients.
Principal investigator: Joana Rosmaninho-Salgado;
Support : FCT (PTDC/SAU-BID/113528/2008); award of Joana Rosmaninho-Salgado with the Medal of Honor for Women in Science awarded by L’Oréal in 2009; Abbott/SPEMD.
Neuropeptide Y in the hypothalamus: what happens when is too much or too low?
NPY, the most potent orexigenic peptide, is expressed in hypothalamic arcuate nucleus (Arc) neurons. In collaboration with L. Pereira de Almeida (Gene Therapy Group, CNC) and with S. Kluger (Viral Vectors Laboratory, Medical School, University of Göttingen, Germany) we developed a recombinant Adeno-Associated Virus vectors encoding for NPY (AAV-NPY) and for microRNA against NPY (AAV-miR-NPY) and injected bilaterally in rat Arc. Eight weeks pos-injection, rats with arc-NPY overexpression are hyperphagic and develop a remarkable obesity (Fig.). Moreover, food deprivation induces an increase on food consumption on control rats, while on both Arc-NPY overexpressing group and Arc-NPY silencing group the increase on food intake was not observed. This study show that silencing or overexpressing Arc-NPY cause changes on eating patterns and behavioural responses and reinforce the role of NPY on energy balance regulation and food deprivation response. These rat models of Arc-NPY modulation are useful tool to study NPY system in the rat hypothalamus.
Support : FCT (PTDC/SAU-FCF/099082/2008).
Neuropeptide Y in the retina: Why? What for?
We showed that NPY and NPY receptors are present in rat retina. In rat retinal neurons, NPY inhibits the toxicity induced by “ecstasy” and by glutamate, and also inhibits the [Ca2]i changes, through the activation of NPY Y1, Y4 and Y5 receptors. Moreover, NPY stimulates the proliferation of retinal progenitor cells through the activation of NPY Y1, Y2, and Y5 receptors as well as the by the NO-guanylyl cyclase pathway. Therefore, NPY receptors are potential neuroprotective or neurorepair targets in retinal degenerative diseases, such as glaucoma.
Colaborators: AF Ambrósio (IBILI) and Félix Carvalho (REQUIMTE).
Alvaro AR et al. (2009) J Neurochem. 109:1508-1515; Alvaro AR et al. (2008) J Neurochem. 105:2501-10. Alvaro AR et al. (2008) Neuroscience. 152:97-105.
Support: FCT (PTDC/SAU-NEU/73119/2006 and PTDC/SAU-NEU/99075/2008).
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| The team |
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| Lígia Sousa-Ferreira |
| PhD student |
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| Magda Santana |
| PhD student |
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| Ana Santos-Carvalho |
| PhD student |
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| Ana Patrícia Marques |
Master student
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| Fábia Vicente |
Master student
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| Jorge Pascoal |
Master student
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| Janete Santos |
undergraduate student
fellowship BII |
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| Publications |
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Alvaro AR, Rosmaninho-Salgado J, Ambrósio AF, Cavadas C. Neuropeptide Y inhibits [Ca(2+)](i) changes in rat retinal neurons through NPY Y(1), Y(4) and Y(5) receptors. J Neurochem. 2009, 109:1508-1515
Rosmaninho-Salgado J, Araújo IM, Alvaro AR, Mendes AF, Ferreira L, Grouzmann E, Mota A, Duarte EP, Cavadas C. Regulation of catecholamine release and tyrosine hydroxylase in human adrenal chromaffin cells by interleukin-1beta: role of neuropeptide Y and nitric oxide. J Neurochem. 2009, 109: 911-22.
Ruohonen ST, Savontaus E, Rinne P, Rosmaninho-Salgado J, Cavadas C, Ruskoaho H, Koulu M, Pesonen U. Stress-Induced Hypertension and Increased Sympathetic Activity in Mice Overexpressing Neuropeptide Y in Noradrenergic Neurons. Neuroendocrinology. 2009: 89:351-60.
Xapelli S, Bernardino L, Ferreira R, Grade S, Silva AP, Salgado JR, Cavadas C, Grouzmann E, Poulsen FR, Jakobsen B, Oliveira CR, Zimmer J, Malva JO. Interaction between neuropeptide Y (NPY) and brain-derived neurotrophic factor in NPY-mediated neuroprotection against excitotoxicity: a role for microglia. Eur J Neurosci. 2008, 27:2089-102.
Alvaro AR, Martins J, Araújo IM, Rosmaninho-Salgado J, Ambrósio AF, Cavadas C. Neuropeptide Y stimulates retinal neural cell proliferation - involvement of nitric oxide. J Neurochem. 2008, 105(6):2501-2510
Alvaro AR, Martins J, Costa AC, Fernandes E, Carvalho F, Ambrósio AF, Cavadas C. Neuropeptide Y protects retinal neural cells against cell death induced by ecstasy. Neuroscience. 2008 , 152:97-105.
Rosmaninho-Salgado J, Araújo IM, Alvaro AR, Duarte EP, Cavadas C. Intracellular signaling mechanisms mediating catecholamine release upon activation of NPY Y1 receptors in mouse chromaffin cells. J Neurochem. 2007 Nov;103(3):896-903.
Alvaro AR, Rosmaninho-Salgado J, Santiago AR, Martins J, Aveleira C, Santos PF, Pereira T, Gouveia D, Carvalho AL, Grouzmann E, Ambrósio AF, Cavadas C. NPY in rat retina is present in neurons, in endothelial cells and also in microglial and Müller cells. Neurochem Int. 2007, 50:757-63.
Cavadas C, Waeber B, Pedrazzini T, Grand D, Aubert JF, Buclin T, Grouzmann E. NPY Y1 receptor is not involved in the hemodynamic response to an acute cold pressor test in mice. Peptides. 2007; 28(2):315-9.
Rosmaninho-Salgado J, Alvaro AR, Grouzmann E, Duarte EP, Cavadas C. Neuropeptide Y regulates catecholamine release evoked by interleukin-1beta in mouse chromaffin cells. Peptides. 2007;28(2):310-4
Cavadas C, Céfai D, Rosmaninho-Salgado J, Vieira-Coelho MA, Moura E, Busso N, Pedrazzini T, Grand D, Rotman S, Waeber B, Aubert JF, Grouzmann E. Deletion of the neuropeptide Y (NPY) Y1 receptor gene reveals a regulatory role of NPY on catecholamine synthesis and secretion. Proc Natl Acad Sci U S A. 2006 ; 103(27):104 97-502.
Silva AP, Xapelli S, Grouzmann E, Cavadas C. The putative neuroprotective role of neuropeptide Y in the central nervous system. Curr Drug Targets CNS Neurol Disord. 2005 Aug;4(4):331-47. Review.
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