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Neuroscience and disease

Neuroendocrinology and Aging

The Mission of Neuroendocrinology and Aging Group is to contribute to develop new knowledge in the aging field, namely to demonstrate that neuroendocrine system and related mechanisms can be targeted in experimental models to delay, stop, and in some examples, reverse manifestations of aging and age-related disorders.

The knowledge generated by our group has been contributing to the hypothesis that aging and age-related disorders could be controlled by using neuroendocrine strategies. These strategies are based on targeting the main brain area involved in the neuroendocrine system - the hypothalamus -, its main functions (circadian rhythm, sleep, food intake, metabolism), and also the hypothalamus-periphery axis.

Objectives:

To investigate the neuroendocrine axis contribution to ageing and age-related disorders
To investigate new strategies to delay aging and age-related disorders by targeting the hypothalamus or by targeting hypothalamic related mechanisms;
To use caloric restriction mimetic approaches, as neuropeptides, new sirtuins-1 activators, circadian rhythm reestablishment to prevent aging and age-related diseases or disabilities (metabolism dysfunction, osteoarthrite (OA), sleep dysfunctions, neurodegenerative diseases);
To understand if and how obstructive sleep apnea (OSA), insomnia or obesity induce or accelerate molecular mechanisms of ageing;

The group members have complementary expertise: establishment of cellular and animal models of aging and age-related disorders (progeria, neurodegenerative disorders, OSA, OA, insomnia, metabolic dysfunction and obesity), evaluation of physiology, cellular and molecular aging markers (namely autophagy, senescence, inflammation), gene transfer approaches, circadian rhythm analysis, medicinal chemistry and histopathological methodologies. Moreover, the group has expertise to organize pre-clinical studies and public engagement activities.

Keywords

Aging

Hypothalamus

Biological clocks

Autofagia

Inflammation

Research Lines

Neuroendocrine axis and aging (PI: Claudia Cavadas)
Hypothalamus: a target to delay aging and age-related disorders (PIs: Célia Aveleira and Claudia Cavadas)
New drugs to target hallmarks of aging and age-related diseases (PIs: Alexandrina F Mendes and Maria Manuel Silva)
Circadian Rhythms in aging and age-related diseases (PIs: Ana Rita Álvaro & Cláudia Cavadas)

Cláudia Cavadas

PhD,Group Leader

Alexandrina Mendes

PhD, Princ. Investigator

Ana dos Santos Carvalho

PhD, Researcher

Ana Maria F. Capitão

PhD, Researcher

Ana Rita Álvaro

PhD, Researcher

Ana Teresa Viegas

PhD, Researcher

Célia Aveleira

PhD, Researcher

Dina Pereira

PhD, Researcher

Sara Carmo Silva

PhD, Researcher

Fernando Judas

MD, PhD

Maria Manuel Silva

PhD, Princ. Investigator

Cátia Sousa

PhD Student

Helena Leal

PhD Student

Laetitia da Silva Gaspar

PhD Student

Marisa Ferreira-Marques

PhD Student

Rodrigo Ribeiro

PhD Student

Ana Catarina Franco

Research Fellow

Bárbara Santos

Research Fellow

Catarina C. Almeida

Research Fellow

Daniela Cristina Costa

Research Fellow

Rodolfo Águas

Research Fellow

Vasco de Almeida Lucas

Research Fellow

Eliana Rita Barbosa

MSc Student

Gabriela Moço

MSc Student

Inês Rodrigues

MSc Student

Alumni

Ongoing Research Projects

NiNjA - New Neuroendocrine strategy for healthy Aging; (Funded by FCT; Ref. PTDC/MED-FAR/30167/2017) PI: Claudia Cavadas; Co-PI: Célia Aveleira
noOSAnoAGEING - Obstructive Sleep Apnea early diagnosis as a new strategy to delay ageing; PI: (Funded by FCT: PTDC/MEC-MCI/29002/2017) PI: Ana Rita Álvaro; Co-PI: Claudia Cavadas; Co-PI: Célia Aveleira
“Neuroendocrine strategies to delay aging - Nutrient sensing and food intake as intervention strategies - WP 5 of Grant “HealthyAging2020” (POCI-01-0145-FEDER-007440; Funded by European Regional Development Fund, through the Centro 2020 Regional Operational Programme: CENTRO-01-0145-FEDER-000012-HealthyAging2020, COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation); PI of WP: Cláudia Cavadas
CARTILFACTORY - Development and Construction of an Automated Large Scale Manufacturing System for Cartilage Engineering Combining 3D Electroplating of Chondrocytes and 3D Cellular Expansion with Mechanical Stimulation in Bioreactor (POCI-01-0145-FEDER-028424); PI of WP: Alexandrina F Mendes
COST Action: An integrative action for multidisciplinary studies on cellular structural networks. COST Action. CA15214. National representative: Cláudia Cavadas 2016-2020

External Collaborations

Amita Sehgal

Perelman School of Medicine, University of Pennsylvania, USA

https://www.med.upenn.edu/sehgallab/

Angela Relógio

Charité-Universitätsmedizin Berlin, Germany

http://sysbio-relogio.com/angela-relogio/

Carlos Lopez Otin

Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain

http://degradome.uniovi.es

David Smith

Sleep Center, Cincinnati Children's Hospital Medical Center, OH, USA

https://www.cincinnatichildrens.org/bio/s/david-smith

João Passos

Cell and Molecular Aging Lab

Mayo Clinic in Rochester, Minnesota, USA

https://www.mayo.edu/research/labs/cell-molecular-aging/overview

João Pedro de Magalhães

Institute of Ageing and Chronic Disease, University of Liverpool, United Kingdom

http://pcwww.liv.ac.uk/~aging/

Joaquim Moita

Centro de Medicina do Sono, Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal

https://www.chuc.min-saude.pt

Xavier Nissan

I-Stem, Paris, France

https://www.istem.eu/en/biotherapies/progeria-project/

Funding Agencies

FCT
Inov C 2020
Progeria Research Foundation, USA
Arrisca C

Selected Publications

Aveleira CA, Ferreira-Marques M, Cortes L, Valero J, Pereira D, Pereira de Almeida L, Cavadas C. Neuropeptide Y Enhances Progerin Clearance and Ameliorates the Senescent Phenotype of Human Hutchinson-Gilford Progeria Syndrome Cells. (2020) J Gerontol A Biol Sci Med Sci.;75(6):1073-1078. doi: 10.1093/gerona/glz280.
Gaspar L.S., Álvaro A.R., Carmo-Silva S., Mendes A.F., Relógio A., Cavadas C. (2019). The importance of determining circadian parameters in pharmacological studies. Br J Pharmacol, 176(16):2827-2847. doi: 10.1111/bph.14712
Carmo-Silva S., Nobrega C., Pereira de Almeida L., Cavadas C. (2017). Unraveling the Role of Ataxin-2 in Metabolism. Trends Endocrinol Metab, 28(4):309-318. doi: 10.1016/j.tem.2016.12.006
Gaspar L.S., Álvaro A.R., Moita J., Cavadas C. (2017). Obstructive Sleep Apnea and Hallmarks of Aging. Trends Mol Med, 23(8):675-692. doi: 10.1016/j.molmed.2017.06.006
Cavadas C., Aveleira C.A., Souza G.F., Velloso L.A. (2016). The pathophysiology of defective proteostasis in the hypothalamus - from obesity to ageing. Nat Rev Endocrinol, 12(12):723-733. doi: 10.1038/nrendo.2016.107
Cunha-Santos J., Duarte-Neves J., Carmona V., Guarente L., Pereira de Almeida L., Cavadas C. (2016). Caloric restriction blocks neuropathology and motor deficits in Machado-Joseph disease mouse models through SIRT1 pathway. Nat Commun, 7:11445. doi: 10.1038/ncomms11445.
Ferreira-Marques M., Aveleira C.A., Carmo-Silva S., Botelho M., Pereira de Almeida L., Cavadas C. (2016). Caloric restriction stimulates autophagy in rat cortical neurons through neuropeptide Y and ghrelin receptors activation. Aging (Albany NY), 8(7):1470-84. doi: 10.18632/aging.100996
Aveleira C.A., Botelho M., Carmo-Silva S., Pascoal J.F., Ferreira-Marques M., Nóbrega C., Cortes L., Valero J., Sousa-Ferreira L., Álvaro A.R, Santana M., Kügler S., Pereira de Almeida L., Cavadas C. (2015). Neuropeptide Y stimulates autophagy in hypothalamic neurons. Proc Natl Acad Sci U S A, 112(13):E1642-51. doi: 10.1073/pnas.1416609112
Botelho M, Cavadas C. Neuropeptide Y: An Anti-Aging Player? (2015) Trends Neurosci. 38(11):701-711. doi: 10.1016/j.tins.2015.08.012.
Aveleira C.A., Botelho M., Cavadas C. (2015). NPY/neuropeptide Y enhances autophagy in the hypothalamus: a mechanism to delay aging? Autophagy, 11(8):1431-3. doi: 10.1080/15548627.2015.1062202

Carmo-Silva S, Nobrega C, Pereira de Almeida L, Cavadas C. Unraveling the Role of Ataxin-2 in Metabolism. Trends Endocrinol Metab. 2017, 28(4):309-318.

Marques AP, Rosmaninho-Salgado J, Estrada M, Cortez V, Nobre RJ, Cavadas C. Hypoxia mimetic induces lipid accumulation through mitochondrial dysfunction and stimulates autophagy in murine preadipocyte cell line. Biochim Biophys Acta. 2017, 1861(3):673-682.

Duarte-Neves J, Pereira de Almeida L and Cavadas C. Neuropeptide Y (NPY) as a therapeutic target for neurodegenerative diseases. Neurobiol Dis. 2016, 95:210-224.

Duarte-Neves J, Gonçalves N, Cunha-Santos J, Simões AT, den Dunnen WF, Hirai H, Kügler S, Cavadas C*, Pereira de Almeida L*. Neuropeptide Y mitigates neuropathology and motor deficits in mouse models of Machado-Joseph disease. Hum Mol Genet. 2015, 24: 5451-5463.

Santana MM, Rosmaninho-Salgado J, Cortez V, Pereira FC, Kaster MP, Aveleira CA, Ferreira M, Álvaro AR, Cavadas C. Impaired adrenal medullary function in a mouse model of depression induced by unpredictable chronic stress. Eur Neuropsychopharmacol. 2015, 25(10):1753-66.

Aveleira CA, Botelho M, Cavadas C. NPY/neuropeptide Y enhances autophagy in the hypothalamus: a mechanism to delay aging? Autophagy 2015, 112(13):E1642-51.

Santos-Carvalho A, Ambrósio AF, Cavadas C. Neuropeptide Y system in the retina: From localization to function. Prog Retin Eye Res. 2015, 47:19-37.

Faria R, Santana MM,. Aveleira CA, Simões C, Maciel E, Melo M, Santinha D, Oliveira MM, Peixoto F, Domingues P, Cavadas C, M. Domingues RM. Alterations in phospholipidomic profile in brain of mouse model of depression induced by chronic unpredictable stress. Neuroscience, 2014, 273:1-11.

Sousa-Ferreira L, Aveleira C, Botelho M, Alvaro AR, Pereira de Almeida L, Cavadas C. Fluoxetine induces proliferation and inhibits differentiation of hypothalamic neuroprogenitor cells in vitro. PLoS One. 2014, 5;9(3):e88917.

Sousa-Ferreira L, Pereira de Almeida L, Cavadas C. Role of hypothalamic neurogenesis in feeding regulation. Trends Endocrinol Metab. 2014, 25(2):80-8.

Sousa-Ferreira L, Pereira de Almeida L, Cavadas C; “microRNAs and obesity”; chapter of the book “Molecular Mechanisms Underpinning the Development of Obesity”, Springer, 2014 (ISBN 978-3-319-12765-1)

Santos-Carvalho A, Álvaro AR, Martins J, Ambrósio AF, Cavadas C. Emerging novel roles of neuropeptide Y in the retina: from neuromodulation to neuroprotection. Prog Neurobiol. 2014, 112:70-9.

Santana MM, Ehrhart-Bornstein M, Cavadas C. Progenitor cells in chromospheres: in response to Arthur S. Tischler. Stem Cells Transl Med. 2013, 2(12):1020-1.

Santos-Carvalho, A R Álvaro, A F Ambrósio, C Cavadas Neuropeptide Y receptors activation protects rat retinal neural cells against necrotic and apoptotic cell death induced by glutamate. Cell Death and Disease 2013, 4, e636

Santos-Carvalho A, Aveleira CA, Elvas F, Ambrósio AF, Cavadas C. Neuropeptide Y Receptors Y1 and Y2 are Present in Neurons and Glial Cells in Rat Retinal Cells in Culture. Invest Ophthalmol Vis Sci. 2013, 17;54(1):429-43.

Vindeirinho J, Costa GN, Correia MB, Cavadas C, Santos PF. Effect of diabetes/hyperglycemia on the rat retinal adenosinergic system. PLoS One. 2013;8(6):e67499.

Santana MM, Chung KF, Vukicevic V, Rosmaninho-Salgado J, Kanczkowski W, Cortez V, Hackmann K, Bastos CA, Mota A, Schrock E, Bornstein SR, Cavadas C*, Ehrhart-Bornstein M*. Isolation, characterization, and differentiation of progenitor cells from human adult adrenal medulla. Stem Cells Transl Med. 2012, 1(11):783-91.

Rosmaninho-Salgado J, Cortez V, Estrada M, Santana MM, Gonçalves A, Marques AP, Cavadas C. Intracellular mechanisms coupled to NPY Y(2) and Y(5) receptor activation and lipid accumulation in murine adipocytes. Neuropeptides 2012, S0143-4179.

Rosmaninho-Salgado J, Marques AP, Estrada M, Santana M, Cortez V, Grouzmann E, Cavadas C. Dipeptidyl-peptidase-IV by cleaving neuropeptide Y induces lipid accumulation and PPAR-γ expression. Peptides 2012, 37(1):49-54.

Cortez V, Santana M, Marques P, Mota A, Rosmaninho-Salgado J, Cavadas C. Regulation of catecholamine release in human adrenal chromaffin cells by ß-adrenoceptors. Neurochem Int. 2012, 60: 387-393.

Martins J, Castelo-Branco M, Oliveiros B, Fernandes E, Carvalho F, Cavadas C and Ambrósio AF - Effects of 3,4-methylenedioxymethamphetamine administration on retinal physiology in the rat. PLoS One 2012, 6(12): e29583.

Costa GN, Vindeirinho J, Cavadas C, Ambrósio AF, Santos PF. Contribution of TNF receptor 1 to retinal neural cell death induced by elevated glucose. Mol Cell Neurosci. 2012, 50 : 113–123

Sousa-Ferreira L, Garrido M, Nascimento-Ferreira I, Nobrega C, Santos-Carvalho A, Álvaro AR, Rosmaninho-Salgado J, Kaster M, Kügler S, Pereira de Almeida L, Cavadas C. Moderate long-term modulation of Neuropeptide Y in the Arcuate Nucleus induces energy balance alterations in adult rats. PLoS One, 2011 6(7):e22333

Sousa-Ferreira L, Álvaro AR, Aveleira C, Santana M, Brandão I, Kügler S, Pereira de Almeida L, Cavadas C. Proliferative hypothalamic neurospheres express NPY, AGRP, POMC, CART and Orexin-A and differentiate to functional neurons expressing appetite-related neuropeptides. PLoS One 2011, 6(5):e19745

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), 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.

Book Chapter; Title “Neuropeptide Y family peptides” by Cláudia Cavadas, Joana Rosmaninho- Salgado, Eric Grouzmann; Book Title: “Bioactive peptides”; edited by John Howl, Sarah Jones. Boca Raton, FL : CRC Press, 2009. ISBN 9781420061147

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, 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, 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. PNAS USA 20

GROUP LEADER AND PRINCIPAL INVESTIGATOR

Cláudia Cavadas, PhD

ORCID

CiênciaID

Cláudia Cavadas holds a PhD in Pharmacology from the Faculty of Pharmacy, University of Coimbra (FFUC). Since 2002, she has been Professor at the FFUC and Group Leader of “Neuroendocrinology and Aging group” at CNC-UC. Cavadas is co-author of 75 papers, mentored more than 50 graduate students and young researchers, and coordinated 15 national and international funded projects. Cláudia Cavadas is Vice-rector at the University of Coimbra (UC), and Director of the Institute for Interdisciplinary Research of the UC.

PRINCIPAL INVESTIGATOR

Alexandrina Mendes, PhD

ORCID

CiênciaID

PRINCIPAL INVESTIGATOR

Ana Rita Álvaro, PhD

ORCID

CiênciaID

PRINCIPAL INVESTIGATOR

Célia Aveleira, PhD

ORCID

CiênciaID

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Funded by ERDF - European Regional Development Fund through COMPETE 2020 and National Funds via FCT - Fundação para a Ciência e Tecnologia, under projects POCI-01-0145-FEDER-007440 e UIDB/04539/2020.