LABORATORIES
Neuroendocrinology laboratory
Neuroendocrinology laboratory
Research
Team
Publications
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Research
The laboratory studies the neurobiology of insulin factors, specifically insulin and IGF-I. These hormones constitute wide-spectrum neuroprotective signals of great relevance in brain homeostasis and therefore in the development of neurodegenerative diseases.
Our data allow us to propose that IGF-I is a prototype neurotrophic factor closely associated with the function of insulin in the brain, whose functioning will help us to understand the physiological mechanisms of neuroprotection in order to imitate or enhance them with new therapeutic compounds. .
From this perspective, the laboratory has described new neuroprotection mechanisms as well as new therapeutic targets for neurodegenerative diseases. We have seen that a loss of IGF-I activity (certainly accompanied by also insulin) at the brain level due to the development of resistance or deficiency underlies many, if not all, types of neurodegenerative problems.
An original contribution from the laboratory that we believe may be essential for the neurobiology of these hormones is that blood IGF-I can enter the brain in both a tonical and regulated manner. We have seen a concerted action between IGF-I and insulin in the control of brain glucose metabolism.
We are currently focused on describing the cellular and molecular pathways of the IGF-I/insulin duo by which different lifestyles (physical exercise, diet, stress, social activity…etc) affect the physiological mechanisms of neuroprotection of these hormones. We use a multidisciplinary approach from molecular mechanism to physiological function.
Most relevant methodology:
We use all cell biology techniques (cell cultures, immunocytochemistry, electrophysiology in slices…etc), biochemistry (immunoassays, enzyme-assays…etc), molecular (cloning and transfections, reporter systems, gene therapy…etc) and physiological (transgenesis, behavioral , whole animal electrophysiology….etc) necessary for a global approach to our work topic.
Team
Director
Jaime Pignatelli, doctor out of agreement
Predoctoral students
Estrella Fernandez de Sevilla, Becaria Predoctoral FPI
Laura Martinez, Becaria Predoctoral Ciberned
Raquel Herrero, Becaria Predoctoral, FPI
Jonathan Zegarra, Becario Predoctoral Universidad de Arequipa, Perú
Research assistants
Roberto Cañadas, Research assistant hired under project
Miguel Garcia, Research assistant CSIC
Publications
Publications
- M.A. Castro-Alamancos, I. TORRES-ALEMAN. Long-term depression of glutamate-induced gamma aminobutyric acid release in cerebellum by insulin-like growth factor I. Proc. Nat. Acad. Sci. (USA) 90: 7386-7390, (1993).
- M.A. Castro-Alamancos, I. TORRES-ALEMAN. Learning of the conditioned eye-blink response is impaired by an antisense insulin-like growth factor I oligonucleotide. Proc. Nat. Acad. Sci. (USA) 91: 10203-10207, (1994).
- I. TORRES-ALEMAN, V. Barrios, A. Lledó, J. Berciano. The insulin-like growth factor system in cerebellar degeneration. Ann. Neurol., 39: 335-342, (1996).
A.M. Fernandez, A. Gonzalez de la Vega, I. TORRES-ALEMAN. Insulin-like growth factor restores motor coordination in a rat model of cerebellar ataxia. Proc. Nat. Acad. Sci. (USA) 95: 1253-1258 (1998).
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I. TORRES-ALEMAN, V. Barrios, J. Berciano. The peripheral insulin-like growth factor system in amyotrophic lateral sclerosis and multiple sclerosis. Neurology 50: 772-776, (1998).
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E. Carro, A. Nuñez, S. Busiguina, I. TORRES-ALEMAN. Circulating insulin-like growth factor I mediates effects of exercise on the brain. J. Neurosci. 20: 2926-2933 (2000).
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J.L. Trejo, E. Carro, I. TORRES-ALEMAN. Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J. Neurosci. 21, 1628-1634 (2001).
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E. Carro, J.L. Trejo, S. Busiguina, I. TORRES-ALEMAN. Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy. J. Neurosci. 21, 5678-5684 (2001).
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E. Carro, J.L. Trejo, T. Gomez-Isla, D. LeRoith, I. TORRES-ALEMAN. Serum insulin-like growth factor I regulates brain amyloid levels. Nature Med. 8, 1390-1397 (2002).
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C. Lopez Lopez, D. LeRoith, I. TORRES-ALEMAN . Insulin-like growth factor I is required for vessel remodelling in the adult brain. Proc. Nat. Acad. Sci. (USA) 101, 9833-9838 (2004).
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E. Carro, C. Spuch, J.L. Trejo, D. Antequera, I. TORRES-ALEMAN. Choroid plexus megalin is involved in neuroprotection by serum insulin-like growth factor I. J. Neurosci. 25, 10884-10893 (2005).
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J.L. Trejo, J. Piriz, M.V. Llorens-Martin, A.M. Fernandez, M. Bolós, D. LeRoith, A. Nuñez, I. TORRES-ALEMAN. Central actions of liver-derived insulin-like growth factor I underlying its pro-cognitive effects. Mol Psych. 12, 1118–1128 (2007).
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A. M. Fernandez, S. Fernandez, P. Carrero, M. Garcia-Garcia, and I.TORRES-ALEMAN. Calcineurin in reactive astrocytes plays a key role in the interplay between pro- and anti-inflammatory signals. J. Neurosci. 27, 8745-8756 (2007).
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C. Lopez-Lopez, M.O. Dietrich, F. Metzger, H. Loetscher, and I. TORRES-ALEMAN. Disturbed cross-talk between insulin-like growth factor I and AMP-activated protein kinase as a possible cause of vascular dysfunction in the APP/PS2 mouse model of Alzheimer´s disease. J. Neurosci. 27, 824-831 (2007).
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T. Nishijima, J. Piriz, S. Duflot, A.M. Fernandez, G. Gaitan, U. Gomez-Pinedo, J.M. Verdugo, F. Leroy, H. Soya, A. Nuñez, TORRES-ALEMAN I. Neuronal activity drives localized blood-brain-barrier transport of serum insulin-like growth factor-I into the CNS. Neuron 67, 834-846 (2010).
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A.M. Fernandez, I. TORRES-ALEMAN. The many faces of insulin-like peptide signaling in the brain. Nature Reviews Neuroscience 13, 225-239 (2012).
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A.M Fernandez, S. Jimenez, M. Mecha, D. Davila, C. Guaza, J. Vitorica, I. TORRES-ALEMAN. Regulation of the phosphatase calcineurin by insulin-like growth factor I unveils a key role astrocytes in Alzheimer´s pathology. Mol Psychiatry 17, 705-718 (2012)
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S. Fernandez, L. Genis, I.TORRES-ALEMAN. A phosphatase-independent gain-of-function mutation in PTEN triggers aberrant cell growth in astrocytes through an autocrine IGF-I loop. Oncogene 33, 4114-22 (2014)
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C. Garcia-Caceres, C. Quarta, Y. Gao, L. Varela, T. Gruber, B. Legutko, M. Jastroch, P. Johansson, J. Ninkovic, C.X. Yi, O. Le Thuc, C. Meyer, P.T. Pfluger, A.M. Fernandez, S. Luquet, S.C. Woods, I. TORRES-ALEMAN, C.R. Kahn, M. Götz, T. Horvath, M.H. Tschöp. Astrocytic insulin signaling couples brain glucose uptake with nutrient availability. Cell 166, 867-880 (2016).
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E. Hernandez-Garzón, AM Fernandez, A Perez-Alvarez, L Genis, P Bascuñana, R Fernandez de la Rosa, M Delgado, MA Pozo, E Moreno, PJ McCormick, A Santi, A Trueba-Saiz, C Garcia-Caceres, M H. Tschöp, A Araque, ED Martin, and I TORRES ALEMAN. The insulin-like growth factor receptor I regulates glucose transport by astrocytes. Glia 64, 1962-1971 (2016).
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A.M. Fernandez, E. Hernandez-Garzón, P. Perez-Domper, A. Perez-Alvarez, S. Mederos, T. Matsui, A. Santi, A. Trueba-Saiz, L. García-Guerra, J. Pose-Utrilla, J. Fielitz, E.N. Olson, R. Fernandez de la Rosa, L. Garcia Garcia, M. Angel Pozo, T. Iglesias, A. Araque, H. Soya, G. Perea, E.D. Martin, I. TORRES-ALEMAN. Insulin regulates astrocytic glucose handling through cooperation with insulin-like growth factor I. Diabetes 66, 2017 (in press) http://dx.doi.org/10.2337/db16-0861.
Contact
Where to find us
Neuroendocrinology lab
Instituto Cajal CSIC. Avda. Doctor Arce, 37. 28002. Madrid
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Doctoral thesis (last years)
- Name: Angel Trueba Saiz
Title: Neurotrophic uncoupling of IGF-1 in Alzheimer’s disease: translation into early diagnosis and involvement of lifestyle risk factors.
Place of presentation: Dept. of Neurosciences, Faculty of Medicine, Autonomous University of Madrid.
Date: February 2015
Grade: Outstanding Cum Laude
Co-directed with Dr. Angel Nuñez - Name: Edwin Hernandez Garzon
Title: Regulation of glucose uptake by astrocytes by insulin factors
Place of presentation: Dept. of Molecular Biology and Biochemistry, Faculty of Sciences, Autonomous University of Madrid.
Date: December 2014
Grade: Outstanding Cum Laude - Name: Carolina Franco Martinez del Solar
Title: IGF-I as a therapeutic agent in Friedreich’s ataxia
Place of presentation: Dept. of Morphology and Neurosciences, Faculty of Medicine, Autonomous University of Madrid.
Date: June 2012
Grade: Outstanding Cum Laude
Patents (in exploitation)
- AUTHORS: C. Carrascosa, C. Lopez, E. Carro, S. Torrado, J. Torrado and I. Torres Aleman
TITLE: Chemical composition of IGF-I for the treatment and prevention of neurodegenerative diseases. Awarded by Madri+d in 2007 for the best patent.
REGISTRATION Nº: WO03/077940 COUNTRY OF PRIORITY: SPAIN
PRIORITY DATE: 2002
OWNER ENTITY: CSIC / Complutense University
COUNTRIES TO WHICH IT HAS BEEN EXTENDED: European Union, Canada, Australia. Pending: USA, Japan
COMPANY/S THAT ARE/ARE OPERATING IT: Igefercia - AUTHORS: A.Trueba, C. Cavada, A. Nuñez and I. Torres Aleman
TITLE: Use of IGF-1 as a reagent for diagnosis and/or early prognosis of Alzheimer’s disease
APPLICATION NO.: ES 201330187 COUNTRY OF PRIORITY: SPAIN
PRIORITY DATE: 2013
OWNER ENTITY: CSIC/UAM
COUNTRIES TO WHICH IT HAS BEEN EXTENDED:
COMPANY/S THAT ARE/ARE OPERATING IT: Igefercia
Neuroscience Research Center dependent on the CSIC. Founded in 1920 and initially directed by Santiago Ramón y Cajal. World reference in the study of the brain. Custodian of the Cajal Legacy.
Activities