Modulation of inflammatory response and glial cells reactivity
in neurodegeneration models

Team of work

Principal InvestigatorBellini

Bellini, María José

Investigator
mariajosebellini@yahoo.com

Falomir Lockhart, EugeniaFalomir Eugenia

Research Fellow
eugefalomir@gmail.com

Dolcetti, Franco Juan CruzDolcetti

Research Fellow
franco.dolcetti@gmail.com

Anesetti, SoledadAnesetti

Dissertation Student

Bigres, AraceliBigres

Support staff
aracelibigres@gmail.com

Lofeudo, Juan ManuelLofeudo

Support staff
juanmalofeudo@hotmail.com

Collaborators from other institutions

García-Segura, Luis Miguel
Instituto Cajal, Madrid, España.

Diz-Chaves, Yolanda
Instituto Cajal, Madrid, España.

Correa, Fernando
Centro de Estudios Farmacológicos y Botánicos (CEFyBO), Facultad de Ciencias Médicas, UBA.

Hereñú, Claudia B.
IFEC- Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba.

Labombarda, Florencia
Instituto de Biología y Medicina Experimental – Consejo Nacional de Investigaciones Científicas y Técnicas - (IBYME -CONICET).

Perelló, Mario
Instituto Multidisciplinario de Biología Celular, IMBICE, La Plata.

Pietranera, Luciana
Instituto de Biología y Medicina Experimental – Consejo Nacional de Investigaciones Científicas y Técnicas - (IBYME -CONICET).

Ramos, Alberto Javier
Instituto de Biología Celular y Neurociencia "PROFESOR EDUARDO DE ROBERTIS" (IBCN), Facultad de Medicina, UBA.

Line overview

Intereses principales:

Nuestro principal interés se centra en dilucidar los mecanismos que llevan a la neurodegeneración durante el envejecimiento, fundamentalmente los relacionados con la respuesta inflamatoria.
El objetivo primordial de nuestro trabajo es desarrollar estrategias terapéuticas que recuperen las poblaciones neuronales afectadas por la edad. La posibilidad de emplear factores neurotróficos que prevengan la neurodegeneración, aumenten la recuperación neuronal y regulen la respuesta inflamatoria es clínicamente relevante.

Inflamación:

La inflamación crónica desempeña un rol importante en las enfermedades neurodegenerativas más comunes.
Una posible diana terapéutica para el tratamiento de la enfermedad puede ser bloquear a los causantes de esa neuroinflamación.
La microglia y los astrocitos son las principales células efectoras que contribuyen a la inflamación cerebral.

Objetivos:
• Investigar los posibles efectos anti-inflamatorios, neuroprotectores y/o restauradores del IGF-1 en roedores envejecientes y modelos experimentales de enfermedades neurodegenerativas.
• Determinar si el envejecimiento y las diferencias sexuales pueden afectar su acción neuroprotectora.
• Dilucidar los mecanismos celulares y moleculares de la actividad antiinflamatoia del IGF-1 en cerebro.
• Estudiar el rol de las células gliales como mediadores de los efectos del IGF-1
• Caracterizar los cambios en la composición lipídica asociados a la edad y al sexo.

Líneas de Trabajo

1-Reprogramación celular y terapia génica para el tratamiento de la neurodegeneración dopaminérgica motora.
Responsable: Eugenia Falomir-Lockhart

La finalidad última de este proyecto es estudiar integralmente el sistema nervioso-motor aplicando estrategias de terapia génica y medicina regenerativa en el sistema dopaminérgico (nigro-estriatal) con el fin de mejorar las deficiencias relacionadas con la edad en las vías motoras del sistema dopaminérgico encefálico.

2-El hipotálamo como centro regulador del envejecimiento- Terapia génica antiinflamatoria.
Responsable:Dolcetti, Franco

La hipótesis central de este plan es que la transferencia de genes neuroprotectores constituye una estrategia efectiva para disminuir la respuesta inflamatoria en el envejecimiento, constituyendo un posible tratamiento de diversos procesos neurodegenerativos asociados a la edad. En particular planteamos que la terapia génica intrahipótalámica para el factor insulino símil de tipo I (IGF-I) modularía la respuesta inmune con el consecuente retraso en la aparición de daños asociados al envejecimiento y/o la mejoría de los mismos una vez se hayan producido.

El envejecimiento es el resultado de múltiples cambios fisiológicos y el hipotálamo puede ser un mediador subyacente representando un blanco de estrategias interventoras para contrarrestar el envejecimiento y las enfermedades relacionadas con el mismo.


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Dancing with Glia: The Role of Astrocytes, Microglia and Oligodendrocytes and their Relation with Neurons in Neuroinflammation and Aging.
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IGF1 Gene Therapy Modifies Microglia in the Striatum of Senile Rats. Frontiers in aging neuroscience.
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Novel adenoviral IGF-1 administration modulates the association between depressive symptoms and aging: Does gender matter?
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Physical, histological, endocrinological and steroidogenical evaluation of male cats postnatally exposed to sexual steroids.
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Estradiol Activates PI3K/Akt/GSK3 Pathway Under Chronic Neurodegenerative Conditions Triggered by Perinatal Asphyxia.
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Exploring the effects of IGF-1 gene therapy to modulate neuroinflammation.
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Deterioro cognitivo asociado a la patología parkinsoniana: El rol del hipocampo.
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2016. Ciencia insitu: Federación Argentina Científica de Estudiantes de la Salud, vol. 1, n° 2, p. 23-27. ISSN 2469-2433

Magnetofection enhances adenoviral vector-based gene delivery in skeletal muscle cells.
Pereyra, A. S; Mykhaylyk, O; Falomir Lockhart, E; Taylor, J. R; Delbono, O; Goya, R. G; Plank, C; Hereñu, C. B.
2016. Journal of Nanomedicine & Nanotechnology 04/2016; 7(364)

Calpain inhibition rescues troponin T3 fragmentation, increases Cav1.1 and enhances skeletal muscle force in aging sedentary mice.
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Troponin T3 regulates nuclear localization of the calcium channel CavB1a subunit in skeletal muscle.
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Therapeutic exercise attenuates neutrophilic lung injury and skeletal muscle wasting.
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2015. Science Translational Medicine. Washington: American Association for the Advancement of Science, vol. 7, n° 278, p. 278-310. ISSN 1946-6234

Cognitive impairment and morphological changes in the dorsal hippocampus of very old female rats.
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Regional research priorities in brain and nervous system disorders.
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Estrogen actions on glial reactivity and inflammation-mediated memory impairment: Sex differences and interaction with other neurotrophic factors.
Bellini, M. J.
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Neuroprotective gene therapy in the aging brain.
Pardo, J; Morel, G. R; Pereyra, A. S; López-León, M; Brown-O. A, Bellini, M. J; Goya, R. G.
2014. Estrogens and Cognition. Psycho-biological and Clinical Aspects: González-Burgos (Ed.) ISBN: 978-81-308-0550-4; pp.97-117

Therapeutic potential of the thymic peptide thymulin.
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Physiology and therapeutic potential of the thymic peptide thymulin.
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Regenerative Medicine for the Aging Brain.
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The Cavβ1a subunit regulates gene expression and suppresses myogenin in muscle progenitor cells.
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DNA nanoparticle-mediated thymulin gene therapy prevents airway remodeling in experimental allergic asthma.
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2014. Curr Gene Ther; 14:24-34

Transferencia génica asistida por campos magnéticos: estudios en células gliales.
Pardo, J; Sosa, Y; Reggiani, P. C; Arciniegas, M. L; Sánchez, F; Goya, R. G.
2013. Acta Bioquímica Clínica Latinoamericana. La Plata: Federacion Bioquímica Provincia Buenos Aires, vol. 47, n° 2, p. 399-406. ISSN 0325-2957

The thymulin-lactotropic axis in rodents: thymectomy, immunoneutralization and gene transfer studies.
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Hypothalamic insulin-like growth factor-I gene therapy prolongs estral cyclicity and protects ovarian structure in middle-aged female rats.
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Magnetic field-assisted gene transfer: Studies in glial cells (in Spanish).
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2013. Acta Bioquímica Latinoamericana; 47: 399-406

Role of copper and cholesterol association in the neurodegenerative process.
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Estradiol and testosterone regulate arginine-vasopressin expression in SH-SY5Y human female neuroblastoma cells through estrogen receptors-α and -β.
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2013. Endocrinology. 154: 2092-100

Prenatal stress increases the expression of proinflammatory cytokines and exacerbates the inflammatory response to LPS in the hippocampal formation of adult male mice.
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Magnetic field-assisted gene delivery: achievements and therapeutic potential.
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Neonatal thymulin gene therapy prevents ovarian dysgenesis and attenuates reproductive derangements in nude female mice.
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Role of thymulin on the somatotropic axis in vivo.
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2012. Life Sciences, Amsterdam: Pergamon - ElSevier Science Ltd, vol. 91, p. 166-171

Influence on Effectiveness of Early Treatment with Anti-TNF Therapy in Rheumatoid Arthritis.
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Selective oestrogen receptor modulators decrease the inflammatory response of glial cells.
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2012. Journal of neuroendocrinology. Oxford: Wiley-Blackwell Publishing, Inc, vol. 24, p. 183-190

Increased romatase expression in the hippocampus of spontaneously hypertensive rats: effects of estradiol administration.
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2011. Neuroscience, 174: p. 151-159

Cytotoxic and genotoxic effects of defence secretion of Ulomoides dermestoides on A549 cells.
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Increased number of neurons in the cervical spinal cord of aged female rats.
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2011. PloS One, 6: e22537

Insulin-like growth factor I gene delivery to astrocytes reduces their inflammatory response to lipopolysaccharide.
Bellini, M. J; Hereñú, C. B; Goya, R. G; García Segura, L. M.
2011. Neuroinflammation, 8: 21

Restorative effect of intracerebroventricular Insulin-like Growth Factor-I gene therapy on motor performance in aging rats.
Nishida, F; Morel, G. R; Hereñú, C. B; Schwerdt, J. I; Goya, R. G; Portiansky, E. L
2011. Neuroscience, 177: 195 - 206

Thymulin-based gene therapy and pituitary function in animal models of aging.
Reggiani, P. C; Poch, B; Cónsole, M. G; Rimoldi, O. J; Schwerdt, J. I; Tüngler, V; García de Bravo, M. M; Dardenne, M; Goya, R. G.
2011. Neuroimmuno-modulation, 18: 350-356

Morphological effects on the corticotrope population by thymulin gene therapy in nude mice.
Martinez, E. V; Reggiani, P. C; Schwerdt, J. I; Goya, R. G; Cónsole, G. M.
2011. Histology and Histopathology; 26: 471-479

Thymulin gene therapy prevents the histomorphometric changes induced by thymulin deficiency in the thyrotrope population of mice.
Martinez, E. V; Reggiani, P. C; Schwerdt, J. I; Goya, R. G; Cónsole, G. M.
2011. Cells, Tissues, Organs, 194: 67-75

Long-term deficiency of circulating and hippocampal insulin-like growth factor I induces depressive behavior; adult mice: a potential model of geriatric depression.
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2011. Neuroscience; 185: 50 - 60

Morphological changes induced by insulin-like growth factor-I gene therapy in pituitary cell populations in experimental prolactinomas.
Camihort, G. A; Hereñú, C. B; Luna, G. C; Rodríguez, S. S; Bracamonte, M. I; Goya, R. G; Cónsole, G. M.
2010. Cells tissues organs. Karger. vol. 191, p. 316-325

Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats.
Morel, G. R; Sosa, Y. E; Bellini, M. J; Carri, N. G; Rodriguez, S, S; Bohn, M. C; Goya, R.
2010. Neuroscience; vol. 167 p. 946 - 953

Decrease in PTEN and increase in Akt expression and neuron size in aged rat spinal cord.
Rodríguez de Amorim, M. A; García-Segura, L. M; Goya, R, G; Portiansky, E.
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Carbohydrates and glycoforms of the major egg perivitellins from Pomacea apple snails (Architaenioglossa: Ampullariidae).
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2010. Neuroscience. Pergamon-Elsevier Science Ltd. vol. 167, p. 946-953

The ependymal route for insulin-like growth factor-1 gene therapy in the brain.
Hereñu C. B; Sonntag W.E; Morel G. R; Portiansky E. L; Goya R. G.
2009. Neuroscience. Elsevier, vol. 163, p. 442-447

Morphological Restoration of Gonadotrope Population by Thymulin Gene Therapy in Nude Mice.
Reggiani P; Martínez E; Ferese C; Goya R; Cónsole G.
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The thymus-neuroendocrine axis: physiology, molecular biology and therapeutic potential of the thymic peptide thymulin.
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2009. Annals of the New York Academy of Sciences. New York: New York Academy of Sciences. Blackwell Publishing, vol. 1153, p. 98-106

Effect of insulin-like growth factor- I gene therapy on the somatotropic axis in experimental prolactinomas.
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2009. Cells Tissues Organs. Basel: Karger AG, vol. 190, p. 20-26

Estrogen inhibits tuberoinfundibular dopaminergic neurons but does not cause irreversible damage.
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2009. Brain Research Bulletin. Amsterdam: Elsevier, vol. 80, n° 6, p. 347-352

Insulin-like growth factor-I gene therapy reverses morphologic changes and reduces hyperprolactinemia in experimental rat prolactinomas.
Console, G. M; Hereñu, C. B; Camihort, G. A; Luna, G. C; Bracamonte, M. I; Morel, G. R; Goya, R. G.
2008. Molecular cancer. Londres: Blackwell Scientific Publications, p. 7-13

Dopaminergic mesencephalic systems and motor performance in very old rats.
Sánchez, H. L; Silva, L. B; Portiansky, E. L; Hereñu, C. B; Goya, R. G.
2008. Neuroscience. USA: Elsevier, vol. 154, n° 4, p. 1598-1606

Preventive action of neonatal gene therapy with the thymic hormone thymulin on the ovarian atrophy of adult nude mice.
Reggiani, P.C; Flamini, M. A; Rodriguez, S. S; Goya, R. G; Barbeito, C. G.
2008. Biocell. Mendoza: IHEM-CONICET, vol. 32, p. 137-137

Potential of gene therapy for restoration of endocrine thymic function in thymus-deficient animal models.
Morel, G. R; Reggiani, P. C; Cónsole, G. M; Rimoldi, O. J; Vesenbeckh, S. M; García De Bravo, M; Rodríguez, S. S; Brown, O. A; Goya, R. G.
2008.Curr gene ther. Bentham Science Publishers, vol. 8 n° 1 p.49-53 ISSN 1566-5232

Potential of gene therapy for restoration of endocrine thymic function in thymus-deficient animal models.
Morel G. R; Reggiani P. C; Console, G. M; Rimoldi, O. J; Vesenbeckh, S. M; Garcia De Bravo M. M; Rodriguez, S. S; Brown, O. A; Goya, R. G.
2007. Curr gene ther... vol. 8, p. 49-53

PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes.
Cristina, C; Diaz Torga, G; Goya, R. G; Kakar, S. S; Perez Millan, M. I; Giannella Neto, D; Bronstein, M. D; Becu Villalobos, D.
2007. Molecular cancer. Inglaterra: BMC. vol. 6, p. 4-9

Fatty acid profiles in hepatic membranes of rats with different levels of circulating estrogen and prolactin.
Bellini, M. J; Carino, M; Tacconi de Gomez Dumm, I. N; Goya, R. G.
2007. Comparative biochemistry and physiology molecular and integrative physiology. USA: Elsevier. vol. 146, p. 470-474

Restorative effect of Insulin-like Growth Factor-I Gene Therapy in the Hypothalamus ofsenile rats with Dopaminergic dysfunction.
Hereñu, C. B; Cristina, C; Rimoldi, O. J; Becu-Villalobos, S; Cambiaggi, V; Portiansky, E. L; Goya, R. G.
2007. Gene therapy. Nature Publishing Group. vol. 14, p. 237-245. ISSN 0969-7128

Thymulin gene therapy prevents the reduction in circulating gonadotropins induced by thymulin deficiency in mice.
Goya, R. G; Reggiani, P. C; Vesenbeckh, S. M; Pleau, J. M; Sosa, Y. E; Console, G. M; Schade, R; Henklein, P; Dardenne, M.
2007. American journal of physiology-endocrinology and metabolism. American Physiological Society. vol. 293, p. 182-187

Implication of oxidative stress, aging and inflammatory processes in neurodegenerative diseases: growth factors as therapeutic approach.
Herrera Macarena Lorena; Falomir-Lockhart, Eugenia; Dolcetti, Franco Juan Cruz; Arnal, Nathalie; Bellini, María Jose; Hereñu, Claudia B.; Disgiulo, Pascual.
2019: Springer, p. 1-465. ISBN 978-3-319-17103-6
10.1007/978-3-319-95360-1_14

Implication of oxidative stress, aging and inflammatory processes in neurodegenerative diseases: growth factors as therapeutic approach.
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Logros y promesas de la medicina regenerativa en el tratamiento de enfermedades neurodegenerativas.
López-León, M; Lehmann, M; Goya, R. G.
2016. Universidad de Murcia (Master); 6º Ed.; Viguera Editores SLU; Barcelona; 2016. Capítulo en el libro “Desordenes del Movimientro”.

Medicina regenerativa para el tratamiento de enfermedades nuerodegenerativas.
López-León, M: Goya, R. G.
2015. Universidad de Murcia (Master); 5º Ed.; Viguera Editores SLU; Barcelona. Capítulo en el libro “Desordenes del Movimientro”

Gene Delivery Systems.
Pereyra, A. S; Hereñu, C. B.; Romanovsky, V; Zgela, V; Bakic, S.
2013. Editorial InTech, p. 165-192. ISBN 978-953-51-1207-5

Neuroendocrine system and aging: growth hormone, thyroid stimulating hormone, prolactin and insulin.
Sonntag William, E; Hereñú, C. B; Goya, R. G.
2008. New York. New Encyclopedia of Neuroscience.

Neuroendocrine Aging: Pituitary-metabolism.
Sonntag W. E; Hereñú, C. B.
2006. New Encyclopedia of Neuroscience; p. 1-18



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