Modulation of inflammatory response and glial cells reactivity
in neurodegeneration models

Team of work

Principal InvestigatorBellini

Bellini, María José

Investigator
mariajosebellini@med.unlp.edu.ar

Cervellini, SofíaCervellini

Research Fellow
soficervellini@gmail.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

Main interests:

Our main interest is focused on elucidate the mechanisms leading to neurodegeneration during aging, basically those related to the inflammatory response.
The essential objective of our work is to develop therapeutic strategies that recover age-affected neuronal populations. The possibility of employing neurotrophic factors that prevent neurodegeneration, increase neuron recovery and regulate inflammatory response is clinically relevant.

Inflammation:

Chronic inflammation plays a key role in most common neurodegenerative diseases.
A possible therapeutic target for the treatment of the disease can be blocking the source of that inflammation.
Microglia and astrocytes are the main effector cells that contribute to brain inflammation.

Objectives:
• To investigate the possible restoring, neuroprotective, and/or anti-inflammatory effects of IGF-I in aging rodents and experimental models of neurodegenerative diseases.
• To determine if aging and sexual differences can affect their neuroprotective action.
• To elucidate the cellular and molecular mechanisms of the anti-inflammatory activity of IGF-I in the brain.
• To study the role of glial cells as mediators of IGF-I effects.
• To characterize the changes in the lipid composition associated to age and sex.

Lines of work

1-Cell reprogramming and gene therapy for the treatment of motor dopaminergic neurodegeneration.
Principal Investigator: Eugenia Falomir-Lockhart

The ultimate objective of the present project is to study comprehensively the motor-nervous system applying strategies of gene therapy and regenerative medicine in the dopaminergic system (nigro-striatal) in order to improve the age-related deficiencies in the motor pathways of the encephalic dopaminergic system.

2-Hypothalamus as aging regulating center - Anti-inflammatory gene therapy.
Principal Investigator:Dolcetti, Franco

The central hypothesis of the present plan is that the transfer of neuroprotective genes constitutes an effective strategy to diminish the inflammatory response in the aging, constituting a possible treatment of diverse age-related neurodegenerative processes. In particular we consider that intrahypothalamic gene therapy for insulin-like growth factor type I (IGF-I) would module the immune response with the subsequent delay in the onset of aging-associated damages and/or their improvement once they have occurred.

Aging is the result of multiple physiological changes, and the hypothalamus can be an underlying mediator representing a target of controlling strategies to counteract aging and aging-related diseases.


IGF1 gene therapy in middle-aged female rats delays reproductive senescence through its effects on hypothalamic GnRH and kisspeptin neurons.
Dolcetti, Franco Juan Cruz; Falomir-Lockhart, Eugenia; Acuña, Francisco; Herrera, Macarena Lorena; Cervellini, Sofia; Barbeito, Claudio Gustavo; Grassi, Daniela; Arevalo, Mariaangeles; Bellini, María José.
2022. Aging. : Impact journals, 2022 - . vol. 1, p. 8615-8632. ISSN 1945-4589
DOI: 10.18632/aging.204360

IGF-1 Gene Transfer Modifies Inflammatory Environment and Gene Expression in the Caudate-Putamen of Aged Female Rat Brain.
Falomir-Lockhart, Eugenia; Dolcetti, Franco Juan Cruz; Herrera, Macarena Lorena; Pennini, Jerónimo; Zappa Villar, María Florencia; Salinas, Gabriela; Portiansky, Enrique; Spittau, Björn; Lacunza, Ezequiel; Hereñú, Claudia Beatriz; Bellini, María José.
2022. Molecular neurobiology. Oregon: HUMANA PRESS INC. vol. 59, n° 6, p. 3337-3352. ISSN 0893-7648
DOI: 10.1007/s12035-022-02791-w

Intramuscular insulin-like growth factor-1 gene therapy modulates reactive microglia after traumatic brain injury.
Herrera, Macarena Lorena; Bandín, Sandra; Champarini, Leandro Gabriel; Hereñú, Claudia Beatriz; Bellini, Maria Jose.
2021. Brain research bulletin. PERGAMON-ELSEVIER SCIENCE LTD, - vol. 175, p. 196-204. ISSN 0361-9230

IGF1 Gene Therapy Reversed Cognitive Deficits and Restored Hippocampal Alterations After Chronic Spinal Cord Injury.
Jure, Ignacio; Lockhart, Eugenia Falomir; De Nicola, Alejandro F.; Bellini, María Jose; Labombarda, Florencia.
2021. Molecular neurobiology. Oregon: HUMANA PRESS INC,- . vol. 58, n° 12, p. 6186-6202. ISSN 0893-7648

Intracisternal IGF-1 gene therapy abrogates kainic acid-induced excitotoxic damage of the rat spinal cord.
Nishida, Fabián; Zanuzzi, Carolina N. (Idéntica Contribución Con El Primer Autor); Sisti, María S.; Falomir Lockhart, Eugenia; Camiña, Agustina E.; Hereñú, Claudia B.; Bellini, María J.; Portiansky, Enrique L.
2020. European journal of neuroscience. Londres: WILEY-BLACKWELL PUBLISHING, INC, 2020 -. vol. 52, n° 5, p. 3339-3352. ISSN 0953-816X
doi.org/10.1111/ejn.14876

Dancing with Glia: The Role of Astrocytes, Microglia and Oligodendrocytes and their Relation with Neurons in Neuroinflammation and Aging.
Macarena Lorena Herrera; Franco Juan Cruz Dolcetti; Eugenia Falomir-Lockhart; Leandro Champarini; Jeronimo Peninni; Claudia B Hereñú; Maria José Bellini.
2020. Open access journal of biomedical science. Biomedscis, 2020 - vol. 3, p. 732-741
doi.org/10.38125/OAJBS.000238

Modulating Glial Cells Phenotype: New Findings and Therapies.
Bellini, María José; Diz-Chaves, Yolanda; Ramos, Alberto Javier.
2020. Frontiers in aging neuroscience. Frontiers Media S.A., 2020 - . vol. 12
doi.org/10.3389/fnagi.2020.594870

Early Cognitive Impairment Behind Nigrostriatal Circuit Neurotoxicity: Are Astrocytes Involved?.
Herrera, Macarena L.; Deza-Ponzio, Romina; Ghersi, Marisa S.; De La?Villarmois, Emilce A.; Virgolini, Miriam B.; Pérez, Mariela F.; Molina, Victor A.; Bellini, María J * Corresponding Author, Equally Contribution; Hereñú, Claudia B. * Corresponding Author, Equally Contribution.
2020. Asn neuro. Thousand Oaks: SAGE, 2020 - vol. 12, ISSN 1759-0914
doi.org/10.1177/1759091420925977

Sex frailty differences in ageing mice: Neuropathologies and therapeutic projections.
Herrera, Macarena Lorena; Basmadjian, Osvaldo Martin; Falomir-Lockhart, Eugenia; Dolcetti, Franco Juan?Cruz; Hereñú, Claudia Beatriz * Corresponding Author, Equally Contribution; Bellini, María José * Corresponding Author, Equally Contribution.
2020. European journal of neuroscience. Londres: WILEY-BLACKWELL PUBLISHING, INC, p. 2827-2837. ISSN 0953-816X
doi.org/10.1111/ejn.14703

IGF1 Gene Therapy Modifies Microglia in the Striatum of Senile Rats. Frontiers in aging neuroscience.
Falomir-Lockhart E; Dolcetti, Franco Juan Cruz; García-Segura, Luis M.; Hereñu, Claudia B.; Bellini, Maria J.
2019: Lausanne: Frontiers Research Foundation. ISSN 1663-4365
doi.org/10.3389/fnagi.2019.00048

Novel adenoviral IGF-1 administration modulates the association between depressive symptoms and aging: Does gender matter?
Herrera, Macarena Lorena; Basmadjian, Osvaldo Martín; Falomir Lockhart, Eugenia; Dolcetti, Franco Juan-Cruz; Hereñú, Claudia Beatriz; Bellini, María José.
2019: Behavioural brain research. Amsterdam: ELSEVIER SCIENCE BV, vol. 372, ISSN 0166-4328
doi.org/10.1016/j.bbr.2019.112050

Physical, histological, endocrinological and steroidogenical evaluation of male cats postnatally exposed to sexual steroids.
Grisolia, M.; Faya, M.; Marchetti, C.; Merlo, M. López; D´Francisco, F.; Bellini, M. J.; Gobello, C.
2019: Theriogenology. Amsterdam: ELSEVIER SCIENCE INC, vol. 138, p. 47-51. ISSN 0093-691X
doi.org/10.1016/j.theriogenology.2019.06.041

Estradiol Activates PI3K/Akt/GSK3 Pathway Under Chronic Neurodegenerative Conditions Triggered by Perinatal Asphyxia.
Saraceno, G. E; Bellini, M. J; García-Segura, L. M; Capani, F.
2018. Frontiers in pharmacology. Lausanne: Frontiers Media. vol. 9.
doi.org/10.3389/fphar.2018.00335

Exploring the effects of IGF-1 gene therapy to modulate neuroinflammation.
Falomir-Lockhart, E; Dolcetti, F. J. C; Anesetti-Nelli, S. J; Hereñu, C. B; Bellini, M. J.
2017. Glia: Wiley-Liss, Div John Wiley & Sons Inc. vol. 65, n° S1, p. 90-91. ISSN 0894-1491

Deterioro cognitivo asociado a la patología parkinsoniana: El rol del hipocampo.
Herrera, M. L; Falomir Lockhart, E; Dolcetti, F. J. C; Bellini, M. J; Hereñu, C. B.
2016. Ciencia insitu: Federación Argentina Científica de Estudiantes de la Salud, vol. 1, n° 2, p. 23-27. ISSN 2469-2433

Estrogen actions on glial reactivity and inflammation-mediated memory impairment: Sex differences and interaction with other neurotrophic factors.
Bellini, M. J.
2015. González-Burgos (Ed.); Nova Science Publishers, July 01, 2015, Pages 155-174

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

Estradiol and testosterone regulate arginine-vasopressin expression in SH-SY5Y human female neuroblastoma cells through estrogen receptors-α and -β.
Grassi, D; Bellini, M. J; Acaz-Fonseca, E; Panzica, G; Garcia-Segura, L. M.
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.
Diz-Chaves, Y; Astiz, M; Bellini, M. J; Garcia-Segura, L. M.
2013. Brain Behavior and Immunity. Amsterdam: Academic Press Inc Elsevier Science. vol. 28, p. 196-206. ISSN 0889-1591

Influence on Effectiveness of Early Treatment with Anti-TNF Therapy in Rheumatoid Arthritis.
Escudero-Vilaplana, V; Ramírez-Herraiz, E; Trovato-López, N; Alañón-Plaza, E; Bellini, M; Herranzalonso, A; Bellón-Cano, J.M; Morell-Baladrón, A; Sanjurjo-Sáez, M.
2012. Journal of pharmacy and pharmaceutical sciences. : Canadian Soc Pharmaceutical Sciences, vol. 15, n° 3, p. 355-360

Selective oestrogen receptor modulators decrease the inflammatory response of glial cells.
Arevalo, M.A; Diz-Chaves, Y; Santos-Galindo, M; Bellini, M.J; Garcia-Segura, L.M.
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.
Pietranera, L; Bellini, M. J; Arévalo, M. A; Goya, R; Brocca, M. E; García Segura, L. M; De Nicola, A. F.
2011. Neuroscience, 174: p. 151-159

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

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

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

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.
Herrera, M. L; Falomir-Lockhart, E; Dolcetti, F. J. C; Arnal, N; Bellini, M. J; Hereñu, C. B; Gargiulo, P. A; Mesones Arroyo, H. L.
2018. Springer, p. 165-176. ISBN 978-3-319-95359-5




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