Ogundele, Olalekan Michael
Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA.
Outeiro, Tiago
Department of Neurodegeneration and Restorative Research, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center Göttingen, Göttingen, Alemania.
Abba, Martín Carlos
Centro de Investigaciones Inmunológicas Básicas y Aplicadas (CINIBA), Facultad de Ciencias Médicas, (UNLP).
Cambiaggi, Vanina
Facultad de Ciencias Veterinarias. U.N.L.P. La Plata. Prov. de Buenos Aires. Argentina.
Hereñú, Claudia B.
IFEC- Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba.
Lacunza, Ezequiel
Centro de Investigaciones Inmunológicas Básicas y Aplicadas (CINIBA), Facultad de Ciencias Médicas, (UNLP).
Portinasky, E. L.
Facultad de Ciencias Veterinarias. U.N.L.P. La Plata. Prov. de Buenos Aires. Argentina.
Zuccolilli, Gustavo
Facultad de Ciencias Veterinarias. U.N.L.P. La Plata. Prov. de Buenos Aires. Argentina.
In humans and in various mammalian species, the aging process generally leads to alterations in plasticity and synaptic transmission in different regions of the brain, and is correlated with behavior, learning and memory imapaiment. The knowledge that aging is the main risk factor for neurodegenerative diseases drives us to want to elucidate the mechanisms that separate the thin line between a brain with normal aging and one like the pathognomonic of Alzheimer's disease or Lewy body dementia.
Our research group has a long history of studying the aging female rat of the Sprague-Dawley strain as a model of spontaneous neural disfunction.
One of the objectives of this line is to characterize the limbic system brain structures such as the hippocampus, amygdala, hypothalamus and related brain structures in the aged (28 months old) and the middle-aged rat (12 months old). of age), which present an age-related cognitive deficit. The characterization is carried out from the cognitive, histopathological and molecular levels.
Cognitive function is assessed using the Barnes Maze which determines spatial reference memory retention and working memory. We also use other methods that determine object recognition memory in different paradigms that evaluate the object location or characteristic (SOR and NOR, respectively).
To analyze the impact of aging on brain structures, immunolabeling techniques (immunohistochemistry and immunofluorescence), are approach white bright, fluorescence and confocal microscopy coupled with morphometric methods based on stereology by software such as Image Pro Plus and Image J.
At the molecular level, gene expression is evaluated in the different brain structures by PCR or RNAseq and protein expression by Western blot.
Another objective is to imitate or reinforce the protective mechanisms that are diminished, silenced or depleted in the aging brain. As a therapeutic strategy we use gene therapy and as a biotechnological tool we construct adenoviral and lentiviral vectors that carry genes such as IGF-I, GDNF, TYROBP and the Yamanaka genes (Sox2, c-Myc, Klf4 and Oct4).
Age-related loss of recognition memory and its correlation with hippocampal and perirhinal cortex changes in female Sprague Dawley rats.
Canatelli-Mallat M, Chiavellini P, Lehmann M, Goya RG, Morel GR.
2022. Behav Brain Res. Oct 28; 435:114026.Epub 2022 Aug 5. PMID: 35940248
doi: 10.1016/j.bbr.2022.114026
Hippocampal DNA Methylation, Epigenetic Age, and Spatial Memory Performance in Young and Old Rats.
Chiavellini P, Lehmann M, Canatelli Mallat M, Zoller JA, Herenu CB, Morel GR, Horvath S, Goya RG.
2022. J Gerontol A Biol Sci Med Sci. Dec 29;77(12):2387-2394. PMID: 35917578
doi: 10.1093/gerona/glac153
Systemic oxidative stress in old rats is associated with both osteoporosis and cognitive impairment.
Torres ML, Wanionok NE, McCarthy AD, Morel GR, Fernández JM.
2021. Exp Gerontol. Dec;156:111596. Epub 2021 Oct 19. PMID: 34678425
doi: 10.1016/j.exger.2021.111596
Therapeutic potential of glial cell line-derived neurotrophic factor and cell reprogramming for hippocampal-related neurological disorders.
Chiavellini, Priscila; Canatelli-Mallat, Martina; Lehmann, Marianne; Goya, Rodolfo; Morel, Gustavo R.
2021. Neural regeneration research. Shangai: SHENYANG EDITORIAL DEPT NEURAL REGENERATION RES, vol. 17, n° 3, p. 469-476. ISSN 1673-5374
Cryopreservation of a Human Brain and Its Experimental Correlate in Rats.
Canatelli-Mallat, Martina; Lascaray, Francisco; Entraigues-Abramson, Maria; Portiansky, Enrique L.; Blamaceda, Néstor; Morel, Gustavo R.; Goya, Rodolfo G.
2020. Rejuvenation research: MARY ANN LIEBERT INC, vol. 23, n° 6, p. 516-525. ISSN 1549-1684
doi.org/10.1089/rej.2019.2245
Mesenchymal Stem Cells Therapy Improved the Streptozotocin-Induced Behavioral and Hippocampal Impairment in Rats.
Zappa Villar, María F.; López Hanotte, Juliette; Pardo, Joaquín; Morel, Gustavo R.; Mazzolini, Guillermo; García, Mariana G; Reggiani, Paula C.
2020. Molecular neurobiology. HUMANA PRESS INC, vol. 57, p. 600-615
doi.org/10.1007/s12035-019-01729-z
Mesenchymal stem cell therapy improves spatial memory and hippocampal structure in aging rats.
Zappa Villar, Maria F.; Lehmann, Marianne; García, Mariana G.; Mazzolini, Guillermo; Morel, Gustavo R.; Cónsole, Gloria M.; Podhajcer, Osvaldo; Reggiani, Paula C.; Goya, Rodolfo G.
2019: Behavioural brain research. Amsterdam: ELSEVIER SCIENCE BV, p. 1-5
doi.org/10.1016/j.bbr.2019.04.001
Umbilical Cord Cell Therapy Improves Spatial Memory in Aging Rats.
Lehmann, Marianne; Zappa-Villar, Maria F.; García, Mariana G.; Mazzolini, Guillermo; Canatelli Mallat, Martina; Morel, Gustavo R.; Reggiani, Paula C.; Goya, Rodolfo G.
2019: Stem cell reviews and reports. SPRINGER HEIDELBERG, vol. 15, n° 4, p. 612-617
doi.org/10.1007/s12015-019-09895-2
Regulatable adenovector harboring the GFP and Yamanaka genes for implementing regenerative medicine in the brain.
Lehmann, Marianne; Canatelli-Mallat, Martina; Chiavellini, Priscila; Morel, Gustavo R.; Reggiani, Paula C.; Hereñú, Claudia B.; Goya, Rodolfo G.
2019: Gene therapy. NATURE PUBLISHING GROUP, vol. 1, n° 1, p. 1-1
doi.org/10.1038/s41434-019-0063-x
IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function.
Pardo, J; Abba, M. C; Lacunza, E; Ogundele, O. M; Paiva, I; Morel, G. R; Outeiro, T. F; Goya, R. G.
2018. Journals of gerontology series a-biological sciences and medical sciences. GERONTOLOGICAL SOC AMER, vol. 14, n° 4, p. 459-467. ISSN 1079-5006
Intracerebroventricular streptozotocin induces impaired Barnes maze spatial memory and reduces astrocyte branching in the CA1 and CA3 hippocampal regions.
Zappa Villar, M. F; López Hanotte, J; Falomir Lockhart, E; Trípodi, L. S; Morel, G. R; Reggiani, P. C.
2018. Journal of neural transmission. General section. SPRINGER WIEN, vol. 125, n° 12, p. 1787-1803. ISSN 0300-9564
Pro-apoptotic effects of low doses of dimethoate in rat brain.
Arnal, N; Morel, G; Marra, C. A; Astiz, M.
2018. Toxicology and applied pharmacology. ACADEMIC PRESS INC ELSEVIER SCIENCE, vol. 363, p. 57-63. ISSN 0041-008X
Identification of a conserved gene signature associated with an exacerbated inflammatory environment in the hippocampus of aging rats.
Pardo, J; Abba, M. C; Lacunza, E; Francelle, L; Morel, G. R; Outeiro, T. F; Goya, R. G.
2017. Hippocampus. Apr;27(4):435-449. Doi: 10.1002/hipo.22703 Epub 2017 Jan 23. PubMed PMID: 28085212
Therapeutic potential of IGF-I on hippocampal neurogenesis and function during aging.
Morel, G. R; Lopez-León, M; Uriarte Donati, M; Reggiani, P. C; Goya, R. G.
2016. Neurogenesis, Austin (Texas): London: Taylor & Francis Group, LLC, vol. 4, n° 1, ISSN 2326-2133
Insulin-like growth factor-I gene therapy increases hippocampal neurogenesis, astrocyte branching and improves spatial memory in female aging rats.
Pardo, J; Uriarte, M; Cónsole, G. M; Reggiani, P; Outeiro, T. F; Morel, G. R; Goya, R. G.
2016. Eur J Neurosci. Aug;44(4):2120-8. Epub 2016 Jun 8. PubMed PMID: 27188415
Doi: 10.1111/ejn.13278
Cognitive impairment and morphological changes in the dorsal hippocampus of very old female rats.
Morel, G; Andersen, T; Pardo, J; Zucolilli, G. O; Cambiaggi, V. L; Hereñú, C; Goya, R. G.
2015. Neuroscience. Amsterdam: PERGAMON-ELSEVIER SCIENCE LTD, p. 189-199. ISSN 0306-4522
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
Gene therapy and cell reprogramming for the aging brain: achievements and promise.
Pardo, J; Morel, G. R; Astiz, M; Schwerdt, M. I; López León, M; Rodríguez, S. S;Hereñú, C. B; Goya, R. G.
2014. Curr Gene Ther; 14:24-34
Role of copper and cholesterol association in the neurodegenerative process.
Arnal, N; Morel, G. R; Tacconi de Alaniz, M. J; Dominici, L; Marra, C. A.
2013. Int J Alzheimers Dis; 2013:414817. doi: 10.1155/2013/414817. Epub 2013 Oct 29.
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
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
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
The thymus-neuroendocrine axis: physiology, molecular biology and therapeutic potential of the thymic peptide thymulin..
Reggiani P.C; Morel G. R; Cónsole G. M; Barbeito C. G; Rodriguez S; Brown O. A; Bellini M. J; Pléau J. M; Dardenne M; Goya R. G.
2009. Annals of the New York Academy of Sciences. New York: New York Academy of Sciences. Blackwell Publishing, vol. 1153, p. 98-106
Estrogen inhibits tuberoinfundibular dopaminergic neurons but does not cause irreversible damage.
Morel, G. R; Caron, R. W; Console, G. M; Soaje, M; Sosa, Y. E; Rodríguez, S. S; Jahn, G. A; Goya, R. G.
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
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
Neuroprotective gene therapy in the aging brain; In: Estrogens and Cognition.
Pardo J, Morel GR, Pereyra AS, López-León M, Brown-OA, Bellini MJ, Goya RG.
2014. Psychobiological and Clinical Aspects, 2014:97-117 ISBN: 978-81-308-0550-4 Editor: González-Burgos, I.
“Expresión génica diferencial de hipocampo en un modelo de envejecimiento cerebral tratado con terapia génica de largo plazo”< Presentación oral.
Trabajo: Pardo, J; Abba, M; Lacunza, E; Schwerdt, J; Cónsole, G; Outeiro, T; Morel, G; Goya, R
2015. Premio al mejor trabajo en investigación básica en el 2º Congreso Internacional de la Facultad de Cs Médicas de la UNLP.
