ONE HEALTH / Noncommunicable chronic diseases / Neurodegenerative diseases

Laboratory of neurobiology and cognition in aging and neurodegenerative diseases

Neurobiology of brain aging and therapies to protect cognitive function

Work team

Principal Investigator

Morel, Gustavo Ramón

gustavmorel@med.unlp.edu.ar

Gómez Martínez, Carlos D.

Investigator

cgomezmartinez@med.unlp.edu.ar

Diana Camila Pasquini

Research Fellow
dpasquini@med.unlp.edu.ar

Collaborators from other institutions

Matiazzi Alicia
Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani - CIC

Tasso, Mariana
Instituto de Nanosistemas - Universidad Nacional de San Martín - UNSM

Franco, Paula
Instituto de Química y Fisicoquímica Biológicas "Prof. Alejandro C. Paladini" - [IQUIFIB] Facultad de Medicina - UBA

Fernández, Juan Manuel
Laboratorio de investigación en osteopatías y metabolismo mineral (LIOMM). Facultad de Ciencias Exactas - UNLP

Mac Carthy, Antonio
Laboratorio de investigación en osteopatías y metabolismo mineral (LIOMM). Facultad de Ciencias Exactas - UNLP

Line overview

In humans and various species of mammals, the aging process generally leads to alterations in plasticity and synaptic transmission in different regions of the brain and is correlated with alterations in behavior, learning, and memory. The knowledge that aging is the main risk factor in neurodegenerative diseases drives us to want to elucidate the thin line that separates a brain with normal aging from a brain with Alzheimer's disease.
Our research group has a long history of studying the female Sprague-Dawley rat as a model of normal brain aging.
One of our lines of research focuses on characterizing the brain structures that make up the limbic system, such as the hippocampus, amygdala, hypothalamus, and related cortical structures, in senescent rats (24 months old) and middle-aged rats (12 months old) and correlating these changes with cognitive deficits. The characterization is carried out at the cognitive, histopathological, and molecular levels.
Cognitive function is assessed using the Barnes Maze, which determines the retention of spatial reference memory, and working memory. We also use other methods that determine object recognition memory in different paradigms that assess the location or characteristics of objects (SOR and NOR, respectively).
To analyze the impact of aging on brain structures, immunostaining techniques (immunohistochemistry and immunofluorescence), white light microscopy, fluorescence, and confocal microscopy coupled with morphometric methods based on stereology using software such as Image Pro Plus and Image J are applied. From the perspective of neuronal functionality, we are installing a system to measure the field potential in the brain.
At the molecular level, gene expression is evaluated in the different brain structures by PCR or RNAseq, and protein expression is evaluated by Western blot.
Another objective is to imitate or reinforce the protective mechanisms that are diminished, silenced, or depleted in brain aging. As a therapeutic strategy, we use drugs such as metformin, genes for gene therapy, and extracellular vesicles derived from microglial cells. To perform gene therapy, we established a biotechnological platform for the construction of adenoviral and lentiviral vectors that express genes such as IGF-I, GDNF, TYROBP and the Yamanaka genes (Sox2, c-Myc, Klf4, and Oct4).

Osteoporosis and Alzheimer´s disease (or Alzheimer´s disease and Osteoporosis).
Wanionok, N. E; Morel, G. R; Fernández, J. M.
2024. Ageing Res Rev. 2024 Aug; 99:102408. Epub 2024 Jul 3. PMID: 38969142 Review.
doi: 10.1016/j.arr.2024.102408

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.

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