Degeneration and development of the nervous system: the role of epigenetic processes

• Grant number: 19/17892-8
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2020
• End date: February 28, 2023
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Alexandre Hiroaki Kihara
• Grantee: Alexandre Hiroaki Kihara
• Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated researchers: Érika Reime Kinjo

Abstract

The complexity of the nervous system materializes both in its formation during development and in processes related to neurodegeneration. Relevant factors in both degeneration and development are those related to epigenetic regulation. In fact, epigenetic regulation seems to be important for tissue response in neurodegenerative processes, including the initial inflammatory response. On the other hand, during development, the availability of genetic information through mechanisms that include microRNA regulation, another process of epigenetic regulation, seems to be fundamental for determining neuronal differentiation. In this project, we are interested in determining aspects related to epigenetic regulation in degeneration and development of the nervous system. Specifically, we intend to evaluate the role of the enzyme EZH2 during spinal cord neurodegeneration after mechanical trauma, as well as argonaute protein 2 (AGO2) in the neuronal differentiation that occurs during retinal development. For this, we will employ molecular and cellular biology techniques. It should be noted that our group masters the proposed methodologies, notably those related to our internships held at research or technological development institutions, such as University of Florida (2011), Plexon Neurotechnology (2011) and Cold Spring Harbor (2012). Our goal is to determine whether control of the activity and expression of the enzyme EZH2 could become a therapeutic target for the treatment of spinal cord injury, as well as AGO2 for degenerative retinal diseases that mainly affect specific neuronal subtypes, such as rods in retinitis pigmentosa, cones in age-related macular degeneration and ganglion cells in glaucoma. This proposal is supported by Dra. Jean X. Jiang (Harvard University / University of Texas Health Science Center, USA), Stephanie M. Willerth (University of Victoria, Canada), Florence E. Perrin (University of Montpellier, France), Sten Rüdiger (Humboldt University, Germany) and other research groups based at the University of São Paulo, UFMG and INPE, as well as postdoctoral students, and graduate and undergraduate students engaged with this proposal. It is important to highlight that the support given to this proposal will be essential for the continuity of projects linked to the FAPESP postdoctoral fellowships (17/ 18977-1), doctorate (16/17329-3), master's degree (17/26388-6, 18/06316-3 and 18/23775-1) and scientific initiation (18/19300-8). Finally, it should be stressed that several research groups from our institution will benefit with this proposal, since UFABC research laboratories are multi-user facilities. (AU)

Scientific publications

(10)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SCHUETTE, PETER J.; IKEBARA, JULIANE M.; MAESTA-PEREIRA, SANDRA; TOROSSIAN, ANITA; SETHI, EKAYANA; KIHARA, ALEXANDRE H.; KAO, JONATHAN C.; REIS, FERNANDO M. C., V; ADHIKARI, AVISHEK. GABAergic CA1 neurons are more stable following context changes than glutamatergic cells. SCIENTIFIC REPORTS, v. 12, n. 1, p. 18-pg., 2022-06-20. (16/17329-3, 17/08668-1, 19/17677-0, 19/17892-8, 15/23092-3)

TRUJILLO, CLEBER A.; RICE, EDWARD S.; SCHAEFER, NATHAN K.; CHAIM, ISAAC A.; WHEELER, EMILY C.; MADRIGAL, ASSAEL A.; BUCHANAN, JUSTIN; PREISSL, SEBASTIAN; WANG, ALLEN; NEGRAES, PRISCILLA D.; et al. Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment. Science, v. 371, n. 6530, p. 694+, FEB 12 2021. (19/15024-9, 19/17892-8, 17/18977-1)

MARINHO, LUCIANA SIMOES RAFAGNIN; CHIARANTIN, GABRIELLY MARIA DENADAI; IKEBARA, JULIANE MIDORI; CARDOSO, DEBORA STERZECK; DE LIMA-VASCONCELLOS, THEO HENRIQUE; HIGA, GUILHERME SHIGUETO VILAR; FERRAZ, MARIANA SACRINI AYRES; DE PASQUALE, ROBERTO; TAKADA, SILVIA HONDA; PAPES, FABIO; et al. The impact of antidepressants on human neurodevelopment: Brain organoids as experimental tools. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, v. 144, p. 10-pg., 2023-03-17. (19/17892-8, 20/16268-6, 20/11451-7, 20/02035-0, 21/11969-9, 20/11667-0, 19/15024-9, 16/17329-3)

MARQUES, BRUNO L.; MACIEL, GIOVANA FIGUEIREDO; BRITO JUNIOR, MARCELLO R.; DIAS, LUCAS D.; SCALZO, SERGIO; SANTOS, ANDERSON K.; KIHARA, ALEXANDRE HIROAKI; SANTIAGO, HELTON DA COSTA; PARREIRA, RICARDO C.; BIRBRAIR, ALEXANDER; et al. Regulatory mechanisms of stem cell differentiation: Biotechnological applications for neurogenesis. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, v. 144, p. 9-pg., 2023-03-17. (19/17892-8, 20/11667-0)

BORGES, F. S.; GABRICKC, E. C.; PROTACHEVICZ, P. R.; HIGA, G. S. V.; LAMEU, E. L.; RODRIGUEZ, P. X. R.; FERRAZ, M. S. A.; SZEZECH JR, J. D.; BATISTA, A. M.; KIHARA, A. H.. Intermittency properties in a temporal lobe epilepsy model. Epilepsy & Behavior, v. 139, p. 9-pg., 2023-01-16. (22/09277-4, 16/16148-5, 22/13761-9, 19/17892-8, 17/18977-1, 19/15024-9, 20/04624-2, 11/19296-1, 15/07311-7)

DE SOUSA, ERICA; MOVIO, MARILIA INES; DE LIMA-VASCONCELLOS, THEO HENRIQUE; DOS SANTOS, GABRIELI BOVI; GOMES, TALITA DOS SANTOS; WALTER, LAIS TAKATA; DA SILVA, DANIELA ALMEIDA; RODRIGUES, TIAGO; CERCHIARO, GISELLE; KIHARA, ALEXANDRE HIROAKI. VDAC1 regulates neuronal cell loss after retinal trauma injury by a mitochondria-independent pathway. CELL DEATH & DISEASE, v. 13, n. 4, p. 14-pg., 2022-04-21. (19/17892-8)

AYRES FERRAZ, MARIANA SACRINI; KIHARA, ALEXANDRE HIROAKI. Beyond randomness: Evaluating measures of information entropy in binary series. PHYSICAL REVIEW E, v. 105, n. 4, p. 13-pg., 2022-04-01. (15/50122-0, 19/15024-9, 19/17892-8)

ALMEIDA, CAYO; PONGILIO, RENAN PASCHOALINO; MOVIO, MARILIA INES; HIGA, GUILHERME SHIGUETO VILAR; RESENDE, RODRIGO RIBEIRO; JIANG, JIANXIONG; KINJO, ERIKA REIME; KIHARA, ALEXANDRE HIROAKI. Distinct Cell-specific Roles of NOX2 and MyD88 in Epileptogenesis. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 10, p. 8-pg., 2022-07-04. (20/11667-0, 19/17892-8)

MOVIO, MARILIA INES; DE LIMA-VASCONCELLOS, THEO HENRIQUE; DOS SANTOS, GABRIELI BOVI; ECHEVERRY, MARCELA BERMUDEZ; COLOMBO, ELISABETTA; MATTOS, LEONARDO S.; RESENDE, RODRIGO RIBEIRO; KIHARA, ALEXANDRE HIROAKI. Retinal organoids from human-induced pluripotent stem cells: From studying retinal dystrophies to early diagnosis of Alzheimer?s and Parkinson?s disease. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, v. 144, p. 10-pg., 2023-03-17. (21/14227-3, 21/03711-1, 19/17892-8, 20/02035-0, 20/11667-0, 21/11969-9, 17/26388-6)

DA SILVA, VICTOR A.; BOBOTIS, BIANCA C.; CORREIA, FELIPE F.; LIMA-VASCONCELLOS, THEO H.; CHIARANTIN, GABRIELLY M. D.; DE LA VEGA, LAURA; LOMBELLO, CHRISTIANE B.; WILLERTH, STEPHANIE M.; MALMONGE, SONIA M.; PASCHON, VERA; et al. The Impact of Biomaterial Surface Properties on Engineering Neural Tissue for Spinal Cord Regeneration. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 17, p. 25-pg., 2023-09-01. (17/12112-9, 18/06316-3, 18/19300-8, 19/17892-8, 19/18921-1, 20/02035-0, 20/11667-0, 21/11969-9, 19/24406-2)