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Evaluation of PTEN compartmentalization on neurogenesis and synaptic plasticity influenced by environmental factors

Grant number: 11/21308-8
Support type:Research Grants - Young Investigators Grants
Duration: January 01, 2013 - December 31, 2016
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Elisa Mitiko Kawamoto Iwashe
Grantee:Elisa Mitiko Kawamoto Iwashe
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Cristoforo Scavone ; Luiz Roberto Giorgetti de Britto ; Rui Curi
Associated scholarship(s):15/25491-2 - Evaluation of the effects of the Klotho protein on the neuronal morphological alteration characteristics of the lack of PTEN protein, BP.MS
14/18689-8 - Evaluation of the PTEN signaling effects over neurogenesis and cognition of mice under a physical exercise regimen, BP.MS
13/20594-2 - Characterization of the PTEN signaling biochemical effects on mice hippocampi under intermittent diet, BP.IC
12/22605-9 - Evaluation of PTEN compartmentalization on neurogenesis and synaptic plasticity influenced by environmental factors, BP.JP


Studies have suggested that both genetic and environmental factors can affect neurogenesis and synaptic plasticity. For example, dietary restriction and physical exercise have both shown to exert beneficial effects in processes associated with aging, as well as cardiovascular, neurodegenerative, and endocrine diseases (i.e. diabetes). A better understanding of the underlying signaling mechanisms can lead to prevention or therapy improvement of central nervous system's related diseases. PTEN (Phosphatase and tensin homolog on chromosome ten) is a tumor suppressor acting or not through its phosphatase activity. Studies have concentrated on investigating mechanisms associated to tumorigenesis. However since PTEN regulates proliferation, survival and cell migration it can be involved in neurogenesis and synaptic plasticity. Its cellular localization can be cytosolic or nuclear, yet its functions in the nucleus are largely understood.This project aims to study the effects of PTEN compartmentalization (cytosol/nucleus) in neurogenesis and synaptic plasticity under the influence of environmental factors like dietary restriction (intermittent fasting) and physical exercise in the hippocampus of PTEN conditional knockout mice.The results of this study will contribute to a better understanding of the signaling pathways directly or indirectly involved with neurogenesis and synaptic plasticity, and could help defining new strategies for the treatment of ailments associated with the deletion or mutation of the PTEN gene such as tumors and, possibly, neurodegenerative diseases. (AU)

Scientific publications
(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)
CABRAL-COSTA, J. V.; ANDREOTTI, D. Z.; MELLO, N. P.; SCAVONE, C.; CAMANDOLA, S.; KAWAMOTO, E. M. Intermittent fasting uncovers and rescues cognitive phenotypes in PTEN neuronal haploinsufficient mice. SCIENTIFIC REPORTS, v. 8, JUN 5 2018. Web of Science Citations: 1.
KINOSHITA, PAULA F.; YSHII, LIDIA M.; ORELLANA, ANA MARIA M.; PAIXAO, AMANDA G.; VASCONCELOS, ANDREA R.; LIMA, LARISSA DE SA; KAWAMOTO, ELISA M.; SCAVONE, CRISTOFORO. Alpha 2 Na+,K+-ATPase silencing induces loss of inflammatory response and ouabain protection in glial cells. SCIENTIFIC REPORTS, v. 7, JUL 7 2017. Web of Science Citations: 2.
CARARO-LOPES, MARINA MINTO; YOKOYAMA MAZUCANTI, CAIO HENRIQUE; SCAVONE, CRISTOFORO; KAWAMOTO, ELISA MITIKO; BERWICK, DANIEL CHARLES. The relevance of alpha-KLOTHO to the central nervous system: Some key questions. AGEING RESEARCH REVIEWS, v. 36, p. 137-148, JUL 2017. Web of Science Citations: 13.

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