EVALUATION OF THE EFFECTS OF SULFORAPHANE OR KETONE BODY TREATMENT IN CELL CULTURE WITH KLOTHO DELETION

• Grant number: 22/09125-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2022
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Elisa Mitiko Kawamoto Iwashe
• Grantee: Isis Oliveira Menezes
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/07427-8 - Aging and neuroprotection: effects of Klotho protein in energetic metabolism, Na,K-ATPase signaling and adaptative response in central nervous system, AP.TEM

Abstract

Neural progenitor cells are cells with capacity for renewal and differentiation into neurons and glia cells, important cell types in the recomposition of brain tissue. Studies with murine neurospheres deficient in Klotho (a protein that at absent or low levels is associated with damage to cognition, synaptic plasticity, and cell proliferation) have already pointed to affected neurogenesis in the postnatal period (damage to proliferation and differentiation), whose negative impacts were attenuated with supplementation with secreted Klotho. Cell exposure to sub-toxic doses of some substances produced during exercise, fasting and caloric restriction can induce a cellular adaptive response to insults (hormesis). Sulforaphane (SF: a plant derivative considered a mimetic of caloric restriction) and ²-hydroxybutyrate can be used in cell cultures to mimic hormetic parameters induced in vivo. SF is pointed as a promising potential phytochemical in the treatment of autistic spectrum disorder, impaired communication and social interaction, and, ²HB acts by attenuating cellular damage in models of Alzheimer's disease (AD) and Parkinson's disease (PD), in addition to reducing, in animal models, the symptoms of AD pathology and protects against motor deficits and neurodegeneration. Considering the complexity and importance of neuronal cell development, and being Klotho important to delay or reverse progenitor cell depletion and neuroprotection, we aim in this research, to identify whether treatments with SF or ²HB would be able to modulate the proliferation and differentiation of neuronal progenitor cells (from C57BL/6 mice) with silenced Klotho (deleted).