A rational approach to improve the biotechnological investigation of lithium in microdosis using induced pluripotent stem cells

• Grant number: 18/05288-6
• Support Opportunities: Scholarships abroad - Research
• Effective date (Start): October 01, 2018
• Effective date (End): January 31, 2019
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Tânia Araújo Viel
• Grantee: Tânia Araújo Viel
• Host Investigator: Julie Kay Andersen
• Host Institution: Escola de Artes, Ciências e Humanidades (EACH). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Research place: Buck Institute for Research on Aging, United States

Abstract

The aging process has attracted the world's attention due to the increased incidence of debilitating and chronic conditions in elderly populations. The number of elderly people is growing throughout the world. Together with this phenomenon, important social, economic, environmental and health challenges have emerged. The interest for studies to better understand biological changes during the aging process is not only related to the lifespan, but most importantly to the healthspan of older individuals and factors that can impact on these changes. As a consequence, in the last few years our research group has concentrated on the influence of environmental changes, in particular the use of functional food nutrients and lithium carbonate (Li2CO3) at microdose levels as neuroprotectants that allow memory maintenance during both natural aging and in conjunction with Alzheimer's disease (AD). It is hypothesized that such treatments can help maintain cognitive function by forming both structural reserves (maintenance of neuronal density and synaptic connectivity) and functional reserves (efficacy of neuronal circuitry). Most of our studies to date have been performed using animal models, observing their behavior and studying the molecular changes in proteins related to neuroplasticity, neuroinflammation and neuroprotection. One of our studies, however, was performed in human patients, where we demonstrated memory maintenance in aged people diagnosed with AD who were also administered low-dose lithium as a complementary therapy to classic pharmacological treatment. Although there are several anatomical, functional and behavioral similarities between rodents and humans, the changes noted in animal models do not necessarily directly reflect the changes which occur during human dementia or natural aging, making the need for relevant human models an essential for the advancement of knowledge and treatment of chronic human diseases. In the present proposal, we plan to use induced pluripotent stem cells (iPSCs)-derived neurons and astrocytes from older individuals to study the molecular mechanisms underlying the neuroprotective effects of of microdose lithium carbonate. As it is already known based on our previous work with AD patients, the personal characteristics of each patient (medical status, cognitive status, functional proteins and molecular mechanisms) will reflect the response of the cells. With this approach, iPSCs-derived neurons and astrocytes are suitable to evaluate the effects of biological compounds and other pharmacological strategies to improve neuronal resistance/protection with the focus on personalized medicine. Measurable success criteria will be based on evaluation of reductions in senescence-associated secreted phenotypes as per Dr. Andersen's recent Cell Reports publication in a comparable PD model (Chinta et al., 2018). (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)

VIEL, TANIA; CHINTA, SHANKAR; RANE, ANAND; CHAMOLI, MANISH; BUCK, HUDSON; ANDERSEN, JULIE. Microdose lithium reduces cellular senescence in human astrocytes - a potential pharmacotherapy for COVID-19?. AGING-US, v. 12, n. 11, p. 10035-10040, JUN 15 2020. (18/05288-6, 19/03486-8)