Evaluation of PTEN compartmentalization on neurogenesis and synaptic plasticity in...
Abstract
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)