The role of Klotho in the uptake of glutamate in astrocytic primary culture

• Grant number: 18/06953-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2018
• End date: November 30, 2019
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Cristoforo Scavone
• Grantee: Paloma Segura de Mello
• 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

Aging is a complex and multifactorial process, associated with molecular, cellular and behavioral alterations. Oxidative stress, neuroinflammation and excitotoxicity are characteristics common to various neuropathological processes of aging as in Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer's disease. The neuronal damage by excitotoxicity occurs, mainly, at the expense of astrocytic deficiencies in glutamate uptake of extracellular excitatory neurotransmitter important for several actions in the Central Nervous System (CNS). The ±-Klotho protein is correlated to an increase in life expectancy for its differents physiological actions and your decreased along the aging is increasingly related to such neurodegeneratives processes. Evidence shows that the Klotho protein are able to modulate the Na+/K+ATPase on the cell surface, important for maintaining the electrochemical gradient necessary for the operation of receptors of glutamate (EAATs), in cell types such as astrocytes and neurons. In addition, the Klotho is possibly able to modulate the inwardly-rectifying potassium channels in astrocytes required for neuronal repolarization, facilitating the excitatory neurotransmitter reuptake and able to control lactate production by astrocytes, essential nutrient to neurons. Considering the various possibilities of operation of Klotho in neurons and astrocytes and the importance of glutamate uptake to prevent excitotoxicity and the consequent death of neurons, the central objective of this study is to verify the effect of that protein in the process of glutamate uptake in primary culture of astrocytes.