Evaluation of the expression of proteins involved in synaptic function and plasticity in Klotho-hypomorphic mice

• Grant number: 22/13804-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2023
• End date: June 30, 2024
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Elisa Mitiko Kawamoto Iwashe
• Grantee: Geovana Rosa Oliveira dos Santos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/06009-6 - Neuroplasticity -induced by challenge Na, K-ATPase, Klotho, glutamate, and neuroinflammation signaling cascades to reveal new therapeutic targets for aging and neurodegenerative diseases, AP.TEM

Abstract

The aging process is characterized by a functional decline of several physiological systems. In the central nervous system, aging may be related to cognitive impairment, as a consequence of changes in synaptic plasticity. Klotho protein is involved in the aging process, participating in some signaling pathways. In the central nervous system, Klotho is synthesized by ependymal cells of the choroid plexus, Purkinje cells and hippocampal neurons, participating in some cognitive processes related to memory, in addition to acting in the regulation of synaptic plasticity in the hippocampus. Klotho gene knockout mice have reduced life expectancy and number of synapses in the hippocampus and memory and learning deficiencies. Synaptophysin, synapsin and postsynaptic density protein 95 (PSD-95) proteins are essential for synaptic function, acting on synaptic plasticity and neurotransmitter release. In addition, N-methyl-D-aspartate (NMDA) and ±-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) glutamatergic receptors are also important for synaptic plasticity, participating in induction of long-term potentiation (LTP) and long-term depression (LTD). Since Klotho-hypomorphic mice seem to have cognitive impairment, the aim of the project is to evaluate the expression of synaptic proteins associated with glutamatergic signaling in the absence of Klotho in the cerebellum and hippocampus of males and females, through of the Western Blotting technique. Thus, it is expected to understand whether the changes in cognitive performance found in these animals may be related to changes in the expression pattern of proteins involved in synaptic function and whether these changes may be linked to sex, since the expression of the Klotho protein is different between males and females.