Possible changes in the expression of klotho protein in the hippocampus, cortex and cerebellum of mice, due to prenatal exposure to valproic acid

• Grant number: 22/15514-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2024
• End date: March 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Elisa Mitiko Kawamoto Iwashe
• Grantee: Bianca Andrade Rodrigues
• 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

Individuals exposed to valproic acid (VPA) during the gestational period, may present some central damage, such as impaired social interaction and the communication, cognitive deficit and stereotyped behaviors, that are commonly expressed in autism. Reductions in klotho protein may be related to central impairments, such as those that these individuals have. If there are klotho reductions induced by VPA in the CNS, they could be correlated to some characteristics presented by individuals who were exposed to VPA during pregnancy, indicating a possible mechanism of action of VPA in the development of central deficits. The hypothesis is that intrauterine exposure to VPA may promote reductions in CNS klotho expression in the offspring, which could result in some changes in affected brain regions, such as: possible reductions in synapses and neuronal changes. The main objective is to investigate whether prenatal exposure to VPA is able to promote changes related to klotho protein in cognitive regions of the CNS (hippocampus, cortex and cerebellum), both in the offspring of male and female mice; and whether these changes related to klotho can lead to changes in synapses or neurons in these cognitive regions. For this investigation we will use mice (males and females, C57BL/6), exposed to VPA. Behavioral tests will be performed; Western Blotting assay, ELISA assay and immunohistochemistry will also be carried out to mark the klotho in central cognitive regions; as well as immunohistochemistry and Western Blotting for evaluation of neurons, synaptophysin (synaptic vesicle marker) and postsynaptic protein of density 95 (PSD-95) for the investigation of synapses. Finally, the groups will be evaluated and compared to their controls.

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)

RODRIGUES, BIANCA ANDRADE; SILVA, JOSIANE DO NASCIMENTO; KAWAMOTO, ELISA MITIKO. Cerebellar Alterations in Autism Spectrum Disorder: A Mini-Review. CEREBELLUM, v. 24, n. 2, p. 5-pg., 2025-02-22. (22/15514-9, 24/03766-9)