Telethon BASSANI GGP20056 - PCDH19-related neurodevelopmental syndrome: unraveling the players of neuronal hyperexcitability in search of new therapeutic targets (DSB.AD004.339)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Institute of neuroscience (IN)

Project manager

SILVIA BASSANI
Phone number: 02 6448 8370
Email: silvia.bassani@in.cnr.it

Abstract

Mutations in PCDH19 (Xq22) cause a neurodevelopmental disorder (NDD) (Epileptic Encephalopathy, Early Infantile, 9; EIEE9) affecting mainly females and characterized by seizures, ASD, ID and schizophrenia. Our preliminary data suggest that PCDH19 loss of function might cause neuronal hyperexcitability by deregulating both GABAergic transmission and Immediate Early Genes (IEGs) expression. According to recent literature, EIEE9 patient's fibroblasts show altered expression of the oxytocin receptor (OXTR). OXTR, which is regulated by estrogens, is also involved in neuronal excitability, GABAergic transmission and gene-expression regulation. Notably, OXT is a promising treatment for NDDs associated to ASD and psychiatric features. We therefore hypothesize a multifaceted role of PCDH19 in neuronal excitability with crucial implications for understanding EIEE9 symptoms, from the E/I unbalance underlying seizures and ASD to cognitive processes, which rely on the wiring of neurons sharing excitability levels. Furthermore, OXT signaling might contribute to EIEE9 etiology, and the validation of this hypothesis might pave the way to new therapeutic strategies.The overall objective of this pro

Start date of activity

01/01/2022

Keywords

PCDH19, neurodevelopment, hyperexcitability

Last update: 14/06/2025