Sara Carracedo 

Title

Opposing effects of neuronal and myeloid P2X4 receptors on ALS progression in SOD1-G93A mice 

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive degeneration of motor neurons (MNs), driven by misfolded protein aggregation and neuroimmune dysregulation. P2X4 receptor, an ATP-gated ion channel expressed in neurons and glial cells, has emerged as a key player in ALS pathogenesis.  

Using double-transgenic SOD1 G93A (SOD1) mice expressing either an internalization-defective P2X4-mCherryIN knock-in or invalidated for the P2X4 gene, we surprisingly showed that both the surface increase of P2X4 or its absence improved disease outcomes and mouse survival. These paradoxical results may reveal complex cell-roles of the P2X4 receptor, so far unexplored. 

In this study, we investigated the distinct neuronal and myeloid roles of the P2X4 receptor in ALS using triple-transgenic mice designed to selectively increase surface P2X4 or delete its expression either in myeloid cells or neurons in SOD1 mice. Our results demonstrated that increased neuronal surface P2X4 accelerates disease progression, while its upregulation in myeloid cells slows disease progression by improving MNs survival while reducing inflammatory processes occurring in the spinal cord. Our findings demonstrate for the first time that the P2X4 receptor exerts cell-dependent and opposing roles in SOD1 mice which could represent a therapeutic target to fight ALS. 

Biography

I hold a Bachelor’s degree in Veterinary Medicine and a Master’s in Neurosciences, having a strong academic background in both, clinical and molecular biology. Currently, I am doing a PhD in Neurosciences at the Institut des Maladies Neurodégéneratives in Bordeaux (France). My PhD aims to understand the neuroimmune interactions associated with spinal motoneurons vulnerability and neuroinflammation occurring in Amyotrophic Lateral Sclerosis (ALS). In addition, this research seeks to have a translational impact with the discovery of new ALS biomarkers. 
 
As I am particularly driven by making scientific information accessible to everyone, I have co-founded the Brainstorm Student Journal at the University of Bordeaux. Brainstorm is a student-led initiative that serves as a platform for neuroscience enthusiasts to share their research. We aim to bridge the gap between neuroscience academia and the general public, ensuring that complex scientific data is communicated efficiently. Another project I have created is Women’s Voices. This project consists on a serie of interviews to female researchers about their scientific contributions and opinions about equity, diversity and gender bias in academia. The goal of Women’s Voices is to increase the visibility of early career female researchers, highlighting their achievements and serving as inspiration for our scientific community. 

https://www.imn-bordeaux.org/en/news/portrait-sara-carracedo-phd-student-at-imn/