PURINERGIC SIGNALING AND BRAIN INFLAMMATION
Department: Neuroscience
Research subject
Adenosine triphosphate (ATP) is a molecule that provide cellular energy to living organisms. In most animal phyla, ATP is also an extracellular signaling molecule that acts through the activation of two main families of membrane receptors, the P2Y and P2X receptors. In the central nervous system, purinergic receptors are expressed by all cell types and are mainly involved in neuro-glial communications. Our team is interested in the functions of P2X receptors, which are ATP-gated cationic channels.
We have to main research interests:
1- To understand the roles of purinergic signaling in neuro-inflammatory conditions.
In pathological conditions purinergic signaling contributes to neuroinflammation. Particularly, expression of different receptors is strongly modified in reactive microglia. We focus our work on the P2X4 receptor which is expressed de novo in reactive microglia where it contributes to inflammatory response and neuronal hyperexcitability. By combining different approaches (transgenic mice, transcriptomic, proteomic, behavior…) we are characterizing the molecular and cellular mechanisms by which P2X4 contributes to different pathologies such as chronic pain, epilepsy or Alzheimer disease. By extension we also investigate microglia heterogeneity during the development of neurodegenerative diseases by NGS/RNAseq.
2- To develop purinergic and inflammatory biosensors
In the brain, purinergic signaling contribute to the release of different pro-inflammatory molecules and to neuro-glial communications, these two actions being closely linked. We seek to characterize the spatio-temporal dynamics of purinergic signaling and of the inflammatory response in normal and pathological conditions, in situ. To that aim, we generate fluorescent biosensors allowing to follow in real time, extracellular ATP signaling or IL1ß processing. Through viral approach, these biosensors can be expressed in any given brain cells.
Our team belongs to the LabEX Ion Channel Science and Therapeutics: http://www.labex-icst.fr/en
Co-immunostaining of P2X4 (red) in reactive microglia (Iba1, green) clustered around amyloid plaques stained
with Amylo Glo (blue) in an 9-months old APP/PS1 mice. Scale bar 20 µm.
Team
Major publications
- Hemonnot A-L, Hua J, Hirbec HE. (2019) Microglia in Alzheimer disease : Well-known targets and new opportunities. Frontiers in Aging Neurosci. doi: 10.3389/fnagi.2019.00233
- Hirbec H, Marmai C, Duroux-Richard I, Roubert C, Esclangon A, Croze S, Lachuer J, Peyroutou R, Rassendren F (2018) The microglial reaction signature revealed by RNAseq from individual mice. Glia 66(5):971-986.
- Sensory neuronal P2RX4 receptors controls BDNF signaling in inflammatory pain. Lalisse S, Hua J, Lenoir M, Linck N, Rassendren F, Ulmann L (2018) Sci Rep 8(1):964.
- Rassendren F and Audinat E (2016) Purinergic signaling in epilepsy. J Neurosci Res. 94:781-793.
- Compan V, Pierredon S, Vanderperre B, Krznar P, Marchiq I, Zamboni N, Pouyssegur J, Martinou JC. (2015) Monitoring Mitochondrial Pyruvate Carrier Activity in Real Time Using a BRET-Based Biosensor: Investigation of the Warburg Effect. Molecular Cell. 201559(3):491-501.