Pathophysiology and Therapeutic Targets of the Blood-Brain Barrier

Leader

Research center

4 avenue de l'Observatoire
75006 Paris

Institution

Inserm
Université Paris Descartes
Université Paris Diderot
MTCI 563

Laboratory

Variabilité de réponses aux psychotropes
UMRS1144

Mots clefs

brain interfaces, psychotropic drugs, psychiatric disorders, transporters, biomarkers
Available to host a PhD student

publications

Jacob A, Hartz AM, Potin S, Coumoul X, Yousif S, Scherrmann JM, Bauer B, Declèves X. (2011) Aryl hydrocarbon receptor-dependent upregulation of Cyp1b1 by TCDD and diesel exhaust particles in rat brain microvessels. Fluids Barriers CNS. Aug 25;8:23.

Ball K, Bouzom F, Scherrmann JM, Walther B, Declèves X. (2012) Development of a physiologically based pharmacokinetic model for the rat central nervous system and determination of an in vitro-in vivo scaling methodology for the blood-brain barrier permeability of two transporter substrates, morphine and oxycodone. J Pharm Sci. 101:4277-92

Yousif S, Chaves C, Potin S, Scherrmann JM, Declèves X. (2012) Induction of P-glycoprotein and Bcrp at the rat blood-brain barrier following a subchronic morphine treatment is mediated through NMDA/COX-2 activation. J Neurochem. 123:491-503

Mérian J, Boisgard R, Decleves X, Thezé B, Texier I, Tavitian B. Synthetic lipid nanoparticles targeting steroid organs. J Nucl Med. 2013 Nov;54(11):1996-2003.

Ball K, Bouzom F, Scherrmann JM, Walther B, Declèves X. A Physiologically Based Modeling Strategy during Preclinical CNS Drug Development. Mol Pharm. 2014 Jan 29.

Lloret-Linares C, Luo H, Rouquette A, Labat L, Poitou C, Tordjman J, Bouillot JL, Mouly S, Scherrmann JM, Bergmann JF, Declèves X. The effect of morbid obesity on morphine glucuronidation.Pharmacol Res. 2016 Sep 5. pii: S1043-6618(16)30855-6. doi: 10.1016/j.phrs.2016.08.031.

Fields of research

Neuropharmacology / cell signaling

Research Theme

Our team "Pathophysiology and therapeutic targets of the blood-brain barrier" was created in 2014 with a membership of Inserm inthe new five-year plan. It comes from the team of the former Inserm U705 (ex Director Prof. JM Scherrmann) which studied for morethan 20 years mechanisms of drug exchange in brain barriers. actually, we study the variability factors of two essential functions ofthe BBB, the maintenance of brain homeostasis towards endogenous compounds and the control of brain exposure to drugs and toxicsubstances. In particular we focus on transporters and metabolic enzymes expressed at the BBB that actively modulate exchangesthrough brain interfaces. Through an integrated experimental approach (from gene to function) using both in vitro (isolated human celland tissue models) and in vivo models (rodent) we try to understand the molecular mechanisms regulating the expression andactivity of these proteins and futher functional consequences of these modulations. Our project in this new five-year plan aimsspecifically to study these variability factors in the context of exposure to drugs of abuse, brain diseases, particularly psychiatric and /or their treatment in connection with the two areas of research "addiction" and "bipolar disorder" of our research unit.

Membres de l'équipe

Fanchon BOURASSET
Stéphanie CHASSEIGNEAUX
Salvatore CISTERNINO
Benoit HOSTEN
Aude JACOB
Marie-Claude MENET
Nathalie RIZZO
Bruno SAUBAMEA
Jean-Michel SCHERRMANN

Lab rotation

Metabolic manipulation of the neurovascular unit

Chercheur responsable: 

DECLEVES Xavier

Dates: 

2 April 2018 - 29 June 2018

Date limite de candidature: 

29 June 2018

Period

~ April-June 2018

Project

Metabolic therapies are emergent and promising approaches for the treatment of neurodegenerative diseases in human patients.  This project aims at characterizing the impact of several diets mimicking those therapeutical approaches (ketogenic diet, caloric restriction, intermittent fasting) on the blood-brain barrier and neurovascular unit in the brain of WT mice and in a murine model of Alzheimer’s disease. Technics employed include magnetic cell sorting of brain cells, RNASeq, confocal imaging, in situ brain perfusion, primary culture of endothelial cells.

Contact

Paris Descartes University / Faculté de Pharmacie - 4, avenue de l’Observatoire 75006 Paris - +33 1 53 73 99 91 - xavier.decleves@parsidescartes.fr ; bruno.saubamea@parisdescartes.fr

Superviseur: 

SAUBAMEA Bruno