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Séminaire impromptu - Giamal LuheshiLeptin as a modulator of inflammation activated immune to brain communication

Abstract :

Une invitation d'Agnès Nadjar de NutriNeuro

Communication between the immune system and the brain is a critical process governing our ability to respond to and mount an effective defense response against invading pathogens. Peripheral immune mediators known as cytokines (e.g. interleukin-1) play an important role in this communication through direct actions in the brain. We have shown previously that a new member of this family, leptin, which is mainly produced by fat in proportion to its mass, and is involved principally in controlling body weight by suppressing appetite, stimulates the production of cytokines in the brain and may act as a new circulating messenger during disease. In addition to inhibiting appetite we also reported, for the first time, that leptin induces fever, which is a hallmark for disease and that leptin is integral to the body's defense mechanisms against bacterial infection and inflammation. Our latest discoveries indicate that the role of this cytokine like hormone in immunity is more complex than first envisaged and rather than acting directly on brain targets of inflammation it instead facilitates the action of other inflammatory molecules. Interestingly we have also made a novel observation linking leptin to the regulation of immune cell trafficking from the circulation to the brain, which we have linked to the regulation of long term sickness behaviours in response to infection or injury. The work to be presented in the seminar will describe a novel route of communication between the peripheral immune system and the brain, and how this can impact on the development of neurodegenerative diseases leading to chronic brain disorders.

Selected publications

Inoue W & Luheshi GN. (2011). Acute starvation alters lipopolysaccharide-induced fever in leptin-dependent and -independent mechanisms in rats. Am J Physiol Regul Integr Comp Physiol. 2010 Dec;299(6):R1709-19

 Rummel, C., Inoue, W., Poole, S. & Luheshi, G.N.  (2010). Leptin regulates leukocyte recruitment into the brain following systemic LPS-induced inflammation. Molec. Psychiatry.15(5):523-34

 LaFrance V, Inoue W, Kan B & Luheshi GN. (2010). Leptin modulates cell morphology and cytokine release from microglia. Brain Behav. Immune. 24(3):358-365

 Rummel, S, Inoue, W, Sachot, S, Poole, S, Hubschle, T & Luheshi, GN. (2008). Selective contribution of IL-6 and leptin to brain inflammatory signals induced by systemic LPS injection in mice. J. Comparative Neurology. 511(3):373-95.

 Sachot, C , Poole, S. &Luheshi, G.N. (2004). Circulating leptin mediates LPS-induced anorexia and fever in rats. J.Physiol. (Lond.). 15;561(Pt 1):263-72.

Agnès Nadjar (agnes.nadjar @ u-bordeaux2.fr)