6875 Boulevard Lasalle
The research focus of our laboratory is the investigation of neuroinflammatory mechanisms involved in the development of psychiatric disorders. In particular we are interested in the role played by the inflammatory circulating mediators cytokines, and more recently adipokines such as leptin, which are involved in regulating both acute and chronic sickness behaviour via direct action in the brain. The work on adipokines in particular has led us to explore the link between the energy status of an individual, their ability to mount an immune response to pathogens and their increased susceptibility to developing psychopathology. In parallel to this work we are exploring the impact of prenatal environmental insults such as bacterial or viral infection and maternal diet on the normal development of the fetal brain. This work is based on the rationale that dysregulation of the mother’s immune response, following the insult can result in neurodevelopmental defects. We believe that this is linked to disruption of normal neuronal network formation involving microglia in the fetal brain, which could lead to brain disorders such as schizophrenia, and autism spectrum disorders in the adult offspring.
-Aguilar-Valles A, Kim J, Jung S, Woodside B, Luheshi GN. (2014). Role of brain transmigrating neutrophils in depression-like behavior during systemic infection. Molec. Psychiatry.9(5):599-606.
-Aguilar-Valles A, Jung S, Poole S, Flores C, Luheshi GN. (2012). Leptin and interleukin-6 alter the function of mesolimbic dopamine neurons in a rodent model of prenatal inflammation. Psychoneuroendocrinology. 2012 Jul;37(7):956-69
-Rummel, C., Inoue, W., Poole, S. and Luheshi, G.N. (2010). Leptin regulates leukocyte recruitment into the brain following systemic LPS-induced inflammation. Molec. Psychiatry. 15:523-534.
-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.
-Pohl J, Woodside, B, & Luheshi, GN. (2009). Changes in hypothalamically mediated acute phase inflammatory responses to lipopolysaccharide in diet-induced obese rats. Endocrinology. 150(11):4901-10.
-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.
-Aguilar-Valles, A, Poole, S, Mistry, Y, Williams, S. & Luheshi, G.N. (2007). Attenuated fever in rats during late pregnancy is linked to suppressed IL-6 production after localised inflammation with turpentine. J.Physiol. (Lond.). 583(1):391-403.
-Ashdown, H., Dumont, Y., Poole, S., Boksa, P. & Luheshi, G.N. (2006). The role of cytokines in mediating effects of prenatal infection on the fetus: Implications for schizophrenia. Molecular Psychiatry. 11(1):47-55.
-Cartmell, T., Poole, S., Turnbull, A.V., Rothwell, N.J. & Luheshi, G.N. (2000). Circulating interleukin (IL)-6 mediates the febrile response to localised inflammation in rats. J.Physiol (Lond.). 526 (3): 653-661.
-Luheshi, G.N., Gardner, J.D., Rushforth, D.A., Loudon, A.S. & Rothwell, N.J. (1999). Leptin actions on food intake and body temperature are mediated by interleukin-1. Proc.Natl.Acad.Sci. USA. 96:7047-7052.
-Gardner, J.D., Rothwell, N.J. & Luheshi, G.N. (1998) Leptin affects food intake via CRF receptor mediated pathways. Nature Neuroscience 1 (2): 103.
-Culhane AC, Hall MD, Rothwell NJ, Luheshi GN. (1998). Cloning of rat brain interleukin-18 cDNA. Mol Psychiatry.3(4):362-6.
Dr Luheshi is a full professor and William Dawson Scholar at the department of Psychiatry, McGill University and an associate member of the department of Neurology and Neurosurgery at the same institution. He received his PhD in 1990 from the university of Newcastle-upon-Tyne, UK where he worked on diabetic neuropathy and neuromuscular transmission. He then joined Professor Dame Nancy Rothwell’s laboratory in the university of Manchester as a post-doctoral fellow investigating the nature of the peripheral immune signal to the brain in response to systemic inflammation. He continued this work following his appointment as lecturer (asst. Professor) in the School of Biological sciences in the same university in 1997, during which time he demonstrated that the appetite suppressing hormone, leptin, shares a number of functional properties with pro-inflammatory cytokines, such as interleukin-6 including action as a neuroimmune mediator. The work on leptin was expanded following relocation of his laboratory to McGill in 2000, and now forms part of a larger project investigating the link between energy status and the immune response using rodent models of diet induced obesity and food restriction.
In addition to this work, he is now directing a research program studying the link between maternal infection during critical stages of gestation on the normal development of the fetal brain. This work was based on the rationale that activation of the maternal immune response, can result in developmental defects of the fetal brain, leading to brain disorders such as schizophrenia and autism in the adult offspring.
William Dawson Scholar
Lourdes Fernandez de Cossio Gomez
Suzanne van der Veldt
Plasticity of the epigenome during early-life stress. Semin Cell Dev Biol. 2017.
Dark microglia: A new phenotype predominantly associated with pathological states. Glia. 2016;64(5):826-39.
Prenatal infection leads to ASD-like behavior and altered synaptic pruning in the mouse offspring. Brain Behav Immun. 2016.
Role of neuroinflammation in the emotional and cognitive alterations displayed by animal models of obesity. Front Neurosci. 2015;9:229.
Role of brain transmigrating neutrophils in depression-like behavior during systemic infection. Mol Psychiatry. 2015;20(3):413-4.
Obesity, adipokines and neuroinflammation. Neuropharmacology. 2015;96(Pt A):124-34.
Leptin modulates the late fever response to LPS in diet-induced obese animals. Brain Behav Immun. 2014;42:41-7.
Prenatal maternal stress exposure and immune function in the offspring. Stress. 2014;17(2):133-48.
Role of brain transmigrating neutrophils in depression-like behavior during systemic infection. Mol Psychiatry. 2014;19(5):599-606.
The effects of dietary saturated fat on basal hypothalamic neuroinflammation in rats. Brain Behav Immun. 2014;36:35-45.
Diet-induced weight gain produces a graded increase in behavioral responses to an acute immune challenge. Brain Behav Immun. 2014;35:43-50.
Leptin is involved in age-dependent changes in response to systemic inflammation in the rat. Brain Behav Immun. 2014;36:128-38.