| MATTHEW
HILL |
 |
|
| RESEARCH INTERESTS Endocannabinoids are the brains endogenous version of THC, the psychoactive constituent of cannabis (similar to how endorphins are the body’s endogenous version of morphine). Over the past few years I have been interested in the role of the endocannabinoid system in the regulation of stress and emotional behavior. Research from us, and others, has demonstrated that endocannabinoid signaling largely acts to decrease stress responses. Deficits in endocannabinoid signaling in rodents can increase neuroendocrine and behavioral responses to stress, and in humans, disruption of endocannabinoid signaling can produce symptoms of depression and anxiety. Interestingly, we have demonstrated that stress can mobilize endocannabinoid signaling, and that this increase in endocannabinoid signaling is required for both the normal recovery from acute stress as well as the larger adaptive processes that occur following repeated exposure to stress. More so, we have found that under conditions of chronic stress, endocannabinoid signaling “breaks down”, and that the loss of this buffer system may be one of the mechanisms by which chronic stress increases the risk of affective illnesses, such as depression and anxiety disorders. This hypothesis has been supported by translational clinical studies we have performed demonstrating that circulating levels of endocannabinoids are reduced individuals afflicted with major depression. The primary
focus of research in my laboratory is to understand the role of
the endocannabinoid system in the effects of stress and glucocorticoids.
Within this focus, my research is particularly interested in determining
the role of the endocannabinoid system in the effects of stress
on a) neuroendocrine function; b) emotional behaviour; c) energy
balance and metabolism; d) neuroinflammation and neurodegeneration.
This is achieved through a systems level approach incorporating
a range of neuroscientific techniques ranging from cellular to behavioural.
In particular, we employ biochemical and pharmacological techniques,
such as radioligand receptor binding and signalling assays, enzyme
activity assays, lipid mass spectrometry, gene expression analysis
and protein quantification through ELISA’s. In addition we
also perform a range of microscope techniques employing neuro-stereology
(3-dimensional neuronal reconstructions to examine dendritic architecture),
immunohistochemistry and immunofluorescence. To compliment this,
we also employ a range of behavioral techniques, ranging from fear
conditioning to the examination of basic emotional and cognitive
processes. Hill, M.N., Hillard, C.J., McEwen, B.S. (2011). Alterations in Corticolimbic Dendritic Morphology and Emotional Behavior in Cannabinoid CB1 Receptor Deficient Mice Parallel the Effects of Chronic Stress. Cerebral Cortex 21(9), 2056-2064. Hill, M.N., McLaughlin, R.J., Pan, B., Fitzgerald, M.F., Roberts, C.J., Lee, T.T., Karatsoreos, I.N., Mackie, K., Viau, V., Pickel, V., McEwen. B.S., Liu, Q.S., Gorzalka, B.B., Hillard, C.J. (2011). Recruitment of Prefrontal Cortical Endocannabinoid Signaling by Glucocorticoids Contributes to Termination of the Stress Response. Journal of Neuroscience 31(29), 10506-10515. Krebs-Kraft, D.L., Hill, M.N., Hillard, C.J., McCarthy, M.M. (2010). Sex Difference in Cell Proliferation in Developing Rat Amygdala Mediated by Endocannabinoids has Implications for Social Behavior. Proceedings of the National Academy of Sciences USA 107(47), 20535-20540. Hill, M.N., Patel, S., Campolongo, P., Tasker, J.G., Wotjak, C.T., Bains, J.S. (2010). Functional Interactions Between Stress and the Endocannabinoid System: From Synaptic Signaling to Behavioral Ouput. Journal of Neuroscience 30(45), 14890-14896. Evanson, N.K., Tasker, J.G., Hill, M.N., Ulrich-Lai, Y.M., Hillard, C.J., Herman, J.P. (2010). Fast-feedback Inhibition of the HPA Axis by Glucocorticoids is Mediated by Endocannabinoid Signaling. Endocrinology 151(10), 4811-4819. Hill, M.N., McLaughlin, R.J., Bingham, B., Shrestha, L., Lee, T.T., Gray, J.M., Hillard, C.J., Gorzalka, B.B., Viau, V. (2010). Endogenous Cannabinoid Signaling is Essential for Stress Adaptation. Proceedings of the National Academy of Sciences USA 107(20), 9406-9411. Hill, M.N., Titterness, A.K., Morrish, A.C., Carrier, E.J., Lee, T.T.-Y., Gil-Mohapel, J., Gorzalka, B.B., Hillard, C.J., Christie, B.R. (2010). Endogenous Cannabinoid Signaling is Required for Voluntary Exercise-induced Enhancement of Progenitor Cell Proliferation in the Hippocampus. Hippocampus 20(4), 513-523. (featured in the New York Times: http://well.blogs.nytimes.com/2011/02/16/phys-ed-what-really-causes-runners-high/) Hill, M.N., McLaughlin, R.J., Morrish, A.C., Viau, V., Floresco, S.B., Hillard, C.J., Gorzalka, B.B. (2009). Suppression of Amygdalar Endocannabinoid Signaling by Stress Contributes to Activation of the Hypothalamic-Pituitary-Adrenal Axis. Neuropsychopharmacology 34(13), 2733-2745. Hill, M.N., Miller, G.E., Carrier, E.J., Gorzalka, B.B., Hillard, C.J. (2009). Circulating Endocannabinoids and N-Acyl Ethanolamines are Differentially Regulated in Major Depression and Following Exposure to Social Stress. Psychoneuroendocrinology 34(8), 1257-1262. Hill, M.N., Gorzalka, B.B. (2009). Impairments in Endocannabinoid Signaling and Depressive Illness. JAMA - Journal of the American Medical Association 301 (11), 1165-1166. Hill, M.N., McEwen, B.S. (2009). Endocannabinoids: The Silent Partner of Glucocorticoids in the Synapse. Proceedings of the National Academy of Sciences USA 106 (12), 4579-4580. Hill, M.N., Ho, W.S., Sinopoli, K.J., Viau, V., Hillard, C.J., Gorzalka, B.B. (2006). Involvement of the Endocannabinoid System in the Ability of Long-term Tricylic Antidepressant Treatment to Suppress Stress-induced Activation of the Hypothalamic-Pituitary-Adrenal Axis. Neuropsychopharmacology 31(12) 2591-2599. Hill, M.N, Patel, S., Carrier, E., Rademacher, D.J., Ormerod, B.K, Hillard, C.J. Gorzalka, B.B. (2005). Down-regulation of Endocannabinoid Signaling in the Hippocampus Following Chronic Unpredictable Stress. Neuropsychopharmacology 30 (3), 508-515. PubMed
|
||
