个人简介

Dr. Christie is a neuroscientist studying the effects of exercise on the brain. His laboratory employs a sophisticated array of electrophysiological, immunohistochemical, molecular and behavioral research methods to elucidate learning and memory mechanisms in the aging brain. My work employs several animal models of developmental disorders, including Fetal Alcohol Syndrome, Fragile-X Syndrome and Rett Syndrome. We hypothesize that these disorders affect a common set of structural and functional features in the hippocampus, and that their effects are functionally similar to those observed in Alzheimer's disease and the senescent brain. In short, all of these disorders involve some degree of altered neurogenesis and synaptic function. I believe that carefully examining what is altered in the hippocampus by each disorder will contribute to a basic understanding of how learning and memory processes occur in the brain.

研究领域

My research investigates how developmental disorders, and other pathological conditions, affect the structure and function of the hippocampal formation, a part of the brain known to be involved in learning and memory processes. I am particularly interested in how the continual introduction of new neurons into the adult brain can promote enhanced learning and memory. Many research programs are based around a single technical approach, and while this can have its advantages, in some cases it is somewhat self-limiting in terms of the types of research questions that can be tackled. The research questions of today and tomorrow, more often than not, will require an interdisciplinary approach to make any substantial headway. Research techniques In my laboratory, we use a number of sophisticated research techniques in a convergent fashion to assess hippocampal structure and function. For instance, we have recently used behavioural analysis, electrophysiology, and immunohistochemistry to show that prenatal exposure to ethanol can impact hippocampal function well into adulthood. In addition we have also shown that exercise can largely ameliorate these hippocampal deficits. In these particular experiments we can show that reduced neurogenesis in the hippocampus recovers, that reduced synapse numbers can be restored, that reduced synaptic function can be restored, and most importantly, that behavioral functioning can be restored to normal levels. In this particular case, we have also just recently become involved in a group of researchers that will try to determine if these same benefits can be seen in humans with FAS/E. This highlights how I like to direct my research to better understand and alleviate a particular problem in an animal model, hopefully in a manner that offers an easy transfer of knowledge to the human population. Research approach Clyde Hertzman, director of the Human Early Learning Partnership (HELP) is fond of using the term "from cell to society", and this really describes the outlook I try to take in my research. I believe that by focusing on how a phenomenon (i.e. neurogenesis) can impact a behavior (i.e. learning) that we will be better able to understand both normal brain function, and how a variety of pathological conditions impact the capacity of the hippocampus. Ultimately, it is my hope to utilize the knowledge we gain about processes such as neurogenesis to help instigate the brain to actually heal itself, and thereby ameliorate the behavioural deficits that are characteristic of a wide range of disorders that involve neurodegeneration. This may sound grandiose at first, but really we have to look no further than our own skin to see how effective self regenerative mechanisms can be when they respond appropriately.

He is particularly interested in the hippocampal formation and has conducted studies to examine its role in learning and memory throughout the lifespan. Researchers in the lab also use animal models of disorders such as Alzheimer's disease, fetal alcohol syndrome (FAS) and fragile-X syndrome to understand how neuropathologies can influence hippocampal structure and function.

近期论文

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Hippocampal Dysfunction and Cognitive Impairment in Fragile-X Syndrome. Bostrom C, Yau SK., Majaess N, Vetrici M, Gil-Mohapel J, Christie BR. Neuroscience & Biobehavioral Reviews (in press). Chronic minocycline treatment improves social recognition memory in adult male Fmr1 knockout mice. Yau, SK, Chiu C, Vetrici M, Christie, BR. Behavioural Brain Research 312(2016) 77-83. The antidepressant-like effect of chronic guanosine treatment is associated with increased hippocampal neuronal differentiation. Bettio LEB, Neis VB, Pazini FL, Brocardo PS, Patten AR, Gil-Mohapel J, Christie BR, Rodrigues ALS. European Journal of Neuroscience. Vol. 43: 1006-1015. doi:10.1111.ejn.13172 Time-course analysis of protein and lipid oxidation in the brains of YAC128 Huntington's disease transgenic mice. Brocardo S, McGinnis E, Christie BR, Gil-Mohapel J. Rejuvenation Research. April 2016, 19(2): 140-148. doi:10.1089/rej.2015.1736. The effects of hormones and physical exercise on hippocampal structural plasticity. Triviño-Paredes J, Patten AR, Gil-Mohapel J, Christie BR. Front Neuroendocrinol. 2016 Mar 14. pii: S0091-3022(16)30009-7. doi:10.1016/j.yfrne.2016.03.001. [Epub ahead of print] Review. PubMed PMID:26989000. Effects of pre-natal alcohol exposure on hippocampal synaptic plasticity: Sex, age and methodological considerations. Christine J. Fontaine, Anna R. Patten, Helle M. Sickmann, Jennifer L. Helfer, Brian R. Christie. Neuroscience & Biobehavioral Reviews 64 (2016) 12-34 Prenatal ethanol exposure impairs temporal ordering behaviours in young adult rats. Anna R. Patten, Scott Sawchuck, Ryan C. Wortman, Patricia S. Brocardo, Joana Gil-Mohapel, Brian R. Christie. Behavioural Brain Research 299 (2016) 81-89 The Benefits of Exercise on Structural and Functional Plasticity in the Rodent Hippocampus of Different Disease Models. Anna R. Patten, Suk Yu Yau, Christine J. Fontaine, Alicia Meconi, Ryan C. Wortman, Brian R. Christie. Brain Plasticity 1 (2015) 97-127 DOI 10.3233/BPL-150016 Enhanced corticosteroid signaling alters synaptic plasticity in the dentate gyrus in mice lacking the fragile X mental retardation protein. M. Ghilan, B.N. Hryciw, P.S. Brocardo, C.A. Bostrom, J. Gil-Mohapel, B.R. Christie. Neurobiology of Disease 77 (2015) 26-34 Tracking Effects of Exercise on Neuronal Plasticity. Henriette van Praag and Brian R. Christie. Brain Plasticity 1(1): 3-4. Time-course analysis of protein and lipid oxidation in the brains of YAC128 Huntington's disease transgenic mice. P.S. Brocardo, E. McGinnis, B.R. Christie and J. Gil-Mohapel. Rejuvenation research. (Sept. 15, Epub ahead of print) The Benefits of Exercise on Structural and Functional Plasticity in the Rodent Hippocampus of Different Disease Models Enhanced corticosteroid signaling alters synaptic plasticity in the dentate gyrus in mice lacking the fragile X mental retardation protein Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin. Yau SY, Li A, Hoo RL, Ching YP, Christie BR, Lee TM, Xu A, So KF. Proc Natl Acad Sci USA. 2014 Nov 4;111(44):15810-5. doi: 10.1073/pnas. 1415219111.Epub 2014 Oct 20. PMID:25331877[PubMed - in process] Free Article Related citatations YAC128 Huntington's disease transgenic mice show enhanced short-term hippocampal synaptic plasticity early in the course of the disease. Ghilan M, Bostrom CA, Hryciw BN, Simpson JM, Christie BR, Gil-Mohapel J. Brain Res. 2014 Sep 18;1581:117-28. doi: 10.1016/j.brainres.2014.06.011. Epub 2014 Jun 17. PMID:24949563 [PubMed - in process] Related citations Prenatal ethanol exposure differentially affects hippocampal neurogenesis in the adolescent and aged brain. Gil-Mohapel J, Titterness AK, Patten AR, Taylor S, Ratzlaff A, Ratzlaff T, Helfer J, Christie BR Neuroscience. 2014 Jul 25;273:174-88. doi: 10.1016/j.neuroscience.2014.05.012.Epub 2014 May 15. PMID: 24846617 [PubMed - in process] Related citations The role of oxidative stress in Huntington's disease: are antioxidants good therapeutic candidates? Gil-Mohapel J, Brocardo PS, Christie BR Curr Drug Targets. 2014 Apr;15(4):454-68. PMID: 24428525 [PubMed - in process] Related Citations