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Dr. Chris Anderson
Principal Investigator & Assistant Professor
Division of Neurodegenerative Disorders
Research Focus
Our primary research focus and expertise centers around the function of central nervous system glial cells called astrocytes in health and disease. Although not all work in the lab involves investigation of astrocytes, the heart of our research program is exploration of the role of astrocytes in intercellular signaling mechanisms involved in cell death and/or demyelination associated with brain injury and neurodegeneration. Since a growing body of evidence supports a role for altered brain blood flow in both vascular and Alzheimer’s-type dementias, a second developing emphasis in our lab is deciphering the role of astrocyte transmitters in intercellular signaling leading to functional hyperemia, or automatic targeted enhanced local blood flow and nutrient supply to regions of brain with elevated neuronal activity and energy demand. Other projects include investigating the neuroprotective effects of the dietary polyunsaturated fatty acid, Conjugated Linoleic Acid (CLA), and assessing the role of the poly(ADP-ribose) polymerase family of nuclear enzymes in cell death and demyelination in tissue culture and animal models of stroke and Multiple Sclerosis.
Why this this work important?
Despite knowledge of astro-glial cells or astrocytes in brain for over 100 years, they have been viewed predominantly as support cells for neurons that do not participate in vital brain functions. In the last 10 years, this has been shown repeatedly to be far from the truth. Astrocytes regulate ion and water homeostasis, neurotransmitter levels, blood–brain barrier maintenance, blood flow, stem cell proliferation, synaptic transmission, and sensorimotor neurotransmission. We are just starting to grasp the reality that given these important physiological functions, astrocytes also likely play an important role in disease and appear to directly contribute to the neuronal loss that typifies CNS disorders including stroke, seizure, Alzheimer's disease and amyotrophic lateral sclerosis (ALS). Our involvement in investigating astrocyte physiology and pathophysiology positions our laboratory at the leading edge of discovery in this relatively new and exciting field.
What techniques and equipment are used in this laboratory?
Our laboratory is committed to a multidisciplinary approach to research and therefore uses tissue culture, brain slice preparations, and in vivo animal models where appropriate. We employ neuronal and astrocyte cultures from various rodent brain regions to investigate mechanisms of cell-cell communication, transmitter regulation and cell death signaling in conditions simulating cerebral ischemia. We use mouse hippocampal slices to investigate intercellular communication and arteriolar diameter in situ using multi-photon excitation coupled with contrast optics. Lastly, we use animal models of cerebral ischemia, Alzheimer’s Disease and Multiple Sclerosis to determine whether our work in vitro has physiological significance.
Noteworthy equipment/assets include:
- Tissue culture suite
- HPLC
- Upright multi-photon imager for brain slice with patch clamp
- Inverted single-photon imager with temperature and CO2 control
- 96-well plate fluorometer, UV/Vis spectrophotometer and luminometer
- Biorad Fluor-S chemiluminescence imager
- Digital gel documentation system
- Cryostat
- Ultracentrifuges
- Two conventional real-time inverted fluorescence imagers (Olympus/PTI and Zeiss/Sutter)
- Surgical suite with Biopac monitoring system and microdialysis
- Animal care facility with professional colony management
About Chris Anderson
Dr. Anderson received undergraduate training in Biochemistry and Toxicology at Simon Fraser University (B.Sc., 1993) in British Columbia. He was awarded a Ph.D. in Pharmacology and Therapeutics from the University of Manitoba in 1998 and received postdoctoral training in Neurology at the University of California, San Francisco (1998-2003 with an intensive training period in cellular imaging as a visiting fellow at New York Medical College in 2002. Since 2004, he has been an Assistant Professor of Pharmacology and Therapeutics at The University of Manitoba and a Principal Investigator in the Division of Neurodegenerative Disorders at the St. Boniface Hospital Research Center. He held a postdoctoral fellowship funded by the Canadian Institutes of Health Research (CIHR) and the Heart and Stroke Foundation of Canada (1999-2002) and is currently a New Investigator of the Heart and Stroke Foundation of Canada (2005-2010). Research operating and infrastructure funding is provided by CIHR, Ajinomoto Amino Acids Research Program, Manitoba Health Research Council, Multiple Sclerosis Society of Canada, Manitoba Medical Service Foundation, Canada Foundation for Innovation, Manitoba Research and Innovation Fund, University of Manitoba, St. Boniface Hospital and Research Foundation, and the Focus on Stroke Partnership.
For more information, contact:
Dr. Chris Anderson
St. Boniface Hospital Research Centre
351 Taché Avenue, Room R4046
Winnipeg, MB R2H 2A6
Canada
Office phone: 204.235.3946
Lab phone: 204.235.3949
Fax: 204.237.4092
E-mail:
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In Detail
Research in my laboratory is focused on two broad topics: mechanisms of neuron death in cerebral ischemia (stroke) and astrocyte function in health and disease. Specific examples of current projects of interest encompassing these topics include the following:
Role of poly(ADP-ribose) polymerase-1 (PARP-1) in cell death – Several neurodegenerative disorders, including stroke, Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, Parkinson’s Disease are associated with elevated oxidative stress in brain tissues. PARP-1 is an abundant nuclear enzyme normally involved in maintaining genomic stability. However, oxidative DNA damage leads to excessive PARP-1 activation, massive depletion of cellular energy currencies, and eventual cell death. Genetic deletion of PARP-1 expression prevents neuron death in rodent stroke models, indicating an important role for PARP-1 in ischemic cell death and suggesting that blocking PARP-1 may be a useful therapeutic strategy in the treatment of stroke. Moreover, several studies suggest that PARP-1 activation is likely a mechanism of cell death that is common to multiple neurodegenerative disorders. My laboratory is interested in deciphering mechanisms by which PARP-1 contributes to the death of neurons and glial cells in conditions simulating cerebral ischemia and other neurodegenerative disorders. We are currently particularly interested in role of PARP-1 activation in astrocytes and the associated effects on astrocyte bioenergetics, glutamate transport systems and glutamate homeostasis. Funded by the CIHR (2004-2009).
Regulation of cerebral blood flow by astrocytes – A hallmark of brain function described in the 19th century is that elevated neuronal activity is accompanied by enhanced local blood flow. This coupling of neuronal energy supply and demand is called functional hyperemia and has been found to be deficient in vascular dementia and animal models of Alzheimer’s Disease. While several possible mechanisms for functional hyperemia have been identified, it was recently discovered that astrocytes play a key role in translating signals generated by working neurons to cerebral arterioles, resulting in increased blood flow. We are interested in the mechanisms involved in this process and how they may be defective in disease. Specifically, we have data to support the hypothesis that vascular NMDA receptors, activated by the gliotransmitter, D-serine, are capable of regulating vascular tone by activating endothelial nitric oxide production. We are currently working to show that astrocytes control vascular tone in situ and cerebral blood flow in vivo by releasing D-serine. Funded by the CIHR and Manitoba Health Research Council (2007-2009).
Regulation of D-serine levels in brain – We are interested in a target that has considerable potential for therapeutic development in stroke over the coming years – the role of D-serine in N-methyl-D-aspartate (NMDA) receptor-mediated neuron death in stroke. NMDA receptors are the major contributor to neuron death in ischemic stroke. While glutamate is the endogenous activator of NMDA receptors that has received the most attention as an excitotoxin, NMDA receptors also have co-activator sites, called glycine sites, which enhance NMDA receptor function. Growing evidence suggests that the amino acid D-serine, rather than glycine, is the major endogenous activator of the glycine site and therefore likely plays a strong role in NMDA receptor activity. Since D-serine is synthesized only in glial cells and astroglial D-serine can mediate astrocyte-neuron communication in synaptic transmission, we are hypothesizing that D-serine released from astroglia reduces neuron survival in cerebral ischemia by acting as a co-activator of neuronal NMDA receptors. We are working to determine how D-serine is taken up into astrocytes and neurons and if and how D-serine is released in cerebral ischemia. We also intend to define the role of D-serine in NMDA receptor function in cerebral ischemia. Funded by Ajinomoto Amino Acid Research Program (2005-2007).
Intercellular communication in brain – While astrocytes have been historically thought of as support cells for neurons, recent developments have proven otherwise by illustrating that astrocytes can receive pre-synaptic input, release neurotransmitters in a vesicular-like fashion, and in turn directly influence crucial parameters such as neuronal excitability, synaptic plasticity and activity-dependent cerebral blood flow. In addition, astrocytes communicate with one another by propagating waves of elevated extracellular Ca2+ from cell to cell. This process has been shown to be mediated by gap junction proteins and extracellular ATP signaling. My lab is interested in all aspects of cell to cell communication involving astrocytes. At this time specific focus is being placed on determining when and how ATP is released from astrocytes and the role purinergic signaling and gap junction proteins play in spreading signals throughout brain initiated by energy failure characteristic of cerebral ischemia.
Role of PARP in Experimental Autoimmune Allergic Encephalomyelitis (EAE) – EAE is a model of inflammatory demyelination with many features similar to human Multiple Sclerosis. PARP is known to play a role in inflammatory processes and non-selective inhibitors of PARP isoforms improve neurological function in rodents with EAE. We are using a relapsing-remitting EAE paradigm in mice lacking PARP-1 or PARP-2 isoforms to prove whether PARP plays a role in EAE and determine which isoform/s is/are responsible for the PARP contribution to EAE progression. Funded by the Multiple Sclerosis Society of Canada (2007).
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