Dr. Chris Anderson


Dr. Christopher M. Anderson
Director, Neuroscience Research Program
Manitoba Research Chair in Neurodegeneration

Kleysen Institute for Advanced Medicine
Health Sciences Centre and University of Manitoba
710 William Avenue, SR424
Winnipeg, MB R3E 0Z3
T: 204-318-2565


One-in-three Canadians will be directly affected by a neurological or psychiatric disorder and the yearly costs of acute care represent the highest portion of the overall financial burden of disease in Canada (14%; source: BrainCanada.ca). When long-term functional deficits and disability resulting from disease are considered, the proportional burden of neurological and psychiatric disorders is amplified to staggering levels, accounting for 38% of years of life lost due to early death and years lived with disability. This is 3-fold greater than the next contributor (cancer, 12.7%). Our overall program strategy is designed to maximize impact on therapeutics in neurological disorders by finding novel mechanisms of brain cell death and neurological debilitation common to multiple forms of brain injury and neurodegeneration. Insight into disease mechanisms with multiple disease relevance stimulates therapeutic development with maximal impact on total human mortality and morbidity.

There is strong consensus that the ability of the brain to properly regulate its own blood supply is impaired in Vascular Dementia and Alzheimer’s Disease, and following stroke and brain trauma. There is also convincing evidence that a process known as excitotoxicity leads to death of brain neurons across a large spectrum of disorders, including stroke, brain trauma, Alzheimer’s Disease, Huntington’s Disease, Parkinson’s Disease, epilepsy and Amyotrophic Lateral Sclerosis (ALS). Our program explores both brain blood flow regulation and excitotoxicity from the cellular level to systems and whole animal models with the goal finding novel therapeutic targets commonly applicable to several neurological syndromes produced by brain injury or long-term neurodegeneration.


The brain is only 2% of body weight yet it receives 10-15% of blood from the heart and uses 20% of body energy consumption. Despite high energy demand, neurons have virtually no reserve energy capacity and are therefore highly dependent on constant delivery of blood-borne glucose and oxygen to match cell activity levels. This is accomplished both by functional hyperemia, which ensures blood flow is directed to brain regions that need it most. Impaired functional hyperemia responses lead to chronic neuronal malnutrition. This is the primary defect in vascular dementia and likely is a determining factor in Alzheimer’s Disease dementia. Similarly, after stroke and brain trauma, hyperemia is impaired in regions surrounding the primary injury site and contributes to progressive neuronal death and functional debilitation.

In recent years, it has become clear that networked syncytia of astrogial cells (astrocytes) play a critical role in coordinating functional hyperemia by coordinating neurovascular coupling, or communication between active neurons and local blood supply vessels resulting in enhanced nutrient delivery. Astrocytes have processes that wrap around synapses and modulate synaptic strength, and processes that terminate in direct apposition with brain arterioles and capillaries. Astrocytes also express receptors for neurotransmitters and release gliotransmitters that affect blood vessel lumen diameter. This makes astrocytes ideally suited to “sense” the degree of synaptic activity and translate this signal to changes in local arteriole diameter. We are interested in how astrocytes contribute to neurovascular coupling and how dysfunction of these mechanisms may lead to neurodegeneration.

Excitotoxicity refers to a deleterious sequence of events, starting with unregulated, elevated extracellular levels of the neurotransmitter, glutamate, and leading to neuronal Ca2+ overload, oxidative stress, mitochondrial damage and neuron death. Excitotoxicity is a primary cause of neuron death in stroke and brain trauma, but is also a prominent feature of several neurodegenerative disorders. Therefore, excitotoxicity is a process that carries multiple disease relevance. Our current focus is on investigating the role that a DNA repair enzyme known as poly(ADP-ribose) polymerase-1 (PARP-1) plays in excitotoxicity. Oxidative stress resulting from excitotoxicity causes single-strand DNA breaks and leads to elevated PARP-1 activity in brain. While PARP-1 participates in normal DNA repair processes, it plays a paradoxically destructive role in the pathophysiology of disorders characterized by extensive oxidative DNA damage. In these situations, PARP-1 activity causes massive NAD+ depletion, glycolytic inhibition and cell death. Accordingly, blocking PARP-1 genetically or pharmacologically promotes cell survival in a variety of neurological disease models, including models of brain ischemia, Parkinson’s Disease and traumatic brain injury. There is strong consensus that PARP-1-induced neuron death is mediated by mitochondrial membrane depolarization and permeability. We are interested in determining how nuclear PARP-1 sends death signals to mitochondria in neurons. We are also interested in how PARP-1 activity in astrocytes causes cell non-autonomous neuronal cell death in excitotoxicity.


LeMaistre Stobart, J.L., Lu, L., Anderson, H.D., Mori, H., and Anderson, C.M. Astrocyte-induced cortical vasodilation is mediated by D-serine and endothelial nitric oxide synthase. Proc Natl Acad Sci USA (2013) 110 (8) 1349-1354.

Kamboj, A., Lu, P., Cossoy, M.B., LeMaistre, J.L., Dolhun, B.A., de Murcia, G. and Anderson, C.M. Poly(ADP-ribose) polymerase-2 contributes to neuroinflammation and neurological dysfunction in mouse experimental autoimmune encephalomyelitis. J Neuroinflam (2013) 10 49-57.

Stobart, J.L. and Anderson, C.M. Multifunctional role of astrocytes as gatekeepers of neuronal energy supply. Front Cell Neurosci (2013) 7 1-21.

Thandapilly, S.J., LeMaistre, J.L., Louis, X.L., Anderson, C.M., Netticadan, T., Anderson, H.D. Vascular and cardiac effects of grape powder in the spontaneously hypertensive rat. Am J Hypertens (2012) 25 1070-1076.

LeMaistre, J.L., Sanders, S.A., Stobart, M.J., Lu, L., Knox, J.D., Anderson, H.D. and Anderson, C.M. Co-activation of NMDA receptors by glutamate and D-serine induces dilation of isolated middle cerebral arteries. J Cereb Blood Flow Metab (2012) 32 537–547.

Hunt, W.T., Kamboj, A., Anderson, H.D. and Anderson, C.M. Protection of cortical neurons from excitotoxicity by conjugated linoleic acid. J Neurochem (2010) 115 123-130.

Hunt, W.T., Salins, P.B, Anderson, C.M. and Amara, F.M. Neuroprotective role of statins in Alzheimer’s disease: anti-apoptotic signalling. Open Neuroscience Journal (2010) 4 13-22.

Tang, K.S., Suh, S.W., Alano, C.C., Hunt, W.T., Shao, Z., Swanson, R.A. and Anderson, C.M. Astrocytic poly(ADP-ribose) polymerase-1 (PARP-1) activation leads to bioenergetic depletion and inhibition of glutamate uptake capacity. Glia (2010) 58 446-457.

Shao, Z., Kamboj, A. and Anderson, C.M. Functional and immunocytochemical characterization of D-serine transporters in cortical neuron and astrocyte cultures. J. Neurosci. Res. (2009) 87 2520-2530.

LeMaistre, J.L. and Anderson, C.M. Custom astrocyte-mediated vasomotor responses to neuronal energy demand. Genome Biol. (2009) 10 209-209.5.

Gliddon, C.M., Shao, Z., LeMaistre, J.L. and Anderson, C.M. Cellular distribution of the neutral amino acid transporter ASCT2 in mouse brain. J. Neurochem. (2009) 108 372-383.

Suh, S.W., Aoyama, K., Alano, C., Anderson, C.M., Hamby, A. and Swanson, R.A. Zinc inhibits astrocyte glutamate uptake by activation of poly(ADP-ribose) polymerase-1. Mol Med. (2007) 13 344-349.

Suh, S.W., Bergher, J., Anderson, C.M., Treadway, J.L., Fosgerau, K. and Swanson, R.A. Astrocyte glycogen maintains neuronal activity during hypoglycaemia: studies with the glycogen phosphorylase inhibitor CP-316,819. J. Pharmacol. Exp. Ther. (2007) 321 40-50.

Anderson, C.M. and Nedergaard, M. Emerging challenges of assigning P2X7 receptor function and immunoreactivity in neurons. Trends Neurosci. (2006) 29 257-262.

Anderson, C.M., Bergher, J. and Swanson R.A. ATP-induced ATP release from astrocytes. J. Neurochem. (2004) 88 246-256.

Anderson, C.M. and Nedergaard, M. Astrocyte mediated control of cerebral microcirculation. Trends Neurosci. (2003) 26 340-344.

Duan, S., Anderson, C.M., Chen, Y., Keung, E.C. and Swanson, R.A. P2X7 receptor-mediated release of excitatory amino acids from astrocytes. J. Neurosci. (2003) 23 1320-1328.

Anderson, C.M., Norquist, B.A., Vesce, S., Nicholls, D.G., Soine, W.H., Duan, S., and Swanson, R.A. Barbiturates induce mitochondrial depolarization and potentiate neuron death. J. Neurosci. (2002) 22 9203-9209.

Christopher M. Anderson
Area of research: Neurodegeneration

Dr. Christopher Anderson
Grant Amount: $651,000 from the Canadian Institutes of Health Research
April 1, 2010 to March 31, 2015

Dr. Christopher Anderson
Grant Amount: $300,000 from Brain Canada for the Manitoba Neuroimaging Platform
August 1, 2014 to July 31, 2017

Dr. Christopher Anderson
Grant Amount: $500,000 Research Chair Award from Research Manitoba
September 1, 2013 to August 31, 2018

Dr. Christopher Anderson
Grant Amount: $991,179 from the Canada Foundation for Innovation and Research Manitoba
July 1, 2013 to June 30, 2017

Dr. Christopher Anderson
Grant Amount: $150,000 from the National Science and Engineering Research Council
April 1, 2010 to March 31, 2015