Roles for Calcium signaling in astrocytes
This research is funded by a CIHR operating grant (2005-2011) and has revealed a major role for astrocytes in the regulation of cerebral blood flow. The experiments will continue the investigations into the mechanisms by which astrocyte regulation of blood vessel tone is mediated by the calcium dependent liberation of arachidonic acid and the subsequent metabolites of arachidonic acid.
Synaptic and non-synaptic regulation of neuronal excitability
These experiments are funded by a CIHR operating grant (2005-2011) and are investigating the modulation of neuronal excitability via alterations of r-type calcium currents and insertion of trpc5 channels, activation of pannexin hemichannels in hippocampal pyramidal neurons and the contribution to seizure discharges, and alterations of synaptic efficacy by immune activation of microglia and astrocytes.
Mechanisms Matching the Brain’s Vascular Energy Supply to Neural Activity, and their Failure in Disease
These experiments are part of the Leducq Fondation Transatlantic Network of Excellence (2008-2013). Directed by Dr. MacVicar, this group of investigators in North America and in Europe will focus on interventions to reduce the pathological decreases in cerebral blood flow that occur after stroke or other vascular insults such as spreading depression associated with migraine or brain trauma. The experiments will determine the roles for astrocytes, pericytes and neuronal inputs in modifying the vascular response to neuronal activity during these pathological events.
Targeting Cell Death
These experiments funded by the Canadian Stroke Network (2008-2010) are focused on determining the best strategies to reduce the impact of ion channel activation and inflammatory processes in triggering cell death following stroke.
1. Dissing-Olesen L, LeDue JM, Rungta RL, Hefendehl JK, Choi HB, & MacVicar BA (2014) Activation of neuronal NMDA receptors triggers transient ATP-mediated microglial process outgrowth. Journal of Neuroscience, 34(32), 10511-27.
2. Mills F, Bartlett TE, Dissing-Olesen L, Wisniewska MB, Kuznicki J, MacVicar BA, Wang YT, Bamji SX. (2014) Cognitive flexibility and long-term depression (LTD) are impaired following ?-catenin stabilization in vivo. Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8631-6. doi: 10.1073/pnas.1404670111. PMID: 24912177
3. Zhang JF, Malik A, Choi HB, Dissing-Olesen L, MacVicar BA. (2014) Microglia CR3 activation triggers long-term synaptic depression in the hippocampus via NADPH oxidase. Neuron, 82(1); 195-207.
4. Wu LJ, Stevens B, MacVicar BA (2013). Microglia in neuronal circuits. Neural Plasticity PMID 586426
5. Rungta RL, Choi HB, Lin PJc, Ko R, Nair J, Manoharan M, Cullis PR, MacVicar BA. (2013). Lipidnanoparticle delivery of siRNA to silence gene expression in the brain. Mol Ther Nucleic Acids, 2:e136
6. Zhu S, Tai C, Petkau TL, Zhange S, Liao C, Dong Z, Wen W, Cheng Q, Tian Wang Y, MacVicar BA, Leavitt BR, Jia W, Cynader MS. (2013). Progranulin promotes activation of microglia/microphage after pilocarpine-induced status epilepticus. Brain Research, 1530: 54-65.
7. Zhou N, Rungta RL, Malik A, Han H, Wu DC, Feighan D MacVicar B.A. (2013) Regenerative glutamate release by presynaptic NMDA receptors contributes to spreading depression. Journal of Cerebral Blood Flow and Metabolism, 33(10), 1582-94.
8. Hines DJ, Choi HB, Hines RM, Phillips AG & Macvicar BA. (2013). Prevention of LPS-induced microglia activation, cytokine production and sickness behavior with TLR4 receptor interfering peptides. PLOS One, 8(3):e60388
9. Fordsmann J, Ko R, Choi HB, Thomsen K, Witgen B, Mathiesen C, Lonstrup M, Piilgaard H, MacVicar BA & Lauritzen M. (2013). Increased 20-HETE synthesis explains reduced cerebral blood flow but not impaired neurovascular coupling after spreading depression in rat cerebral cortex. Journal of Neuroscience. 33:2562-2572.
10. Choi HB, Gordon GRJ, Zhou N, Tai C, Rungta R, Martinez, J, Milner TA, Ryu JK, MacLarnon JG, Tresguerres M, Levin LR, Buck J & MacVicar BA. (2012). Metabolic communication between astrocytes and neurons via bicarbonate-responsive soluble adenylyl cyclase. Neuron, 75; 1094-1104.