View online: http://www.sbrc.ca/2012/11/pharmacology-invited-speaker-lecture-dr-long- jun-wu/
Invited Speaker Lecture - Dr. Long-Jun Wu
DATE: Friday, Nov 16, 2012 TIME: 12:00 noon LOCATION: A229 Chown Bldg., Bannatyne Campus ** **Video-linked to R1002 SBHR Bldg. (St. Boniface Campus)
http://www.sbrc.ca/wp-content/uploads/2012/11/web_Long-Jun-photo.jpg Long-Jun Wu, PhD Assistant Professor Department of Cell Biology and Neuroscience Rutgers University New Brunswick, NJ
TOPIC: Microglia-neuron communication in normal and diseased brain
The long-term goal of my lab is to understand microglia-neuron communication in the brain. Microglia are the principal immune-response cells in the central nervous system. Resting microglia constantly survey the microenvironment in the normal brain. Upon brain dysfunction, microglia are activated and exert detrimental or beneficial effects on the surrounding neurons. Microglia have remarkably fast and dynamic activities in both the normal and pathological brain. An exciting possibility is that they are communicating with neurons through ion channel mechanisms. In neuronal circuits, microglia are assumed to be crucial to synaptic pruning and plasticity, yet no direct evidence has been identified. Microglia are strongly activated in pathological conditions such as pain, stroke and neurodegeneration, however, the molecular mechanisms for microglial activation and function in brain diseases are still controversial.
Overall, we are interested in three interrelated topics on microglia-neuron communication: (1) The ion channel mechanism of microglia-neuron communication; (2) Microglia in synaptic function; and (3) Microglia's contribution to neuropathic pain. We have been exploring microglia chemotaxis (Wu et al., Glia, 2007, Fig.1), microglia in synaptic plasticity (Wu and Zhuo, J Neurophysiol, 2008), as well as an unique microglial voltage-gated proton channel, Hv1, in the brain (Wu et al., Nat Neurosci, 2012). Taking Hv1 proton channel as an entry point, our initial project will study direct communication from microglia to neurons through microglial Hv1. We will then explore how microglia function in neuronal circuits under normal and pain conditions. The results from our studies would advance the understanding of microglia function in the brain and provide therapeutic targets for neuropathic pain treatment.
SELECTED PUBLICATIONS
Research Articles
1. Wu LJ*, Wu G*, Sharif MR, Baker A, Jia Y, Fahey FH, Luo HR, Feener EP, Clapham DE. 2012. The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke. Nature Neuroscience, 15(4): 565-573. 2. Jin J, Wu LJ, Jun J, Cheng X, Xu H, Andrews NC, Clapham DE. 2012. The channel kinase, TRPM7, is required for early embryonic development. Proceedings of the National Academy of Science, USA, 109(5): E225-233. 3. Wang H*, Xu H*, Wu LJ*, Kim SS*, Chen T, Koga K, Descalzi G, Gong B, Vadakkan KI, Zhang X, Kaang BK, Zhuo M. 2011. Identification of an adenylyl cyclase inhibitor for treating neuropathic and inflammatory pain. Science Translational Medicine, 3 (65): 65ra3 4. Slusky I, Abumaria N, Wu LJ, Huang C, Zhang L, Li B, Zhao X, Govindarajan A, Zhao MG, Zhuo M, Tonegawa S, Liu G. 2010. Enhancement of learning and memory by elevating brain magnesium. Neuron, 65 (2): 165-177. 5. Wu LJ, Mellstrom B, Wang H, Ren M, Domingo S, Kim SS, Li XY, Chen T, Naranjo JR, Zhuo M. 2010. DREAM (Downstream Regulatory Element Antagonist Modulator) contributes to synaptic depression and contextual fear memory. Molecular Brain, 3 (1): 3. 6. Wu LJ, Li X, Chen T, Ren M, Zhuo M. 2009. Characterization of intracortical synaptic connections in the mouse anterior cingulate cortex using dual patch clamp recording. Molecular Brain, 2 (1): 32. 7. Wu LJ, Steenland HK, Kim SS, Isiegas C, Ted A, Kaang BK, Zhuo M. 2008. Enhancement of presynaptic glutamate release and persistent inflammatory pain by increasing neuronal cAMP in the anterior cingulate cortex. Molecular Pain, 4 (1): 40. 8. Wang H*, Wu LJ*, Kim SS*, Lee FJ, Gong B, Toyoda H, Ren M, Xu H, Liu F, Zhao MG, Zhuo M. 2008. FMRP acts as a key messenger for dopamine modulation in the forebrain. Neuron, 59 (4): 634-647. 9. Xu H*, Wu LJ*, Wang H*, Zhang X, Vadakkan KI, Kim SS, Steenland HW, Zhuo M. 2008. Presynaptic and postsynaptic amplifications of neuropathic pain in the anterior cingulate cortex. Journal of Neuroscience, 28 (29): 7445-7453. 10. Hines RM*, Wu LJ*, Hines DJ, Steenland H, Mansour S, Dahlhaus R, Singaraja RR, Cao X, Sammler E, Hormuzdi SG, Zhuo M, El-Husseini A. 2008. Synaptic imbalance, stereotypies and impaired social interactions in mice with altered neuroligin 2 expression. Journal of Neuroscience, 28 (24): 6055-6067. 11. Wang H, Wu LJ, Zhang F, Zhuo M. 2008. Roles of calcium-stimulated adenylyl cyclase and calmodulin-dependent protein kinase IV in the regulation of FMRP by Group I metabotropic glutamate receptors. Journal of Neuroscience, 28 (17): 4385-4397. 12. Zhang F, Vadakkan K, Kim SS, Wu LJ, Shang Y, Zhuo M. 2008. Selective activation of microglia in spinal cord but not higher cortical regions following nerve injury in adult mouse. Molecular Pain, 4 (1): 15. 13. Wu LJ*, Zhang XH*, Fukushima H, Zhang F, Wang H, Toyoda H, Li BM, Kida S, Zhuo M. 2008. Genetic enhancement of trace fear memory and cingulate potentiation in mice overexpressing Ca2+/calmodulin-dependent protein kinase IV. European Journal of Neuroscience, 27 (8): 1923-1932. 14. Wu LJ, Zhuo M. 2008. Resting microglial motility is independent of synaptic plasticity in mammalian brain. Journal of Neurophysiology, 99 (4): 2026-2032. 15. Wu LJ*, Ren M*, Wang H*, Kim SS, Cao X, Zhuo M. 2008. Neurabin contributes to hippocampal long-term potentiation and contextual fear memory. PLoS ONE, 3 (1): e1407. 16. Duan B*, Wu LJ*, Yu YQ, Ding Y, Jing L, Xu L, Chen J, Xu TL. 2007. Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity. Journal of Neuroscience, 27 (41): 11139-11148. 17. Wu LJ, Vadakkan KI, Zhuo M. 2007. ATP-induced chemotaxis of microglial processes requires P2Y receptor-activated initiation of outward potassium currents. Glia, 55 (8): 810-821. 18. Wu LJ, Xu H, Ren M, Cao X, Zhuo M. 2007. Pharmacological isolation of postsynaptic currents mediated by NR2A- and NR2B-containing NMDA receptors in the anterior cingulate cortex. Molecular Pain, 3 (1): 11. 19. Wu LJ, Xu H, Ren M, Zhuo M. 2007. Genetic and Pharmacological studies of GluR5 modulation of inhibitory synaptic transmission in the anterior cingulate cortex of adult mice. Developmental Neurobiology, 67 (2): 146-157. 20. Wu LJ*, Ko S*, Toyoda H*, Zhao MG*, Xu H, Vadakkan KI, Ren M, Knifed E, Shum F, Quan J, Zhang XH, Zhuo M. 2007. Increased anxiety-like behavior and enhanced synaptic efficacy in the amygdala of GluR5 knockout mice. PLoS ONE, 2 (1): e167. 21. Zhao MG*, Ko S*, Wu LJ*, Toyoda H*, Xu H, Quan J, Jia Y, Li JG, Ren M, Xu Z, Zhuo M. 2006. Enhanced presynaptic neurotransmitter release in the anterior cingulate cortex of the mice with chronic pain. Journal of Neuroscience, 26 (35): 8923-8930. 22. Wu LJ, Toyoda H, Zhao MG, Lee YS, Tang J, Ko S, Jia Y, Shum F, Zerbinatti CV, Bu G, Wei F, Xu TL, Muglia LJ, Chen ZF, Auberson YP, Kaang BK, Zhuo M. 2005. Upregulation of forebrain NMDA NR2B receptors contributes to behavioral sensitization after inflammation. Journal of Neuroscience, 25 (48): 11107-11116. 23. Zhao MG*, Toyoda H*, Lee YS*, Wu LJ*, Ko S*, Zhang XH*, Jia Y, Shum F, Xu H, Li BM, Kaang BK, Zhuo M. 2005. Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory. Neuron, 47 (6): 859-872. 24. Wu LJ, Zhao MG, Toyoda H, Ko S, Zhuo M. 2005. Kainate receptor-mediated synaptic transmission in the adult anterior cingulate cortex. Journal of Neurophysiology, 94 (3): 1805-1813. 25. Wu LJ, Duan B, Mei YD, Gao J, Chen JG, Zhuo M, Xu L, Wu M, Xu TL. 2004. Characterizations of acid-sensing ion channels in dorsal horn neurons of rat spinal cord. Journal of Biological Chemistry, 279 (42): 43716-43724. 26. Wu LJ, Li Y, Xu TL. 2002. Co-release and interaction of two inhibitory co-transmitters in rat sacral dorsal commissural neurons. NeuroReport, 13 (7): 977-981. 27. Wu LJ, Lu Y, Xu TL. 2001. A novel mechanical dissociation technique for studying acutely isolated maturing Drosophila central neurons. Journal of Neuroscience Methods, 108 (2): 199-206.
Reviews
1. Wu LJ, Sweet TB, Clapham DE. 2010. Current progress in the mammalian TRP ion channel family. Pharmacological Reviews, 62 (3): 381-404. 2. Wu LJ, Zhuo M. 2009. Targeting the NMDA receptor subunit NR2B for the treatment of neuropathic pain. Neurotherapeutics, 6 (4): 693-702. 3. Wu LJ, Wang YT, Zhuo M. 2009. Hook-up of GluA2, GRIP and liprin-alpha for cholinergic muscarinic receptor-dependent LTD in the hippocampus. Molecular Brain, 2 (1): 17. 4. Wu LJ, Kim SS, Zhuo M. 2008. Molecular targets of anxiety: from membrane to nucleus. Neurochemical Research, 33 (10): 1925-1932. 5. Wu LJ, Ko S, Zhuo M. 2007. Kainate receptor and pain: from dorsal root ganglion to the anterior cingulate cortex. Current Pharmaceutical Design, 13 (15): 1597-1605. 6. Wu LJ, Zhuo M. 2006. Supraspinal electrophysiological models for studying chronic pain. Drug Discovery Today: Disease Models, 3 (4): 405-411. 7. Wu LJ, Xu H, Ko S, Yoshimura M, Zhuo M. 2005. Feed-forward inhibition: a novel cellular mechanism for the analgesic effect of substance P. Molecular Pain, 1 (1): 34
For more information:
Ben Albensi Seminar Coordinator & Associate Professor, Pharmacology & Therapeutics
T: 204.235.3942 E: balbensi@sbrc.ca
Kelly Jorundson Administrative Manager Division of Neurodegenerative Disorders St. Boniface Hospital Research Department of Pharmacology & Therapeutics University of Manitoba
Tel: 204.235.3939 Fax: 204.237.4092 Email: kjorund@sbrc.ca OR kjorund@yahoo.ca Website: www.sbrc.ca/dnd OR www.umanitoba.ca/medicine/units/pharmacology
