报告题目：Microglia-neuron communication in epilepsy
报告人: Long-Jun Wu （伍龙军） Assistant Professor
报告时间: 2015年6月26日（周五）14：00
报告地点: 18新利体育 神经18新利备用网站 所会议室
报告人简介：
EDUCATION
2008 — 2011 Postdoctoral fellow, Children's Hospital Boston, Harvard Medical School, USA (Mentor: Prof. David Clapham)
2004 — 2008 Postdoctoral fellow, Department of Physiology, University of Toronto, Canada (Mentor: Prof. Min Zhuo)
2003 —2004 Visiting graduate student, Department of Physiology, University of Toronto, Canada (Mentor: Prof. Min Zhuo).
1999 — 2004 Ph.D. in Neurobiology and Biophysics, University of Science and Technology of China, China (Mentor: Prof. Tian-Le Xu)
1995 —1999 B.S. in Biology, School of Life Sciences, Anhui University, China
WORK EXPRIENCE
2012 — Assistant Professor, Department of Cell Biology and Neuroscience, Rutgers University, USA
2011 — 2012 Instructor, Children’s Hospital Boston, Harvard Medical School, USA
2009 — 2010 Teaching assistant in Introduction to Neuroscience, Department of Neurobiology, Harvard Medical School, USA
2007 — 2008 Research associate, Department of Physiology, University of Toronto, Canada
2004 Research assistant, Institute of Neurosciences, Chinese Academy of Sciences, China
2001 Teaching assistant in Photography and Imaging in Biology, University of Science and Technology of China
PUBLICATIONS
Research Articles (#equal contribution, *Corresponding author):
1. Eyo UB, Gu N, De S, Dong H, Richardson JR, Wu LJ*. 2015. Modulation of microglial process convergence toward neuronal dendrites by extracellular calcium. Journal of Neuroscience, 35(6): 2417-2422.
2. Eyo UB, Peng J, Swiatkowski P, Mukherjee A, Bispo A, Wu LJ*. 2014. Neuronal hyperactivity recruits microglial processes via neuronal NMDA receptors and microglial P2Y12 receptors after status epilepticus. Journal of Neuroscience, 34 (32): 10528-10540.
3. 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. (Highlighted by Nature Reviews Neurology, 2012, 8:179)
4. 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. (Highlighted by Nature Reviews Drug Discovery, 2011, 10:176; Commented by Science Translational Medicine, 2011, 3:65ps1; Evaluated by Faculty of 1000)
5. 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. (Highlighted by Nature, 2008, 455: 266; Commented by Nature, 2008, 455: 607-8)
ABSTRACT
Epilepsy represents a neurological disorder that can manifest in uncontrolled seizures in patients. Microglia are exquisitely sensitive to disruptions in the central nervous system. Since epilepsy is characterized by neuronal hyperactivity rooted in excessive glutamate release and ionic imbalance, it is conceivable that microglia respond to and regulate neuronal activities during the pathology. Here, we found an increased number of microglial primary processes in the hippocampus during kainic acid-induced seizure activity. Consistently, global glutamate induced robust microglial process extension (MPE) towards neurons making increased contact with neurons in both brain slices and in the intact brain in vivo. The mechanism of the glutamate-induced MPE involves the activation of neuronal NMDA receptors, calcium influx, subsequent ATP release, and microglial response through P2Y12 receptors. In addition, we serendipitously found that extracellular Ca2+ reduction induced microglial processes to converge at distinct sites, a phenomena we termed microglial process convergence (MPC). Our studies revealed that MPC occur independent of astrocytic functions and are not directed towards astrocytes but target neuronal dendrites. Similar to glutamate-induced MPE, extracellular Ca2+-dependent MPC is also mediated by ATP and microglial P2Y12 receptor. Finally, we found that P2Y12 knockout mice exhibited reduced seizure-induced increases in microglial process numbers and worsened kainic acid-induced seizure behaviors. These studies are the first to investigate the microglial dynamics and discovered MPE and MPC during acute epilepsy. Our results elucidate the molecular mechanisms underlying microglia-neuron communication that may be potentially neuroprotective in the epileptic brain. Studying microglia-neuron communication in epilepsy informs the development of novel therapies targeting microglia in the treatment of epileptic disorders.
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2015-06-25