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个人简介

张玲, 2005年毕业于复旦大学神经生物学研究所,获博士学位;2007-2010年于哈佛大学医学院’Brigham & Women’s Hospital” 麻醉系疼痛中心接受博士后训练。 2011年加入同济大学,任同济大学转化医学高等研究院副研究员;2013年至今任同济大学医学院教授,博士生导师。任同济大学医学院感觉神经生物学实验室PI; 同济大学医学院神经系统整合课程负责人。近年来主要从事痛觉和痒觉以及睡眠的神经机制的研究,研究结果发表在Nat Med, J Neurosci, Pain, J Invest Dermatol,Curr Biol等国际权威杂志,曾得到Nat Med, Nat Rev Drug Discov等多个杂志评论和哈佛媒体Focus的采访报道,论文被引用>1400 (数据来自web of science)。研究课题受到科技部重大专项、国家自然基金面上以及上海浦江人才计划等项目资助。任中国神经科学学会感觉运动分会、麻醉与脑功能分会、中国生理学会疼痛转化研究委员会、中华医学会疼痛学分会委员;中国研究型医院学会神经再生与康复委员会神经环路重建与修复组常务委员;《中国疼痛医学杂志》编委。

研究领域

主要对痛觉、痒觉以及相关的情感和睡眠障碍的神经机制进行研究,研究进展如下: 一、痛觉研究方面的主要工作。1、针对慢性痛的脊髓中枢敏化机制,尤其是脊髓背角神经元和胶质细胞之间的相互作用在慢性痛的产生和维持中的机制深入研究。在脊髓水平首次证明小胶质细胞分泌的炎症因子和趋化因子可直接通过改变背角神经元的兴奋性而参与慢性痛的调控(JNS 2008; JNS 2009; Pain 2011);阐明炎症对抗因子“Resolvin”抑制炎症痛的作用及其外周和中枢神经机制(Nat Med 2010)。2、在脊髓上中枢证明了前扣带皮层经延髓背侧网状核到脊髓背角的这一新的下行调控通路及其对慢性痛的产生和维持的易化性调控作用(EJN 2005);前扣带皮层对中央外侧核的直接投射以及对丘脑中央外侧核痛敏神经元电活动的可塑性调节,为前扣带皮层参与 痛情绪反应提供了形态学和电生理学的证据(BRB 2010)。 二、痒觉研究方面的主要工作。除了参与了哈佛大学Qiu-Fu Ma实验室“vGluT2参与痛抑制痒的分子机制”的课题 研究(Neuron 2010)和Duke大学Ru-Rong Ji实验室“TLR3对痒的调控”的课题研究(JCI 2012),我们还首次证明了1、脊髓背角神经元ERK 信号参与急慢性痒的产生和维持的细胞机制和分子机制(Mol Brain,2014;Sci Reps 2015);2、提出组胺H4R通过持续地激活脊髓背角的PERK介导接触性皮炎的慢性骚痒(J Invest Dermatol 2018);3、阐明初级感觉神经元上的TLR2的异二聚体的激活分别通过不同的TRPs离子通道介导痛觉和痒觉行为(Neuronsci 2020);以及初级感觉神经元的转录因子ZBTB20通过调控TRPV1和TRPA1介导痒觉的调控(Front Med 2021)。 三、痛觉、痒觉以及相关的情感和睡眠障碍的神经环路机制方面的研究进展。1、与复旦大学脑科学研究院张玉秋教授及团队合作,揭示了前扣带皮层的雌激素β(ERβ)和GPER受体对疼痛引起的负性情绪的调节机制(Anesthesiology 2020);VLO以及丘脑Sm-VLO环路对神经病理性疼痛引起的负性情绪的调控JCI insight 2020);2、与上海交通大学医学院附属第一人民医院穆迪博士及团队合作,揭示脑干蓝斑核到丘脑PVT核的去甲肾上腺素能投射通过激活α1受体促进麻醉的快速觉醒(iScience 2021a);丘脑VB核对痛觉和痒觉信息的处理以及TRN到VB的抑制性投射环路对痛觉和痒觉的调控 (iScience 2021b)。3、证明脑干蓝斑核去甲肾上腺素能神经元向下丘脑VLPO的投射,分别通过调控VLPO的两类神经元对觉醒产生协同作用,并详细介绍了在自由活动小鼠同步记录皮层脑电和多通道电极阵列记录蓝斑核神经元放电的实验方法(Curr Biol 2021; STAR Protocol 2021)。

近期论文

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Jia X, Li ZY, Shen XF, Zhang Y, Zhang L, Zhang L* High-intensity swimming alleviates nociception and neuroinflammation in a mouse model of chronic postischemia pain by activating the resolvin E1-chemerin receptor 23 axis in the spinal cord. Neural Regen Res, 2023. 18(11):2535-2542. Zhu YB, Wang Y, Hua XX, Xu L, Liu MZ, Zhang R, Liu PF, Li JB, Zhang L*, Mu D*. PBN-PVT projections modulate negative affective states in mice. Elife. 2022;11. DOI: 10.7554/elife.68372 Comment on Chen G, Chen Z, Zhu Y. How the brain processes negative emotions. Elife. 2022;11 DOI: 10.7554/eLife.77550 Xu L, Liu MZ, Yang YY, Wang Y, Hua XX, Du LX, Zhu JY, Shen Y, Wang YQ, Zhang L, Mi WL, Mu D. Geraniol enhances inhibitory inputs to the paraventricular thalamic nucleus and induces sedation in mice. Phytomedicine. 2022;98:153965. DOI: 10.1016/j.phymed.2022.153965 Liu PF, Wang Y, Xu L, Xiang AF, Liu MZ, Zhu YB, Jia X, Zhang R, Li JB, Zhang L*, Mu D*. Modulation of itch and pain signals processing in ventrobasal thalamus by thalamic reticular nucleus. iScience. 2022;25(1):103625. https://doi.org/10.1016/j.isci.2021.103625 Liang Y, Shi W*, Hu D, Xiang A, Zhang L*. Protocol for recording the discharge of locus coeruleus neurons in free-moving mice during different sleep-wake stages. STAR Protocol 2021; https://doi.org/10.1016/j.xpro.2021.100981 Wang Y, Xu L, Liu MZ, Hu DD, Fang F, Xu DJ, Zhang R, Hua XX, Li JB, Zhang L, Huang LN, Mu D. Norepinephrine modulates wakefulness via alpha1 adrenoceptors in paraventricular thalamic nucleus. iScience. 2021;24(9):103015. https://doi.org/10.1016/j.isci.2021.103015 Feng Q, Xu X, Wei C, Li Y, Wang M, Lv C, Wu J, Dai Y, Han Y, Lesniak MS, Fan H, Zhang L*., Cheng Y*. The Dynamic Interactions between Nanoparticles and Macrophages Impact Their Fate in Brain Tumors. Small. 2021:e2103600. https://doi.org/10.1002/smll.202103600 Liang Y, Shi W, Xiang A, Hu D, Wang L*, Zhang L*. The NAergic locus coeruleus-ventrolateral preoptic area neural circuit mediates rapid arousal from sleep. Curr Biol. 2021. https://doi.org/10.1016/j.cub.2021.06.031 Jia X, Dai MH, Ren AJ, Wang TT, Zhang WJ*, Zhang L*. ZBTB20 in Nociceptive Neurons of the Trigeminal Ganglia Regulates Pruritus. Front Med (Lausanne). 2021;8:626554. https://doi.org/10.3389/fmed.2021.626554 Wang TT, Xu XY, Lin W, Hu DD, Shi W, Jia X, Wang H, Song NJ, Zhang YQ, Zhang L*. Activation of Different Heterodimers of TLR2 Distinctly Mediates Pain and Itch. Neuroscience. 2020;429:245-255. https://doi.org/10.1016/j.neuroscience.2020.01.010 Zang KK, Xiao X, Chen LQ, Yang Y, Cao QL, Tang YL, Lv SS, Cao H, Zhang L, Zhang YQ. Distinct Function of Estrogen Receptors in the Rodent Anterior Cingulate Cortex in Pain-related Aversion. Anesthesiology. 2020;133(1):165-184. https://doi.org/10.1097/aln.0000000000003324 Sheng HY, Lv SS, Cai YQ, Shi W, Lin W, Liu TT, Lv N, Cao H, Zhang L, Zhang YQ. Activation of ventrolateral orbital cortex improves mouse neuropathic pain-induced anxiodepression. JCI Insight. 2020;5(19). https://doi.org/10.1172/jci.insight.133625 Huang K, Hu DD, Bai D, Wu ZY, Chen YY, Zhang YJ, Lv X, Wang QX*, Zhang L*. Persistent Extracellular Signal-Regulated Kinase Activation by the Histamine H4 Receptor in Spinal Neurons Underlies Chronic Itch. J Invest Dermatol. 2018;138(8):1843-1850. https://doi.org/10.1016/j.jid.2018.02.019 Lang B, Zhang L, Jiang G, Hu L, Lan W, Zhao L, Hunter I, Pruski M, Song NN, Huang Y, Zhang L, St Clair D, McCaig CD, Ding YQ. Control of cortex development by ULK4, a rare risk gene for mental disorders including schizophrenia. Sci Rep. 2016;6:31126. https://doi.org/10.1038/srep31126 Jiang GY, Dai MH, Huang K, Chai GD, Chen JY, Chen L, Lang B, Wang QX, St Clair D, McCaig C, Ding YQ*, Zhang L*. Neurochemical characterization of pERK-expressing spinal neurons in histamine-induced itch. Sci Rep. 2015;5:12787. https://doi.org/10.1038/srep12787 Zhang L*, Jiang GY, Song NJ, Huang Y, Chen JY, Wang QX, Ding YQ*. Extracellular signal-regulated kinase (ERK) activation is required for itch sensation in the spinal cord. Mol Brain. 2014;7:25. https://doi.org/10.1186/1756-6606-7-25 Hu L, Lan W, Guo H, Chai GD, Huang K, Zhang L, Huang Y, Chen XF, Zhang L, Song NN, Chen L, Lang B, Wang Y, Wang QX, Zhang JB, McCaig C, Xu L, Ding YQ. A mouse line for inducible and reversible silencing of specific neurons. Mol Brain. 2014;7:68. https://doi.org/10.1186/s13041-014-0068-8 Huang Y, Song NN, Lan W, Zhang Q, Zhang L, Zhang L, Hu L, Chen JY, Zhao CJ, Li L, Xu L, Ding YQ. Sensory input is required for callosal axon targeting in the somatosensory cortex. Mol Brain. 2013;6:53. https://doi.org/10.1186/1756-6606-6-53 Liu T, Berta T, Xu ZZ, Park CK, Zhang L, Lu N, Liu Q, Liu Y, Gao YJ, Liu YC, Ma Q, Dong X, Ji RR. TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice. J Clin Invest. 2012;122(6):2195-2207. https://doi.org/10.1172/jci45414 Zhang L*, Berta T, Xu ZZ, Liu T, Park JY, Ji RR*. TNF-alpha contributes to spinal cord synaptic plasticity and inflammatory pain: distinct role of TNF receptor subtypes 1 and 2. Pain. 2011;152(2):419-427. https://doi.org/10.1016/j.pain.2010.11.014 Zhang L*, Zhao ZQ. Plasticity changes of neuronal activities in central lateral nucleus by stimulation of the anterior cingulate cortex in rat. Brain Res Bull. 2010;81(6):574-578. https://doi.org/10.1016/j.brainresbull.2009.12.009 Xu ZZ#, Zhang L#, Liu T, Park JY, Berta T, Yang R, Serhan CN, Ji RR. Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions. Nat Med. 2010;16(5):592-597, 591p following 597. https://doi.org/10.1038/nm.2123 Liu Y, Abdel Samad O, Zhang L, Duan B, Tong Q, Lopes C, Ji RR, Lowell BB, Ma Q. VGLUT2-dependent glutamate release from nociceptors is required to sense pain and suppress itch. Neuron. 2010;68(3):543-556. https://doi.org/10.1016/j.neuron.2010.09.008 Gao YJ, Zhang L, Ji RR. Spinal injection of TNF-alpha-activated astrocytes produces persistent pain symptom mechanical allodynia by releasing monocyte chemoattractant protein-1. Glia. 2010;58(15):1871-1880. https://doi.org/10.1002/glia.21056 Gao YJ, Zhang L, Samad OA, Suter MR, Yasuhiko K, Xu ZZ, Park JY, Lind AL, Ma Q, Ji RR. JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain. J Neurosci. 2009;29(13):4096-4108. https://doi.org/10.1523/jneurosci.3623-08.2009 Kawasaki Y#, Zhang L#, Cheng JK, Ji RR. Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord. J Neurosci. 2008;28(20):5189-5194. https://doi.org/10.1523/jneurosci.3338-07.2008 Zhang L, Zhang Y, Zhao ZQ. Anterior cingulate cortex contributes to the descending facilitatory modulation of pain via dorsal reticular nucleus. Eur J Neurosci. 2005;22(5):1141-1148. https://doi.org/10.1111/j.1460-9568.2005.04302.x

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