Location : homepage Laboratories Core Laboratories Zhong Chen Research
Research Interests:
The research interests of Chen’s lab focus on:
1) the histamine and histamine receptors in retractable epilepsy and the diseases related to neural excitatory damage, and a potential neuroprotective approach utilizing carnosine-histidine-histamine pathway.
2) the antiepileptic function of low frequency stimulation in treating retractable epilepsy.
3) neural damage and its pharmacotherapy.
Using the molecular and cellular technology, electrophysiological experiment on brain slice as well as in vivo experiments, we are pursuing on investigating the function of histamine and histamine receptors in pathogenesis of epilepsy, ischemic brain damage, and chronic pain, elucidating the pathogenesis of retractable epilepsy and its deep brain stimulation treatment, as well as the search of histamine precursors or novel H3 receptor antagonists. We have made several important discoveries which throw light on the understanding and treatment of cerebral diseases such as epilepsy and cerebral ischemia. Many of our papers are published in central journals in pharmacology and neuroscience.
Selected Peer-Reviewed Publications (last five years):
Yu J, Lou GD, Yue JX, Tang YY, Hou WW, Shou WT, Ohtsu H, Zhang SH, Chen Z*. Effects of histamine on spontaneous neuropathic pain induced by peripheral axotomy. Neurosci Bull. , in Press
Fan YY, Zhang XN, He P, Shen Z, Shen Y, Wang XF, Hu WW, Chen Z*.Transient lack of glucose but not O2 is involved in ischemic postconditioning-induced neuroprotection. CNS Neurosci Ther., in Press.
Hu WW, Fang Q, Xu ZH, Yan HJ, He P, Zhong K, Fan YY, Yang Y, Zhang XN, Zhang CY, Ohtsu H, Xu TL, Chen Z*. Chronic H1-Antihistamine treatment increases seizure susceptibility after withdrawal by impairing glutamine synthetase. CNS Neurosci Ther. 2012;18(8):683-690. DOI:10.1111/j.1755-5949.2012.00356.x.
Hu WW, Yang Y, Wang Z, Shen Z, Zhang XN, Wang GH, Chen Z*. H1-antihistamines induce vacuolation in astrocytes through macroautophagy. Toxicol Appl Pharmacol. 2012;260 (2):115-123. DOI: 10.1016/j.taap.2012.01.020
Zhong K, Wu DC, Jin MM, Xu ZH, Wang Y, Hou WW, Li XM, Zhang SH, Chen Z*. Wide therapeutic time-window of low-frequency stimulation at the subiculum for temporal lobe epilepsy treatment in rats. Neurobiol Dis. 2012;48(1):20-26. DOI: 10.1016/j.nbd.2012.05.011
Xu ZH, Wang Y, Jin MM, Yue JX, Xu CL, Ying XY, Wu DC, Zhang SH, Chen Z*. Polarity-dependent effect of low-frequency stimulation on amygdaloid kindling in rats. Brain Stimul. 2012, [Epub ahead of print].
Ma J, Xiong JY, Hou WW, Yan HJ, Sun Y, Huang SW, Jin L, Wang Y, Hu WW, Chen Z*. Protective effect of carnosine on subcortical ischemic vascular dementia in mice. CNS Neurosci Ther. 2012 ,18(9):745-753. DOI: 10.1111/j.1755-5949.2012.00362.x.
Hu WW, Chen Z*. Role of histamine and its receptors in cerebral ischemia. ACS Chem Neurosci. 2012,3 (4):238-247.
Wang RR, Zhang XN, Zhang JX, Fan YY, Shen Y, Hu WW, Chen Z*. Oxygen-glucose deprivation induced glial scar-like change in astrocytes. PLoS One. 2012;7(5):e37574. DOI: 10.1371/journal.pone.0037574
Dou Y, Wu HJ, Li HQ, Qin S, Wang YE, Li J, Lou HF, Chen Z, Li XM, Luo QM, Duan S*. Microglial migration mediated by ATP-induced ATP release from lysosomes. Cell Res. 2012;22(6):1022-1033. DOI: 10.1038/cr.2012.10.
He G, Hu J, Li T, Ma X, Meng J, Jia M, Lu J, Ohtsu H, Chen Z, Luo X*. The arrhythmogenic effect of sympathetic histamine in mouse hearts subjected to acute ischemia. Mol Med. 2012;18(1):1-9. DOI: 10.2119/molmed.2011.00225.
Zhong WX, Wang YB, Peng L, Ge XZ, Zhang J, Liu SS, Zhang XN, Xu ZH, Chen Z, Luo JH*. Lanthionine synthetase C-like protein 1 interacts with and inhibits cystathionine beta-synthase: a target for neuronal antioxidant defense. J Biol Chem. 2012;287(41):34189-34201. DOI: 10.1074/jbc.M112.383646.
Shi WZ, Zhao CZ, Zhao B, Zheng XL, Fang SH, Lu YB, Zhang WP, Chen Z, Wei EQ*. Aquaporin-4 deficiency attenuates acute lesions but aggravates delayed lesions and microgliosis after cryoinjury to mouse brain. Neurosci Bull. 2012;28(1):61-68. DOI: 10.1007/s12264-012-1063-7.
Fan YY, Hu WW, Dai HB, Zhang JX, Zhang LY, He P, Shen Y, Ohtsu H, Wei EQ, Chen Z*. Activation of the central histaminergic system is involved in hypoxia-induced stroke tolerance in adult mice. J Cerebr Blood F Met. 2011;31(1):305-14. DOI: 10.1038/jcbfm.2010.94
Jin MM, Chen Z*. Role of gap junctions in epilepsy. Neurosci Bull. 2011;27(6):389-406. DOI: 10.1007/s10827-012-0386-8
Li KX, Lu YM, Xu ZH, Zhang J, Zhu JM, Zhang JM, Cao SX, Chen XJ, Chen Z, Luo JH, Duan S, Li XM*. Neuregulin 1 regulates excitability of fast-spiking neurons through Kv1.1 and acts in epilepsy. Nat Neurosci. 2011;15(2):267-73. DOI: 10.1038/nn.3006
Yan M, Dai H, Ding T, Dai A, Zhang F, Yu L, Chen G, Chen Z*. Effects of dexmedetomidine on the release of glial cell line-derived neurotrophic factor from rat astrocyte cells. Neurochem Int. 2011;58(5):549-557. DOI: 10.1016/j.neuint.2011.01.013
Fang Q, Chen Z*. Increased asynchronous GABA release causes more inhibition in human epileptic brain? Acta Pharmacol Sin. 2012;33(7):859-860. DOI: 10.1038/aps.2012.92
Gong YX, Zhang WP, Shou WT, Zhong K, Chen Z*. Morphine induces conditioned place preference behavior in histidine decarboxylase knockout mice. Neurosci Lett. 2010;468(2):115-119. DOI: 10.1016/j.neulet.2009.10.079
Gong YX, Shou WT, Feng B, Zhang WP, Wang HJ, Ohtsu H, Chen Z*. Ameliorating effect of histamine on impairment of cued fear extinction induced by morphine withdrawal in histidine decarboxylase gene knockout mice. Acta Pharmacol Sin. 2010;31(11):1431-1437. DOI: 10.1038/aps.2010.136
Li JM, Zeng YJ, Peng F, Li L, Yang TH, Hong Z, Lei D, Chen Z, Zhou D*. Aberrant glutamate receptor 5 expression in temporal lobe epilepsy lesions. Brain Res. 2010,1311:166-174. DOI: 10.1016/j.brainres.2009.11.024
Shen Y, He P, Fan YY, Zhang JX, Yan HJ, Hu WW, Ohtsu H, Chen Z*. Carnosine protects against permanent cerebral ischemia in histidine decarboxylase knock-out mice through reducing glutamate excitotoxicity. Free Radical Bio Med. 2010 1;48(5):727-735. DOI:10.1016/j.freeradbiomed.
Sun HL, Zhang SH, Zhong K, Xu ZH, Zhu W, Fang Q, Wu DC, Hu WW, Xiao B, Chen Z*. Mode-dependent effect of low-frequency stimulation targeting the hippocampal CA3 subfield on amygdala-kindled seizures in rats. Epilepsy Res. 2010; 90:83-90. DOI: 10.1016/j.eplepsyres.2010.03.011
Wang S, Wu DC, Fan XN, Zhu MZ, Hu QY, Zhou D, Ding MP, Chen Z*. Mediodorsal thalamic stimulation is not protective against seizures induced by amygdaloid kindling in rats. Neurosci Lett. 2010;481(2):97-101. DOI: 10.1016/j.neulet.2010.06.060
Stöckigt J, Chen Z, Ruppert M*. Enzymatic and chemo-enzymatic approaches towards natural and non-natural alkaloids: indoles, isoquinolines, and others. Top Curr Chem.2010;297:67-103.
Xu ZH, Wu DC, Fang Q, Zhong K, Wang S, Sun HL, Zhang SH, Chen Z*. Therapeutic time window of low frequency stimulation at entorhinal cortex for amygdaloid-kindling seizures in rats. Epilepsia. 2010; 51(9):1861-1864. DOI: 10.1111/j.1528-1167.2010.02663.x
Gong N, Li Y, Cai GQ, Niu RF, Fang Q, Wu K, Chen Z, Lin LN, Xu L, Fei J, Xu TL*. GABA transporter-1 activity modulates hippocampal theta oscillation and theta burst stimulation-induced long-term potentiation. J Neurosci. 2009;29(50):15836-15845. DOI: 10.1523/JNEUROSCI.4643-09.2009
Gao F, Guo Y, Zhang H, Wang S, Wang J, Wu JM, Chen Z, Ding MP*. Anterior thalamic nucleus stimulation modulates regional cerebral metabolism: an FDG-MicroPET study in rats. Neurobiol Dis. 2009;34(3):477-483. DOI: 10.1016/j.nbd.2009.03.001
Xu LS, Fan YY, He P, Zhang WP, Hu WW, Chen Z*. Ameliorative effects of histamine on spatial memory deficits induced by scopolamine infusion into bilateral dorsal or ventral hippocampus as evaluated by radial-arm maze task. Clin Exp Pharmacol Physiol. 2009;36(8):816-821. DOI: 10.1111/j.1440-1681.2009.05157.x 97.
Li CT, Zhang WP, Lu YB, Fang SH, Yuan YM, Qi LL, Zhang LH, Huang XJ, Zhang L, Chen Z, Wei EQ*. Oxygen-glucose deprivation activates 5-lipoxygenase mediated by oxidative stress through the p38 mitogen-activated protein kinase pathway in PC12 cells. J Neurosci Res. 2009;87(4):991-1001. DOI: 10.1002/jnr.21913
Zhang SH, Sun HL, Fang Q, Zhong K, Wu DC, Wang S, Chen Z*. Low-frequency stimulation of the hippocampal CA3 subfield is anti-epileptogenic and anti-ictogenic in rat amygdaloid kindling model of epilepsy. Neurosci Lett. 2009;455(1): 51-55. DOI: 10.1016/j.neulet.2009.03.041
Wu DC, Zhu-Ge ZB, Yu CY, Fang Q, Wang S, Jin CL, Zhang SH, Chen Z*. Low-frequency stimulation of the tuberomammillary nucleus facilitates electrical amygdaloid-kindling acquisition in Sprague-Dawley rats. Neurobiol Dis. 2008;32(1):151-156. DOI: 10.1016/j.nbd.2008.07.002
Wu DC, Xu ZH, Wang S, Fang Q, Hu DQ, Li Q, Sun HL, Zhang SH, Chen Z*. Time-dependent effect of low-frequency stimulation on amygdaloid-kindling seizures in rats. Neurobiol Dis. 2008;31(1):74-79. DOI: 10.1016/j.nbd.2008.03.007
Zhang SH, Sun QX, Seltzer Z, Cao DY, Wang HS, Chen Z, Zhao Y*. Paracrine-like excitation of low-threshold mechanoceptive C-fibers innervating rat hairy skin is mediated by substance P via NK-1 receptors. Brain Res Bull. 2008;31;75(1):138-145. DOI: 10.1016/j.brainresbull.2007.08.003
Shen Y, Zhang S, Fu L, Hu W, Chen Z*. Carnosine attenuates mast cell degranulation and histamine release induced by oxygen-glucose deprivation. Cell Biochem Funct. 2008;26(3):334-338. DOI: 10.1002/cbf.1447
Fu Q, Dai H, Hu W, Fan Y, Shen Y, Zhang W, Chen Z*. Carnosine protects against Abeta42-induced neurotoxicity in differentiated rat PC12 cells. Cell Mol Neurobiol. 2008;28(2):307-316. DOI: 10.1007/s10571-007-9235-0
Hu WW, Onuma T, Birukawa N, Abe M, Ito E, Chen Z, Urano A*. Change of morphology and cytoskeletal protein gene expression during dibutyryl cAMP-induced differentiation in C6 glioma cells. Cell Mol Neurobiol. 2008;28(4):519-528. DOI: 10.1007/s10571-007-9229-y
Wang S, Wu DC, Ding MP, Li Q, Zhu-Ge ZB, Zhang SH, Chen Z*. Low-frequency stimulation of cerebellar fastigial nucleus inhibits amygdaloid kindling acquisition in Sprague-Dawley rats. Neurobiol Dis. 2008;29(1):52-58. DOI: 10.1016/j.nbd.2007.07.027
Hu WW, Yan H, Birukawa, Abe M, Ito E, Tsujii K, Chen Z*, Urano A. Morphology of C6 glioma cells on a water-repellent fractal alkyl ketene dimer surface. Current Nanoscience. 2008; 4(3): 224-231. DOI: 10.2174/157341308785161118
Huang XJ, Zhang WP, Li CT, Shi WZ, Fang SH, Lu YB, Chen Z, Wei EQ*. Activation of CysLT receptors induces astrocyte proliferation and death after oxygen-glucose deprivation. Glia. 2008;56:27-37. DOI: 10.1002/glia.20588
Liu CQ, Hu DN, Liu FX, Chen Z, Luo JH*. Apomorphine-induced turning behavior in 6-hydroxydopamine lesioned rats is increased by histidine and decreased by histidine decarboxylase, histamine H1 and H2 receptor antagonists, and an H3 receptor agonist. Pharmacol Biochem Behav. 2008; 90(3):325-330. DOI: 10.1016/j.pbb.2008.03.010
Wang K, Shen HH, Huang HQ, Chen JC, Chen Z*. Acetamide-45 inhibited hyperresponsiveness and airway inflammation in mice partly depending on phosphodiesterase activity suppression. Acta Pharmacol Sin. 2008;29(10):1195-1201. DOI: 10.1111/j.1745-7254.2008.00846.x