Please wait a minute...
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2009, Vol. 3 Issue (3) : 330-335     DOI: 10.1007/s11684-009-0051-4
Research articles |
Protective effects of nicotine on gamma-aminobutyric acid neurons and dopaminergic neurons in mice with Parkinson disease
Lei FU MD 1, Dezheng GONG BM 1, Yan PENG 1, Dongmei WANG BM 1, Hong XU 1, Yue LI MD 2, Dengqin YU BS 2, Yanhui FENG MD 2, Shengming YIN PhD 2, Jin GONG 3, Yiping SUN PhD 4,
1.Lab of Physiological Function, College of Basic Medicine, Dalian Medical University, Dalian 116044, China; 2.Department of Physiology, College of Basic Medicine, Dalian Medical University, Dalian 116044, China; 3.Department of Anatomy, College of Basic Medicine, Dalian Medical University, Dalian 116044, China; 4.Lab of Physiological Function, College of Basic Medicine, Dalian Medical University, Dalian 116044, China;Department of Physiology, College of Basic Medicine, Dalian Medical University, Dalian 116044, China;
Download: PDF(323 KB)  
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract  This study aimed to investigate the protective effect of nicotine on dopaminergic neurons and its mechanisms in mice with Parkinson disease (PD) induced by 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP). C57BL/6J mice were injected with MPTP for 8 days to establish a PD model. Nicotine was given for 10 days in the nicotine therapeutic group. Animals were examined behaviorally with the pole test and traction test. Tyrosine hydroxylase (TH) and γ-aminobutyric acid (GABA) were determined by using the immunocytochemistry (ICC) method. The ultrastructural changes of the caudate nucleus (CN) were observed under electron microscopy. The results showed that pretreatment with nicotine could improve the dyskinesia of PD mice markedly. Simultaneously, TH-positive (P < 0.01) neurons and GABA-positive (P < 0.05) neurons in the nicotine therapeutic group were significantly more than those in the model group. The ultrastructural injury of the nicotine therapeutic group was also ameliorated. Nicotine has protective effects on the γ-aminobutyric acid neurons and dopaminergic neurons in the MPTP-treated mice.
Keywords Parkinson disease      nicotine      dopaminergic neuron      gamma-aminobutyric acid neuron      
Issue Date: 05 September 2009
URL:     OR
Dauer W, Przedborski S. Parkinson’s disease:mechanisms and models. Neuron, 2003, 39(6): 889―909

doi: 10.1016/S0896-6273(03)00568-3
Carr L A, Rowell P P. Attenuation of 1-methyl-4-phenyl-1,2, 3, 6-tetrahydropyridine-induced neurotoxicity by tobacco smoke. Neuropharmacology, 1990, 29(3): 311―314

doi: 10.1016/0028-3908(90)90019-N
Jansen A M, Fuxe K, Goldstein M. Differential effects of acute and chronic nicotine treatmenton MPTP-(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)induced degenerationof nigrostriatal dopamine neurons in the black mouse. Clin Investig, 1992, 70(3,4): 232―238
Parain K, Marchand V, Dumery B, Hirsch E. Nicotine,but not cotinine, partially protects dopaminergic neurons againstMPTP-induced degeneration in mice. BrainRes, 2001, 890(2): 347―350

doi: 10.1016/S0006-8993(00)03198-X
Maggio R, Riva M, Vaglini F, Fronai F, Molteni R, Armogida M, Racagni G, Corsini G U. Nicotine prevents experimentalparkinsonism in rodents and induces striatal increase of neurotrophicfactors. J Neurochem, 1998, 71(6): 2439―2446
Maggio R, Riva M, Vaglini F, Fronai F, Racagni G, Corsini G U. Striatal increase of neurotrophic factors as a mechanismof nicotine protection in experimental parkinsonism. J Neural Transm, 1997, 104(10): 1113―1123

doi: 10.1007/BF01273324
Belluardo N, Blum M, Mudo G, Andbjer B, Fuxe K. Acute intermittent nicotinetreatment produces regional increases of basic fibroblast growth factormessenger RNA and protein in the tel- and diencephalon of the rat. Neuroscience, 1998, 83(3): 723―740

doi: 10.1016/S0306-4522(97)00323-0
Arai N, Misugi K, Goshima Y, Misu Y. Evaluationof a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treatedC57 black mouse model for parkinsonism. Brain Res, 1990, 515(1,2): 57―63
Jakowec M W, Petzinger G M. 1-methyl-4-phenyl-1, 2, 3,6-tetrahydropyridine-lesioned model of parkinson's disease, with emphasison mice and nonhuman primates. Comp Med, 2004, 54(5): 497―513
Fredriksson A, Archer T. MPTP-induced behaviouraland biochemical deficits: a parametric analysis. J Neural Transm Park Dis Dement Sect, 1994, 7(2): 123―132

doi: 10.1007/BF02260967
Przedborski S, Jackson-Lewis V. Mechanisms of MPTP toxicity. Mov Disord, 1998, 13(Suppl 1): 35―38
Dawson T, Mandir A, Lee M. Animal models of PD: pieces of the same puzzle? Neuron, 2002, 35(2): 219―222

doi: 10.1016/S0896-6273(02)00780-8
Sedelis M, Hofele K, Auburger G W, Morgan S, Huston J P, Schwarting R K. MPTP susceptibility in the mouse: behavioral, neurochemical,and histological analysis of gender and strain differences. Behav Genet, 2000, 30(3): 171―182

doi: 10.1023/A:1001958023096
Beal M F. Experimental models of parkinson’s disease. Nat Rev Neurosci, 2001, 2(5): 325―334

doi: 10.1038/35072550
Yu X, Sun L, Luo X, Xu Z, An L. Investigation of the neuronal death mode induced by glutamatetreatment in serum-, antioxidant-free primary cultured cortical neurons. Brain Res Dev Brain Res, 2003, 145(2): 263―268

doi: 10.1016/j.devbrainres.2003.08.008
Limatola C, Lauro C, Catalano M, Ciotti M T, Bertollini C, Di Angelantonio S, Ragozzino D, Eusebi F. Chemokine CX3CL1 protectsrat hippocampal neurons against glutamate-mediated excitotoxicity. J Neuroimmunol, 2005, 166(1,2): 19―28
Kikuchi S, Kim S U. Glutamate neurotoxicity inmesencephalic dopaminergic neurons in culture. J Neurosci Res, 1993, 36(5): 558―569

doi: 10.1002/jnr.490360508
Plaitakis A, Shashidharan P. Glutamate transport and metabolismin dopaminergic neurons of substantia nigra: implications for thepathogenesis of Parkinson's disease. JNeurol, 2000, 247 (Suppl 2): II25―35

doi: 10.1007/PL00007757
Konitsiotis S, Blanchet P J, Verhagen L, Lamers E, Chase T N. AMPA receptor blockade improveslevodopa-induced dyskinesia in MPTP monkeys. Neurology, 2000, 54(8): 1589―1595
Hadj Tahar A, Gregoire L, Darre A, Bélanger N, Meltzer L, Bédard P J. Effect of a selective glutamate antagoniston L-dopa-induced dyskinesias in drug-naive parkinsonian monkeys. Neurobiol Dis, 2004, 15(2): 171―176

doi: 10.1016/j.nbd.2003.10.007
Herrero M T, Barcia C, Navarro J M. Functional anatomy of thalamus and basal ganglia. Childs Nerv Syst, 2002, 18(8): 386―404

doi: 10.1007/s00381-002-0604-1
Wichmann T, Kliem M A, DeLong M R. Antiparkinsonian and behavioral effects of inactivationof the substantia nigra pars reticulata in hemiparkinsonian primates. Exp Neurol, 2001, 167(2): 410―424

doi: 10.1006/exnr.2000.7572
Winkler C, Bentlage C, Nikkhah G, Samii M, Björklund A. Intranigral transplants ofGABA-rich striatal tissue induce behavioral recovery in the rat Parkinsonmodel and promote the effects obtained by intrastriatal dopaminergictransplants. Exp Neurol, 1999, 155(2): 165―186

doi: 10.1006/exnr.1998.6916
[1] Dan Xiao, Nanshan Zhong, Chunxue Bai, Qingyu Xiu, Canmao Xie, Dayi Hu, Yun Mao, Roland Perfekt, Elisabeth Kruse, Qing Li, John Jiangnan Liu, Chen Wang. Nicotine gum or patch treatment for smoking cessation and smoking reduction: a multi-centre study in Chinese physicians[J]. Front Med, 2014, 8(1): 84-90.
Full text