title: Protective effect of INI-0602, a gap junction inhibitor, on dopaminergic neurodegeneration of mice with unilateral 6-hydroxydopamine injection.
abstract: INI-0602, a novel gap junction hemichannel inhibitor, was administered to hemi-Parkinsonism mice generated by striatal 6-hydroxydopamine injection. INI-0602 prevented the toxic activation of microglia, such as the increased number of the activated form, enlargement of cell bodies and induction of proinflammatory cytokines, such as IL-1β and TNFα, in the ipsilateral striatum. On the other hand, INI-0602 induced the expression of neurotrophic factors, such as brain-derived neurotrophic factor and NT-4/5, in the 6-hydroxydopamine-treated striatum. INI-0602 treatment blocked not only dopaminergic loss in both the striatum and substantia nigra, but also apomorphine-induced rotational behavior.
authors.affiliation: Department of Brain Function, Division of Stress Adaptation and Protection, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi, 464-8601, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Kenji
authors.initials: K
authors.lastname: Ono
authors.forename: Makoto
authors.initials: M
authors.lastname: Sawada
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D007839:Functional Laterality / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016627:Oxidopamine / Q000633:toxicity*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; C491049:Aif1 protein, mouse; D019208:Brain-Derived Neurotrophic Factor; D002135:Calcium-Binding Proteins; D006576:Heterocyclic Compounds, 4 or More Rings; C000599854:INI-0602; D053583:Interleukin-1beta; D008840:Microfilament Proteins; D018696:Neuroprotective Agents; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
references.citation: J Neurochem. 2001 Feb;76(3):846-54
references.pmid: 11158256
references.citation: Neurosci Lett. 2001 Oct 19;312(2):95-8
references.pmid: 11595343
references.citation: Trends Neurosci. 1996 Aug;19(8):312-8
references.pmid: 8843599
references.citation: J Biol Chem. 2005 Mar 18;280(11):10444-54
references.pmid: 15640150
references.citation: PLoS One. 2011;6(6):e21108
references.pmid: 21712989
references.citation: Ann Med. 2002;34(7-8):491-500
references.pmid: 12553488
references.citation: J Biol Chem. 2002 Nov 1;277(44):42136-43
references.pmid: 12207012
references.citation: J Neurosci. 2005 Mar 9;25(10):2566-75
references.pmid: 15758166
references.citation: Trends Neurosci. 2000 Oct;23(10 Suppl):S86-91
references.pmid: 11052225
references.citation: Science. 2008 Aug 8;321(5890):848-51
references.pmid: 18687967
references.citation: Parkinsonism Relat Disord. 2007;13 Suppl 3:S259-62
references.pmid: 18267247
references.citation: CNS Neurol Disord Drug Targets. 2009 Dec;8(6):475-91
references.pmid: 19702565
references.citation: Int J Dev Neurosci. 1995 Jun-Jul;13(3-4):253-64
references.pmid: 7572279
references.citation: Trends Cell Biol. 2010 Feb;20(2):92-101
references.pmid: 19944606
references.citation: Exp Neurol. 2008 Nov;214(1):144-6
references.pmid: 18775425
references.citation: Brain Res. 1989 Jun 12;489(2):247-53
references.pmid: 2501002
references.citation: Biochem Soc Trans. 2007 Nov;35(Pt 5):1127-32
references.pmid: 17956294
references.citation: J Neural Transm Suppl. 2000;(58):143-51
references.pmid: 11128604
references.citation: Annu Rev Immunol. 2009;27:119-45
references.pmid: 19302036
references.citation: J Biol Chem. 2006 Jul 28;281(30):21362-21368
references.pmid: 16720574
references.citation: Brain Res. 2005 Feb 9;1034(1-2):11-24
references.pmid: 15713255
references.citation: Neuroscience. 1996 May;72(2):355-63
references.pmid: 8737406
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2009 Mar 17;33(2):181-98
references.pmid: 19162118
references.citation: Cell Mol Neurobiol. 2006 Jul-Aug;26(4-6):781-802
references.pmid: 16823625
references.citation: J Immunol. 1992 Oct 15;149(8):2736-41
references.pmid: 1383325
references.citation: Biochim Biophys Acta. 1997 Nov 28;1362(1):77-86
references.pmid: 9434102