Relationship between Microglial Activation and Dopaminergic Neuronal Loss in 6-OHDA-induced Parkinsonian Animal Model (6-OHDA로 유도된 파킨슨 증후군의 동물 모델에서 도파민성 신경세포의 손실과 미세아교세포 활성 사이의 관계)

이진숙; LEE Ji Yong (이지용); Won Gil Cho (조원길); 양영철; 조병필

doi:10.11637/aba.2013.26.1.13

Relationship between Microglial Activation and Dopaminergic Neuronal Loss in 6-OHDA-induced Parkinsonian Animal Model

Anatomy & Biological Anthropology
Abbr : Anat Biol Anthropol
2013, 26(1), pp.13~23
DOI : 10.11637/aba.2013.26.1.13
Publisher : 대한체질인류학회
Research Area : Medicine and Pharmacy > Anatomy

이진숙 ¹, LEE Ji Yong ¹, Won Gil Cho ¹, 양영철 ¹, 조병필 ¹

¹연세대학교

Accredited

ABSTRACT

This study assessed the dynamics of morphological and immunophenotypic properties of activated microglia in a 6-hydroxydopamine (6-OHDA) induced Parkinsonian animal model. Neurodegeneration in the substantia nigra pars compacta (SNc) was induced by unilateral injection of 6-OHDA into the medial forebrain bundle. Parkinsonian animal model were sacrificed at 1, 2, 4 and 8 weeks after 6-OHDA injection. Changes in the functional activity of activated microglia were identified using different monoclonal antibodies: OX6 for major histocompatibility complex (MHC) class II, ED1 for phagocytic activity. Phagocytic microglia, characterized by ED1- or OX6-immunoreactivity, appeared in the SNc at 1 week after 6-OHDA injection, activated microglia selectively adhered to degenerating axons, dendrites and dopaminergic neuron somas in the SNc. This was followed by significant loss of these fibers and nigral dopaminergic neurons. Activation of microglia into phagocytic stage was most pronounced at 2 week after 6-OHDA injection and gradually subsided, but phagocytic microglia persisted until 8 weeks after 6-OHDA injection. Taken together, our results indicate that activated microglia is lead to persistently neuron cell death and promotes loss of dopaminergic neuron by degeneration of the dopaminergic neurons.

KEYWORDS

Parkinsonian, 6-hydroxydopamine, Dopaminergic neuron, Microglia

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[journal] Beal MF / 1995 / Aging, energy, and oxidative stress in neurodegenerative diseases / Ann Neurol 38 : 357~366

[journal] Jenner P / 1998 / Oxidative mechanisms in nigral cell death in Parkinson’s disease / Mov Disord 13 : 24~34

[journal] Gerlach M / 2002 / Altered brain metabolism of iron as a cause of neurodegenerative diseases? / J Neurochem 63 : 793~807

[journal] Saporito MS / 1992 / Dopaminergic neurotoxicity of 1-methyl-4-phenylpyridinium analogs in cultured neurons: relationship to the dopamine uptake system and inhibition of mitochondrial respiration / The Journal of pharmacology and experimental therapeutics 260 : 1400~1409

[journal] Cassarino DS / 1997 / Elevated reactive oxygen species and antioxidant enzyme activities in animal and cellular models of Parkinson’s disease / Biochim Biophys Acta 1362 : 77~86

[journal] Foley P / 2000 / Influence of neurotoxins and oxidative stress on the onset and progression of Parkinson’s disease / J Neurol 247 : 82~94

[journal] Factor SA / 2004 / Trauma as an etiology of parkinsonism: a historical review of the concept / Mov Disord 3 : 30~36

[journal] Ling Z / 2002 / In utero bacterial endotoxin exposure causes loss of tyrosine hydroxylase neurons in the postnatal rat midbrain / Mov Disord 17 : 116~124

[journal] McGeer P / 1988 / Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains / Neurology 38 : 1285~1285

[journal] Lawson LJ / 1990 / Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain / Neuroscience 39 : 151~170

[journal] Kim WG / 2000 / Regional difference in susceptibility to lipopolysaccharide- induced neurotoxicity in the rat brain: role of microglia / J Neurosci 20 : 6309~6316

[journal] Knott C / 2000 / Inflammatory regulators in Parkinson’s disease: iNOS, lipocortin-1, and cyclooxygenases- 1 and -2 / Mol Cell Neurosci 16 : 724~739

[journal] Cicchetti F / 2002 / Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats monitored by immunohistochemistry and PET imaging / Eur J Neurosci 15 : 991~998

[journal] O’Callaghan JP / 1990 / Characterization of the origins of astrocyte response to injury using the dopaminergic neurotoxicant, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Brain Res 521 : 73~80

[journal] Kurkowska-Jastrzebska I / 1999 / The inflammatory reaction following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication in mouse / Exp Neurol 156 : 50~61

[journal] Graeber M / 2004 / Axotomy of the rat facial nerve leads to increased CR3 complement receptor expression by activated microglial cells / J Neurosci Res 21 : 18~24

[journal] Streit WJ / 2004 / Functional plasticity of microglia: a review / Glia 1 : 301~307

[journal] 2Du Y / 2001 / Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease / Proc Natl Acad Sci U S A 98(14669)

[journal] Thomas M, Le WD / 2004 / Minocycline: neuroprotective mechanisms in Parkinson’s disease / Curr Pharm Des 10 : 679~686

[journal] Park EM / 2005 / Ibuprofen protects ischemia-induced neuronal injury via up-regulating interleukin-1 receptor antagonist expression / Neuroscience 132 : 625~631

[journal] Liu B / 2000 / Naloxone protects rat dopaminergic neurons against inflammatory damage through inhibition of microglia activation and superoxide generation / J Pharmacol Exp Ther : 607~617

[journal] Betarbet R / 2000 / Chronic systemic pesticide exposure reproduces features of Parkinson’s disease / Nat Neurosci 3 : 1301~1306

[journal] Kostrzewa RM / 1974 / Pharmacological actions of 6-hydroxydopamine / Pharmacol Rev 26 : 199~288

[journal] Davis GC / 1979 / Chronic Parkinsonism secondary to intravenous injection of meperidine analogues / Psychiatry Res 1 : 249~254

[journal] Tseng JL / 1997 / GDNF reduces drug-induced rotational behavior after medial forebrain bundle transection by a mechanism not involving striatal dopamine / J Neurosci 17 : 325~333

[journal] Sugama S / 2003 / Temporal and sequential analysis of microglia in the substantia nigra following medial forebrain bundle axotomy in rat / Neuroscience 116 : 925~933

[journal] Akiyama H / 1989 / Microglial response to 6-hydroxydopamine- induced substantia nigra lesions / Brain Res 489 : 247~253

[journal] Chao CC / 1992 / Activated microglia mediate neuronal cell injury via a nitric oxide mechanism / J Immunol 149 : 2736~2741

[journal] Rogove AD / 1998 / Neurotoxic responses by microglia elicited by excitotoxic injury in the mouse hippocampus / Curr Biol 8 : 19~25

[journal] Takeuchi A / 2001 / Microglial NO induces delayed neuronal death following acute injury in the striatum / Eur J Neurosci 10 : 1613~1620

[journal] Depino AM / 2003 / Microglial activation with atypical proinflammatory cytokine expression in a rat model of Parkinson’s disease / Eur J Neurosci 18 : 2731~2742

[journal] Rodriguez-Pallares J / 2008 / Brain angiotensin enhances dopaminergic cell death via microglial activation and NADPHderived ROS / Neurobiol Dis 31 : 58~73

[journal] Bokoch GM / 2003 / NADPH oxidases: not just for leukocytes anymore! / Trends Biochem Sci 28 : 502~508

[journal] Zekry D / 2008 / A role for NOX NADPH oxidases in Alzheimer’s disease and other types of dementia? / IUBMB life 55 : 307~313

[journal] Lindenau J / 2000 / Cellular distribution of superoxide dismutases in the rat CNS / Glia 29 : 25~34

[journal] Cho BP / 2005 / Pathological dynamics of activated microglia following medial forebrain bundle transection / Glia 53 : 92~102

[journal] Cho BP / 2003 / Microglial phagocytosis of dopamine neurons at early phases of apoptosis / Cell Mol Neurobiol 23 : 551~560

This paper was written with support from the National Research Foundation of Korea.

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Anatomy & Biological Anthropology 2023 KCI Impact Factor : 0.33

Relationship between Microglial Activation and Dopaminergic Neuronal Loss in 6-OHDA-induced Parkinsonian Animal Model

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* References for papers published after 2023 are currently being built.

Anatomy & Biological Anthropology 2023 KCI Impact Factor : 0.33

Relationship between Microglial Activation and Dopaminergic Neuronal Loss in 6-OHDA-induced Parkinsonian Animal Model

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