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{"title"=>"Striatal neuroinflammation promotes parkinsonism in rats", "type"=>"journal", "authors"=>[{"first_name"=>"Dong Yong", "last_name"=>"Choi", "scopus_author_id"=>"23970151400"}, {"first_name"=>"Mei", "last_name"=>"Liu", "scopus_author_id"=>"57192923069"}, {"first_name"=>"Randy L.", "last_name"=>"Hunter", "scopus_author_id"=>"12798358100"}, {"first_name"=>"Wayne A.", "last_name"=>"Cass", "scopus_author_id"=>"7004396563"}, {"first_name"=>"Jignesh D.", "last_name"=>"Pandya", "scopus_author_id"=>"7003697137"}, {"first_name"=>"Patrick G.", "last_name"=>"Sullivan", "scopus_author_id"=>"7402033421"}, {"first_name"=>"Eun Joo", "last_name"=>"Shin", "scopus_author_id"=>"7202356437"}, {"first_name"=>"Hyoung Chun", "last_name"=>"Kim", "scopus_author_id"=>"36065569300"}, {"first_name"=>"Don M.", "last_name"=>"Gash", "scopus_author_id"=>"24426193700"}, {"first_name"=>"Guoying", "last_name"=>"Bing", "scopus_author_id"=>"7004276368"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"19424495", "sgr"=>"65549091886", "doi"=>"10.1371/journal.pone.0005482", "scopus"=>"2-s2.0-65549091886", "pui"=>"354579473", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203"}, "id"=>"71e0e487-2d46-35f0-9c9c-86deeec0775d", "abstract"=>"BACKGROUND: Sporadic Parkinson's disease (PD) is a progressive neurodegenerative disorder with unknown cause, but it has been suggested that neuroinflammation may play a role in pathogenesis of the disease. Neuroinflammatory component in process of PD neurodegeneration was proposed by postmortem, epidemiological and animal model studies. However, it remains unclear how neuroinflammatory factors contribute to dopaminergic neuronal death in PD.\\n\\nFINDINGS: In this study, we analyzed the relationship among inducible nitric oxide synthase (iNOS)-derived NO, mitochondrial dysfunction and dopaminergic neurodegeneration to examine the possibility that microglial neuroinflammation may induce dopaminergic neuronal loss in the substantia nigra. Unilateral injection of lipopolysaccharide (LPS) into the striatum of rat was followed by immunocytochemical, histological, neurochemical and biochemical analyses. In addition, behavioral assessments including cylinder test and amphetamine-induced rotational behavior test were employed to validate ipsilateral damage to the dopamine nigrostriatal pathway. LPS injection caused progressive degeneration of the dopamine nigrostriatal system, which was accompanied by motor impairments including asymmetric usage of forelimbs and amphetamine-induced turning behavior in animals. Interestingly, some of the remaining nigral dopaminergic neurons had intracytoplasmic accumulation of alpha-synuclein and ubiquitin. Furthermore, defect in the mitochondrial respiratory chain, and extensive S-nitrosylation/nitration of mitochondrial complex I were detected prior to the dopaminergic neuronal loss. The mitochondrial injury was prevented by treatment with L-N(6)-(l-iminoethyl)-lysine, an iNOS inhibitor, suggesting that iNOS-derived NO is associated with the mitochondrial impairment.\\n\\nCONCLUSIONS: These results implicate neuroinflammation-induced S-nitrosylation/nitration of mitochondrial complex I in mitochondrial malfunction and subsequent degeneration of the nigral dopamine neurons.", "link"=>"http://www.mendeley.com/research/striatal-neuroinflammation-promotes-parkinsonism-rats", "reader_count"=>58, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>15, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>2, "Student > Master"=>8, "Student > Bachelor"=>4, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>15, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>19, "Student > Postgraduate"=>2, "Student > Master"=>8, "Student > Bachelor"=>4, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>28, "Medicine and Dentistry"=>12, "Neuroscience"=>4, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>12}, "Neuroscience"=>{"Neuroscience"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>28}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Unspecified"=>{"Unspecified"=>4}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Republic of Singapore"=>1, "Netherlands"=>1, "United States"=>2, "Ireland"=>1, "Australia"=>1}, "group_count"=>1}

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/444901", "https://ndownloader.figshare.com/files/444918", "https://ndownloader.figshare.com/files/444937"], "description"=>"<div><h3>Background</h3><p>Sporadic Parkinson's disease (PD) is a progressive neurodegenerative disorder with unknown cause, but it has been suggested that neuroinflammation may play a role in pathogenesis of the disease. Neuroinflammatory component in process of PD neurodegeneration was proposed by postmortem, epidemiological and animal model studies. However, it remains unclear how neuroinflammatory factors contribute to dopaminergic neuronal death in PD.</p><h3>Findings</h3><p>In this study, we analyzed the relationship among inducible nitric oxide synthase (iNOS)-derived NO, mitochondrial dysfunction and dopaminergic neurodegeneration to examine the possibility that microglial neuroinflammation may induce dopaminergic neuronal loss in the substantia nigra. Unilateral injection of lipopolysaccharide (LPS) into the striatum of rat was followed by immunocytochemical, histological, neurochemical and biochemical analyses. In addition, behavioral assessments including cylinder test and amphetamine-induced rotational behavior test were employed to validate ipsilateral damage to the dopamine nigrostriatal pathway. LPS injection caused progressive degeneration of the dopamine nigrostriatal system, which was accompanied by motor impairments including asymmetric usage of forelimbs and amphetamine-induced turning behavior in animals. Interestingly, some of the remaining nigral dopaminergic neurons had intracytoplasmic accumulation of α-synuclein and ubiquitin. Furthermore, defect in the mitochondrial respiratory chain, and extensive S-nitrosylation/nitration of mitochondrial complex I were detected prior to the dopaminergic neuronal loss. The mitochondrial injury was prevented by treatment with L-N⁶-(l-iminoethyl)-lysine, an iNOS inhibitor, suggesting that iNOS-derived NO is associated with the mitochondrial impairment.</p><h3>Conclusions</h3><p>These results implicate neuroinflammation-induced S-nitrosylation/nitration of mitochondrial complex I in mitochondrial malfunction and subsequent degeneration of the nigral dopamine neurons.</p></div>", "links"=>[], "tags"=>["striatal", "neuroinflammation", "promotes", "parkinsonism", "rats"], "article_id"=>147682, "categories"=>["Neuroscience"], "users"=>["Dong-Young Choi", "Mei Liu", "Randy L. Hunter", "Wayne A. Cass", "Jignesh D. Pandya", "Patrick G. Sullivan", "Eun-Joo Shin", "Hyoung-Chun Kim", "Don M. Gash", "Guoying Bing"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0005482.s001", "https://dx.doi.org/10.1371/journal.pone.0005482.s002", "https://dx.doi.org/10.1371/journal.pone.0005482.s003"], "stats"=>{"downloads"=>5, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Striatal_Neuroinflammation_Promotes_Parkinsonism_in_Rats/147682", "title"=>"Striatal Neuroinflammation Promotes Parkinsonism in Rats", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-05-08 02:08:02"}
• {"files"=>["https://ndownloader.figshare.com/files/899365"], "description"=>"<p>The increased iNOS expression occurs at 6 hr post LPS injection, which is sustained for three days in the striatum, and one day in the substantia nigra (n = 3/group, * p<0.05, ** p<0.01 vs. control) (A,B). The OX-6 immunoreactivity in the LPS-injected striatum is markedly increased one week after LPS injections compared to control or the naïve side, and immunoreactivity of OX-6 gradually decreased over time. However, the immunoreactivity is still positive four weeks after LPS (C, top). OX-6-positive microglia appear in the substantia nigra one week after intrastriatal LPS injection, and the immunoreactivity peaks at two weeks and then decreases to some extent at four weeks (C, bottom). Scale bar: 50 µm.</p>", "links"=>[], "tags"=>["activation", "elevation", "inos", "substantia", "nigra", "striatum", "intrastriatal", "lps"], "article_id"=>569796, "categories"=>["Neuroscience"], "users"=>["Dong-Young Choi", "Mei Liu", "Randy L. Hunter", "Wayne A. Cass", "Jignesh D. Pandya", "Patrick G. Sullivan", "Eun-Joo Shin", "Hyoung-Chun Kim", "Don M. Gash", "Guoying Bing"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005482.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Microglial_activation_and_elevation_of_iNOS_expression_in_both_the_substantia_nigra_and_striatum_following_intrastriatal_LPS_injection_/569796", "title"=>"Microglial activation and elevation of iNOS expression in both the substantia nigra and striatum following intrastriatal LPS injection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-05-08 02:43:16"}
• {"files"=>["https://ndownloader.figshare.com/files/898847"], "description"=>"<p>(A) Representative TH immunostaining of coronal midbrain sections demonstrates that the numbers of TH-positive neurons and fibers in the substantia nigra pars compacta are gradually reduced by intrastriatal LPS injection. Note that TH-positive neurons in the medial substantia nigra pars compacta and ventral tegmental area are spared; scale bar: 200 µm. (B) Stereological cell counts of the TH-positive neurons in the substantia nigra pars compacta (n = 5–6/group, ** p<0.01, *** p<0.001). (C) The substantia nigra pars compacta is outlined with an orange dashed line (top). High magnification image of Nissl stainings suggest loss of the nigral dopaminergic neurons, at four weeks following LPS injection (bottom); scale bar: 200 µm. (D) Silver staining is hardly seen in the substantia nigra ipsilateral to vehicle treatment. However, abundant silver grain-deposits are observed in the neurons (arrows) and fibers (arrow heads) in the substantia nigra ipsilateral to the intrastriatal LPS injections, indicating there is ongoing neurodegenerative process in the region. Scale bar: 20 µm.</p>", "links"=>[], "tags"=>["degeneration", "nigral", "dopaminergic", "neurons", "intrastriatal"], "article_id"=>569286, "categories"=>["Neuroscience"], "users"=>["Dong-Young Choi", "Mei Liu", "Randy L. Hunter", "Wayne A. Cass", "Jignesh D. Pandya", "Patrick G. Sullivan", "Eun-Joo Shin", "Hyoung-Chun Kim", "Don M. Gash", "Guoying Bing"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005482.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Progressive_degeneration_of_the_nigral_dopaminergic_neurons_after_intrastriatal_LPS_/569286", "title"=>"Progressive degeneration of the nigral dopaminergic neurons after intrastriatal LPS.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-05-08 02:34:46"}
• {"files"=>["https://ndownloader.figshare.com/files/899268"], "description"=>"<p>(A) Ipsilateral rotational behavior in the unilateral LPS-injected animals is significantly increased relative to vehicle-treated animals when amphetamine was administered (n = 5–6/group; * p<0.05). (B) The cylinder test revealed that asymmetric forelimb use is increased significantly after intrastriatal LPS and was sustained for four weeks (n = 5–6/group; ** p<0.01).</p>", "links"=>[], "tags"=>["deficits", "intrastriatal"], "article_id"=>569721, "categories"=>["Neuroscience"], "users"=>["Dong-Young Choi", "Mei Liu", "Randy L. Hunter", "Wayne A. Cass", "Jignesh D. Pandya", "Patrick G. Sullivan", "Eun-Joo Shin", "Hyoung-Chun Kim", "Don M. Gash", "Guoying Bing"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005482.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Behavioral_deficits_following_intrastriatal_LPS_/569721", "title"=>"Behavioral deficits following intrastriatal LPS.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-05-08 02:42:01"}
• {"files"=>["https://ndownloader.figshare.com/files/899148"], "description"=>"<p>(A) Photomicrograph of double immunofluorescent labeling with antibodies against TH (red) and α-synuclein (green) show that intrastriatal LPS mediates marked TH-positive cell loss in the substantia nigra ipsilateral to the injection. Scale bar: 100 µm. (B) High magnification images of the top photograph demonstrate that some of the spared TH-positive neurons have accumulated α-synuclein in their cytoplasm (arrow heads). Scale bar: 20 µm. (C) Immunofluorescent staining displays ubiquitin accumulation in the cytoplasm of the nigral TH-positive neurons (arrow heads). Scale bar: 20 µm. (D–E) Increase of proteinase K-resistant α-synuclein (D) or ubiquitin (E) in the substantia nigra after LPS injection. Scale bar: 50 µm.</p>", "links"=>[], "tags"=>["accumulation", "ubiquitin", "nigral", "th-positive", "neurons", "weeks", "intrastriatal"], "article_id"=>569578, "categories"=>["Neuroscience"], "users"=>["Dong-Young Choi", "Mei Liu", "Randy L. Hunter", "Wayne A. Cass", "Jignesh D. Pandya", "Patrick G. Sullivan", "Eun-Joo Shin", "Hyoung-Chun Kim", "Don M. Gash", "Guoying Bing"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005482.g003", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cytoplasmic_accumulation_of_945_synuclein_and_ubiquitin_in_the_nigral_TH_positive_neurons_at_four_weeks_after_intrastriatal_LPS_/569578", "title"=>"Cytoplasmic accumulation of α-synuclein and ubiquitin in the nigral TH-positive neurons at four weeks after intrastriatal LPS.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-05-08 02:39:38"}
• {"files"=>["https://ndownloader.figshare.com/files/898990"], "description"=>"<p>(A) Silver staining reveals that there is no silver-positive stained fibers in the vehicle treated striatum while an abundance of silver grain-deposits are observed in the LPS injected striatum, suggesting the degeneration of axonal fibers (arrows). Scale bar: 20 µm. (B) Immunostaining for DARPP-32 shows that the GABAergic neurons are intact following LPS injections. Western blot for DARPP-32 and its quantification indicate that there is no significant alteration in the expression of DARPP-32 after LPS challenge. Scale bar: 200 µm. (C) HPLC analysis shows that intrastriatal LPS injection depletes 58% of the striatal dopamine relative to control at four weeks. The DOPAC level is not affected; however, HVA is significantly increased. The turnover ratios of DOPAC/dopamine and HVA/dopamine are dramatically increased (n = 7/group; ** p<0.01, *** p<0.001).</p>", "links"=>[], "tags"=>["terminal", "degeneration", "striatum", "intrastriatal"], "article_id"=>569435, "categories"=>["Neuroscience"], "users"=>["Dong-Young Choi", "Mei Liu", "Randy L. Hunter", "Wayne A. Cass", "Jignesh D. Pandya", "Patrick G. Sullivan", "Eun-Joo Shin", "Hyoung-Chun Kim", "Don M. Gash", "Guoying Bing"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005482.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Axonal_terminal_degeneration_in_the_striatum_following_intrastriatal_LPS_/569435", "title"=>"Axonal terminal degeneration in the striatum following intrastriatal LPS.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-05-08 02:37:15"}
• {"files"=>["https://ndownloader.figshare.com/files/899469"], "description"=>"<p>Intrastriatal LPS injection increases 3-nitrotyrosine (3-NT) level in complex I three days after LPS injection. Treatment with L-NIL appears to prevent the LPS-induced elevation of mitochondrial protein nitration (A,B). Isolated nigral and striatal mitochondria complex I proteins have an increase in S-nitrosylation three days after LPS injection. L-NIL treatment appears to prevent the LPS-induced increase of S-nitrosylation (C,D). S+S: saline treated and saline injected; S+L: saline-treated and LPS-injected; N+S: L-NIL-treated and saline-injected; and N+L: L-NIL-treated and LPS-injected; SN: substantia nigra (n = 4/group; * p<0.05 vs. S+S, and # p<0.05, p<0.01 vs. S+L).</p>", "links"=>[], "tags"=>["mitochondrial", "intrastriatal"], "article_id"=>569918, "categories"=>["Neuroscience"], "users"=>["Dong-Young Choi", "Mei Liu", "Randy L. Hunter", "Wayne A. Cass", "Jignesh D. Pandya", "Patrick G. Sullivan", "Eun-Joo Shin", "Hyoung-Chun Kim", "Don M. Gash", "Guoying Bing"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0005482.g007", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nitration_S_nitrosylation_of_mitochondrial_complex_I_after_intrastriatal_LPS_/569918", "title"=>"Nitration/S-nitrosylation of mitochondrial complex I after intrastriatal LPS.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-05-08 02:45:18"}

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Relative Metric

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F1000Prime