Comparative Analysis of the Effects of Neurotrophic Factors CDNF and GDNF in a Nonhuman Primate Model of Parkinson’s Disease
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{"title"=>"Comparative Analysis of the Effects of Neurotrophic Factors CDNF and GDNF in a Nonhuman Primate Model of Parkinson's Disease", "type"=>"journal", "authors"=>[{"first_name"=>"Enrique", "last_name"=>"Garea-Rodríguez", "scopus_author_id"=>"55343228700"}, {"first_name"=>"Ave", "last_name"=>"Eesmaa", "scopus_author_id"=>"42961204700"}, {"first_name"=>"Päivi", "last_name"=>"Lindholm", "scopus_author_id"=>"7006315648"}, {"first_name"=>"Christina", "last_name"=>"Schlumbohm", "scopus_author_id"=>"6602862300"}, {"first_name"=>"Jessica", "last_name"=>"König", "scopus_author_id"=>"55343214000"}, {"first_name"=>"Birgit", "last_name"=>"Meller", "scopus_author_id"=>"8703360600"}, {"first_name"=>"Kerstin", "last_name"=>"Krieglstein", "scopus_author_id"=>"7006511219"}, {"first_name"=>"Gunther", "last_name"=>"Helms", "scopus_author_id"=>"55608011300"}, {"first_name"=>"Mart", "last_name"=>"Saarma", "scopus_author_id"=>"7006268869"}, {"first_name"=>"Eberhard", "last_name"=>"Fuchs", "scopus_author_id"=>"7202162909"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84960977115", "scopus"=>"2-s2.0-84960977115", "issn"=>"19326203", "pui"=>"608920410", "doi"=>"10.1371/journal.pone.0149776", "pmid"=>"26901822"}, "id"=>"d71fe22a-7151-3be4-a91c-a023267d86c2", "abstract"=>"Cerebral dopamine neurotrophic factor (CDNF) belongs to a newly discovered family of evolutionarily conserved neurotrophic factors. We demonstrate for the first time a therapeutic effect of CDNF in a unilateral 6-hydroxydopamine (6-OHDA) lesion model of Parkinson's disease in marmoset monkeys. Furthermore, we tested the impact of high chronic doses of human recombinant CDNF on unlesioned monkeys and analyzed the amino acid sequence of marmoset CDNF. The severity of 6-OHDA lesions and treatment effects were monitored in vivo using 123I-FP-CIT (DaTSCAN) SPECT. Quantitative analysis of 123I-FP-CIT SPECT showed a significant increase of dopamine transporter binding activity in lesioned animals treated with CDNF. Glial cell line-derived neurotrophic factor (GDNF), a well-characterized and potent neurotrophic factor for dopamine neurons, served as a control in a parallel comparison with CDNF. By contrast with CDNF, only single animals responded to the treatment with GDNF, but no statistical difference was observed in the GDNF group. However, increased numbers of tyrosine hydroxylase immunoreactive neurons, observed within the lesioned caudate nucleus of GDNF-treated animals, indicate a strong bioactive potential of GDNF.", "link"=>"http://www.mendeley.com/research/comparative-analysis-effects-neurotrophic-factors-cdnf-gdnf-nonhuman-primate-model-parkinsons-diseas", "reader_count"=>23, "reader_count_by_academic_status"=>{"Researcher"=>2, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>3, "Student > Master"=>5, "Other"=>2, "Student > Bachelor"=>4}, "reader_count_by_user_role"=>{"Researcher"=>2, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>3, "Student > Master"=>5, "Other"=>2, "Student > Bachelor"=>4}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>12, "Medicine and Dentistry"=>5, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Finland"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/4409935"], "description"=>"<p>In the tolerability approach (upper scheme) high concentrations of CDNF (10 or 15μg per day) were intrastriatally delivered for 28 days via osmotic minipumps followed by subsequent histopathological assessment. Efficacy of CDNF and GDNF was tested in the 6-OHDA model (lower scheme). Treatment effects were evaluated <i>in vivo</i> by SPECT imaging and post mortem IHC.</p>", "links"=>[], "tags"=>["Neurotrophic Factors CDNF", "tyrosine hydroxylase immunoreactive neurons", "Comparative Analysis", "lesioned animals", "unlesioned monkeys", "dopamine transporter binding activity", "OHDA", "neurotrophic factor", "lesion model", "acid sequence", "treatment effects", "marmoset CDNF", "Nonhuman Primate Model", "marmoset monkeys", "lesioned caudate nucleus", "neurotrophic factors", "GDNF group", "dopamine neurons", "SPECT", "Quantitative analysis"], "article_id"=>2733442, "categories"=>["Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Science Policy"], "users"=>["Enrique Garea-Rodríguez", "Ave Eesmaa", "Päivi Lindholm", "Christina Schlumbohm", "Jessica König", "Birgit Meller", "Kerstin Krieglstein", "Gunther Helms", "Mart Saarma", "Eberhard Fuchs"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0149776.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Time_course_of_experiments_/2733442", "title"=>"Time course of experiments.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-22 09:36:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/4409968"], "description"=>"<p>Sections were stained for DAT (A / C) and TH (B / D). The affected brain areas showed moderate dopaminergic integrity after treatment with CDNF (A / B) and GDNF (C / D). Scale bar: 100μm.</p>", "links"=>[], "tags"=>["Neurotrophic Factors CDNF", "tyrosine hydroxylase immunoreactive neurons", "Comparative Analysis", "lesioned animals", "unlesioned monkeys", "dopamine transporter binding activity", "OHDA", "neurotrophic factor", "lesion model", "acid sequence", "treatment effects", "marmoset CDNF", "Nonhuman Primate Model", "marmoset monkeys", "lesioned caudate nucleus", "neurotrophic factors", "GDNF group", "dopamine neurons", "SPECT", "Quantitative analysis"], "article_id"=>2733475, "categories"=>["Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Science Policy"], "users"=>["Enrique Garea-Rodríguez", "Ave Eesmaa", "Päivi Lindholm", "Christina Schlumbohm", "Jessica König", "Birgit Meller", "Kerstin Krieglstein", "Gunther Helms", "Mart Saarma", "Eberhard Fuchs"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0149776.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Immunohistochemistry_of_the_caudate_nucleus_was_performed_at_the_end_of_experiment_/2733475", "title"=>"Immunohistochemistry of the caudate nucleus was performed at the end of experiment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-22 09:36:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/4410031"], "description"=>"<p>Signal peptide sequences have been omitted.</p>", "links"=>[], "tags"=>["Neurotrophic Factors CDNF", "tyrosine hydroxylase immunoreactive neurons", "Comparative Analysis", "lesioned animals", "unlesioned monkeys", "dopamine transporter binding activity", "OHDA", "neurotrophic factor", "lesion model", "acid sequence", "treatment effects", "marmoset CDNF", "Nonhuman Primate Model", "marmoset monkeys", "lesioned caudate nucleus", "neurotrophic factors", "GDNF group", "dopamine neurons", "SPECT", "Quantitative analysis"], "article_id"=>2733511, "categories"=>["Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Science Policy"], "users"=>["Enrique Garea-Rodríguez", "Ave Eesmaa", "Päivi Lindholm", "Christina Schlumbohm", "Jessica König", "Birgit Meller", "Kerstin Krieglstein", "Gunther Helms", "Mart Saarma", "Eberhard Fuchs"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0149776.t002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Amino_acid_identity_of_CDNF_proteins_between_human_and_selected_nonhuman_primates_calculated_by_EMBOSS_Needle_software_/2733511", "title"=>"Amino acid identity (%) of CDNF proteins between human and selected nonhuman primates calculated by EMBOSS Needle software.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2016-02-22 09:36:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/4409941"], "description"=>"<p>Perivascular infiltrates positive for CD3 and CD20 were observed in two animals (animals # 13864 and # 12887) out of four analysed. MAC-positive macrophages/activated microglia were absent. Scale bar = 100μm.</p>", "links"=>[], "tags"=>["Neurotrophic Factors CDNF", "tyrosine hydroxylase immunoreactive neurons", "Comparative Analysis", "lesioned animals", "unlesioned monkeys", "dopamine transporter binding activity", "OHDA", "neurotrophic factor", "lesion model", "acid sequence", "treatment effects", "marmoset CDNF", "Nonhuman Primate Model", "marmoset monkeys", "lesioned caudate nucleus", "neurotrophic factors", "GDNF group", "dopamine neurons", "SPECT", "Quantitative analysis"], "article_id"=>2733448, "categories"=>["Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Science Policy"], "users"=>["Enrique Garea-Rodríguez", "Ave Eesmaa", "Päivi Lindholm", "Christina Schlumbohm", "Jessica König", "Birgit Meller", "Kerstin Krieglstein", "Gunther Helms", "Mart Saarma", "Eberhard Fuchs"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0149776.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Histopathological_assessment_of_the_caudate_nucleus_of_chronically_CDNF_infused_animals_CDNF_15_g_day_for_28_days_totally_420_g_/2733448", "title"=>"Histopathological assessment of the caudate nucleus of chronically CDNF-infused animals (CDNF: 15μg/day for 28 days; totally 420 μg).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-22 09:36:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/4409980"], "description"=>"<p>TH-positive neurons showed a typical branching pattern (B/C). The number of TH-positive neurons was significantly increased in the GDNF treated lesioned caudate nucleus (A) compared to CDNF treated animals (p < 0.05). Moreover, a high fraction of small TH-positive structures (D) and TH-positive varicosities (E) were observed within the GDNF-treated lesioned caudate. Mean. *p < 0.05. Scale bar, 25μm.</p>", "links"=>[], "tags"=>["Neurotrophic Factors CDNF", "tyrosine hydroxylase immunoreactive neurons", "Comparative Analysis", "lesioned animals", "unlesioned monkeys", "dopamine transporter binding activity", "OHDA", "neurotrophic factor", "lesion model", "acid sequence", "treatment effects", "marmoset CDNF", "Nonhuman Primate Model", "marmoset monkeys", "lesioned caudate nucleus", "neurotrophic factors", "GDNF group", "dopamine neurons", "SPECT", "Quantitative analysis"], "article_id"=>2733484, "categories"=>["Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Science Policy"], "users"=>["Enrique Garea-Rodríguez", "Ave Eesmaa", "Päivi Lindholm", "Christina Schlumbohm", "Jessica König", "Birgit Meller", "Kerstin Krieglstein", "Gunther Helms", "Mart Saarma", "Eberhard Fuchs"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0149776.g005", "stats"=>{"downloads"=>2, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Structural_effects_of_GDNF_treatment_on_TH_immunoreactivity_was_observed_within_the_lesioned_caudate_nucleus_B_E_/2733484", "title"=>"Structural effects of GDNF treatment on TH-immunoreactivity was observed within the lesioned caudate nucleus (B—E).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-22 09:36:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/4409896", "https://ndownloader.figshare.com/files/4409905", "https://ndownloader.figshare.com/files/4409914", "https://ndownloader.figshare.com/files/4409917", "https://ndownloader.figshare.com/files/4409920"], "description"=>"<div><p>Cerebral dopamine neurotrophic factor (CDNF) belongs to a newly discovered family of evolutionarily conserved neurotrophic factors. We demonstrate for the first time a therapeutic effect of CDNF in a unilateral 6-hydroxydopamine (6-OHDA) lesion model of Parkinson’s disease in marmoset monkeys. Furthermore, we tested the impact of high chronic doses of human recombinant CDNF on unlesioned monkeys and analyzed the amino acid sequence of marmoset CDNF. The severity of 6-OHDA lesions and treatment effects were monitored <i>in vivo</i> using <sup>123</sup>I-FP-CIT (DaTSCAN) SPECT. Quantitative analysis of <sup>123</sup>I-FP-CIT SPECT showed a significant increase of dopamine transporter binding activity in lesioned animals treated with CDNF. Glial cell line-derived neurotrophic factor (GDNF), a well-characterized and potent neurotrophic factor for dopamine neurons, served as a control in a parallel comparison with CDNF. By contrast with CDNF, only single animals responded to the treatment with GDNF, but no statistical difference was observed in the GDNF group. However, increased numbers of tyrosine hydroxylase immunoreactive neurons, observed within the lesioned caudate nucleus of GDNF-treated animals, indicate a strong bioactive potential of GDNF.</p></div>", "links"=>[], "tags"=>["Neurotrophic Factors CDNF", "tyrosine hydroxylase immunoreactive neurons", "Comparative Analysis", "lesioned animals", "unlesioned monkeys", "dopamine transporter binding activity", "OHDA", "neurotrophic factor", "lesion model", "acid sequence", "treatment effects", "marmoset CDNF", "Nonhuman Primate Model", "marmoset monkeys", "lesioned caudate nucleus", "neurotrophic factors", "GDNF group", "dopamine neurons", "SPECT", "Quantitative analysis"], "article_id"=>2733427, "categories"=>["Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Science Policy"], "users"=>["Enrique Garea-Rodríguez", "Ave Eesmaa", "Päivi Lindholm", "Christina Schlumbohm", "Jessica König", "Birgit Meller", "Kerstin Krieglstein", "Gunther Helms", "Mart Saarma", "Eberhard Fuchs"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0149776.s001", "https://dx.doi.org/10.1371/journal.pone.0149776.s002", "https://dx.doi.org/10.1371/journal.pone.0149776.s003", "https://dx.doi.org/10.1371/journal.pone.0149776.s004", "https://dx.doi.org/10.1371/journal.pone.0149776.s005"], "stats"=>{"downloads"=>7, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Comparative_Analysis_of_the_Effects_of_Neurotrophic_Factors_CDNF_and_GDNF_in_a_Nonhuman_Primate_Model_of_Parkinson_s_Disease/2733427", "title"=>"Comparative Analysis of the Effects of Neurotrophic Factors CDNF and GDNF in a Nonhuman Primate Model of Parkinson’s Disease", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2016-02-22 09:36:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/4409989"], "description"=>"<p>Identical amino acids are marked with an asterisk, physicochemically highly similar with a colon, and similar with a dot. Predicted signal sequences (SignalP 4.1 Server <a href=\"http://www.cbs.dtu.dk/services/SignalP/\" target=\"_blank\">http://www.cbs.dtu.dk/services/SignalP/</a>) of marmoset, chimpanzee and macaque CDNF (residues 1–26; underlined) are equal in length to the verified signal peptide of human CDNF [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0149776#pone.0149776.ref001\" target=\"_blank\">1</a>]. Eight conserved cysteine residues with identical spacing of the mature CDNF are indicated in yellow. N-linked glycosylation site of human CDNF at position 57N [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0149776#pone.0149776.ref013\" target=\"_blank\">13</a>] and O-linked glycosylation site at position 181T [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0149776#pone.0149776.ref052\" target=\"_blank\">52</a>] is indicated in green. The C-terminal ER-retention motif KAEL/KTEL is boxed. Alpha-helical regions of CDNF are indicated above the sequences according to [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0149776#pone.0149776.ref007\" target=\"_blank\">7</a>] (helices α1-α5 and turn of 3<sub>10</sub> helix) and [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0149776#pone.0149776.ref009\" target=\"_blank\">9</a>] (helices α6-α8). The division between N-terminal saposin-like domain and C-terminal SAP-domain is indicated by a vertical dashed line.</p>", "links"=>[], "tags"=>["Neurotrophic Factors CDNF", "tyrosine hydroxylase immunoreactive neurons", "Comparative Analysis", "lesioned animals", "unlesioned monkeys", "dopamine transporter binding activity", "OHDA", "neurotrophic factor", "lesion model", "acid sequence", "treatment effects", "marmoset CDNF", "Nonhuman Primate Model", "marmoset monkeys", "lesioned caudate nucleus", "neurotrophic factors", "GDNF group", "dopamine neurons", "SPECT", "Quantitative analysis"], "article_id"=>2733493, "categories"=>["Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Science Policy"], "users"=>["Enrique Garea-Rodríguez", "Ave Eesmaa", "Päivi Lindholm", "Christina Schlumbohm", "Jessica König", "Birgit Meller", "Kerstin Krieglstein", "Gunther Helms", "Mart Saarma", "Eberhard Fuchs"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0149776.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Alignment_of_marmoset_Cj_human_Hs_chimpanzee_Pt_and_macaque_Mm_CDNF_amino_acid_sequences_by_CLUSTAL_O_version_1_2_0_software_/2733493", "title"=>"Alignment of marmoset (Cj), human (Hs), chimpanzee (Pt), and macaque (Mm) CDNF amino acid sequences by CLUSTAL O (version 1.2.0) software.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-22 09:36:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/4409959"], "description"=>"<p>(A) Representative <sup>123</sup>I-FP-CIT SPECT images of CDNF (upper row) and GDNF treated (lower row) marmosets. Reduced DAT-binding was observed after mild 6-OHDA lesions when targeted to the caudate nucleus (middle row, indicated by arrows). Treatment via intracerebral injection of either 20 μg of CDNF (upper row) or 20 μg of GDNF (lower row), lead to obvious recovery on the level of DAT integrity (indicated by arrows). (B, C) Treatment effects were evaluated by quantitative analysis of <sup>123</sup>I-FP-CIT SPECT. Animals showed a significant increase of DAT-binding (*p = 0.023, [F<sub>2,11</sub> = 33.32, p < 0.001]) when treated with CDNF (B). In the GDNF group single animals responded to the treatment with GDNF (C, animals #5 and #6). However, no significant recovery was observed in the GDNF-treated group. *p < 0.05, **p < 0.01, NS = not significant.</p>", "links"=>[], "tags"=>["Neurotrophic Factors CDNF", "tyrosine hydroxylase immunoreactive neurons", "Comparative Analysis", "lesioned animals", "unlesioned monkeys", "dopamine transporter binding activity", "OHDA", "neurotrophic factor", "lesion model", "acid sequence", "treatment effects", "marmoset CDNF", "Nonhuman Primate Model", "marmoset monkeys", "lesioned caudate nucleus", "neurotrophic factors", "GDNF group", "dopamine neurons", "SPECT", "Quantitative analysis"], "article_id"=>2733469, "categories"=>["Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Science Policy"], "users"=>["Enrique Garea-Rodríguez", "Ave Eesmaa", "Päivi Lindholm", "Christina Schlumbohm", "Jessica König", "Birgit Meller", "Kerstin Krieglstein", "Gunther Helms", "Mart Saarma", "Eberhard Fuchs"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0149776.g003", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Comparative_Analysis_of_the_Effects_of_Neurotrophic_Factors_CDNF_and_GDNF_in_a_Nonhuman_Primate_Model_of_Parkinson_s_Disease_Fig_3/2733469", "title"=>"Comparative Analysis of the Effects of Neurotrophic Factors CDNF and GDNF in a Nonhuman Primate Model of Parkinson’s Disease - Fig 3", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-22 09:36:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/4410010"], "description"=>"<p>Histopathological scoring was based on HE-staining and CD3 immunohistochemistry (- no, + mild, ++ moderate, +++ severe). CDNF-ir distribution (See also <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0149776#pone.0149776.s002\" target=\"_blank\">S2 Fig</a>) was semi quantitatively assessed on coronal sections (- no signal, + low, ++ moderate, +++ high).</p>", "links"=>[], "tags"=>["Neurotrophic Factors CDNF", "tyrosine hydroxylase immunoreactive neurons", "Comparative Analysis", "lesioned animals", "unlesioned monkeys", "dopamine transporter binding activity", "OHDA", "neurotrophic factor", "lesion model", "acid sequence", "treatment effects", "marmoset CDNF", "Nonhuman Primate Model", "marmoset monkeys", "lesioned caudate nucleus", "neurotrophic factors", "GDNF group", "dopamine neurons", "SPECT", "Quantitative analysis"], "article_id"=>2733502, "categories"=>["Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Evolutionary Biology", "Biological Sciences not elsewhere classified", "Science Policy"], "users"=>["Enrique Garea-Rodríguez", "Ave Eesmaa", "Päivi Lindholm", "Christina Schlumbohm", "Jessica König", "Birgit Meller", "Kerstin Krieglstein", "Gunther Helms", "Mart Saarma", "Eberhard Fuchs"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0149776.t001", "stats"=>{"downloads"=>1, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Tolerability_of_chronic_CDNF_delivery_concentrations_of_CDNF_in_comparison_to_the_degree_of_histopathology_and_CDNF_ir_tissue_distribution_/2733502", "title"=>"Tolerability of chronic CDNF delivery: concentrations of CDNF in comparison to the degree of histopathology and CDNF-ir tissue distribution.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2016-02-22 09:36:03"}

PMC Usage Stats | Further Information

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{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}
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