Pallidal Hyperdopaminergic Innervation Underlying D2 Receptor-Dependent Behavioral Deficits in the Schizophrenia Animal Model Established by EGF
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{"title"=>"Pallidal hyperdopaminergic innervation underlying d2 receptor-dependent behavioral deficits in the schizophrenia animal model established by EGF", "type"=>"journal", "authors"=>[{"first_name"=>"Hidekazu", "last_name"=>"Sotoyama", "scopus_author_id"=>"6603144111"}, {"first_name"=>"Yingjun", "last_name"=>"Zheng", "scopus_author_id"=>"56130633200"}, {"first_name"=>"Yuriko", "last_name"=>"Iwakura", "scopus_author_id"=>"7102119703"}, {"first_name"=>"Makoto", "last_name"=>"Mizuno", "scopus_author_id"=>"7402730537"}, {"first_name"=>"Miho", "last_name"=>"Aizawa", "scopus_author_id"=>"41861082400"}, {"first_name"=>"Ksenia", "last_name"=>"Shcherbakova", "scopus_author_id"=>"54380924500"}, {"first_name"=>"Ran", "last_name"=>"Wang", "scopus_author_id"=>"55717762400"}, {"first_name"=>"Hisaaki", "last_name"=>"Namba", "scopus_author_id"=>"7102859773"}, {"first_name"=>"Hiroyuki", "last_name"=>"Nawa", "scopus_author_id"=>"7006558045"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-80053957614", "doi"=>"10.1371/journal.pone.0025831", "issn"=>"19326203", "pui"=>"362735242", "sgr"=>"80053957614", "isbn"=>"1932-6203", "pmid"=>"22022452"}, "id"=>"e10151e9-7b61-32bd-bbc1-25943192f45d", "abstract"=>"Epidermal growth factor (EGF) is one of the ErbB receptor ligands implicated in schizophrenia neuropathology as well as in dopaminergic development. Based on the immune inflammatory hypothesis for schizophrenia, neonatal rats are exposed to this cytokine and later develop neurobehavioral abnormality such as prepulse inhibition (PPI) deficit. Here we found that the EGF-treated rats exhibited persistent increases in tyrosine hydroxylase levels and dopamine content in the globus pallidus. Furthermore, pallidal dopamine release was elevated in EGF-treated rats, but normalized by subchronic treatment with risperidone concomitant with amelioration of their PPI deficits. To evaluate pathophysiologic roles of the dopamine abnormality, we administered reserpine bilaterally to the globus pallidus to reduce the local dopamine pool. Reserpine infusion ameliorated PPI deficits of EGF-treated rats without apparent aversive effects on locomotor activity in these rats. We also administered dopamine D1-like and D2-like receptor antagonists (SCH23390 and raclopride) and a D2-like receptor agonist (quinpirole) to the globus pallidus and measured PPI and bar-hang latencies. Raclopride (0.5 and 2.0 µg/site) significantly elevated PPI levels of EGF-treated rats, but SCH23390 (0.5 and 2.0 µg/site) had no effect. The higher dose of raclopride induced catalepsy-like changes in control animals but not in EGF-treated rats. Conversely, local quinpirole administration to EGF-untreated control rats induced PPI deficits and anti-cataleptic behaviors, confirming the pathophysiologic role of the pallidal hyperdopaminergic state. These findings suggest that the pallidal dopaminergic innervation is vulnerable to circulating EGF at perinatal and/or neonatal stages and has strong impact on the D2-like receptor-dependent behavioral deficits relevant to schizophrenia.", "link"=>"http://www.mendeley.com/research/pallidal-hyperdopaminergic-innervation-underlying-d2-receptordependent-behavioral-deficits-schizophr", "reader_count"=>27, "reader_count_by_academic_status"=>{"Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>10, "Student > Master"=>1, "Other"=>4, "Student > Bachelor"=>2, "Professor"=>1, "Student > Postgraduate"=>1}, "reader_count_by_user_role"=>{"Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>10, "Student > Master"=>1, "Other"=>4, "Student > Bachelor"=>2, "Professor"=>1, "Student > Postgraduate"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>6, "Neuroscience"=>3, "Psychology"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Neuroscience"=>{"Neuroscience"=>3}, "Psychology"=>{"Psychology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Japan"=>1, "Brazil"=>1, "United Kingdom"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/725657"], "description"=>"<p>Different doses of the D1-like receptor antagonist [SCH23390; 0 µg (vehicle), 0.5 µg or 2 µg per site] or the D2-like receptor antagonist [raclopride; 0 µg (vehicle alone), 0.5 µg or 2 µg per site] were administered to both hemispheres of the globus pallidus of EGF and control rats. (A) Cannula placement was confirmed in fixed brains, and four out of 69 rats were excluded from the final data analysis due to incorrect cannula placement. Rats receiving SCH23390 (B) or raclopride (C) were subjected to PPI test with 75-, 80- and 85-dB prepulse stimuli combined with a 120-dB startle tone. Pulse-alone startle responses to a 120-dB tone were measured in arbitrary units and are shown in the inset. Bars indicate mean ± SEM (N = 8–9 for each group). Data of rats receiving vehicle alone (control) were shared in (B) and (C). *P<0.05, **P<0.01, compared with vehicle-infused controls; +P<0.05, ++P<0.01, compared with vehicle-infused EGF rats by Fisher's LSD.</p>", "links"=>[], "tags"=>["pallidal", "infusion", "dopamine", "receptor", "antagonists", "ppi"], "article_id"=>395995, "categories"=>["Chemistry", "Biochemistry", "Neuroscience", "Physiology", "Mental Health"], "users"=>["Hidekazu Sotoyama", "Yingjun Zheng", "Yuriko Iwakura", "Makoto Mizuno", "Miho Aizawa", "Ksenia Shcherbakova", "Ran Wang", "Hisaaki Namba", "Hiroyuki Nawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025831.g006", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_pallidal_infusion_of_dopamine_receptor_antagonists_on_PPI_deficits_/395995", "title"=>"Effects of pallidal infusion of dopamine receptor antagonists on PPI deficits.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 13:53:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/725220"], "description"=>"<p>Coronal sections of the striatum containing medial and caudal globus pallidus (1.2 and 1.6 mm posterior from the bregma) were prepared from control and EGF-treated rats and immunostained with anti-TH antibody (N = 3–4 rats per group). TH-immunoreactive fibers in medial (A, B) and caudal (C, D) globus pallidus of control (A, C) and EGF rats (B, D) are shown. A lateral area of the globus pallidus is marked with a window, enlarged 2-fold, and presented in the top-right corner of each picture. ST; striatum, GP; globus pallidus, ic; internal capsule. Scale bar, 500 µm.</p>", "links"=>[], "tags"=>["tyrosine", "hydroxylase-positive", "fibers", "terminals", "globus"], "article_id"=>395562, "categories"=>["Chemistry", "Biochemistry", "Neuroscience", "Physiology", "Mental Health"], "users"=>["Hidekazu Sotoyama", "Yingjun Zheng", "Yuriko Iwakura", "Makoto Mizuno", "Miho Aizawa", "Ksenia Shcherbakova", "Ran Wang", "Hisaaki Namba", "Hiroyuki Nawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025831.g002", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunohistochemical_analysis_of_tyrosine_hydroxylase_positive_fibers_and_terminals_in_the_globus_pallidus_/395562", "title"=>"Immunohistochemical analysis of tyrosine hydroxylase-positive fibers and terminals in the globus pallidus.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 13:51:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/725098"], "description"=>"<p>EGF or cytochrome c (control) was daily injected (s.c.) into neonatal rats from PND2 to PND10, and rats were bred until adulthood (PND 56). (A) Levels of tyrosine hydroxylase (TH) immunoreactivity in brain tissue homogenates were determined by ELISA and presented as a ratio of control levels (mean ± SEM). Tissue contents of dopamine (B) and its metabolite DOPAC (C) were measured by HPLC. (D) Tissue lysates from the globus pallidus of EGF rats and controls (8 weeks old, N = 4) were subjected to immunoblotting for antibodies directed against TH, vesicular monoamine transporter 2 (VMAT2), dopamine beta hydroxylase (DβH), dopamine D1 receptor (D1R), dopamine D2 receptor (D2R), and β-actin (an internal control). Immunoreactivity was measured by densitometric analysis and its percentage ratio to that of control rats was calculated (mean ± SEM). Abbreviations; medial prefrontal cortex (prelimbic cortex; mPFC), striatum (STR), nucleus accumbens (NAC), cingulate cortex (Cg), globus pallidus (GP), amygdala (AMG), hypothalamus (Hyp), subthalamic nucleus (STN), and substantia nigra (SN). *P<0.05, **P<0.01 by two-tailed t-test.</p>", "links"=>[], "tags"=>["neonatal", "egf", "tyrosine", "hydroxylase", "dopamine", "metabolism"], "article_id"=>395431, "categories"=>["Chemistry", "Biochemistry", "Neuroscience", "Physiology", "Mental Health"], "users"=>["Hidekazu Sotoyama", "Yingjun Zheng", "Yuriko Iwakura", "Makoto Mizuno", "Miho Aizawa", "Ksenia Shcherbakova", "Ran Wang", "Hisaaki Namba", "Hiroyuki Nawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025831.g001", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_neonatal_EGF_challenge_on_tyrosine_hydroxylase_and_dopamine_metabolism_at_the_adult_stage_/395431", "title"=>"Effects of neonatal EGF challenge on tyrosine hydroxylase and dopamine metabolism at the adult stage.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 13:50:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/725322"], "description"=>"<p>Neonatal rats were treated with EGF or cytochrome c (control) as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0025831#pone-0025831-g001\" target=\"_blank\">Figure 1</a>. Risperidone (1 mg/kg, i.p.) was administered to some of the EGF-treated rats for 14 days at the adult stage. (A) The location of dialysis probe was examined and is shown in rat brain atlas. Six rats were excluded for incorrect probe placement. The digit represents the distance from the bregma. (B) PPI levels were monitored in control, EGF-treated and EGF+risperidone-treated animals following microdialysis. (C) Pulse-alone startle responses and PPI levels were monitored in control, EGF-treated and EGF+risperidone-treated animals following microdialysis. (D) Basal concentrations of dopamine in dialysates were monitored for 150 min, dopamine release was evoked by perfusion of 80 mM KCl over 60 min (solid bar), and then monitored over 150 min. Data represent dopamine concentrations in 30-min fractions (nM, mean ± SEM, N = 11–13 rats per group). There was a significant interaction between time and dopamine release [F(12,198) = 2.72, P = 0.002]. *P<0.05, ***P<0.001, compared with controls and ++P<0.01, compared with EGF-treated rats by Fisher's LSD.</p>", "links"=>[], "tags"=>["dopamine", "enhanced", "egf-treated", "rats", "normalized"], "article_id"=>395668, "categories"=>["Chemistry", "Biochemistry", "Neuroscience", "Physiology", "Mental Health"], "users"=>["Hidekazu Sotoyama", "Yingjun Zheng", "Yuriko Iwakura", "Makoto Mizuno", "Miho Aizawa", "Ksenia Shcherbakova", "Ran Wang", "Hisaaki Namba", "Hiroyuki Nawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025831.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pallidal_dopamine_release_enhanced_in_EGF_treated_rats_and_normalized_with_risperidone_/395668", "title"=>"Pallidal dopamine release enhanced in EGF-treated rats and normalized with risperidone.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 13:52:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/725790"], "description"=>"<p>A dopamine D2-like agonist, quinpirole (QUIN) (5 µg per site), or vehicle was administered to both hemispheres of the GP of naïve rats. (A) Cannula placement was confirmed in fixed brains, and one out of 18 rats was excluded from the final data analysis due to incorrect cannula placement. Fifteen minutes after quinpirole injection, pulse-alone startles (B) and PPI scores (C) were measured with 75-, 80- and 85-dB prepulse stimuli combined with a 120-dB startle tone. Bars indicate mean ± SEM (n = 8 or 9 each). *p<0.05, **p<0.01, compared with vehicle-infused controls by Fisher LSD.</p>", "links"=>[], "tags"=>["pallidal", "infusion", "dopamine", "d2-like", "agonist"], "article_id"=>396129, "categories"=>["Chemistry", "Biochemistry", "Neuroscience", "Physiology", "Mental Health"], "users"=>["Hidekazu Sotoyama", "Yingjun Zheng", "Yuriko Iwakura", "Makoto Mizuno", "Miho Aizawa", "Ksenia Shcherbakova", "Ran Wang", "Hisaaki Namba", "Hiroyuki Nawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025831.g007", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_pallidal_infusion_of_a_dopamine_D2_like_agonist_on_PPI_/396129", "title"=>"Effects of pallidal infusion of a dopamine D2-like agonist on PPI.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 13:54:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/725911"], "description"=>"<p>(A) Cannula placement was confirmed in fixed brains, and four out of 63 rats were excluded from the final data analysis due to incorrect cannula placement. The bar-hang test consisted of 3 blocks with 20-min intervals. Vehicle, raclopride (B; 0.5 and 2.0 µg per site) or quinpirole (QUIN) (C; 10.0 µg per site) was bilaterally injected into the globus pallidus of EGF and control (CON) rats after block #1. In each session we measured the latency until one of the paws of rats was removed from the horizontal bar (mean ± SEM, N = 8–9 rats each). *P<0.05, **P<0.01, ***P<0.001, compared with vehicle-infused control rats; +P<0.05, ++P<0.01, +++P<0.001, compared with the value of session #1 by Fisher's LSD. Note: The pallidal infusion of the D2-like receptor agonist to control rats (green star) significantly reduced the latency.</p>", "links"=>[], "tags"=>["immobility", "bar-hang", "pallidal", "infusion", "dopamine", "receptor", "antagonist"], "article_id"=>396253, "categories"=>["Chemistry", "Biochemistry", "Neuroscience", "Physiology", "Mental Health"], "users"=>["Hidekazu Sotoyama", "Yingjun Zheng", "Yuriko Iwakura", "Makoto Mizuno", "Miho Aizawa", "Ksenia Shcherbakova", "Ran Wang", "Hisaaki Namba", "Hiroyuki Nawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025831.g008", "stats"=>{"downloads"=>0, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Measurement_of_immobility_in_the_bar_hang_test_following_pallidal_infusion_of_the_dopamine_receptor_antagonist_and_agonist_/396253", "title"=>"Measurement of immobility in the bar-hang test following pallidal infusion of the dopamine receptor antagonist and agonist.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 13:55:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/725532"], "description"=>"<p>EGF and control (CON) rats received local reserpine- or vehicle-infusion to both hemispheres of the GP. (A) Cannula placement was confirmed in fixed brains, and two out of 36 rats were excluded from the final data analysis due to incorrect cannula placement. (B) Two hours after pallidal infusion, rats were placed in the automated activity monitoring chamber for 60 min. Data represent horizontal movement (cm) for every 5 min (mean ± SEM, N = 7–9 for each group). (C) Following locomotor test, an unfamiliar male rat was placed in the same chamber. The number and duration of sniffing behaviors of operated rats were counted for 10 min. Bars indicate mean ± SEM (N = 8–9 for each group). **p<0.01, ***p<0.001 by Fisher's LSD, compared with vehicle-infused controls.</p>", "links"=>[], "tags"=>["pallidal", "reserpine", "infusion", "locomotor"], "article_id"=>395882, "categories"=>["Chemistry", "Biochemistry", "Neuroscience", "Physiology", "Mental Health"], "users"=>["Hidekazu Sotoyama", "Yingjun Zheng", "Yuriko Iwakura", "Makoto Mizuno", "Miho Aizawa", "Ksenia Shcherbakova", "Ran Wang", "Hisaaki Namba", "Hiroyuki Nawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025831.g005", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Influences_of_pallidal_reserpine_infusion_on_locomotor_activity_and_social_interaction_/395882", "title"=>"Influences of pallidal reserpine infusion on locomotor activity and social interaction.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 13:53:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/725464"], "description"=>"<p>(A) Startle responses of EGF and control (CON) rats were triggered with 120-dB tone pulse and PPI scores were measured with 75-, 80-, and 85-dB prepulse stimuli 120 min after local vehicle or reserpine infusion to both hemispheres of the globus pallidus. Pulse-alone startle responses to a 120-dB tone were measured in arbitrary units and are shown in the inset. (C) To match pulse-alone startle responses between EGF and control rats, 110-dB and 120-dB pulses were given to EGF and control rats, respectively, as shown in the insert. Following PPI test in (A) and (C), dopamine content was measured in the globus pallidus (GP) and neighboring striatum and shown in (B) and (D), respectively. Bars indicate mean ± SEM (N = 8–9 each). *P<0.05, **P<0.01, ***P<0.001, compared with vehicle-infused control rats; ++P<0.01, +++P<0.001, compared with vehicle-infused EGF rats by Fisher's LSD.</p>", "links"=>[], "tags"=>["pallidal", "reserpine", "infusion", "prepulse"], "article_id"=>395809, "categories"=>["Chemistry", "Biochemistry", "Neuroscience", "Physiology", "Mental Health"], "users"=>["Hidekazu Sotoyama", "Yingjun Zheng", "Yuriko Iwakura", "Makoto Mizuno", "Miho Aizawa", "Ksenia Shcherbakova", "Ran Wang", "Hisaaki Namba", "Hiroyuki Nawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025831.g004", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_pallidal_reserpine_infusion_on_prepulse_inhibition_/395809", "title"=>"Effects of pallidal reserpine infusion on prepulse inhibition.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 13:52:51"}

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