Assessment of Cytochrome C Oxidase Dysfunction in the Substantia Nigra/Ventral Tegmental Area in Schizophrenia
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{"title"=>"Assessment of cytochrome C oxidase dysfunction in the substantia nigra/ventral tegmental area in schizophrenia", "type"=>"journal", "authors"=>[{"first_name"=>"Matthew W.", "last_name"=>"Rice", "scopus_author_id"=>"55226425100"}, {"first_name"=>"Kristen L.", "last_name"=>"Smith", "scopus_author_id"=>"56233323200"}, {"first_name"=>"Rosalinda C.", "last_name"=>"Roberts", "scopus_author_id"=>"35732128100"}, {"first_name"=>"Emma", "last_name"=>"Perez-Costas", "scopus_author_id"=>"6507660615"}, {"first_name"=>"Miguel", "last_name"=>"Melendez-Ferro", "scopus_author_id"=>"6506729506"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"373399335", "isbn"=>"1932-6203", "sgr"=>"84903388664", "issn"=>"19326203", "pmid"=>"24941246", "scopus"=>"2-s2.0-84903388664", "doi"=>"10.1371/journal.pone.0100054"}, "id"=>"2f5953ee-d090-3fcb-9cb1-d5d5b1b5f626", "abstract"=>"Perturbations in metabolism are a well-documented but complex facet of schizophrenia pathology. Optimal cellular performance requires the proper functioning of the electron transport chain, which is constituted by four enzymes located within the inner membrane of mitochondria. These enzymes create a proton gradient that is used to power the enzyme ATP synthase, producing ATP, which is crucial for the maintenance of cellular functioning. Anomalies in a single enzyme of the electron transport chain are sufficient to cause disruption of cellular metabolism. The last of these complexes is the cytochrome c oxidase (COX) enzyme, which is composed of thirteen different subunits. COX is a major site for oxidative phosphorylation, and anomalies in this enzyme are one of the most frequent causes of mitochondrial pathology. The objective of the present report was to assess if metabolic anomalies linked to COX dysfunction may contribute to substantia nigra/ventral tegmental area (SN/VTA) pathology in schizophrenia. We tested COX activity in postmortem SN/VTA from schizophrenia and non-psychiatric controls. We also tested the protein expression of key subunits for the assembly and activity of the enzyme, and the effect of antipsychotic medication on subunit expression. COX activity was not significantly different between schizophrenia and non-psychiatric controls. However, we found significant decreases in the expression of subunits II and IV-I of COX in schizophrenia. Interestingly, these decreases were observed in samples containing the entire rostro-caudal extent of the SN/VTA, while no significant differences were observed for samples containing only mid-caudal regions of the SN/VTA. Finally, rats chronically treated with antipsychotic drugs did not show significant changes in COX subunit expression. These findings suggest that COX subunit expression may be compromised in specific sub-regions of the SN/VTA (i.e. rostral regions), which may lead to a faulty assembly of the enzyme and a greater vulnerability to metabolic insult.", "link"=>"http://www.mendeley.com/research/assessment-cytochrome-c-oxidase-dysfunction-substantia-nigraventral-tegmental-area-schizophrenia", "reader_count"=>17, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>4, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>2, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>4, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>2, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>3, "Neuroscience"=>4, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Neuroscience"=>{"Neuroscience"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1538553"], "description"=>"<p>Analyses were carried independently for rostro-caudal and mid-caudal samples. Demographic and sample variables were tested in separated tests. Abbreviations: <b>R<sup>2</sup>a</b>, adjusted R squared. <b>pH</b>, brain pH. <b>PMI,</b> postmortem interval.</p>", "links"=>[], "tags"=>["anatomy", "nervous system", "neuroanatomy", "Neural pathways", "Biochemistry", "hormones", "catecholamines", "dopamine", "metabolism", "Energy metabolism", "proteins", "protein synthesis", "Neurochemistry", "Neurochemicals", "neuroscience", "Mental health and psychiatry", "schizophrenia", "Pathology and laboratory medicine", "anatomical pathology", "neuropathology", "experiments", "independently", "regression"], "article_id"=>1060571, "categories"=>["Biological Sciences"], "users"=>["Matthew W. Rice", "Kristen L. Smith", "Rosalinda C. Roberts", "Emma Perez-Costas", "Miguel Melendez-Ferro"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100054.t002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Note_that_experiments_were_run_independently_for_each_outcome_measure_thus_independent_multiple_regression_tests_were_run_for_each_outcome_measure_/1060571", "title"=>"Note that experiments were run independently for each outcome measure, thus, independent multiple regression tests were run for each outcome measure.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-06-18 02:45:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1538552"], "description"=>"<p>Abbreviations: A, atypical antipsychotic; AA, African American; APD, antipsychotic drug; ASCVD, arteriosclerotic cardiovascular disease; C, control case; COD, cause of death; CUT, chronic undifferentiated type; DVT, deep vein thrombosis; F, female; M, male; MI, myocardial infarction; NOS, not otherwise specified; MVA, motor vehicle accident; PMI, postmortem interval; SD, standard deviation; SZ, schizophrenia case; SZ subtype, schizophrenia subtype; T, typical antipsychotic; TD, tardive dyskinesia; un, unknown; UNK, unknown medication at time of death; W, white.</p>", "links"=>[], "tags"=>["anatomy", "nervous system", "neuroanatomy", "Neural pathways", "Biochemistry", "hormones", "catecholamines", "dopamine", "metabolism", "Energy metabolism", "proteins", "protein synthesis", "Neurochemistry", "Neurochemicals", "neuroscience", "Mental health and psychiatry", "schizophrenia", "Pathology and laboratory medicine", "anatomical pathology", "neuropathology", "cases"], "article_id"=>1060570, "categories"=>["Biological Sciences"], "users"=>["Matthew W. Rice", "Kristen L. Smith", "Rosalinda C. Roberts", "Emma Perez-Costas", "Miguel Melendez-Ferro"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100054.t001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographic_and_clinical_data_of_the_cases_used_for_the_study_/1060570", "title"=>"Demographic and clinical data of the cases used for the study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-06-18 02:45:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1538547"], "description"=>"<p>For each subunit, western blot images of all the samples assessed in schizophrenia and control cases are shown at the top of each panel, together with an image of the same western blot membrane reincubated for the detection of actin. An outlier is indicated with a red box surrounding the case number. Bar graphs indicate the mean calibrated optical density (OD) and standard deviation. Scatter plots are shown on the right with a horizontal bar indicating the mean. A) Analysis of COX Subunit IV-I expression. Subunit IV-I protein expression showed significant (*) differences between the two groups (OD mean ± SD: schizophrenia: 0.43541±0.20501; control: 0.84416±0.56772). B) Analysis of COX Subunit IV-II protein expression. Subunit IV-II protein expression did not differ significantly between schizophrenia and control cases (OD mean ± SD: schizophrenia: 1.340±0.2261; control: 1.354±0.3104).</p>", "links"=>[], "tags"=>["anatomy", "nervous system", "neuroanatomy", "Neural pathways", "Biochemistry", "hormones", "catecholamines", "dopamine", "metabolism", "Energy metabolism", "proteins", "protein synthesis", "Neurochemistry", "Neurochemicals", "neuroscience", "Mental health and psychiatry", "schizophrenia", "Pathology and laboratory medicine", "anatomical pathology", "neuropathology", "cox", "subunits", "iv-i", "iv-ii", "samples", "containing", "rostro-caudal"], "article_id"=>1060565, "categories"=>["Biological Sciences"], "users"=>["Matthew W. Rice", "Kristen L. Smith", "Rosalinda C. Roberts", "Emma Perez-Costas", "Miguel Melendez-Ferro"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100054.g004", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_COX_subunits_IV_I_and_IV_II_in_samples_containing_the_entire_rostro_caudal_extent_of_the_human_SN_VTA_/1060565", "title"=>"Analysis of COX subunits IV-I and IV-II in samples containing the entire rostro-caudal extent of the human SN/VTA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-18 02:45:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1538546"], "description"=>"<p>For each subunit, western blot images of all the samples assessed in schizophrenia and control cases are shown at the top of each panel, together with an image of the same western blot membrane reincubated for the detection of actin. Outliers are indicated with a red box surrounding the case number. Bar graphs indicate the mean calibrated optical density (OD) and standard deviation. Scatter plots are shown on the right with a horizontal bar indicating the mean. A) Analysis of COX Subunit I expression. Subunit I protein expression did not differ significantly between schizophrenia and control cases (OD mean ± SD: schizophrenia: 0.6182±0.07451; control: 0.6014±0.08532). B) Analysis of COX Subunit II expression. There were significant (*) differences for subunit II expression between schizophrenia and controls (OD mean ± SD: schizophrenia: 0.21719±0.02887; control: 0.4751±0.1954). C) Analysis of COX Subunit III expression. Subunit III protein expression did not differ significantly between schizophrenia and control cases (OD mean ± SD: schizophrenia: 0.8153±0.3878; control: 0.5388±0.1281).</p>", "links"=>[], "tags"=>["anatomy", "nervous system", "neuroanatomy", "Neural pathways", "Biochemistry", "hormones", "catecholamines", "dopamine", "metabolism", "Energy metabolism", "proteins", "protein synthesis", "Neurochemistry", "Neurochemicals", "neuroscience", "Mental health and psychiatry", "schizophrenia", "Pathology and laboratory medicine", "anatomical pathology", "neuropathology", "cox", "subunits", "iii", "samples", "containing", "rostro-caudal"], "article_id"=>1060564, "categories"=>["Biological Sciences"], "users"=>["Matthew W. Rice", "Kristen L. Smith", "Rosalinda C. Roberts", "Emma Perez-Costas", "Miguel Melendez-Ferro"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100054.g003", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_COX_subunits_I_II_and_III_in_samples_containing_the_entire_rostro_caudal_extent_of_the_human_SN_VTA_/1060564", "title"=>"Analysis of COX subunits I, II, and III in samples containing the entire rostro-caudal extent of the human SN/VTA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-18 02:45:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1538551"], "description"=>"<p>Western blot images of the expression of each COX subunit in all animals from the three treatment groups are shown at the top of each panel. Each western blot membrane was reincubated for the detection of actin. The bar graphs indicate the mean calibrated optical density (OD) and standard deviation. Scatter plots are shown on the right with a horizontal bar indicating the mean. A) Analysis of COX subunit IV-I. Subunit IV-I protein expression did not differ significantly among the three treatment groups (OD mean ± SD: control: 1.084±0.2609; haloperidol: 1.021±0.3270; olanzapine: 1.098±0.3559). B) Analysis of COX subunit IV-II. Subunit IV-II protein expression did not differ significantly among the three treatment groups (OD mean ± SD: control: 0.6829±0.1375; haloperidol: 0.8100±0.1611; olanzapine: 0.7551±0.08140).</p>", "links"=>[], "tags"=>["anatomy", "nervous system", "neuroanatomy", "Neural pathways", "Biochemistry", "hormones", "catecholamines", "dopamine", "metabolism", "Energy metabolism", "proteins", "protein synthesis", "Neurochemistry", "Neurochemicals", "neuroscience", "Mental health and psychiatry", "schizophrenia", "Pathology and laboratory medicine", "anatomical pathology", "neuropathology", "cytochrome", "oxidase", "subunits", "iv-i", "iv-ii", "animals", "treated", "antipsychotic"], "article_id"=>1060569, "categories"=>["Biological Sciences"], "users"=>["Matthew W. Rice", "Kristen L. Smith", "Rosalinda C. Roberts", "Emma Perez-Costas", "Miguel Melendez-Ferro"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100054.g008", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_cytochrome_c_oxidase_subunits_IV_I_and_IV_II_in_the_SN_VTA_of_animals_treated_with_antipsychotic_drugs_/1060569", "title"=>"Analysis of cytochrome c oxidase subunits IV-I and IV-II in the SN/VTA of animals treated with antipsychotic drugs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-18 02:45:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1538549"], "description"=>"<p>For each subunit, western blot images of all the samples assessed in schizophrenia and control cases are shown at the top of each panel, together with an image of the same western blot membrane reincubated for the detection of actin. Bar graphs indicate the mean calibrated optical density (OD) and standard deviation. Scatter plots are shown on the right with a horizontal bar indicating the mean. A) Analysis of COX Subunit IV-I. Subunit IV-I protein expression did not differ significantly between schizophrenia and control cases (OD mean ± SD: schizophrenia: 1.336±0.4237; control: 1.789±0.4741). B) Analysis of COX Subunit IV-II. Subunit IV-II protein expression did not differ significantly between schizophrenia and control cases (OD mean ± SD: schizophrenia: 1.279±0.3895; control: 1.097±0.1950).</p>", "links"=>[], "tags"=>["anatomy", "nervous system", "neuroanatomy", "Neural pathways", "Biochemistry", "hormones", "catecholamines", "dopamine", "metabolism", "Energy metabolism", "proteins", "protein synthesis", "Neurochemistry", "Neurochemicals", "neuroscience", "Mental health and psychiatry", "schizophrenia", "Pathology and laboratory medicine", "anatomical pathology", "neuropathology", "cox", "subunits", "iv-i", "iv-ii", "mid-caudal"], "article_id"=>1060567, "categories"=>["Biological Sciences"], "users"=>["Matthew W. Rice", "Kristen L. Smith", "Rosalinda C. Roberts", "Emma Perez-Costas", "Miguel Melendez-Ferro"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100054.g006", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_COX_subunits_IV_I_and_IV_II_protein_expression_in_the_mid_caudal_human_SN_VTA_/1060567", "title"=>"Analysis of COX subunits IV-I and IV-II protein expression in the mid-caudal human SN/VTA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-18 02:45:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1538550"], "description"=>"<p>Western blot images of the expression of each COX subunit in all animals from the three treatment groups are shown at the top of each panel. Each western blot membrane was reincubated for the detection of actin. Bar graphs indicate the mean calibrated optical density (OD) and standard deviation. Scatter plots are shown on the right with a horizontal bar indicating the mean. A) Analysis of COX subunit I. Subunit I protein expression did not differ significantly among the three treatment groups (OD mean ± SD: control: 0.4753±0.06210; haloperidol: 0.5145±0.1158; olanzapine: 0.4731±0.1025). B) Analysis of COX subunit II. Subunit II protein expression did not differ significantly among the three treatment groups (OD mean ± SD: control: 0.4740±0.1118; haloperidol: 0.5535±0.1312; olanzapine: 0.5564±0.1121). C) Analysis of COX subunit III. Subunit III protein expression did not differ significantly among the three treatment groups (OD mean ± SD: control: 1.480±0.4543; haloperidol: 1.609±0.2989; olanzapine: 1.455±0.4438).</p>", "links"=>[], "tags"=>["anatomy", "nervous system", "neuroanatomy", "Neural pathways", "Biochemistry", "hormones", "catecholamines", "dopamine", "metabolism", "Energy metabolism", "proteins", "protein synthesis", "Neurochemistry", "Neurochemicals", "neuroscience", "Mental health and psychiatry", "schizophrenia", "Pathology and laboratory medicine", "anatomical pathology", "neuropathology", "cox", "subunits", "iii", "animals", "treated", "antipsychotic"], "article_id"=>1060568, "categories"=>["Biological Sciences"], "users"=>["Matthew W. Rice", "Kristen L. Smith", "Rosalinda C. Roberts", "Emma Perez-Costas", "Miguel Melendez-Ferro"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100054.g007", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_COX_subunits_I_II_and_III_in_the_SN_VTA_of_animals_treated_with_antipsychotic_drugs_/1060568", "title"=>"Analysis of COX subunits I, II, and III in the SN/VTA of animals treated with antipsychotic drugs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-18 02:45:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1538548"], "description"=>"<p>For each subunit, western blot images of all the samples assessed in schizophrenia and control cases are shown at the top of each panel, together with an image of the same western blot membrane reincubated for the detection of actin. Outliers are indicated with a red box surrounding the case number. Bar graphs indicate the mean calibrated optical density (OD) and standard deviation. Scatter plots are shown on the right with a horizontal bar indicating the mean. A) Analysis of COX Subunit I. Subunit I protein expression did not differ significantly between schizophrenia and control cases (OD mean ± SD: schizophrenia: 0.6355±0.1680; control: 0.5998±0.1213). B) Analysis of COX Subunit II. Subunit II protein expression did not differ significantly between schizophrenia and control cases (OD mean ± SD: schizophrenia: 0.9332±0.3837; control: 1.352±0.7247). C) Analysis of COX Subunit III. Subunit III protein expression did not differ significantly between schizophrenia and control cases (OD mean ± SD: schizophrenia: 0.5228±0.08916; control: 0.8408±0.5324).</p>", "links"=>[], "tags"=>["anatomy", "nervous system", "neuroanatomy", "Neural pathways", "Biochemistry", "hormones", "catecholamines", "dopamine", "metabolism", "Energy metabolism", "proteins", "protein synthesis", "Neurochemistry", "Neurochemicals", "neuroscience", "Mental health and psychiatry", "schizophrenia", "Pathology and laboratory medicine", "anatomical pathology", "neuropathology", "cox", "subunits", "iii", "mid-caudal"], "article_id"=>1060566, "categories"=>["Biological Sciences"], "users"=>["Matthew W. Rice", "Kristen L. Smith", "Rosalinda C. Roberts", "Emma Perez-Costas", "Miguel Melendez-Ferro"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100054.g005", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_COX_subunits_I_II_and_III_protein_expression_in_the_mid_caudal_human_SN_VTA_/1060566", "title"=>"Analysis of COX subunits I, II, and III protein expression in the mid-caudal human SN/VTA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-18 02:45:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/1538545"], "description"=>"<p>A) Representative images of thionin-stained sections and COX histochemistry in the SN/VTA and red nucleus from schizophrenia and control cases. Dashed lines in the thionin-stained sections show the masks used for the delineation of the region of interest. B) Top panel shows the logarithm of optical density (log OD) for COX activity in the SN/VTA (geometric mean with bar representing the 95% confidence interval). The mid panel shows a scatter plot of the individual data. The horizontal bar in each scatter plot indicates the geometric mean OD. The bottom panel shows COX activity in the red nucleus.</p>", "links"=>[], "tags"=>["anatomy", "nervous system", "neuroanatomy", "Neural pathways", "Biochemistry", "hormones", "catecholamines", "dopamine", "metabolism", "Energy metabolism", "proteins", "protein synthesis", "Neurochemistry", "Neurochemicals", "neuroscience", "Mental health and psychiatry", "schizophrenia", "Pathology and laboratory medicine", "anatomical pathology", "neuropathology", "cox", "samples", "containing", "rostro-caudal"], "article_id"=>1060563, "categories"=>["Biological Sciences"], "users"=>["Matthew W. Rice", "Kristen L. Smith", "Rosalinda C. Roberts", "Emma Perez-Costas", "Miguel Melendez-Ferro"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0100054.g001", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_COX_activity_in_samples_containing_the_entire_rostro_caudal_extent_of_the_human_SN_VTA_/1060563", "title"=>"Analysis of COX activity in samples containing the entire rostro-caudal extent of the human SN/VTA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-18 02:45:27"}

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