Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://repositorio.unifesp.br/xmlui/handle/11600/62156 https://doi.org/10.1038/s41598-020-75616-2 |
Resumo: | Nuclear distribution element-like 1 (NDEL1) enzyme activity is important for neuritogenesis, neuronal migration, and neurodevelopment. We reported previously lower NDEL1 enzyme activity in blood of treated first episode psychosis and chronic schizophrenia (SCZ) compared to healthy control subjects, with even lower activity in treatment resistant chronic SCZ patients, implicating NDEL1 activity in SCZ. Herein, higher NDEL1 activity was observed in the blood and several brain regions of a validated animal model for SCZ at baseline. In addition, long-term treatment with typical or atypical antipsychotics, under conditions in which SCZ-like phenotypes were reported to be reversed in this animal model for SCZ, showed a significant NDEL1 activity reduction in blood and brain regions which is in line with clinical data. Importantly, these results support measuring NDEL1 enzyme activity in the peripheral blood to predict changes in NDEL1 activity in the CNS. Also, acute administration of psychostimulants, at levels reported to induce SCZ-like phenotype in normal rat strains, increased NDEL1 enzyme activity in blood. Therefore, alterations in NDEL1 activity after treatment with antipsychotics or psychostimulants may suggest a possible modulation of NDEL1 activity secondary to neurotransmission homeostasis and provide new insights into the role of NDEL1 in SCZ pathophysiology. |
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Nani, João Victor [UNIFESP]Lee, Richard SYonamine, Camila M. [UNIFESP]Sant'Anna, Osvaldo A.Juliano, Maria A. [UNIFESP]Gadelha, Ary [UNIFESP]Mari, Jair J. [UNIFESP]Hayashi, Mirian A. F. [UNIFESP]http://lattes.cnpq.br/55593093952321472021-10-29T13:54:48Z2021-10-29T13:54:48Z2020-10-28Scientific Reports, London, v. 10, n. 1, p. 1-12, 28 Oct. 20202045-2322https://repositorio.unifesp.br/xmlui/handle/11600/62156https://doi.org/10.1038/s41598-020-75616-210.1038/s41598-020-75616-2Nuclear distribution element-like 1 (NDEL1) enzyme activity is important for neuritogenesis, neuronal migration, and neurodevelopment. We reported previously lower NDEL1 enzyme activity in blood of treated first episode psychosis and chronic schizophrenia (SCZ) compared to healthy control subjects, with even lower activity in treatment resistant chronic SCZ patients, implicating NDEL1 activity in SCZ. Herein, higher NDEL1 activity was observed in the blood and several brain regions of a validated animal model for SCZ at baseline. In addition, long-term treatment with typical or atypical antipsychotics, under conditions in which SCZ-like phenotypes were reported to be reversed in this animal model for SCZ, showed a significant NDEL1 activity reduction in blood and brain regions which is in line with clinical data. Importantly, these results support measuring NDEL1 enzyme activity in the peripheral blood to predict changes in NDEL1 activity in the CNS. Also, acute administration of psychostimulants, at levels reported to induce SCZ-like phenotype in normal rat strains, increased NDEL1 enzyme activity in blood. Therefore, alterations in NDEL1 activity after treatment with antipsychotics or psychostimulants may suggest a possible modulation of NDEL1 activity secondary to neurotransmission homeostasis and provide new insights into the role of NDEL1 in SCZ pathophysiology.12 p.engNature ResearchScientific ReportsEnzymesBiochemistryNeuroscienceDiseases of the nervous systemSchizophreniaEvaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychoticsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPEscola Paulista de Medicina (EPM)FarmacologiaOutraFarmacologiaORIGINAL41598_2020_Article_75616.pdf41598_2020_Article_75616.pdfapplication/pdf1298954${dspace.ui.url}/bitstream/11600/62156/1/41598_2020_Article_75616.pdfb92ad109a868e6607927274d5633f115MD51open 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Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-05-23T05:20:27Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.pt_BR.fl_str_mv |
Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics |
title |
Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics |
spellingShingle |
Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics Nani, João Victor [UNIFESP] Enzymes Biochemistry Neuroscience Diseases of the nervous system Schizophrenia |
title_short |
Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics |
title_full |
Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics |
title_fullStr |
Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics |
title_full_unstemmed |
Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics |
title_sort |
Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics |
author |
Nani, João Victor [UNIFESP] |
author_facet |
Nani, João Victor [UNIFESP] Lee, Richard S Yonamine, Camila M. [UNIFESP] Sant'Anna, Osvaldo A. Juliano, Maria A. [UNIFESP] Gadelha, Ary [UNIFESP] Mari, Jair J. [UNIFESP] Hayashi, Mirian A. F. [UNIFESP] |
author_role |
author |
author2 |
Lee, Richard S Yonamine, Camila M. [UNIFESP] Sant'Anna, Osvaldo A. Juliano, Maria A. [UNIFESP] Gadelha, Ary [UNIFESP] Mari, Jair J. [UNIFESP] Hayashi, Mirian A. F. [UNIFESP] |
author2_role |
author author author author author author author |
dc.contributor.authorLattes.pt_BR.fl_str_mv |
http://lattes.cnpq.br/5559309395232147 |
dc.contributor.author.fl_str_mv |
Nani, João Victor [UNIFESP] Lee, Richard S Yonamine, Camila M. [UNIFESP] Sant'Anna, Osvaldo A. Juliano, Maria A. [UNIFESP] Gadelha, Ary [UNIFESP] Mari, Jair J. [UNIFESP] Hayashi, Mirian A. F. [UNIFESP] |
dc.subject.por.fl_str_mv |
Enzymes Biochemistry Neuroscience Diseases of the nervous system Schizophrenia |
topic |
Enzymes Biochemistry Neuroscience Diseases of the nervous system Schizophrenia |
description |
Nuclear distribution element-like 1 (NDEL1) enzyme activity is important for neuritogenesis, neuronal migration, and neurodevelopment. We reported previously lower NDEL1 enzyme activity in blood of treated first episode psychosis and chronic schizophrenia (SCZ) compared to healthy control subjects, with even lower activity in treatment resistant chronic SCZ patients, implicating NDEL1 activity in SCZ. Herein, higher NDEL1 activity was observed in the blood and several brain regions of a validated animal model for SCZ at baseline. In addition, long-term treatment with typical or atypical antipsychotics, under conditions in which SCZ-like phenotypes were reported to be reversed in this animal model for SCZ, showed a significant NDEL1 activity reduction in blood and brain regions which is in line with clinical data. Importantly, these results support measuring NDEL1 enzyme activity in the peripheral blood to predict changes in NDEL1 activity in the CNS. Also, acute administration of psychostimulants, at levels reported to induce SCZ-like phenotype in normal rat strains, increased NDEL1 enzyme activity in blood. Therefore, alterations in NDEL1 activity after treatment with antipsychotics or psychostimulants may suggest a possible modulation of NDEL1 activity secondary to neurotransmission homeostasis and provide new insights into the role of NDEL1 in SCZ pathophysiology. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020-10-28 |
dc.date.accessioned.fl_str_mv |
2021-10-29T13:54:48Z |
dc.date.available.fl_str_mv |
2021-10-29T13:54:48Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Scientific Reports, London, v. 10, n. 1, p. 1-12, 28 Oct. 2020 |
dc.identifier.uri.fl_str_mv |
https://repositorio.unifesp.br/xmlui/handle/11600/62156 https://doi.org/10.1038/s41598-020-75616-2 |
dc.identifier.issn.none.fl_str_mv |
2045-2322 |
dc.identifier.doi.none.fl_str_mv |
10.1038/s41598-020-75616-2 |
identifier_str_mv |
Scientific Reports, London, v. 10, n. 1, p. 1-12, 28 Oct. 2020 2045-2322 10.1038/s41598-020-75616-2 |
url |
https://repositorio.unifesp.br/xmlui/handle/11600/62156 https://doi.org/10.1038/s41598-020-75616-2 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Scientific Reports |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
12 p. |
dc.publisher.none.fl_str_mv |
Nature Research |
publisher.none.fl_str_mv |
Nature Research |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
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1802764217971900416 |