Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology

Background: The cortico-cerebellar-thalamic-cortical circuit has been implicated in the emergence of psychotic symptoms in schizophrenia (SZ). The kynurenine pathway (KP) has been linked to alterations in glutamatergic and monoaminergic neurotransmission and to SZ symptomatology through the producti...

Descripción completa

Detalles Bibliográficos
Autores: Ben Afia, Amira, Vila, Èlia, MacDowell, Karina S., Ormazabal Herrero, Aida, Leza, Juan Carlos, Haro Abad, Josep Maria, Artuch Iriberri, Rafael, Ramos Josemaría, Belén, García Bueno, Borja
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/186522
Acceso en línea:https://hdl.handle.net/2445/186522
Access Level:acceso abierto
Palabra clave:Esquizofrènia
Oxidoreductases
Escorça frontal
Cerebel
Compostos heterocíclics
Schizophrenia
Prefrontal cortex
Cerebellum
Heterocyclic compounds
id ES_cd852f6b11cf3effe8ee19dc3049ffcc
oai_identifier_str oai:diposit.ub.edu:2445/186522
network_acronym_str ES
network_name_str España
repository_id_str
spelling Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatologyBen Afia, AmiraVila, ÈliaMacDowell, Karina S.Ormazabal Herrero, AidaLeza, Juan CarlosHaro Abad, Josep MariaArtuch Iriberri, RafaelRamos Josemaría, BelénGarcía Bueno, BorjaEsquizofrèniaOxidoreductasesEscorça frontalCerebelCompostos heterocíclicsSchizophreniaOxidoreductasesPrefrontal cortexCerebellumHeterocyclic compoundsBackground: The cortico-cerebellar-thalamic-cortical circuit has been implicated in the emergence of psychotic symptoms in schizophrenia (SZ). The kynurenine pathway (KP) has been linked to alterations in glutamatergic and monoaminergic neurotransmission and to SZ symptomatology through the production of the metabolites quinolinic acid (QA) and kynurenic acid (KYNA). Methods: This work describes alterations in KP in the post-mortem prefrontal cortex (PFC) and cerebellum (CB) of 15 chronic SZ patients and 14 control subjects in PFC and 13 control subjects in CB using immunoblot for protein levels and ELISA for interleukins and QA and KYNA determinations. Monoamine metabolites were analysed by high-performance liquid chromatography and SZ symptomatology was assessed by Positive and Negative Syndrome Scale (PANSS). The association of KP with inflammatory mediators, monoamine metabolism and SZ symptomatology was explored. Results: In the PFC, the presence of the anti-inflammatory cytokine IL-10 together with IDO2 and KATII enzymes decreased in SZ, while TDO and KMO enzyme expression increased. A network interaction analysis showed that in the PFC IL-10 was coupled to the QA branch of the kynurenine pathway (TDO-KMO-QA), whereas IL-10 associated with KMO in CB. KYNA in the CB inversely correlated with negative and general PANSS psychopathology. Although there were no changes in monoamine metabolite content in the PFC in SZ, a network interaction analysis showed associations between dopamine and methoxyhydroxyphenylglycol degradation metabolite. Direct correlations were found between general PANSS psychopathology and the serotonin degradation metabolite, 5-hydroxyindoleacetic acid. Interestingly, KYNA in the CB inversely correlated with 5-hydroxyindoleacetic acid in the PFC. Conclusions: Thus, this work found alterations in KP in two brain areas belonging to the cortico-cerebellar-thalamic-cortical circuit associated with SZ symptomatology, with a possible impact across areas in 5-HT degradation.BioMed Central2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/186522Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s12974-021-02260-6Journal of Neuroinflammation, 2021, vol. 18, num. 1, p. 198https://doi.org/10.1186/s12974-021-02260-6cc-by (c) Ben Afia, Amira et al., 2021https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1865222026-05-27T06:46:51Z
dc.title.none.fl_str_mv Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology
title Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology
spellingShingle Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology
Ben Afia, Amira
Esquizofrènia
Oxidoreductases
Escorça frontal
Cerebel
Compostos heterocíclics
Schizophrenia
Oxidoreductases
Prefrontal cortex
Cerebellum
Heterocyclic compounds
title_short Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology
title_full Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology
title_fullStr Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology
title_full_unstemmed Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology
title_sort Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology
dc.creator.none.fl_str_mv Ben Afia, Amira
Vila, Èlia
MacDowell, Karina S.
Ormazabal Herrero, Aida
Leza, Juan Carlos
Haro Abad, Josep Maria
Artuch Iriberri, Rafael
Ramos Josemaría, Belén
García Bueno, Borja
author Ben Afia, Amira
author_facet Ben Afia, Amira
Vila, Èlia
MacDowell, Karina S.
Ormazabal Herrero, Aida
Leza, Juan Carlos
Haro Abad, Josep Maria
Artuch Iriberri, Rafael
Ramos Josemaría, Belén
García Bueno, Borja
author_role author
author2 Vila, Èlia
MacDowell, Karina S.
Ormazabal Herrero, Aida
Leza, Juan Carlos
Haro Abad, Josep Maria
Artuch Iriberri, Rafael
Ramos Josemaría, Belén
García Bueno, Borja
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Esquizofrènia
Oxidoreductases
Escorça frontal
Cerebel
Compostos heterocíclics
Schizophrenia
Oxidoreductases
Prefrontal cortex
Cerebellum
Heterocyclic compounds
topic Esquizofrènia
Oxidoreductases
Escorça frontal
Cerebel
Compostos heterocíclics
Schizophrenia
Oxidoreductases
Prefrontal cortex
Cerebellum
Heterocyclic compounds
description Background: The cortico-cerebellar-thalamic-cortical circuit has been implicated in the emergence of psychotic symptoms in schizophrenia (SZ). The kynurenine pathway (KP) has been linked to alterations in glutamatergic and monoaminergic neurotransmission and to SZ symptomatology through the production of the metabolites quinolinic acid (QA) and kynurenic acid (KYNA). Methods: This work describes alterations in KP in the post-mortem prefrontal cortex (PFC) and cerebellum (CB) of 15 chronic SZ patients and 14 control subjects in PFC and 13 control subjects in CB using immunoblot for protein levels and ELISA for interleukins and QA and KYNA determinations. Monoamine metabolites were analysed by high-performance liquid chromatography and SZ symptomatology was assessed by Positive and Negative Syndrome Scale (PANSS). The association of KP with inflammatory mediators, monoamine metabolism and SZ symptomatology was explored. Results: In the PFC, the presence of the anti-inflammatory cytokine IL-10 together with IDO2 and KATII enzymes decreased in SZ, while TDO and KMO enzyme expression increased. A network interaction analysis showed that in the PFC IL-10 was coupled to the QA branch of the kynurenine pathway (TDO-KMO-QA), whereas IL-10 associated with KMO in CB. KYNA in the CB inversely correlated with negative and general PANSS psychopathology. Although there were no changes in monoamine metabolite content in the PFC in SZ, a network interaction analysis showed associations between dopamine and methoxyhydroxyphenylglycol degradation metabolite. Direct correlations were found between general PANSS psychopathology and the serotonin degradation metabolite, 5-hydroxyindoleacetic acid. Interestingly, KYNA in the CB inversely correlated with 5-hydroxyindoleacetic acid in the PFC. Conclusions: Thus, this work found alterations in KP in two brain areas belonging to the cortico-cerebellar-thalamic-cortical circuit associated with SZ symptomatology, with a possible impact across areas in 5-HT degradation.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/186522
url https://hdl.handle.net/2445/186522
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s12974-021-02260-6
Journal of Neuroinflammation, 2021, vol. 18, num. 1, p. 198
https://doi.org/10.1186/s12974-021-02260-6
dc.rights.none.fl_str_mv cc-by (c) Ben Afia, Amira et al., 2021
https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Ben Afia, Amira et al., 2021
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869419862173941760
score 15,300724

Similares en LA Referencia