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

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dc.contributor.authorBen Afia, Amira
dc.contributor.authorVila, Èlia
dc.contributor.authorOrmazabal, Aida
dc.contributor.authorHaro, Josep M.
dc.contributor.authorArtuch, Rafael
dc.contributor.authorRamos, Belén
dc.contributor.authorMac-Dowell Mata, Karina Soledad
dc.contributor.authorLeza Cerro, Juan Carlos
dc.contributor.authorGarcía Bueno, Borja
dc.date.accessioned2024-01-30T18:40:12Z
dc.date.available2024-01-30T18:40:12Z
dc.date.issued2021-09-12
dc.description.abstractBackground: 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.
dc.description.departmentDepto. de Farmacología y Toxicología
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.sponsorshipMINECO-FEDER
dc.description.sponsorshipInstituto de Salud Carlos III
dc.description.sponsorshipERDF
dc.description.sponsorshipCIBERSAM
dc.description.statuspub
dc.identifier.citationAfia AB, Vila È, MacDowell KS, Ormazabal A, Leza JC, Haro JM, Artuch R, Ramos B, Garcia-Bueno B. Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology. J Neuroinflammation. 2021 Sep 12;18(1):198. doi: 10.1186/s12974-021-02260-6. PMID: 34511126.
dc.identifier.doi10.1186/s12974-021-02260-6
dc.identifier.issn1742-2094
dc.identifier.officialurlhttps://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-021-02260-6
dc.identifier.relatedurlhttps://pubmed.ncbi.nlm.nih.gov/34511126/
dc.identifier.urihttps://hdl.handle.net/20.500.14352/96775
dc.issue.number1
dc.journal.titleJournal of Neuroinflammation
dc.language.isoeng
dc.publisherBioMed Central
dc.relation.projectIDSAF2016-75500-R
dc.relation.projectIDMS16/00153
dc.relation.projectIDCP16/00153
dc.relation.projectIDFI19/00080
dc.rightsAttribution 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.cdu616.89
dc.subject.cdu616.89-007
dc.subject.cdu612.8
dc.subject.cdu612.8-092.19
dc.subject.keyword5-Hydroxyindoleacetic acid
dc.subject.keywordCortico-cerebellar-thalamic-cortical circuit
dc.subject.keywordKynurenine pathway
dc.subject.keywordMonoamine oxidase A
dc.subject.keywordPANSS scale
dc.subject.keywordSchizophrenia
dc.subject.ucmCiencias Biomédicas
dc.subject.unesco24 Ciencias de la Vida
dc.titleKynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number18
dspace.entity.typePublication
relation.isAuthorOfPublicationd7de3e71-d141-4e63-ab4c-a71249846532
relation.isAuthorOfPublication60ff0835-366b-4a2b-9c1e-4533824ea881
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relation.isAuthorOfPublication.latestForDiscoveryd7de3e71-d141-4e63-ab4c-a71249846532
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