Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia : relationship with monoamines and symptomatology
Afia, Amira Ben (University of Monastir)
Vila, Èlia (Institut de Recerca Sant Joan de Déu)
Macdowell, Karina S (Centro de Investigación Biomédica en Red de Salud Mental)
Ormazabal, Aida (Institut de Recerca Sant Joan de Déu)
Leza, Juan Carlos (Centro de Investigación Biomédica en Red de Salud Mental)
Haro Abad, Josep Maria (Institut de Recerca Sant Joan de Déu)
Artuch, R. (Institut de Recerca Sant Joan de Déu)
Ramos, Belén (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Garcia-Bueno, Borja (Centro de Investigación Biomédica en Red de Salud Mental)

Date:	2021
Abstract:	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). 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. 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. 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. The online version contains supplementary material available at 10. 1186/s12974-021-02260-6.
Grants:	Ministerio de Economía, Industria y Competitividad SAF2016-75500-R Instituto de Salud Carlos III MS16/00153-CP16/00153 Instituto de Salud Carlos III FI19/00080
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Schizophrenia ; Cortico-cerebellar-thalamic-cortical circuit ; Kynurenine pathway ; 5-Hydroxyindoleacetic acid ; Monoamine oxidase A ; PANSS scale
Published in:	Journal of neuroinflammation, Vol. 18 (September 2021) , art. 198, ISSN 1742-2094

DOI: 10.1186/s12974-021-02260-6
PMID: 34511126

15 p, 1.7 MB

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