RT Journal Article
T1 Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology
A1 Ben Afia, Amira
A1 Vila, Èlia
A1 Ormazabal, Aida
A1 Haro, Josep M.
A1 Artuch, Rafael
A1 Ramos, Belén
A1 Mac-Dowell Mata, Karina Soledad
A1 Leza Cerro, Juan Carlos
A1 García Bueno, Borja
AB 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.
PB BioMed Central
SN 1742-2094
YR 2021
FD 2021-09-12
LK https://hdl.handle.net/20.500.14352/96775
UL https://hdl.handle.net/20.500.14352/96775
LA eng
NO Afia 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.
NO MINECO-FEDER
NO Instituto de Salud Carlos III
NO ERDF
NO CIBERSAM
DS Docta Complutense
RD 18 jul 2024