PMID- 34054556
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210601
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Paliperidone Reversion of Maternal Immune Activation-Induced Changes on Brain 
      Serotonin and Kynurenine Pathways.
PG  - 682602
LID - 10.3389/fphar.2021.682602 [doi]
LID - 682602
AB  - Emerging evidence indicates that early-life exposure to environmental factors may 
      increase the risk for schizophrenia via inflammatory mechanisms. Inflammation can 
      alter the metabolism of tryptophan through the oxidative kynurenine pathway to 
      compounds with neurotoxic and neuroprotective activity and compromise serotonin 
      (5-HT) synthesis. Here we investigate the role of serotonergic and kynurenine 
      pathways in the maternal immune activation (MIA) animal model of schizophrenia. 
      The potential reversion exerted by long-term antipsychotic treatment was also 
      evaluated. MIA was induced by prenatal administration of 
      polyinosinic:polycytidylic acid (poly (I:C)) in mice. Expression of different 
      proteins and the content of different metabolites involved in the function of 
      serotonergic and kynurenine pathways was assessed by RT-PCR, immunoblot and ELISA 
      analyses in frontal cortex of the offspring after puberty. MIA decreased tissue 
      5-HT content and promoted changes in the expression of serotonin transporter, 
      5-HT(2A) and 5-HT(2C) receptors. Expression of indoleamine 2,3-dioxygenase 2 
      (IDO2) and kynurenine 3-monooxygenase (KMO) was increased by poly (I:C) whereas 
      kynurenine aminotransferase II and its metabolite kynurenic acid were not 
      altered. Long-term paliperidone was able to counteract MIA-induced changes in 
      5-HT and KMO, and to increase tryptophan availability and tryptophan 
      hydroxylase-2 expression in poly (I:C) mice but not in controls. MIA-induced 
      increase of the cytotoxic risk ratio of kynurenine metabolites 
      (quinolinic/kynurenic acid) was also reversed by paliperidone. MIA induces 
      specific long-term brain effects on serotonergic activity. Such effects seem to 
      be related with alternative activation of the kynurenine metabolic pathway 
      towards a cytotoxic status. Atypical antipsychotic paliperodine partially 
      remediates abnormalities observed after MIA.
CI  - Copyright (c) 2021 MacDowell, Munarriz-Cuezva, Meana, Leza and Ortega.
FAU - MacDowell, Karina S
AU  - MacDowell KS
AD  - Department of Pharmacology and Toxicology, Faculty of Medicine, University 
      Complutense of Madrid (UCM), Madrid, Spain.
AD  - Centro de Investigacion Biomedica en Red de Salud Mental CIBERSAM, Bizkaia, 
      Madrid, Spain.
AD  - Instituto de Investigacion Hospital 12 de Octubre (i+12), IUIN-UCM, Madrid, 
      Spain.
FAU - Munarriz-Cuezva, Eva
AU  - Munarriz-Cuezva E
AD  - Centro de Investigacion Biomedica en Red de Salud Mental CIBERSAM, Bizkaia, 
      Madrid, Spain.
AD  - Department of Pharmacology, University of the Basque Country UPV/EHU, Leioa, 
      Bizkaia, Spain.
FAU - Meana, J Javier
AU  - Meana JJ
AD  - Centro de Investigacion Biomedica en Red de Salud Mental CIBERSAM, Bizkaia, 
      Madrid, Spain.
AD  - Department of Pharmacology, University of the Basque Country UPV/EHU, Leioa, 
      Bizkaia, Spain.
AD  - Biocruces Bizkaia Health Research Institute, Barakaldo, Bizkaia, Spain.
FAU - Leza, Juan C
AU  - Leza JC
AD  - Department of Pharmacology and Toxicology, Faculty of Medicine, University 
      Complutense of Madrid (UCM), Madrid, Spain.
AD  - Centro de Investigacion Biomedica en Red de Salud Mental CIBERSAM, Bizkaia, 
      Madrid, Spain.
AD  - Instituto de Investigacion Hospital 12 de Octubre (i+12), IUIN-UCM, Madrid, 
      Spain.
FAU - Ortega, Jorge E
AU  - Ortega JE
AD  - Centro de Investigacion Biomedica en Red de Salud Mental CIBERSAM, Bizkaia, 
      Madrid, Spain.
AD  - Department of Pharmacology, University of the Basque Country UPV/EHU, Leioa, 
      Bizkaia, Spain.
AD  - Biocruces Bizkaia Health Research Institute, Barakaldo, Bizkaia, Spain.
LA  - eng
PT  - Journal Article
DEP - 20210513
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8156415
OTO - NOTNLM
OT  - atypical antipsychotics
OT  - kynurenine
OT  - maternal immune activation
OT  - polyinosinic:polycytidylic acid (poly(I:C))
OT  - schizophrenia
OT  - serotonin
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/06/01 06:00
MHDA- 2021/06/01 06:01
PMCR- 2021/05/13
CRDT- 2021/05/31 06:07
PHST- 2021/03/18 00:00 [received]
PHST- 2021/04/30 00:00 [accepted]
PHST- 2021/05/31 06:07 [entrez]
PHST- 2021/06/01 06:00 [pubmed]
PHST- 2021/06/01 06:01 [medline]
PHST- 2021/05/13 00:00 [pmc-release]
AID - 682602 [pii]
AID - 10.3389/fphar.2021.682602 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 May 13;12:682602. doi: 10.3389/fphar.2021.682602. 
      eCollection 2021.