PMID- 37939988
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20231216
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 961
DP  - 2023 Dec 15
TI  - The PPARalpha agonist fenofibrate reduces the cytokine imbalance in a maternal immune 
      activation model of schizophrenia.
PG  - 176172
LID - S0014-2999(23)00686-6 [pii]
LID - 10.1016/j.ejphar.2023.176172 [doi]
AB  - Maternal infections during pregnancy may increase the risk of psychiatric 
      disorders in offspring. We recently demonstrated that activation of peroxisome 
      proliferator-activate receptor-alpha (PPARalpha), with the clinically available agonist 
      fenofibrate (FEN), attenuates the neurodevelopmental disturbances induced by 
      maternal immune activation (MIA) in rat offspring. We hypothesized that 
      fenofibrate might reduce MIA-induced cytokine imbalance using a MIA model based 
      on the viral mimetic polyriboinosinic-polyribocytidilic acid [poly (I:C)]. By 
      using the Bio-Plex Multiplex-Immunoassay-System, we measured 
      cytokine/chemokine/growth factor levels in maternal serum and in the fetal brain 
      of rats treated with fenofibrate, at 6 and 24 h after poly (I:C). We found that 
      MIA induced time-dependent changes in the levels of several 
      cytokines/chemokines/colony-stimulating factors (CSFs). Specifically, the 
      maternal serum of the poly (I:C)/control (CTRL) group showed increased levels of 
      (i) proinflammatory chemokine macrophage inflammatory protein 1-alpha (MIP-1alpha), 
      (ii) tumor necrosis factor-alpha (TNF-alpha), the monocyte chemoattractant protein-1 
      (MCP-1), the macrophage (M-CSF) and granulocyte-macrophage colony-stimulating 
      factor (GM-CSF). Conversely, in the fetal brain of the poly (I:C)/CTRL group, 
      interleukin 12p70 and MIP-1alpha levels were lower than in vehicle (veh)/CTRL group. 
      Notably, MIP-1alpha, TNF-alpha, keratinocyte derived chemokine (GRO/KC), GM-CSF, and 
      M-CSF levels were lower in the poly (I:C)/FEN than in poly (I:C)/CTRL rats, 
      suggesting the protective role of the PPARalpha agonist. PPARalpha might represent a 
      therapeutic target to attenuate MIA-induced inflammation.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Mostallino, Rafaela
AU  - Mostallino R
AD  - Department of Biomedical Sciences, University of Cagliari, 09042, Monserrato, 
      Italy.
FAU - Santoni, Michele
AU  - Santoni M
AD  - Department of Biomedical Sciences, University of Cagliari, 09042, Monserrato, 
      Italy.
FAU - Sagheddu, Claudia
AU  - Sagheddu C
AD  - Department of Biomedical Sciences, University of Cagliari, 09042, Monserrato, 
      Italy.
FAU - Serra, Valentina
AU  - Serra V
AD  - Institute for Genetic and Biomedical Research, National Research Council (CNR), 
      Lanusei, Italy.
FAU - Orru, Valeria
AU  - Orru V
AD  - Institute for Genetic and Biomedical Research, National Research Council (CNR), 
      Lanusei, Italy.
FAU - Pistis, Marco
AU  - Pistis M
AD  - Department of Biomedical Sciences, University of Cagliari, 09042, Monserrato, 
      Italy; Neuroscience Institute, National Research Council of Italy, Section of 
      Cagliari, Italy; Unit of Clinical Pharmacology, University Hospital, Cagliari, 
      Italy. Electronic address: mpistis@unica.it.
FAU - Castelli, M Paola
AU  - Castelli MP
AD  - Department of Biomedical Sciences, University of Cagliari, 09042, Monserrato, 
      Italy. Electronic address: castelli@unica.it.
LA  - eng
PT  - Journal Article
DEP - 20231106
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Cytokines)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - 0 (Chemokine CCL3)
RN  - U202363UOS (Fenofibrate)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - 0 (PPAR alpha)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Chemokines)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Humans
MH  - Female
MH  - Pregnancy
MH  - Rats
MH  - Animals
MH  - Cytokines
MH  - Granulocyte-Macrophage Colony-Stimulating Factor
MH  - Chemokine CCL3
MH  - *Fenofibrate/pharmacology/therapeutic use
MH  - Macrophage Colony-Stimulating Factor
MH  - PPAR alpha
MH  - *Schizophrenia/drug therapy
MH  - Tumor Necrosis Factor-alpha
MH  - Chemokines
MH  - Poly I-C/pharmacology
OTO - NOTNLM
OT  - Chemokines
OT  - Colony-stimulating factors
OT  - Cytokines
OT  - MIA
OT  - Neurodevelopmental disorders
OT  - Poly (I:C)
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that might have appeared 
      to influence the work reported in this paper.
EDAT- 2023/11/09 00:42
MHDA- 2023/12/17 13:19
CRDT- 2023/11/08 19:18
PHST- 2023/07/28 00:00 [received]
PHST- 2023/10/27 00:00 [revised]
PHST- 2023/10/30 00:00 [accepted]
PHST- 2023/12/17 13:19 [medline]
PHST- 2023/11/09 00:42 [pubmed]
PHST- 2023/11/08 19:18 [entrez]
AID - S0014-2999(23)00686-6 [pii]
AID - 10.1016/j.ejphar.2023.176172 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2023 Dec 15;961:176172. doi: 10.1016/j.ejphar.2023.176172. Epub 
      2023 Nov 6.