RT Journal Article
T1 Paliperidone reverts Toll-like receptor 3 signaling pathway activation and cognitive deficits in a maternal immune activation mouse model of schizophrenia
A1 Mac-Dowell Mata, Karina Soledad
A1 Munarriz Cuezva, Eva
A1 Caso Fernández, Javier Rubén
A1 Muñoz Madrigal, José Luis
A1 Zabala, Arantzazu
A1 Meana, J. Javier
A1 García Bueno, Borja
A1 Leza Cerro, Juan Carlos
AB The pathophysiology of psychotic disorders is multifactorial, including alterations in the immune system caused by exogenous or endogenous factors. Epidemiological and experimental studies indicate that infections during the gestational period represent a risk factor to develop schizophrenia (SZ) along lifetime. Here, we tested the hypothesis that the antipsychotic paliperidone regulates immune-related brain effects in an experimental model of SZ. A well described prenatal immune activation model of SZ in mice by maternal injection of the viral mimetic poly(I:C) during pregnancy was used. Young-adult offspring animals (60PND) received paliperidone ip (0.05 mg/kg) for 21 consecutive days. One day after last injection, animals were submitted to a cognitive test and brain frontal cortex (FC) samples were obtained for biochemical determinations. The adults showed an activated innate immune receptor TLR-3 signaling pathway, oxidative/nitrosative stress and accumulation of pro-inflammatory mediators such as nuclear transcription factors (i.e., NFκB) and inducible enzymes (i.e., iNOS) in FC. Chronic paliperidone blocked this neuroinflammatory response possibly by the synergic activation and preservation of endogenous antioxidant/anti-inflammatory mechanisms such as NRF2 and PPARγ pathways, respectively. Paliperidone administration also stimulated the alternative polarization of microglia to the M2 anti-inflammatory profile. In addition, paliperidone treatment improved spatial working memory deficits of this SZ-like animal model. In conclusion, chronic administration of paliperidone to young-adult mice prenatally exposed to maternal immune (MIA) challenge elicits a general preventive anti-inflammatory/antioxidant effect at both intracellular and cellular polarization (M1/M2) level in FC, as well as ameliorates specific cognitive deficits.
PB Elsevier
SN 0028-3908
YR 2017
FD 2017-04
LK https://hdl.handle.net/20.500.14352/95925
UL https://hdl.handle.net/20.500.14352/95925
LA eng
NO MacDowell, K.S., Munarriz-Cuezva, E., Caso, J.R., Madrigal, J.L.M., Zabala, A., Meana, J.J., García-Bueno, B., Leza, J.C., Paliperidone reverts Toll-like receptor 3 signaling pathway activation and cognitive deficits in a maternal immune activation mouse model of schizophrenia, Neuropharmacology (2017), doi: 10.1016/j.neuropharm.2016.12.025.
NO Instituto de Salud Carlos III
NO MINECO
NO CIBERSAM
NO Basque Government
NO ERDF Funds
NO Fundación Santander-UCM
DS Docta Complutense
RD 18 mar 2026