RT Journal Article
T1 Risperidone administered during adolescence induced metabolic, anatomical and inflammatory/oxidative changes in adult brain: A PET and MRI study in the maternal immune stimulation animal model
A1 Casquero-Veiga, Marta
A1 García-García, David
A1 Pérez-Caballero, Laura
A1 Torres-Sánchez, Sonia
A1 Berrocoso, Esther
A1 Desco, Manuel
A1 Soto-Montenegro, María Luisa
A1 Mac-Dowell Mata, Karina Soledad
A1 Fraguas Herráez, David
A1 Leza Cerro, Juan Carlos
A1 Arango López, Celso
AB Inflammation and oxidative stress (IOS) are considered key pathophysiological elements in the development of mental disorders. Recent studies demonstrated that the antipsychotic risperidone elicits an antiinflammatory effect in the brain. We administered risperidone for 2-weeks at adolescence to assess its role in preventing brain-related IOS changes in the maternal immune stimulation (MIS) model at adulthood. We also investigated the development of volumetric and neurotrophic abnormalities in areas related to the HPA-axis. Poly I:C (MIS) or saline (Sal) were injected into pregnant Wistar rats on GD15. Male offspring received risperidone or vehicle daily from PND35-PND49. We studied 4 groups (8-15 animals/group): Sal-vehicle, MIS-vehicle, Sal-risperidone and MIS-risperidone. [18F]FDG-PET and MRI studies were performed at adulthood and analyzed using SPM12 software. IOS and neurotrophic markers were measured using WB and ELISA assays in brain tissue. Risperidone elicited a protective function of schizophrenia-related IOS deficits. In particular, risperidone elicited the following effects: reduced volume in the ventricles and the pituitary gland; reduced glucose metabolism in the cerebellum, periaqueductal gray matter, and parietal cortex; higher FDG uptake in the cingulate cortex, hippocampus, thalamus, and brainstem; reduced NFκB activity and iNOS expression; and increased enzymatic activity of CAT and SOD in some brain areas. Our study suggests that some schizophrenia-related IOS changes can be prevented in the MIS model. It also stresses the need to search for novel strategies based on anti-inflammatory compounds in risk populations at early stages in order to alter the course of the disease.
PB Elsevier
SN 0924-977X
YR 2019
FD 2019-07
LK https://hdl.handle.net/20.500.14352/96795
UL https://hdl.handle.net/20.500.14352/96795
LA eng
NO Casquero-Veiga M, García-García D, MacDowell KS, Pérez-Caballero L, Torres-Sánchez S, Fraguas D, Berrocoso E, Leza JC, Arango C, Desco M, Soto-Montenegro ML. Risperidone administered during adolescence induced metabolic, anatomical and inflammatory/oxidative changes in adult brain: A PET and MRI study in the maternal immune stimulation animal model. Eur Neuropsychopharmacol. 2019 Jul;29(7):880-896. doi: 10.1016/j.euroneuro.2019.05.002. PMID: 31229322.
NO Ministerio de Ciencia, Innovación y Universidades
NO Instituto de Salud Carlos III
NO CIBERSAM
NO ERDF
NO Delegación del Gobierno para el Plan Nacional sobre Drogas
NO Fundación Alicia Koplowitz
NO Madrid Regional Government
DS Docta Complutense
RD 18 jul 2024