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 MacDowell, Karina S.
A1 Perez-Caballero, Laura
A1 Torres Sánchez, Sonia
A1 Fraguas, David
A1 Berrocoso Domínguez, Esther María
A1 Leza, Juan Carlos
A1 Arango, C.
A1 Desco, Manuel
A1 Soto-Montenegro, María Luisa
A2 Neurociencias
A2 Psicología
K1 Dopamine antagonist
K1 FDG-PET
K1 Inflammation/oxidonitrosative stress
K1 Poly I:C
K1 Risperidone
K1 Schizophrenia
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 http://hdl.handle.net/10498/34782
UL http://hdl.handle.net/10498/34782
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 09-nov-2026