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oai:docta.ucm.es:20.500.14352/958622025-07-11T23:47:11Zcom_20.500.14352_14col_20.500.14352_15

Risperidone normalizes increased inflammatory parameters and restores anti-inflammatory pathways in a model of neuroinflammation Mac-Dowell Mata, Karina Soledad García Bueno, Borja Muñoz Madrigal, José Luis Parellada, Mara Arango López, Celso Micó, Juan A. Leza Cerro, Juan Carlos Parellada Redondo, María José 615.01 615.03 615.21 615.214 Antipsychotics LPS Neuroinflammation Risperidone Schizophrenia Ciencias Biomédicas 32 Ciencias Médicas Inflammation, caused by both external and endogenous factors, has been implicated as a main pathophysiological feature of chronic mental illnesses, including schizophrenia. An increase in pro-inflammatory cytokines has been described both in experimental models and in schizophrenia patients. However, not much is known about the effects that antipsychotic drugs have on intra- and intercellular mechanisms controlling inflammation. The aim of the present study was to investigate the possible anti-inflammatory effect of a standard schizophrenia treatment not only at the level of soluble mediators, but also at intra- and intercellular inflammatory pathways. The present study was conducted in a model of mild neuroinflammation using a lipopolysaccharide (LPS) challenge that was not an endotoxaemic dose (0.5 mg/kg i.p.) in young adult rats. Main results: single doses of risperidone (0.3–3.0 mg/kg i.p.) prevented increased inflammatory parameters induced by LPS in brain cortex [expression of inflammatory cytokines, interleukin (IL)-1β and tumour necrosis factor (TNF)-α, activity of the inducible inflammatory enzymes nitric oxide synthase and cyclooxygenase, p38 mitogen-activated protein kinase (MAPK) and inflammatory nuclear transcription factor κB] and restored anti-inflammatory pathways decreased by LPS challenge (deoxyprostaglandins and peroxisome proliferator activated receptor γ). This is the first study demonstrating that risperidone elicits a preventive effect on the anti-inflammatory arm of the homeostatic mechanism controlling inflammation in a model of mild encephalitis in rats. Our findings suggest a possible protective effect of risperidone on brain cells. Instituto de Salud Carlos III Ministerio de Ciencia e Innovación (España) Centro de Investigación Biomédica En Red de Salud Mental Depto. de Farmacología y Toxicología Depto. de Medicina Legal, Psiquiatría y Patología Fac. de Medicina TRUE pub 2024-01-29T10:45:39Z 2024-01-29T10:45:39Z 2013 journal article VoR https://hdl.handle.net/20.500.14352/95862 1469-5111 10.1017/s1461145711001775 1461-1457 eng FIS 10/123 MacDowell KS, García-Bueno B, Madrigal JL, Parellada M, Arango C, Micó JA, Leza JC. Risperidone normalizes increased inflammatory parameters and restores anti-inflammatory pathways in a model of neuroinflammation. Int J Neuropsychopharmacol. 2013 Feb;16(1):121-35. doi: 10.1017/S1461145711001775. PMID: 22176740. restricted access application/pdf Oxford University Press