Sex influences in the preventive effects of peripubertal supplementation with N-3 polyunsaturated fatty acids in mice exposed to the two-hit model of schizophrenia.

Autor: da Costa AEM; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil., Gomes NS; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil., Gadelha Filho CVJ; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil., Linhares MGOES; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil., da Costa RO; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil., Chaves Filho AJM; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil., Cordeiro RC; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil., Vasconcelos GS; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil., da Silva FER; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil., Araujo TDS; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil., Vasconcelos SMM; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil., Lucena DF; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil., Macêdo DS; Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil; National Institute for Translational Medicine (INCT-TM, CNPq), Ribeirão Preto, SP, Brazil. Electronic address: danielle.macedo@ufc.br.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2021 Apr 15; Vol. 897, pp. 173949. Date of Electronic Publication: 2021 Feb 16.
DOI: 10.1016/j.ejphar.2021.173949
Abstrakt: Schizophrenia is a devastating neurodevelopmental disorder. The animal model based on perinatal immune activation, as first-hit, combined with peripubertal stress, as a second hit, has gained evidence in recent years. Omega-3 polyunsaturated fatty acids (n3-PUFAs) is being a promise for schizophrenia prevention. Nevertheless, the influence of sex in schizophrenia neurobiology and prevention has been neglected. Thus, the present study evaluates the preventive effects of n3-PUFAs in both sexes' mice submitted to the two-hit model and the participation of oxidative changes in this mechanism. The two-hit consisted of polyI:C administration from postnatal days (PNs) 5-7, and unpredictable stress from PNs35-43. n3-PUFAs were administered from PNs30-60. Prepulse inhibition of the startle reflex (PPI), social interaction, and Y-maze tests were conducted between PNs70-72 to evaluate positive-, negative-, and cognitive-like schizophrenia symptoms. We assessed brain oxidative changes in brain areas and plasma. Both sexes' two-hit mice presented deficits in PPI, social interaction, and working memory that were prevented by n3-PUFAs. In two-hit females, n3-PUFAs prevented increments in nitrite levels in the prefrontal cortex (PFC), hippocampus, striatum, and plasma TBARS levels. In two-hit males, n3-PUFAs prevented the increase in TBARS in the PFC, hippocampus, and striatum. Notably, male mice that received only n3-PUFAs without hit exposure presented impairments in working memory and social interaction. These results add further preclinical evidence for n3-PUFAs as an accessible and effective alternative in preventing behavioral and oxidative changes related to schizophrenia but call attention to the need for precaution in this indication due to hit- and sex-sensitive issues.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE