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da Costa, Ayane Edwiges Moura; Gomes, Nayana Soares; Gadelha Filho, Carlos Venício Jatai; Linhares, Maria Gabrielle Oliveira e Silva; da Costa, Roberta Oliveira; Chaves Filho, Adriano José Maia; Cordeiro, Rafaela Carneiro; Vasconcelos, Germana Silva; da Silva, Francisco Eliclécio Rodrigues; Araujo, Tatiane da Silva; Vasconcelos, Silvânia Maria Mendes; Lucena, David Freitas; Macêdo, Danielle S.
European journal of pharmacology, 04/2021, Letnik: 897Journal Article
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. •N3–PUFAs peripubertal administration prevents schizophrenia symptoms in the two-hit model.•Male mice administered N3–PUFAs and not exposed to the two-hit model presented memory and social impairments.•Sex influenced the oxidative alterations observed in the two-hit model.•N3–PUFAs preventive effects against two-hit oxidative alterations were brain area- and sex-related.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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