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Low-dose candesartan prevents schizophrenia-like behavioral alterations in a neurodevelopmental two-hit model of schizophrenia

Vasconcelos, Germana Silva ; dos Santos Júnior, Manuel Alves ; Monte, Aline Santos ; da Silva, Francisco Eliclécio Rodrigues ; Lima, Camila Nayane de Carvalho ; Moreira Lima Neto, Abelardo Barbosa ; Medeiros, Ingridy da Silva ; Teixeira, Antonio Lucio ; de Lucena, David Freitas ; Vasconcelos, Silvânia Maria Mendes ; Macedo, Danielle S.

Progress in neuro-psychopharmacology & biological psychiatry, 2021-12, Vol.111, p.110348-110348, Article 110348 [Periódico revisado por pares]

England: Elsevier Inc

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Título:
Low-dose candesartan prevents schizophrenia-like behavioral alterations in a neurodevelopmental two-hit model of schizophrenia
Autor: Vasconcelos, Germana Silva ; dos Santos Júnior, Manuel Alves ; Monte, Aline Santos ; da Silva, Francisco Eliclécio Rodrigues ; Lima, Camila Nayane de Carvalho ; Moreira Lima Neto, Abelardo Barbosa ; Medeiros, Ingridy da Silva ; Teixeira, Antonio Lucio ; de Lucena, David Freitas ; Vasconcelos, Silvânia Maria Mendes ; Macedo, Danielle S.
Assuntos: Angiotensin II Type 1 Receptor Blockers - administration & dosage ; Animals ; AT1 receptor ; Benzimidazoles - administration & dosage ; Biphenyl Compounds - administration & dosage ; Candesartan ; Disease Models, Animal ; Female ; Hippocampus - drug effects ; Interleukin-1beta - metabolism ; Lipid Peroxidation ; Male ; Mice ; Neuroprotective Agents ; Poly I-C ; Pregnancy ; Receptor, Angiotensin, Type 1 - drug effects ; Schizophrenia ; Schizophrenia - chemically induced ; Sex difference ; Sex Factors ; Tetrazoles - administration & dosage ; Tumor Necrosis Factor-alpha - metabolism
É parte de: Progress in neuro-psychopharmacology & biological psychiatry, 2021-12, Vol.111, p.110348-110348, Article 110348
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SourceType-Scholarly Journals-1
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Descrição: Schizophrenia is a severe mental disorder with complex etiopathogenesis. Based on its neurodevelopmental features, an animal model induced by “two-hit” based on perinatal immune activation followed by peripubertal unpredictable stress was proposed. Sex influences the immune response, and concerning schizophrenia, it impacts the age of onset and symptoms severity. The neurobiological mechanisms underlying the influence of sex in schizophrenia is poorly understood. Our study aimed to evaluate sex influence on proinflammatory and oxidant alterations in male and female mice exposed to the two-hit model of schizophrenia, and its prevention by candesartan, an angiotensin II type 1 receptor (AT1R) blocker with neuroprotective properties. The two-hit model induced schizophrenia-like behavioral changes in animals of both sexes. Hippocampal microglial activation alongside the increased expression of NF-κB, and proinflammatory cytokines, namely interleukin (IL)-1β and TNF-α, were observed in male animals. Conversely, females presented increased hippocampal and plasma levels of nitrite and plasma lipid peroxidation. Peripubertal administration of low-dose candesartan (0.3 mg/kg PO) prevented behavioral, hippocampal, and systemic changes in male and female mice. While these results indicate the influence of sex on inflammatory and oxidative changes induced by the two-hit model, candesartan was effective in both males and females. The present study advances the neurobiological mechanisms underlying sex influence in schizophrenia and opens new avenues to prevent this devasting mental disorder. •The two-hit model induced schizophrenia-like behavioral changes in both sexes' animals.•Male two-hit mice had hippocampal microglial activation and high levels of pro-inflammatory cytokines.•Low-dose candesartan peripubertal administration prevented behavioral changes induced by two-hit.•Low-dose candesartan prevented hippocampal and systemic changes in male and female mice.
Editor: England: Elsevier Inc
Idioma: Inglês

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Low-dose candesartan prevents schizophrenia-like behavioral alterations in a neurodevelopmental two-hit model of schizophrenia

England: Elsevier Inc

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