Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Neonatal Rotenone Administration Induces Psychiatric Disorder-Like Behavior and Changes in Mitochondrial Biogenesis and Synaptic Proteins in Adulthood

Texto completo
Autor(es):
Siena, Amanda [1, 2] ; Yuzawa, Jessica Mayumi Camargo [2] ; Ramos, Aline Camargo [3] ; Henrique, Elisandra [2] ; Brito, Mariana Dutra [2] ; Calvazara, Mariana Bendlin [4] ; Rosenstock, Tatiana Rosado [1, 5]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept Pharmacol, Sao Paulo - Brazil
[2] Santa Casa Sao Paulo Sch Med Sci, Sao Paulo - Brazil
[3] Univ Fed Sao Paulo, Sao Paulo - Brazil
[4] Fac Israelita Ciencias Saude Albert Einstein, Sao Paulo - Brazil
[5] Univ Birmingham, Inst Canc & Genom Sci, Coll Med & Dent Sci, Birmingham B15 2TT, W Midlands - England
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: Molecular Neurobiology; v. 58, n. 7, p. 3015-3030, JUL 2021.
Citações Web of Science: 1
Resumo

Since psychiatric disorders are associated with changes in the development of the nervous system, an energy-dependent mechanism, we investigated whether mitochondrial inhibition during the critical neurodevelopment window in rodents would be able to induce metabolic alterations culminating in psychiatric-like behavior. We treated male Wistar rat puppies (P) with rotenone (Rot), an inhibitor of mitochondrial complex I, from postnatal days 5 to 11 (P5-P11). We demonstrated that at P60 and P120, Rot-treated animals showed hyperlocomotion and deficits in social interaction and aversive contextual memory, features observed in animal models of schizophrenia, autism spectrum disorder, and attention deficit hyperactivity disorder. During adulthood, Rot-treated rodents also presented modifications in CBP and CREB levels in addition to a decrease in mitochondrial biogenesis and Nrf1 expression. Additionally, NFE2L2-activation was not altered in Rot-treated P60 and P120 animals; an upregulation of pNFE2L2/ NFE2L2 was only observed in P12 cortices. Curiously, ATP/ADP levels did not change in all ages evaluated. Rot administration in newborn rodents also promoted modification in Rest and Mecp2 expression, and in synaptic protein levels, named PSD-95, Synaptotagmin-1, and Synaptophysin in the adult rats. Altogether, our data indicate that behavioral abnormalities and changes in synaptic proteins in adulthood induced by neonatal Rot administration might be a result of adjustments in CREB pathways and alterations in mitochondrial biogenesis and Nrf1 expression, rather than a direct deficiency of energy supply, as previously speculated. Consequently, Rot-induced psychiatric-like behavior would be an outcome of alterations in neuronal paths due to mitochondrial deregulation. (AU)

Processo FAPESP: 16/12039-7 - A modulação de lisinas(K)-deacetilases e o seu papel no metabolismo, dinâmica e degradação mitocondrial: possível neuroproteção para a esclerose lateral amiotrófica
Beneficiário:Mariana Dutra Brito
Modalidade de apoio: Bolsas no Brasil - Mestrado
Processo FAPESP: 15/02041-1 - O papel das lisinas(K)-deacetilases para a neuroproteção de desordens mitocondriais: perspectivas de terapia epigenética para a esclerose lateral amiotrófica e esquizofrenia
Beneficiário:Tatiana Rosado Rosenstock
Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores