Regulation of monoamine levels by typical and atypical antipsychotics in Caenorhabditis elegans mutant for nuclear distribution element genes

Autor(es)

Campeiro, Joana D. `Arc ; Nani, V, Joap ; Monte, Gabriela G. ^[1] ; Almeida, Priscila G. C. ^[1] ; Mori, Marcelo A. ^[2] ; Hayashi, Mirian A. F. ^[1]

Afiliação do(s) autor(es)

^[1] Nani, Joap, V, Campeiro, Joana D. 'Arc, Univ Fed Sao Paulo UNIFESP, Escola Paulista Med EPM, Dept Pharmacol, Rua 3 Maio 100 Ed INFAR, 3rd Floor, BR-04044 Sao Paulo - Brazil

^[2] Univ Estadual Campinas UNICAMP, Inst Biol, Dept Biochem & Tissue Biol, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NEUROCHEMISTRY INTERNATIONAL; v. 147, JUL 2021.
• Citações Web of Science: 0

Resumo

Mammalian nuclear distribution genes encode proteins with essential roles in neuronal migration and brain formation during embryogenesis. The implication of human nuclear distribution genes, namely nudC and NDE1 (Nuclear Distribution Element 1)/NDEL1 (Nuclear Distribution Element-Like 1), in psychiatric disorders including schizophrenia and bipolar disorder, has been recently described. The partial loss of NDEL1 expression results in neuronal migration defects, while ndel1 null knockout (KO) leads to early embryonic lethality in mice. On the other hand, loss-of-function of the orthologs of nuclear distribution element genes (nud) in Caenorhabditis elegans renders viable worms and influences behavioral endophenotypes associated with dopaminergic and serotoninergic pathways. In the present work, we evaluated the role of nud genes in monoamine levels at baseline and after the treatment with typical or atypical antipsychotics. Dopamine, serotonin and octopamine levels were significantly lower in homozygous loss-of-function mutant worms KO for nud genes compared with wild-type (WT) C. elegans at baseline. While treatment with antipsychotics determined significant differences in monoamine levels in WT, the nud KO mutant worms appear to respond differently to the treatment. According to the best of our knowledge, we are the first to report the influence of nud genes in the monoamine levels changes in response to antipsychotic drugs, ultimately placing the nuclear distribution genes family at the cornerstone of pathways involved in the modulation of monoamines in response to different classes of antipsychotic drugs. (AU)

• Processo FAPESP: 19/09207-3 - Estudo do(s) mecanismo(s) molecular(es) e celular(es) em transtornos mentais
• Beneficiário: João Victor Silva Nani
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/02413-1 - Validação da crotamina como biomarcador e avaliação do seu potencial uso na terapia de doenças humanas
• Beneficiário: Mirian Akemi Furuie Hayashi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/13112-8 - Estudo dos mecanismos moleculares e celulares em transtornos mentais: estudos clínicos e modelos animais
• Beneficiário: Mirian Akemi Furuie Hayashi
• Modalidade de apoio: Auxílio à Pesquisa - Temático