Behavioral and metabolic effects of the atypical antipsychotic ziprasidone on the nematode Caenorhabditis elegans.
Atypical antipsychotics are associated with metabolic syndrome, primarily associated with weight gain. The effects of Ziprasidone, an atypical antipsychotic, on metabolic syndrome has yet to be evaluated. Here in, we evaluated lipid accumulation and behavioral changes in a new experimental model, the nematode Caenorhabditis elegans (C. elegans). Behavioral parameters in the worms were evaluated 24 h after Ziprasidone treatment. Subsequently, lipid accumulation was examined using Nile red, LipidTox green and BODIPY labeling. Ziprasidone at 40 µM for 24 h effectively decreased the fluorescence labeling of all markers in intestinal cells of C. elegans compared to control (0.16% dimethyl sulfoxide). Ziprasidone did not alter behaviors related to energetic balance, such as pharynx pumping, defecation cycles and movement. There was, however, a reduction in egg-production, egg-laying and body-length in nematodes exposed to Ziprasidone without any changes in the progression of larval stages. The serotoninergic pathway did not appear to modulate Ziprasidone's effects on Nile red fluorescence. Additionally, Ziprasidone did not alter lipid accumulation in daf-16 or crh-1 deletion mutants (orthologous of the transcription factors DAF-16 and CREB, respectively). These results suggest that Ziprasidone alters reproductive behavior, morphology and lipid reserves in the intestinal cells of C. elegans. Our results highlight that the DAF-16 and CREB transcription factors are essential for Ziprasidone-induced fat store reduction.
INCT de Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Priscila
P
Gubert
Gabriel Costa
GC
Aguiar
Tácito
T
Mourão
Jessika Cristina
JC
Bridi
Alexandre Guimarães
AG
Barros
Félix Alexandre
FA
Soares
Marco Aurélio
MA
Romano-Silva
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D020869:Gene Expression Profiling; D050356:Lipid Metabolism / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone