Apoptosis-related genes induced in response to ketamine during early life stages of zebrafish. (5th September 2017)

• Record Type: Journal Article
• Authors: Félix, Luís M.; Serafim, Cindy; Valentim, Ana M.; Antunes, Luís M.; Matos, Manuela; Coimbra, Ana M.
• Is Part Of: Toxicology letters. Volume 279(2017)
• Page Start: 1
• Page End: 8
• Publication Date: 2017-09-05
• Subjects: Ketamine -- Gene expression -- Apoptosis -- Development -- Proliferation -- Zebrafish; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2017.07.888
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Changes in apoptotic and proliferation programs were stage-dependent. A cooperative mechanism between cellular death and proliferation is proposed for blastula exposure. The acquisition of apoptotic competence was related to apoptotic signals after gastrula exposure. Both p53-dependent and -independent pathways were associated with gastrula-induced apoptosis. After segmentation exposure, repair mechanisms appear to be activated. Abstract: Increasing evidence supports that ketamine, a widely used anaesthetic, potentiates apoptosis during development through the mitochondrial pathway of apoptosis. Defects in the apoptotic machinery can cause or contribute to the developmental abnormalities previously described in ketamine-exposed zebrafish. The involvement of the apoptotic machinery in ketamine-induced teratogenicity was addressed by assessing the apoptotic signals at 8 and 24 hpf following 20 min exposure to ketamine at three stages of early zebrafish embryo development (256 cell, 50% epiboly and 1–4 somites stages). Exposure at the 256-cell stage to ketamine induced an up-regulation of casp8 and pcna at 8 hpf while changes in pcna at the mRNA level were observed at 24 hpf. After the 50% epiboly stage exposure, the mRNA levels of casp9 were increased at 8 and 24 hpf while aifm1 was affected at 24 hpf. Both tp53 and pcna expressions were increased at 8 hpf. After exposure during the 1–4 somites stage, no meaningful changes on transcript levels were observed. The distribution of apoptotic cells and the caspase-like enzymatic activities of caspase-3 and -9 were not affected by ketamine exposure. It is proposed that ketamine exposure at the 256-cell stage induced a cooperative mechanism between proliferation and cellular death while following exposure at the 50% epiboly, a p53-dependent and -independent caspase activation may occur. Finally, at the 1–4 somites stage, the defence mechanisms are already fully in place to protect against ketamine-insult. Thus, ketamine teratogenicity seems to be dependent on the functional mechanisms present in each developmental stage.