4 years ago

Ketamine induces hippocampal apoptosis through a mechanism associated with the caspase-1 dependent pyroptosis

Ketamine, a pediatric anesthetic, is widely used in clinical practice. There was growing evidence showing that ketamine can promote neuronal death in developing brains of both humans and animals. In this study, we used in vivo neonatal and juvenile mouse models to induce ketamine-related neurotoxicity in the hippocampus. Active caspase-3 and -9 proteins, which are responsible for the release of cytochrome C, and the mitochondrial translocation of p53, which is associated with mitochondrial apoptosis, were found to be significantly up-regulated in the ketamine-induced hippocampal neurotoxicity. Furthermore, we demonstrated that the levels of pyroptosis-related proteins, including caspase-1 and -11, NOD-like receptor family, pyrin domain containing 3 (NLRP3), and IL-1β and IL-18, significantly increased after multiple doses of ketamine administration. We speculated that ketamine triggered the formation of NLRP3 and caspase-1 complex and its translocation to the mitochondria. In consistent with this, ketamine treatment was found to induce pyroptosis in mouse primary hippocampal neurons, which was characterized by increased pore formation and elevated lactate dehydrogenase release in mitochondria. Silencing caspase-1 with lentivirus-mediated short hairpin RNA (shRNA) significantly decreased the levels of not only pyroptosis-related proteins but also mitochondrial apoptosis-associated proteins in mouse primary hippocampal neurons. We conclude that caspase-1-dependent pyroptosis is an important event which may be an essential pathway involved in the mitochondria-associated apoptosis in ketamine-induced hippocampal neurotoxicity.

Publisher URL: www.sciencedirect.com/science

DOI: S0028390817304525

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.