Impact of anesthetics on rat hippocampus and neocortex: A comprehensive proteomic study based on label-free mass spectrometry
David Astapenko,
Marie Vajrychova,
Ivo Fabrik,
Rudolf Kupcik,
Kristyna Pimkova,
Vojtech Tambor,
Vera Radochova,
Vladimir Cerny
Affiliations
David Astapenko
Department of Anesthesiology and Intensive Care, University Hospital Hradec Kralove, Charles University, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic; Faculty of Health Sciences, Technical University in Liberec, Liberec, Czech Republic
Marie Vajrychova
Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic; Corresponding author. Biomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, 500 05, Hradec Kralove, Czech Republic.
Ivo Fabrik
Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
Rudolf Kupcik
Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
Kristyna Pimkova
Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic; Biocev, 1st Faculty of Medicine, Charles University in Prague, Czech Republic
Vojtech Tambor
Biomedical Research Center, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
Vera Radochova
Vivarium Department, Faculty of Military Health Sciences, University of Defence, Brno, Czech Republic
Vladimir Cerny
Department of Anesthesiology and Intensive Care, University Hospital Hradec Kralove, Charles University, Faculty of Medicine in Hradec Kralove, Hradec Kralove, Czech Republic; Dept. of Anesthesiology, Perioperative Medicine and Intensive Care, Hospital Bory, Bratislava, Slovak Republic
Anesthesia is regarded as an important milestone in medicine. However, the negative effect on memory and learning has been observed. In addition, the impact of anesthetics on postoperative cognitive functions is still discussed. In this work, in vivo experiment simulating a general anesthesia and ICU sedation was designed to assess the impact of two intravenous (midazolam, dexmedetomidine) and two inhalational (isoflurane, desflurane) agents on neuronal centers for cognition (neocortex), learning, and memory (hippocampus). More than 3600 proteins were quantified across both neocortex and hippocampus. Proteomic study revealed relatively mild effects of anesthetics, nevertheless, protein dysregulation uncovered possible different effect of isoflurane (and midazolam) compared to desflurane (and dexmedetomidine) to neocortical and hippocampal proteins. Isoflurane induced the upregulation of hippocampal NMDAR and other proteins of postsynaptic density and downregulation of GABA signaling, whereas desflurane and dexmedetomidine rather targeted mitochondrial VDAC isoforms and protein regulating apoptotic activity.