Roles of c-Fos, EGR-1, PKA, and PKC in cognitive dysfunction in rats after propofol anesthesia

Authors

  • Xuena Zhang Department of Anesthesiology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China
  • Yun Yue Department of Anesthesiology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China
  • Anshi Wu Department of Anesthesiology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China

DOI:

https://doi.org/10.1590/s2175-97902022e18807

Keywords:

Propofol, Hippocampus, c-Fos, EGR-1, PKA, PKC

Abstract

This study aimed to investigate possible changes in the spatial memory of rats and the expression or activity of EGR-1, c-Fos, PKA, and PKC after propofol anesthesia. Thirty-six Sprague-Dawley rats aged 20 months and 36 Sprague-Dawley rats aged three months were each randomly divided into three groups: the control group, the Morris Water Maze (MWM) group, and the propofol group. In the propofol groups of both young and aged rats, the rats were anesthetized by propofol for two or four hours and then performed the MWM test two days or two weeks after anesthesia to assess cognitive function. EGR-1, c-Fos, PKA, and PKC expressions in the rat hippocampus were determined via immunohistochemistry. For the older rats, the escape latency in the P4h/2d group was significantly prolonged (P < 0.05), and the learning curve was right-shifted in the P4h/2w group (P < 0.05). The expression levels of EGR-1, c-Fos, PKA, and PKC in the MWM groups were significantly higher than those in the control groups (P < 0.05). In the P4h/2d group of aged rats, the expression levels of both PKA and PKC were decreased compared with those of the MWM groups. The decreased expression of both protein kinases may be responsible for the observed impairment after propofol anesthesia.

Downloads

Download data is not yet available.

References

Arya A, Gangwar A, Singh SK, Roy M, Das M, Sethy NK, et al. Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK-PKC-CBP signaling cascade. Int J Nanomed. 2016,11:1159-73.

Besnard A, Galan-Rodriguez B, Vanhoutte P, Caboche J. Elk-1 a transcription factor with multiple facets in the brain. Front Neurosci. 2011;5:35.

Boehm J, Kang MG, Johnson RC, Esteban J, Huganir RL, Malinow R. Synaptic incorporation of AMPA receptors during LTP is controlled by a PKC phosphorylation site on GluR1. Neuron. 2006;51(2):213-25.

Carter SD, Mifsud KR, Reul JM. Distinct epigenetic and gene expression changes in rat hippocampal neurons after Morris water maze training. Front Behav Neurosci. 2015;9:156.

Colombo PJ, Gallagher M. Individual differences in spatial memory among aged rats are related to hippocampal PKC gamma immunoreactivity. Hippocampus. 2002;12(2):285-9.

Han D, Jin J, Fang H, Xu G. Long-term action of propofol on cognitive function and hippocampal neuroapoptosis in neonatal rats. Int J Clin Exp Med. 2015;8(7):10696-704.

Kidambi S, Yarmush J, Berdichevsky Y, Kamath S, Fong W, Schianodicola J. Propofol induces MAPK/ERK cascade dependent expression of c-Fos and Egr-1 in rat hippocampal slices. BMC Res Notes. 2010;3:201.

Li M1, Zhang X, Wu A, Wang Z, Li J, Yue Y. Propofol- induced age-different hypocampal long-term potentiation is associated with F-actin polymerization in rats. Cell Biochem Biophys. 2015;71(2):1059-66.

Liu RY, Neveu C, Smolen P, Cleary LJ, Byrne JH. Superior long-term synaptic memory induced by combining dual pharmacological activation of PKA and ERK with an enhanced training protocol. Learn Mem. 2017;24(7):289-297.

Narita M, Imai S, Oe K, Narita M, Kubota C, Yajima Y, et al. Induction of c-fos expression in the mouse brain associated with hyperalgesia induced by intrathecal injection of protein kinase C activator. Brain Res. 2004;1015(1-2):189-93.

Rodríguez-Durán LF, Escobar ML. NMDA receptor activation and PKC but not PKA lead to the modification of the long-term potentiation in the insular cortex induced by conditioned taste aversion: differential role of kinases in metaplasticity. Behav Brain Res . 2014;266:58-62.

Russo R, Cattaneo F, Lippiello P, Cristiano C, Zurlo F, Castaldo M, et al. Motor coordination and synaptic plasticity deficits are associated with increased cerebellar activity of NADPH oxidase, CAMKII, and PKC at preplaque stage in the TgCRND8 mouse model of Alzheimer’s disease. Neurobiol Aging. 2018;68:123-133.

Sacai H, Sasaki-Hamada S, Sugiyama A, Saitoh A, Mori K, Yamada M, et al. The impairment in spatial learning and hippocampal LTD induced through the PKA pathway in juvenile-onset diabetes rats are rescued by modulating NMDA receptor function. Neurosci Res. 2014;81-82:55-63.

Schoen J, Husemann L, Tiemeyer C, Lueloh A, Sedemund- Adib B, Berger K-U, et al. Cognitive function after sevoflurane- vs propofol-based anaesthesia for on-pump cardiac surgery: a randomized controlled trial. Br J Anaesth. 2011;106(6):840-50.

Simpson CS, Morris BJ. Induction of c-fos and zif/268 gene expression in rat striatal neurons, following stimulation of D1-like dopamine receptors, involves protein kinase A and protein kinase C. Neuroscience. 1995;68(1):97-106.

Tachibana S, Hayase T, Osuda M, Kazuma S, Yamakage M. Recovery of postoperative cognitive function in elderly patients after a long duration of desflurane anesthesia: a pilot study. J Anesth. 2015;29(4):627-30.

Takigami S, Sunada H, Lukowiak K, Kuzirian AM, Alkon DL, Sakakibara M. Protein kinase C mediates memory consolidation of taste avoidance conditioning in Lymnaea stagnalis. Neurobiol Learn Mem . 2014;111:9-18.

Vitolo OV, Sant’Angelo A, Costanzo V, Battaglia F, Arancio O, Shelanski M. Amyloid beta -peptide inhibition of the PKA/ CREB pathway and long-term potentiation: reversibility by drugs that enhance cAMP signaling. Proc Natl Acad Sci U S A. 2002;99(20):13217-21.

Waltereit R, Weller M. Signalingfrom cAMP/PKAto MAPKand synaptic plasticity. Mol Neurobiol. 2003;27(1):99-106.

Zhang X, Liu Y, Feng C, Yang S, Wang Y, Wu A-S, et al. Proteomic profiling of the insoluble fractions in the rat hippocampus post-propofol anesthesia. Neurosci Lett. 2009;465(2):165-70.

Zhong Y, Chen J, Li L, Qin Y, Wei Y, Pan S, et al. PKA- CREB-BDNF signaling pathway mediates propofol-induced long-term learning and memory impairment in hippocampus of rats. Brain Res . 2018;1691:64-74.

Downloads

Published

2022-11-17

Issue

Section

Original Article

How to Cite

Roles of c-Fos, EGR-1, PKA, and PKC in cognitive dysfunction in rats after propofol anesthesia. (2022). Brazilian Journal of Pharmaceutical Sciences, 58. https://doi.org/10.1590/s2175-97902022e18807