Rapid astroglial stress response and elevation of endogenous BiP levels promote neuronal survival in hippocampal slice cultures
1 Institute of Anatomy, Department of Molecular Embryology, Medical Faculty, University of Freiburg, Freiburg, Germany.
2 Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Medical Faculty, University of Freiburg, Freiburg 79104, Germany.
3 Institute of Neuroanatomical, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
4 Max-Planck-Institute for Immunology and Epigenetics, Stübeweg 51, 79108 Freiburg, Germany.
5 Research Centre for Infectious Diseases, Department of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, 5005, Australia.
6 Institute of Anatomy II, University of Cologne, Faculty of Medicine, Cologne, Germany.
7 Center of Basics in NeuroModulation (NeuroModulBasics), Medical Faculty, University of Freiburg, Freiburg, Germany.
Research Article
World Journal of Biology Pharmacy and Health Sciences, 2021, 07(02), 019–031.
Article DOI: 10.30574/wjbphs.2021.7.2.0078
Publication history:
Received on 24 June 2021; revised on 27 July 2021; accepted on 29 July 2021
Abstract:
A hallmark of neurodegenerative diseases is the accumulation of protein aggregates, the formation of which is prevented by chaperone proteins. BiP is the central chaperone in the endoplasmic reticulum. In this study we investigated the pattern of BiP in tunicamycin-stressed murine organotypic hippocampal slice cultures (OHCs). In stressed OHCs highest apoptotic rates occur in neurons of the CA1 regions and the dentate gyrus, in which we found BiP levels to be lowest. Highest BiP protein levels were found in astrocytes. Cell culture experiments indicated that the stress response of glial cells is faster and stronger than in neuronal cells. We hypothesize that the rapid and pronounced BiP expression in astrocytes helps to maintain the fine-balanced micromilieu necessary for survival of neurons. SubAB is a toxin, which cleaves and inactivates BiP. Low dosages of SubAB did not elicit a specific glial response and apoptosis was not induced in a specific hippocampal subfield. Mild prestressing with SubAB promoted neuronal viability in tunicamycin-treated OHCs. We conclude that preconditioning of hippocampal tissue with stressors that elevate endogenous chaperone levels exert a protective effect thereby promoting neuronal survival. These experiments strengthen the thesis that preconditoning with mild stressors positively affects the survival of neuronal cells.
Keywords:
Chaperone; Organotypic hippocampal slice cultures; Neuronal survival; Astrocytes; Tunicamycin
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