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Comparative Examination of Temporal Glyoxalase 1 Variations Following Perforant Pathway Transection, Excitotoxicity, and Controlled Cortical Impact Injury

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Abstract

Following acute neuronal lesions, metabolic imbalance occurs, the rate of glycolysis increases, and methylglyoxal (MGO) forms, finally leading to metabolic dysfunction and inflammation. The glyoxalase system is the main detoxification system for MGO and is impaired following excitotoxicity and stroke. However, it is not known yet whether alterations of the glyoxalase system are also characteristic for other neuronal damage models. Neuronal damage was induced in organotypic hippocampal slice cultures by transection of perforant pathway (PPT; 5 min to 72 h) and N-methyl-d-aspartate (NMDA; 50 μM for 4 h) or in vivo after controlled cortical impact (CCI) injury (2 h to 14 days). Temporal and spatial changes of glyoxalase I (GLO1) were investigated by Western blot analyses and immunohistochemistry. In immunoblot, the GLO1 protein content was not significantly affected by PPT at all investigated time points. As described previously, NMDA treatment led to a GLO1 increase 24 and 48 h after the lesion, whereas PPT increased GLO1 immunoreactivity within neurons only at 48 h postinjury. Immunohistochemistry of brain tissue subjected to CCI unveiled positive GLO1 immunoreactivity in neurons and astrocytes at 1 and 3 days after injury. Two hours and 14 days after CCI, no GLO1 immunoreactivity was observed. GLO1 protein content changes are associated with excitotoxicity but seemingly not to fiber transection. Cell-specific changes in GLO1 immunoreactivity after different in vitro and in vivo lesion types might be a common phenomenon in the aftermath of neuronal lesions.

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Author notes

  1. Daniel-Christoph Wagner

    Present address: Institute for Pathology, Langenbeckstrasse 1, 55131, Mainz, Germany

Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06097, Halle, Saale, Germany

    Philipp Pieroh, Mojgan Dabbagh Nazari, Chalid Ghadban & Faramarz Dehghani

  2. Department of Orthopedics, Trauma and Plastic Surgery, University of Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany

    Philipp Pieroh

  3. Fraunhofer Institute for Cell Therapy and Immunology, Perlickstrasse 1, 04107, Leipzig, Germany

    Daniel-Christoph Wagner

  4. Institute for Neurosurgical Pathophysiology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131, Mainz, Germany

    Beat Alessandri & Mojgan Dabbagh Nazari

  5. Institute of Anatomy, University of Leipzig, Liebigstrasse 13, 04103, Leipzig, Germany

    Angela Ehrlich & Constance Hobusch

  6. Department of Biochemistry, University of Leipzig, Johannisallee 30, 04107, Leipzig, Germany

    Gerd Birkenmeier

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Contributions

P.P., G.B., and F.D. conceived and designed the experiments; P.P., B.A., M.D.-N., A.E, C.G., and C.H. performed the experiments; P.P., D-C.W., G.B., and F.D. analyzed the data; B.A., M.D.-N., D-C.W., J.B., G.B., and F.D contributed reagents/materials/analysis tools; P.P., B.A., D-C.W., G.B., and F.D wrote the paper.

Corresponding author

Correspondence to Faramarz Dehghani.

Ethics declarations

All animal experiments were performed in accordance with the Policy on Ethics and the Policy on the Use of Animals in Neuroscience Research as indicated in the directive 2010/63/EU of the European Parliament and of the Council of the European Union on the protection of animals used for scientific purposes. The local authorities approved controlled cortical impact experiments for care and use of laboratory animals (State of Rhineland-Palatinate: 1.5 177-07/051-31), and experiments were performed under all efforts to minimize suffering.

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The authors declare that they have no conflict of interest.

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Pieroh, P., Wagner, DC., Alessandri, B. et al. Comparative Examination of Temporal Glyoxalase 1 Variations Following Perforant Pathway Transection, Excitotoxicity, and Controlled Cortical Impact Injury. Neurotox Res 33, 412–421 (2018). https://doi.org/10.1007/s12640-017-9808-8

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