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Cerebrolysin Alleviating Effect on Glutamate-Mediated Neuroinflammation Via Glutamate Transporters and Oxidative Stress

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Abstract

Glutamate, one of the most important excitatory neurotransmitters, acts as a signal transducer in peripheral tissues and endocrine cells. Excessive glutamate secretion has been shown to cause excitotoxicity and neurodegenerative disease. Cerebrolysin is a mixture of enzymatically treated peptides derived from pig brain including neurotrophic factors, like brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and ciliary neurotrophic factor (CNTF). The present study investigated the protective effects of cerebrolysin on glutamate transporters (EAAT 1, EAAT 2) and cytokines (IL-1β and IL-10) activity in glutamate-mediated neurotoxicity. Primary cortex neuron culture was exposed to glutamate and successively treated with various cerebrolysin concentrations for 24 and 48 h. Our data showed that cerebrolysin primarily protects neurons by decreasing glutamate concentration in the synaptic cleft. In addition, Cerebrolysin can decrease oxidative stress and neuron cell damage by increasing antioxidant activity and decreasing inflammation cytokine levels.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey, 25240

    Seydanur Avci

  2. Department of Molecular Biology and Genetics, Faculty of Science, Ataturk University, Erzurum, Turkey, 25240

    Sukran Gunaydin

  3. Department of Histology and Embryology, Kutahya Health Sciences University, Kutahya, Turkey, 43000

    Neziha Senem Ari

  4. Department of Molecular Biology and Genetics, Erzurum Technical University, Erzurum, Turkey, 25050

    Emine Karaca Sulukoglu

  5. Department of Physiology, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey, 25240

    Ozlem Erol Polat

  6. Department of Medical Pharmacology, Faculty of Medicine, Ataturk University, 25240, Erzurum, Turkey

    Ibrahim Gecili, Yesim Yeni, Aysegul Yilmaz & Ahmet Hacimuftuoglu

  7. Department of Medical Pharmacology, Faculty of Medicine, Bilecik Seyh Edebali University, 11230, Bilecik, Turkey

    Sidika Genc & Ali Taghizadehghalehjoughi

  8. Department of Pathology, Faculty of Veterinary Medicine, Ataturk University, 25240, Erzurum, Turkey

    Serkan Yildirim & Muhammed Yasser Mokresh

  9. Department of Histology and Embryology, Faculty of Medicine, Bilecik Seyh Edebali University, 11230, Bilecik, Turkey

    Damla Gul Findik

  10. Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003, Heraklion, Greece

    Aristidis Tsatsakis

  11. Department of Biochemistry, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 020956, Bucharest, Romania

    Denisa Margina

  12. Department of Cardiology, University General Hospital of Larissa, Terma Mazourlo, 41110, Larissa, Greece

    Konstantinos Tsarouhas

  13. School of Biomedical Sciences, Oklahoma State University Center for Health Sciences, Tulsa, OK, USA

    David R. Wallace

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  1. Seydanur Avci
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  18. Ali Taghizadehghalehjoughi
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Contributions

Conceptualization, Ali Taghizadehghalehjoughi and Kostas Tsarouhas; methodology, Sidika Genc; software, Sukran Gunaydin and Seydanur Avci; formal analysis, Neziha Senem Ari; investigation, Emine Karaca, Ibrahim Gecili, and Ozlem Erol Polat; data curation, Yesim Yeni and Aysegul Yilmaz; writing—original draft preparation, Ahmet Hacimuftuoglu, Aristidis Tsatsakis, and Serkan Yildirim; writing—review and editing, Denisa Margina, David R. Wallace, and Damla Gul Findik; visualization, D.F.; supervision, Ali Taghizadehghalehjoughi and Kostas Tsarouhas; project administration, Muhammed Yasser Mokresh.

Corresponding authors

Correspondence to Konstantinos Tsarouhas or Ali Taghizadehghalehjoughi.

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Ethics Approval

This study was conducted at the Medical Experimental Research Center at Ataturk University (Erzurum, Turkey). This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The animal use protocol was reviewed and approved by the Ethical Committee of Ataturk University, study protocol 04–2100268999/30.09.2021.

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Avci, S., Gunaydin, S., Ari, N.S. et al. Cerebrolysin Alleviating Effect on Glutamate-Mediated Neuroinflammation Via Glutamate Transporters and Oxidative Stress. J Mol Neurosci 72, 2292–2302 (2022). https://doi.org/10.1007/s12031-022-02078-8

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