Open Access

Prolonged use of temozolomide leads to increased anxiety and decreased content of aggrecan and chondroitin sulfate in brain tissues of aged rats

  • Authors:
    • Anastasia V. Strokotova
    • Dmitry K. Sokolov
    • Olga P. Molodykh
    • Elena V. Koldysheva
    • Evgenii E. Kliver
    • Victor S. Ushakov
    • Maxim O. Politko
    • Nadezhda V. Mikhnevich
    • Galina M. Kazanskaya
    • Svetlana V. Aidagulova
    • Elvira V. Grigorieva
  • View Affiliations

  • Published online on: November 22, 2023     https://doi.org/10.3892/br.2023.1695
  • Article Number: 7
  • Copyright: © Strokotova et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chemotherapy with temozolomide (TMZ) is an essential part of anticancer therapy used for malignant tumors (mainly melanoma and glioblastoma); however, the long‑term effects on patient health and life quality are not fully investigated. Considering that tumors often occur in elderly patients, the present study was conducted on long‑term (4 months) treatment of adult Wistar rats (9 months old, n=40) with TMZ and/or dexamethasone (DXM) to investigate potential behavioral impairments or morphological and molecular changes in their brain tissues. According to the elevated plus maze test, long‑term use of TMZ affected the anxiety of the adult Wistar rats, although no significant deterioration of brain morphology or cellular composition of the brain tissue was revealed. The expression levels of all studied heparan sulfate (HS) proteoglycans (HSPGs) (syndecan‑1, syndecan‑3, glypican‑1 and HSPG2) and the majority of the studied chondroitin sulfate (CS) proteoglycans (CSPGs) (decorin, biglycan, lumican, brevican, neurocan aggrecan, versican, Cspg4/Ng2, Cspg5 and phosphacan) were not affected by TMZ/DXM, except for neurocan and aggrecan. Aggrecan was the most sensitive proteoglycan to TMZ/DXM treatment demonstrating downregulation of its mRNA and protein levels following TMZ (‑10‑fold), DXM (‑45‑fold) and TMZ‑DXM (‑80‑fold) treatment. HS content was not affected by TMZ/DXM treatment, whereas CS content was decreased 1.5‑2.5‑fold in the TMZ‑ and DXM‑treated brain tissues. Taken together, the results demonstrated that treatment of adult Wistar rats with TMZ had long‑term effects on the brain tissues, such as decreased aggrecan core protein levels and CS chain content and increased anxiety of the experimental animals.
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Spandidos Publications style
Strokotova AV, Sokolov DK, Molodykh OP, Koldysheva EV, Kliver EE, Ushakov VS, Politko MO, Mikhnevich NV, Kazanskaya GM, Aidagulova SV, Aidagulova SV, et al: Prolonged use of temozolomide leads to increased anxiety and decreased content of aggrecan and chondroitin sulfate in brain tissues of aged rats. Biomed Rep 20: 7, 2024
APA
Strokotova, A.V., Sokolov, D.K., Molodykh, O.P., Koldysheva, E.V., Kliver, E.E., Ushakov, V.S. ... Grigorieva, E.V. (2024). Prolonged use of temozolomide leads to increased anxiety and decreased content of aggrecan and chondroitin sulfate in brain tissues of aged rats. Biomedical Reports, 20, 7. https://doi.org/10.3892/br.2023.1695
MLA
Strokotova, A. V., Sokolov, D. K., Molodykh, O. P., Koldysheva, E. V., Kliver, E. E., Ushakov, V. S., Politko, M. O., Mikhnevich, N. V., Kazanskaya, G. M., Aidagulova, S. V., Grigorieva, E. V."Prolonged use of temozolomide leads to increased anxiety and decreased content of aggrecan and chondroitin sulfate in brain tissues of aged rats". Biomedical Reports 20.1 (2024): 7.
Chicago
Strokotova, A. V., Sokolov, D. K., Molodykh, O. P., Koldysheva, E. V., Kliver, E. E., Ushakov, V. S., Politko, M. O., Mikhnevich, N. V., Kazanskaya, G. M., Aidagulova, S. V., Grigorieva, E. V."Prolonged use of temozolomide leads to increased anxiety and decreased content of aggrecan and chondroitin sulfate in brain tissues of aged rats". Biomedical Reports 20, no. 1 (2024): 7. https://doi.org/10.3892/br.2023.1695