Potential Neurotoxic Effects of Glioblastoma-Derived Exosomes in Primary Cultures of Cerebellar Neurons via Oxidant Stress and Glutathione Depletion

High-grade gliomas are the most fatal brain tumors. Grade 4 gliomas are called glioblastoma multiforme (GBM), which are associated with the poorest survival and a 5-year survival rate of less than 4%. Many patients with GBM developed concomitant cognitive dysfunctions and epilepsy. Although the cogn...

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Bibliographic Details
Published in:Antioxidants 2022-06, Vol.11 (7), p.1225
Main Authors: Genc, Sidika, Pennisi, Manuela, Yeni, Yesim, Yildirim, Serkan, Gattuso, Giuseppe, Altinoz, Meric A., Taghizadehghalehjoughi, Ali, Bolat, Ismail, Tsatsakis, Aristidis, Hacımüftüoğlu, Ahmet, Falzone, Luca
Format: Article
Language:English
Subjects:
Acids
Antibiotics
Antioxidants
Apoptosis
Brain cancer
Brain tumors
Cancer therapies
Cell culture
Cerebellum
Cognitive ability
Edema
Epilepsy
exosome
Exosomes
Glioblastoma
Glioblastoma multiforme
Glutathione
Medical prognosis
Neurons
Neurotoxicity
Oxidants
oxidative stress
Penicillin
Proteins
Statistical analysis
Stem cells
Tumors
Vitamin E
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Summary:High-grade gliomas are the most fatal brain tumors. Grade 4 gliomas are called glioblastoma multiforme (GBM), which are associated with the poorest survival and a 5-year survival rate of less than 4%. Many patients with GBM developed concomitant cognitive dysfunctions and epilepsy. Although the cognitive decline is well defined in glioblastomas, the neurotoxic factors underlying this pathology are not well understood in GBM patients. In this study, we aimed to investigate whether GBM-derived exosomes play a role in neuronal toxicity. For this purpose, exosomes obtained from T98G and U373 GBM cells were applied to primary neuron culture at different concentrations. Subsequently, MTT, LDH, GSH, TAS, and TOS tests were performed. Both GBM-derived exosomes induced a dose-dependent and statistically significant increase of LDH release in cerebellar neurons. MTT assay revealed as both T98G and U373 GBM-derived exosomes induced dose-dependent neurotoxic effects in cerebellar neurons. To the best of our knowledge, this study is the first study demonstrating the toxic potential of GBM-derived exosomes to primary neurons, which may explain the peritumoral edema and cognitive decline in GBM patients.
ISSN:2076-3921
2076-3921
DOI:10.3390/antiox11071225