Mitochondrial-associated impairments of temozolomide on neural stem/progenitor cells and hippocampal neurons.

摘要: Abstract Primary brain tumor patients often experience neurological, cognitive, and depressive symptoms that profoundly affect quality of life. The DNA alkylating agent, temozolomide (TMZ), along with radiation therapy forms the standard care for glioblastoma (GBM) – most common aggressive all cancers. Numerous studies have reported TMZ disrupts hippocampal neurogenesis causes spatial learning deficits in rodents; however, effect on mature neurons has not been addressed. In this study, we examined mitochondrial-mediated mechanisms involving TMZ-induced neural damage primary rat stem/progenitor cells (NSC) neurons. inhibited mtDNA replication transcription mitochondrial genes (ND1 Cyt b) NSC by 24 h, whereas neuronal was less pronounced. Transmission electron microscopy imaging revealed degradation TMZ-treated NSC. Acute exposure (4 h) caused a rapid reduction dendritic branching loss postsynaptic density-95 (PSD95) puncta dendrites. Longer impaired respiratory activity, increased oxidative stress, induced apoptosis presented findings suggest may be more vulnerable to than upon acute exposure; however long-term results dysfunction damage, which associated delayed cognitive impairments.