دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Mitochondrial-associated impairments of temozolomide on neural stem/progenitor cells and hippocampal neurons.
المؤلفون: Lomeli N; Department of Pathology & Laboratory Medicine, University of California Irvine, Irvine, CA, USA. Electronic address: nrlomeli@uci.edu., Di K; Department of Neurology, University of California Irvine, Irvine, CA, USA; Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, USA. Electronic address: kdi@uci.edu., Pearre DC; Department of Obstetrics and Gynecology, University of California, Irvine, Orange, CA, USA. Electronic address: dcholaki@uci.edu., Chung TF; Department of Neurology, University of California Irvine, Irvine, CA, USA. Electronic address: tzufengc@uci.edu., Bota DA; Department of Pathology & Laboratory Medicine, University of California Irvine, Irvine, CA, USA; Department of Neurology, University of California Irvine, Irvine, CA, USA; Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, USA; Department of Neurological Surgery, University of California Irvine, Irvine, CA, USA. Electronic address: dbota@uci.edu.
المصدر: Mitochondrion [Mitochondrion] 2020 May; Vol. 52, pp. 56-66. Date of Electronic Publication: 2020 Feb 08.
نوع المنشور: Comparative Study; Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100968751 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-8278 (Electronic) Linking ISSN: 15677249 NLM ISO Abbreviation: Mitochondrion Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam ; New York : Elsevier Science, c2001-
مواضيع طبية MeSH: Hippocampus/*cytology , Mitochondria/*drug effects , Neural Stem Cells/*cytology , Temozolomide/*adverse effects, Animals ; Cell Survival/drug effects ; Cells, Cultured ; Cytochromes b/genetics ; DNA Replication/drug effects ; Disease Models, Animal ; Hippocampus/drug effects ; Hippocampus/metabolism ; Humans ; Mitochondria/genetics ; Mitophagy ; NADH Dehydrogenase/genetics ; Neural Stem Cells/drug effects ; Neural Stem Cells/metabolism ; Rats ; Spatial Learning/drug effects ; Transcription, Genetic/drug effects
مستخلص: 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 of care for glioblastoma (GBM) - the most common and aggressive of all brain cancers. Numerous studies have reported that TMZ disrupts hippocampal neurogenesis and causes spatial learning deficits in rodents; however, the effect of TMZ on mature hippocampal neurons has not been addressed. In this study, we examined the mitochondrial-mediated mechanisms involving TMZ-induced neural damage in primary rat neural stem/progenitor cells (NSC) and hippocampal neurons. TMZ inhibited mtDNA replication and transcription of mitochondrial genes (ND1 and Cyt b) in NSC by 24 h, whereas the effect of TMZ on neuronal mtDNA transcription was less pronounced. Transmission electron microscopy imaging revealed mitochondrial degradation in TMZ-treated NSC. Acute TMZ exposure (4 h) caused a rapid reduction in dendritic branching and loss of postsynaptic density-95 (PSD95) puncta on dendrites. Longer TMZ exposure impaired mitochondrial respiratory activity, increased oxidative stress, and induced apoptosis in hippocampal neurons. The presented findings suggest that NSC may be more vulnerable to TMZ than hippocampal neurons upon acute exposure; however long-term TMZ exposure results in neuronal mitochondrial respiratory dysfunction and dendritic damage, which may be associated with delayed cognitive impairments.
(Copyright © 2020 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)
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معلومات مُعتمدة: T32 NS082174 United States NS NINDS NIH HHS; UL1 TR001414 United States TR NCATS NIH HHS; T32 CA060396 United States CA NCI NIH HHS; P30 CA062203 United States CA NCI NIH HHS; K08 NS072234 United States NS NINDS NIH HHS; R25 GM055246 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: Chemotherapy; Hippocampal neurons; Mitochondria; Neural stem/progenitor cells; Neurotoxicity; Oxidative stress; Temozolomide
المشرفين على المادة: 9035-37-4 (Cytochromes b)
EC 1.6.99.3 (NADH Dehydrogenase)
EC 7.1.1.2 (mt-Nd1 protein, rat)
YF1K15M17Y (Temozolomide)
تواريخ الأحداث: Date Created: 20200212 Date Completed: 20210607 Latest Revision: 20210607
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7415494
DOI: 10.1016/j.mito.2020.02.001
PMID: 32045717
قاعدة البيانات: MEDLINE
الوصف
تدمد:1872-8278
DOI:10.1016/j.mito.2020.02.001