دورية أكاديمية
أعرض في EDS

Cisplatin induces BDNF downregulation in middle-aged female rat model while BDNF enhancement attenuates cisplatin neurotoxicity.

التفاصيل البيبلوغرافية
العنوان: Cisplatin induces BDNF downregulation in middle-aged female rat model while BDNF enhancement attenuates cisplatin neurotoxicity.
المؤلفون: Lomeli N; Department of Neurology, University of California Irvine, Irvine, CA, USA., Pearre DC; Gynecologic Oncology, Providence Specialty Medical Group, Burbank, CA, USA., Cruz M; Department of Neurology, University of California Irvine, Irvine, CA, USA., Di K; Department of Neurology, University of California Irvine, Irvine, CA, USA., Ricks-Oddie JL; Center for Statistical Consulting, Department of Statistics, University of California Irvine, Irvine, CA, USA; Biostatistics, Epidemiology and Research Design Unit, Institute for Clinical and Translational Sciences, University of California Irvine, Irvine, CA, USA., Bota DA; Department of Neurology, University of California Irvine, Irvine, CA, USA; Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, USA. Electronic address: dbota@hs.uci.edu.
المصدر: Experimental neurology [Exp Neurol] 2024 May; Vol. 375, pp. 114717. Date of Electronic Publication: 2024 Feb 08.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Academic Press Country of Publication: United States NLM ID: 0370712 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2430 (Electronic) Linking ISSN: 00144886 NLM ISO Abbreviation: Exp Neurol Subsets: MEDLINE
أسماء مطبوعة: Publication: Orlando Fl : Academic Press
Original Publication: New York.
مواضيع طبية MeSH: Cisplatin*/toxicity , Brain-Derived Neurotrophic Factor*/metabolism, Rats ; Animals ; Female ; Rats, Sprague-Dawley ; Down-Regulation ; Quality of Life ; Riluzole/pharmacology ; Hippocampus/metabolism ; Disks Large Homolog 4 Protein
مستخلص: Cancer-related cognitive impairments (CRCI) are neurological complications associated with cancer treatment, and greatly affect cancer survivors' quality of life. Brain-derived neurotrophic factor (BDNF) plays an essential role in neurogenesis, learning and memory. The reduction of BDNF is associated with the decrease in cognitive function in various neurological disorders. Few pre-clinical studies have reported on the effects of chemotherapy and medical stress on BDNF levels and cognition. The present study aimed to compare the effects of medical stress and cisplatin on serum BDNF levels and cognitive function in 9-month-old female Sprague Dawley rats to age-matched controls. Serum BDNF levels were collected longitudinally during cisplatin treatment, and cognitive function was assessed by novel object recognition (NOR) 14 weeks post-cisplatin initiation. Terminal BDNF levels were collected 24 weeks after cisplatin initiation. In cultured hippocampal neurons, we screened three neuroprotective agents, riluzole (an approved treatment for amyotrophic lateral sclerosis), as well as the ampakines CX546 and CX1739. We assessed dendritic arborization by Sholl analysis and dendritic spine density by quantifying postsynaptic density-95 (PSD-95) puncta. Cisplatin and exposure to medical stress reduced serum BDNF levels and impaired object discrimination in NOR compared to age-matched controls. Pharmacological BDNF augmentation protected neurons against cisplatin-induced reductions in dendritic branching and PSD-95. Ampakines (CX546 and CX1739) and riluzole did not affect the antitumor efficacy of cisplatin in vitro. In conclusion, we established the first middle-aged rat model of cisplatin-induced CRCI, assessing the contribution of medical stress and longitudinal changes in BDNF levels on cognitive function, although future studies are warranted to assess the efficacy of BDNF enhancement in vivo on synaptic plasticity. Collectively, our results indicate that cancer treatment exerts long-lasting changes in BDNF levels, and support BDNF enhancement as a potential preventative approach to target CRCI with therapeutics that are FDA approved and/or in clinical study for other indications.
Competing Interests: Declaration of competing interest The authors do not have any potential conflicts of interest to disclose.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: TL1 TR001415 United States TR NCATS NIH HHS; T32 NS082174 United States NS NINDS NIH HHS; R01 CA263806 United States CA NCI 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
فهرسة مساهمة: Keywords: Ampakine; BDNF; Chemobrain); Cisplatin; Hippocampal neurons; Neurotoxicity; Ovarian cancer; PSD-95; Riluzole; cancer-related cognitive impairments (CRCI
المشرفين على المادة: Q20Q21Q62J (Cisplatin)
0 (Brain-Derived Neurotrophic Factor)
7LJ087RS6F (Riluzole)
0 (Disks Large Homolog 4 Protein)
تواريخ الأحداث: Date Created: 20240209 Date Completed: 20240401 Latest Revision: 20240512
رمز التحديث: 20240512
مُعرف محوري في PubMed: PMC11087041
DOI: 10.1016/j.expneurol.2024.114717
PMID: 38336286
قاعدة البيانات: MEDLINE
الوصف
تدمد:1090-2430
DOI:10.1016/j.expneurol.2024.114717