American Association for Cancer Research
Browse

Supplementary Table 2 from Nicotinamide Mononucleotide Prevents Cisplatin-Induced Cognitive Impairments

Download (23.92 kB)
dataset
posted on 2023-03-31, 04:26 authored by Ki Hyun Yoo, Jason J. Tang, Mohammad Abdur Rashid, Chang Hoon Cho, Ana Corujo-Ramirez, Jonghoon Choi, Mun Gyeong Bae, Danielle Brogren, John R. Hawse, Xiaonan Hou, S. John Weroha, Alfredo Oliveros, Lindsey A. Kirkeby, Joseph A. Baur, Mi-Hyeon Jang

Detailed information for statistical analysis

Funding

NIH

Mayo Clinic Breast Cancer SPORE

National Cancer Institute

Find out more...

Regenerative Medicine Minnesota

Eagles 5th District Cancer Telethon Funds

Mayo Clinic SPORE in Ovarian Cancer

2019 The Bosarge Family Foundation–Waun Ki Hong Scholar Award for Regenerative Cancer Medicine from the American Association for Cancer Research

History

ARTICLE ABSTRACT

Chemotherapy-induced cognitive impairment (CICI) is often reported as a neurotoxic side effect of chemotherapy. Although CICI has emerged as a significant medical problem, meaningful treatments are not currently available due to a lack of mechanistic understanding underlying CICI pathophysiology. Using the platinum-based chemotherapy cisplatin as a model for CICI, we show here that cisplatin suppresses nicotinamide adenine dinucleotide (NAD+) levels in the adult female mouse brain in vivo and in human cortical neurons derived from induced pluripotent stem cells in vitro. Increasing NAD+ levels through nicotinamide mononucleotide (NMN) administration prevented cisplatin-induced abnormalities in neural progenitor proliferation, neuronal morphogenesis, and cognitive function without affecting tumor growth and antitumor efficacy of cisplatin. Mechanistically, cisplatin inhibited expression of the NAD+ biosynthesis rate-limiting enzyme nicotinamide phosphoribosyl transferase (Nampt). Selective restoration of Nampt expression in adult-born neurons was sufficient to prevent cisplatin-induced defects in dendrite morphogenesis and memory function. Taken together, our findings suggest that aberrant Nampt-mediated NAD+ metabolic pathways may be a key contributor in cisplatin-induced neurogenic impairments, thus causally leading to memory dysfunction. Therefore, increasing NAD+ levels could represent a promising and safe therapeutic strategy for cisplatin-related neurotoxicity. Increasing NAD+ through NMN supplementation offers a potential therapeutic strategy to safely prevent cisplatin-induced cognitive impairments, thus providing hope for improved quality of life in cancer survivors.

Usage metrics

    Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC