期刊
NEUROTHERAPEUTICS
卷 20, 期 3, 页码 838-852出版社
SPRINGER
DOI: 10.1007/s13311-022-01339-z
关键词
BDNF; Chemotherapy; Chemobrain; Cognitive function; Riluzole; Neurogenesis
Breast cancer patients treated with doxorubicin (ADR) experience reduced levels of BDNF, leading to cognitive impairments. The orally active BDNF-enhancing medication riluzole (RZ) improves hippocampal-dependent learning and memory function, reduces anxiety-like behavior, and protects against neuroinflammation. RZ also prevents chemotherapy-induced reductions in BDNF levels and promotes dentate neurogenesis.
Cancer-related cognitive impairment (CRCI) considerably affects the quality of life of millions of cancer survivors. Brain-derived neurotrophic factor (BDNF) has been shown to promote survival, differentiation, and maintenance of in vivo dentate neurogenesis, and chemotherapy induces a plethora of physiological and cellular alterations, including a decline in neurogenesis and increased neuroinflammation linked with cognitive impairments. In our clinical studies, breast cancer patients treated with doxorubicin (Adriamycin((R)), ADR) experienced a significant reduction in the blood levels of BDNF that was associated with a higher risk of CRCI. Our past rodent studies in CRCI have also shown a significant reduction in dentate neurogenesis accompanied by cognitive impairment. In this study, using a female mouse model of ADR-induced cognitive decline, we tested the impact of riluzole (RZ), an orally active BDNF-enhancing medication that is FDA-approved for amyotrophic lateral sclerosis. ADR-treated mice receiving RZ in the drinking water for 1 month showed significant improvements in hippocampal-dependent learning and memory function (spatial recognition), fear extinction memory consolidation, and reduced anxiety-like behavior. RZ prevented chemotherapy-induced reductions of BDNF levels in the hippocampus. Importantly, RZ mitigated chemotherapy-induced loss of newly born, immature neurons, dentate neurogenesis, and neuroinflammation. In conclusion, this data provides pre-clinical evidence for a translationally feasible approach to enhance the neuroprotective effects of RZ treatment to prevent CRCI.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据