Journal
NEUROCHEMICAL RESEARCH
Volume 44, Issue 11, Pages 2460-2469Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-019-02882-6
Keywords
HDAC6; Chemotherapy; Cognitive; Cisplatin
Categories
Funding
- National Natural Science Foundation of China [81601225, U1804174]
- Henan Provincial Key Research and Development and Promotion Project [192102310081]
- Science and Technology Innovation Talents in the Universities of Henan Province [20HASTIT044]
- Science & Technology Innovation teams in Universities of Henan Province [18IRTSTHN026]
- Outstanding Youth of Science and Technology Innovation in Henan Province [184100510006]
- Student Research Training Program of Henan University of Science and Technology [2019314]
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Chemotherapy-related cognitive impairment (CRCI) is a potential long-term side effect during cancer treatment. There are currently no effective treatments for CRCI. Reduction or inhibition of histone deacetylase 6 (HDAC6) has been considered a possible therapeutic strategy for cognitive deficits. HDAC6 inhibition recently has been shown to reverse chemotherapy-induced peripheral neuropathy effectively. In the present study, we examined the effect of HDAC6 inhibitor ACY-1215 (Ricolinostat) on cisplatin-induced brain damage and cognitive deficits in mice. Our results showed that ACY-1215 ameliorated behavioral deficits and dendritic spine loss and increased synaptic density in cisplatin-treated mice. Mechanistically, HDAC6 inhibitor ACY-1215 enhanced alpha-tubulin acetylation in the hippocampus of cisplatin-treated mice. Furthermore, ACY-1215 recovered cisplatin-induced impaired mitochondrial transport and mitochondrial dysfunction in the hippocampus. Our results suggest that inhibition of HDAC6 improves established cisplatin-induced cognitive deficits by the restoration of mitochondrial and synaptic impairments. These results offer prospective approaches for CRCI, especially because ACY1215 currently serves as an add-on cancer therapy during clinical trials. [GRAPHICS] .
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