• Dongmei Wang, Bei Wang, Yumei Liu, Xiaohui Dong, Yanwei Su, and Sanqiang Li.
• Medical College, Henan University of Science and Technology, Luoyang, 471023, People's Republic of China. wdmzgadyx@hotmail.com.
• Neurochem. Res. 2019 Nov 1; 44 (11): 2460-2469.

AbstractChemotherapy-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 α-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.

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