Abstract |
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 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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Authors | Dongmei Wang, Bei Wang, Yumei Liu, Xiaohui Dong, Yanwei Su, Sanqiang Li |
Journal | Neurochemical research
(Neurochem Res)
Vol. 44
Issue 11
Pg. 2460-2469
(Nov 2019)
ISSN: 1573-6903 [Electronic] United States |
PMID | 31571096
(Publication Type: Journal Article)
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Chemical References |
- Histone Deacetylase Inhibitors
- Hydroxamic Acids
- Neuroprotective Agents
- Pyrimidines
- Hdac6 protein, mouse
- Histone Deacetylase 6
- Cisplatin
- ricolinostat
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Topics |
- Animals
- Cisplatin
- Cognitive Dysfunction
(chemically induced, prevention & control)
- Dendritic Spines
(drug effects)
- Hippocampus
(drug effects)
- Histone Deacetylase 6
(antagonists & inhibitors)
- Histone Deacetylase Inhibitors
(pharmacokinetics, therapeutic use)
- Hydroxamic Acids
(pharmacokinetics, therapeutic use)
- Male
- Mice, Inbred C57BL
- Mitochondria
(drug effects)
- Neuroprotective Agents
(pharmacokinetics, therapeutic use)
- Pyrimidines
(pharmacokinetics, therapeutic use)
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