HDAC6 inhibition reverses long-term doxorubicin-induced cognitive dysfunction by restoring microglia homeostasis and synaptic integrity

• Published in: Theranostics Vol. 12; no. 2; pp. 603 - 619
• Main Authors: McAlpin, Blake R, Mahalingam, Rajasekaran, Singh, Anand K, Dharmaraj, Shruti, Chrisikos, Taylor T, Boukelmoune, Nabila, Kavelaars, Annemieke, Heijnen, Cobi J
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 2022; Ivyspring International Publisher
• Subjects: Animals; Blood-brain barrier; Breast cancer; Cancer therapies; Chemotherapy; Cognitive ability; Cognitive Dysfunction - chemically induced; Cognitive Dysfunction - drug therapy; Cytokines; Disks Large Homolog 4 Protein - metabolism; Dose-Response Relationship, Drug; Doxorubicin - antagonists & inhibitors; Drug dosages; FDA approval; Female; Gene expression; Genotype & phenotype; Hippocampus - cytology; Hippocampus - drug effects; Histone Deacetylase 6 - antagonists & inhibitors; Homeostasis - drug effects; Laboratory animals; Memory; Mice; Mice, Inbred C57BL; Microglia - drug effects; Mitochondria - drug effects; Morphology; Pyridazines - pharmacology; Research Paper; Synapses - drug effects; Transcription, Genetic - drug effects; New York; United States > US; HDAC6 inhibition; chemobrain; chemotherapy-induced cognitive dysfunction; single-nucleus RNA sequencing; microglia

Breast cancer is the most common female malignancy in both the developed and developing world. Doxorubicin is one of the most commonly used chemotherapies for breast cancer. Unfortunately, up to 60% of survivors report long-term chemotherapy-induced cognitive dysfunction (CICD) characterized by defi...