Senolytic treatment alleviates doxorubicin-induced chemobrain

Vivekananda Budamagunta, Ashok Kumar, Asha Rani, Sahana Manohar Sindhu, Yang Yang, Daohong Zhou, Thomas C. Foster

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Doxorubicin (Dox), a widely used treatment for cancer, can result in chemotherapy-induced cognitive impairments (chemobrain). Chemobrain is associated with inflammation and oxidative stress similar to aging. As such, Dox treatment has also been used as a model of aging. However, it is unclear if Dox induces brain changes similar to that observed during aging since Dox does not readily enter the brain. Rather, the mechanism for chemobrain likely involves the induction of peripheral cellular senescence and the release of senescence-associated secretory phenotype (SASP) factors and these SASP factors can enter the brain to disrupt cognition. We examined the effect of Dox on peripheral and brain markers of aging and cognition. In addition, we employed the senolytic, ABT-263, which also has limited access to the brain. The results indicate that plasma SASP factors enter the brain, activating microglia, increasing oxidative stress, and altering gene transcription. In turn, the synaptic function required for memory was reduced in response to altered redox signaling. ABT-263 prevented or limited most of the Dox-induced effects. The results emphasize a link between cognitive decline and the release of SASP factors from peripheral senescent cells and indicate some differences as well as similarities between advanced age and Dox treatment.

Original languageEnglish (US)
Article numbere14037
JournalAging cell
Volume23
Issue number2
DOIs
StatePublished - Feb 2024

Keywords

  • chemobrain
  • cognition
  • inflammation
  • oxidative stress
  • senolytic NMDA receptor
  • transcription

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Fingerprint

Dive into the research topics of 'Senolytic treatment alleviates doxorubicin-induced chemobrain'. Together they form a unique fingerprint.

Cite this