The diuretic amiloride attenuates doxorubicin-induced chemobrain in rats: Behavioral and mechanistic study

Ali, Alaa E.; Elsherbiny, Doaa M.; Azab, Samar S.; El‐Demerdash, Ebtehal

doi:10.1016/j.neuro.2021.10.002

Cited by 1 publication

(1 citation statement)

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“…The current study confirmed that Dox impairs episodic spatial and contextual memory in rats as measured on the watermaze and inhibitory avoidance (Ali et al., 2020 , 2022 ; Lal et al., 2023 ; Liedke et al., 2009 ). In the current study, we demonstrate that cognitive impairment was linked to peripheral inflammation and oxidative stress, which impaired NMDAR function.…”

Section: Discussionsupporting

confidence: 86%

Senolytic treatment alleviates doxorubicin‐induced chemobrain

Budamagunta,

Kumar,

Rani

et al. 2024

Aging Cell

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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.

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