Senolytics prevent age-associated changes in female mice brain

Abstract

Purpose: Considering that the combination of dasatinib and quercetin (D + Q) demonstrated a neuroprotective action, as well as that females experience a decline in hormonal levels during aging and this is linked to increased susceptibility to Alzheimer's disease, in this study we evaluated the effect of D + Q on inflammatory and oxidative stress markers and on acetylcholinesterase and Na⁺, K⁺-ATPase activities in brain of female mice.

Methods: Female C57BL/6 mice were divided in Control and D (5 mg/kg) + Q (50 mg/kg) treated. Treatment was administered via gavage for three consecutive days every two weeks starting at 30 days of age. The animals were euthanized at 6 months of age and at 14 months of age.

Results: Results indicate an increase in reactive species (RS), thiol content and lipid peroxidation followed by a reduction in nitrite levels and superoxide dismutase, catalase and glutathione S-transferase activity in the brain of control animals with age. D+Q protected against age-associated increase in RS and catalase activity reduction. Acetylcholinesterase activity was increased, while Na⁺, K⁺-ATPase activity was reduced at 14 months of age and D+Q prevented this reduction.

Conclusion: These data demonstrate that D+Q can protect against age-associated neurochemical alterations in the female brain.

Keywords: Acetylcholinesterase; Brain; Dasatinib; Na(+), K(+)-ATPase; Quercetin; Redox status.