Senolytics prevent age-associated changes in female mice brain

• Published in: Neuroscience letters 2024-03, Vol.826, p.137730-137730, Article 137730
• Main Authors: Faria, Olivia Wyse, de Aguiar, Mayara Sandrielly Soares, de Mello, Julia Eisenhardt, Alvez, Fernando Lopez, Luduvico, Karina Pereira, Garcia, Driele Neske, Schneider, Augusto, Masternak, Michal M., Spanevello, Roselia Maria, Stefanello, Francieli Moro
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; Acetylcholinesterase - metabolism; Adenosine Triphosphatases; Animals; Antioxidants - pharmacology; Brain; Brain - metabolism; Catalase - metabolism; Dasatinib; Female; Mice; Mice, Inbred C57BL; Na+, K+-ATPase; Oxidative Stress; Quercetin; Quercetin - pharmacology; Rats; Rats, Wistar; Redox status; Senotherapeutics; Superoxide Dismutase - metabolism
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2024.137730

[Display omitted] •Senolytic compounds as neuroprotectors.•Senolytic compounds reduce reactive species.•Senolytic compounds against neuroinflammation. 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. 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 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. These data demonstrate that D+Q can protect against age-associated neurochemical alterations in the female brain.