Liposomal Nanoparticle-Encapsulated Sirtuin 1 (SIRT1) Agonist Reduces Cognitive Impairment of Leukopenia Rats by Inhibiting Hcy Expression Through Brain Derived Neurotrophic Factor/Tropomyosin Receptor Kinase B (BDNF/TrkB) Pathway

Abstract

The crucial role of Sirtuin 1 (SIRT1) and Tropomyosin receptor kinase B (TrkB) pathway in regulating learning and memory has already been validated. Occurrence of leukoaraiosis (LA) is closely related to Hcy level. This study mainly explored the significance of liposomal nanoparticle-encapsulated SIRT1 agonist in modulating cognitive impairment of LA rats regarding Homocysteine (Hcy) level and TrkB pathway. Totally, 40 healthy female rats were collected and assigned into blank, empty vector, SIRT1 agonist, vector+agonist groups for testing the role of liposomal nanoparticle-encapsulated SIRT1 agonist in cognitive abilities of rats. Besides, expression patterns of SIRT1 and BDNF in hippocampus and Hcy level in plasma were also determined. We observed improved alternation rate in Y-maze test in SIRT1 agonist and vector+agonist groups relative to blank and empty vector groups (p < 0.05, SIRT1 agonist group < vector+agonist group). Increased RI and reduction in latency were seen in the SIRT1 agonist and vector+agonist groups relative to blank and empty vector groups (p < 0.05). No significant difference was noted in the RI between SIRT1 agonist and vector+agonist groups, as well as between blank and empty vector groups (p > 0.05). Besides, it was evident that the SIRT1 agonist and vector+agonist groups displayed elevated BDNF protein expression but reduced Hcy level (p < 0.05, vs. blank group). The liposomal nanoparticle-encapsulated SIRT1 agonist has a definite effect on reversing the cognitive impairment in rats with LA by limiting the Hcy level through the TrkB pathway.