Lipoxin A4 methyl ester ameliorates cognitive deficits induced by chronic cerebral hypoperfusion through activating ERK/Nrf2 signaling pathway in rats

Lipoxin A4 methyl ester alleviates vascular cognition impairment by regulating the expression of proteins related to autophagy and ER stress in the rat hippocampus

“…Thus, in CCH, mTORC1 is likely the relevant mTORC isoform. One interesting finding of our study is that the expression of t-mTOR in the hippocampus decreased at day 20 following 2VO surgery [26], albeit with no statistical significance, suggesting that CCH not only regulates the phosphorylation of mTOR, but also affects the gene expression of mTOR at the level of transcription or translation. Nevertheless, LXA 4 ME prevented the downregulation of mTOR expression and mTOR phosphorylation in 2VO rats.…”

“…Autophagy and ERS mechanisms may play various roles in different disease conditions. In addition, our study has certain limitations, including the fact that only male rats were examined, and that we studied only one time point after 2VO surgery (i.e., 14 days before the Morris water maze tests [26]). Moreover, we did not test any mTOR inhibitors.…”

“…It was reported that LXA 4 ME significantly reduced cerebral ischemia/reperfusion injury by ameliorating blood-brain barrier dysfunction, regulating inflammation-related signaling pathways and decreasing the production of pro-inflammatory cytokines [23][24][25]. In our previous study, we demonstrated the protective effect of LXA 4 ME on cognitive impairments in 2VO rats by activating the extracellular signal regulated kinase/nuclear factor erythroid 2-related factor 2 (ERK/Nrf2) signaling pathway [26]. In the experiments described here, we tested the idea that LXA 4 ME might alleviate cognitive deficits by targeting some autophagy-and ERrelated factors in 2VO rats.…”

“…All efforts were made to alleviate animal suffering and minimize the number of animals used. As such, the results of the Morris water maze test performed in our previous study were used here [26]. The details of the 2VO surgery and the microinjection procedures of LXA 4 ME were published previously [26].…”

“…As such, the results of the Morris water maze test performed in our previous study were used here [26]. The details of the 2VO surgery and the microinjection procedures of LXA 4 ME were published previously [26]. We used the same paraffin-embedded rat brains and frozen hippocampus tissue, which were stored at -80ºC until needed.…”