3.1 Overexpression of Lf in astrocytes reduces Aβ burden and improves cognitive ability in APP/PS1 mice
The MWM was a classical animal behavior experiment to assess the spatial learning and memory capacity of mice. In the visible platform tests, the Astro-Lf mice exhibited a shorter escape latency and path length compared to the other gene-type mice, whereas the WT mice, APP/PS1 mice and APP/PS1/Lf mice had no significant difference in the escape latency (Fig. 1A) or path length (Fig. 1B), indicating that overexpression of Lf in astrocytes may promote the vision or motility in WT mice, neither in APP/PS1 mice. However, in the hidden platform tests, the APP/PS1/Lf mice spent less time (Fig. 1C) and travelled shorter lengths (Fig. 1D-E) than APP/PS1 mice to search the hidden platform on day 5. Moreover, APP/PS1/Lf mice exhibited more crossing times than those of APP/PS1 mice (Fig. 1F), suggesting that astrocytic Lf overexpression rescued the cognitive impairments of APP/PS1 mice.
After the end of animal behavior tests, mice were sacrificed and the brains were harvested. Immunostaining results showed significant reductions in the number of Aβ plaque and the area of Aβ plaque in both the cortexes and hippocampus of APP/PS1/Lf mice compared to those in APP/PS1 mice (Fig. 1G-I). The decreased Aβ loads in the APP/PS1/Lf mice were also confirmed by immunoblotting as shown in Fig. 1J. These data suggested that astrocytic Lf overexpression effectively reduced the Aβ burden in APP/PS1 mouse brains, and subsequently enhanced the cognitive capacity of APP/PS1 mice.