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.