Figure 6.

Rescue of cognitive function in Aβ_1–42-infused adult rat brain upon Rheb-Myc expression

(A) Experimental flowchart shows a bilateral infusion of Aβ_1–42 oligomers and Rheb-Myc plasmid that was done in adult rat hippocampus. After 15 days of incubation, different behavioral assays were carried out followed by sacrificing the animals. (B–D) Rescue of wait latency in Aβ_1–42-infused adult rat brain upon Rheb-Myc expression. Passive avoidance assessment of memory performance was done, and the graph shows the acquisition process of experimental subjects. The rats that were able to enter the dark chamber within 300 s were selected as eligible for testing. The bar diagram reveals the wait latency in different experimental sets of rats. Rats having Rheb-Myc plasmid infused along with Aβ_1–42 showed higher wait latency on the probing day, as compared to the animals having only Aβ_1–42 infusion (D) (n = 7). (E–H) Novel object recognition test to show that the short-term memory recognition capability has been restored by Rheb-Myc expression in Aβ_1–42-injected animals. Aβ_1–42 and Rheb-Myc expression plasmid co-infused animals showed improvement in novel object identification capacity as compared to the Aβ_1–42-infused rodents (F). The Rheb-Myc-Aβ_1–42 co-infused animals also showed an increased preferential index and discrimination index as compared to the Aβ_1–42-infused group of animals, indicating improvement in learning and memory function (G and H) (n = 7). (I and J) The elevated plus maze analysis showed improvement in cognitive ability in Rheb-Myc-expressing animals. The retention transfer latency (RTL) was measured in all control and Aβ_1–42-infused groups, and the difference of initial transfer latency (ITL) and RTL was plotted along with the ITL and RTL separately (n = 7). For statistical significance, a minimum of three independent experiments were considered in each case unless otherwise mentioned. Animal data are represented as means ± SEM and analyzed by one-way ANOVA followed by Bonferroni’s test. p value <0.05 corresponds to ∗. In EPM data in panel J, # stands for significance between all the RTL data between all the animal groups, ∗ denotes significance between (ITL-RTL) data between all the animal groups.