GALR2 and the Y1R agonists intranasally administered increased cell proliferation in the ventral Hippocampus
We evaluated the impact of GALR2 agonist M1145 and the Y1R agonist intranasally co-injected on adult ventral hippocampal cell proliferation by using the proliferating cell nuclear antigen (PCNA). M1145 and the Y1R agonist coadministration significantly increased cell proliferation, as demonstrated by the number of PCNA-IR cells, specifically in the sub-granular zone (Sgz) of the dentate gyrus compared to control (one-way ANOVA, F4,15 = 12.38, p<0.001, Newman–Keuls post-hoc test: p<0.001) (Figure 2 a,b,d), M1145 (Newman–Keuls post-hoc test: p<0.001) and Y1R agonist groups (Newman–Keuls post-hoc test: p<0.05) (Figure 2 a,b,d). The addition of GALR2 antagonist M871 completely blocked the M1145 and the Y1R agonist effects in the dentate gyrus (Newman–Keuls post-hoc test: p<0.01) (Figure 2 b), validating the participation of GALR2 in the Y1R/GALR2 agonist interaction to stimulate cell proliferation on the ventral hippocampus.
Moreover, the intranasal administration of the Y1R agonist alone induced an increase in the number of PCNA positive cells in the subgranular zone (Sgz) of the ventral hippocampus (Figure 2 a,b) compared with the control and M1145 groups Newman-Keuls post-hoc test: p<0.05) (Figure 2 a,b). However, the intranasal delivery of M1145 alone lacked effects on the numbers of PCNA-IR profiles (Figure 2b) compared with the control group (Figure 2 a–c).