Enhanced cell proliferation is related to increased brain-derived neurotrophic factor (BDNF) upon M1145 and Y1R agonist agonist coactivation
To study the cellular mechanism related to the observed effects on cell proliferation, we study the BDNF expression on the ventral hippocampal dentate gyrus (DG) after M1145 and/or Y1R agonist administration. BDNF-positive cells were found specifically in the subgranular zone (Sgz) of the ventral hippocampus, and some scattered cells were observed in the polymorphic layer (P) of the ventral DG (Figure 3a). Stereological quantification of BDNF positive cells demonstrated a significant increase after the intranasal coinjection of M1145 and YR1 agonist compared to control (one-way ANOVA, F4, 15 = 11.12, p < 0.001, Newman-Keuls post-hoc test: p<0.001), M1145 (Newman-Keuls post-hoc test: p<0.001) or the YR1 agonist alone (Newman-Keuls post-hoc test: p<0.05) (Figure 3 a-d).
The injection of the Y1R agonist induced a significant increase in the number of BDNF-positive cells in the ventral dentate gyrus (Newman-Keuls post-hoc test: p<0.05) (Figure 3 b) compared with the control and the M1145 groups. However, the injection of M1145 alone lacked effects on the number of BDNF-positive cells in the ventral DG. Likewise to the PCNA-IR response described above, the presence of the GALR2 antagonist M871 completely blocked the increase induced by the coinjection (Newman-Keuls post-hoc test: p<0.05) (Figure 3 b), demonstrating the involvement of GALR2 in this interaction.