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.