Notch1 signaling pathway involves in hippocampal neurogenesis on depressive-like rat models

Objective To investigate whether the effect of fluoxetine on hippocampal neurogenesis involves Notch1 signaling after chronic stress. Methods Sixty-eight male Sprague-Dawley rats were divided into control group, control + fluoxetine group, depression model group and depression model + fluoxetine group. Chronic unpredictable mild stress (CUMS) was used to make up depression animal model. The function of Notch1 signaling was measured by real-time PCR and western blotting. Simultaneously,hippocampal neurogenesis was monitored by assessing cell proliferation and survival. Results (1) Before starting CUMS protocol, the animals exhibited equivalent weight, sucrose preference, number of squares crossed, number of rearing, and immobility time in behavioral test. Twenty-eight days after CUMS protocol,these parameters were significantly difference in rats exposed to CUMS compared with the controls (sucrose preference, number of squares crossed, number of grooming and rearing, and immobility time, P<0. 01).Administration of fluoxetine was shown to dramatically improve the depression behavior (P<0. 01) .(2) The cell proliferation [(3047. 61 ± 158. 29) vs. (1900. 33 ± 104. 10)] and survive [(2704. 21 ±154. 31) vs. (1845.33 ± 126.88)] were increased after fluoxetine administration in rats with depression (P<0. 01). (3) Fluoxetine increased mRNA expressions of Notch1 signaling components [NICD mRNA (0. 23 ±0. 01) vs. (0. 10 ±0.01), Hes1 mRNA (0. 56 ±0.04) vs. (0. 28 ±0.02), Hes5 mRNA (0. 24 ±0.02) vs. (0.10 ±0.02), Jag1 mRNA (0.82 ±0.06) vs. (0.56 ±0.03)] in the rat hippocampus compared with the CUMS group (P<0. 01 or P<0. 001). Fluoxetine enhanced protein levels of Notch1 signaling components [NICD(1.99 ±0.07) vs. (0.53 ±0.10), Hes5(0. 64 ±0. 04) vs. (0.37 ±0.09),Jag1 (2. 34 ± 0. 13) vs. (0. 68 ± 0. 17)] in the rat hippocampus compared with the CUMS group (P <0.01). Conclusion The up-regulation of the Notch1 pathway with chronic fluoxetine administration might partly contribute to increased neurogenesis in the rat hippocampus with depression. Key words: Fluoxetine;  Depression;  Signal transduction;  Nerve regeneration;  Chronic unpredictable mild stress