Abstract
Baicalin isolated from Scutellaria baicalensis possesses antidepressant abilities through its relation to hippocampal neurogenesis. Current research has found that baicalin can promote the proliferation of hippocampal granule cells, however, the detailed mechanism of baicalin on the survival and maturation of hippocampal granule cells has yet to be sufficiently explored. The purpose of this study was to evaluate whether baicalin could facilitate the survival and maturation of hippocampal granule cells, and to explore its potential mechanism. The chronic corticosterone (CORT)-induced mouse model of depression was used to assess antidepressant-like effects of baicalin and to illuminate possible molecular mechanisms by which baicalin affects hippocampal neurogenesis. The survival and maturation of granule cells were measured by immunohistochemistry, immunofluorescence and Golgi staining. The expression of Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (AKT)/glycogen synthase kinase-3β (GSK3β)/β-catenin pathway related proteins were measured by western blot analysis. PI3K inhibitor LY292002 and AKT inhibitor Perifosine were administered to HT-22 cells to explore the relationship between the PI3K/AKT/GSK3β/β-catenin pathway and baicalin. The results of the study illustrated that baicalin significantly decreased chronic CORT-induced depressive-like behaviors and reduced serum corticosterone levels. In addition, baicalin (administered at 60 mg/kg) reversed chronic CORT-induced lesions on hippocampal granule cells. Moreover, baicalin significantly increased the phosphorylation rate of PI3K, AKT, GSK3β, and total β-catenin. The study found that administration of LY292002/Perifosine counteracted the effects of baicalin in HT-22 cells. These results demonstrate that baicalin can alleviate chronic CORT-induced depressive-like behaviors through promoting survival and maturation of adult-born hippocampal granule cells and exhibiting protective effect on hippocampal neuron morphology. We propose the underlying mechanisms involve the activation of the PI3K/AKT/GSK3β/β-catenin pathway.
Highlights
Depression is considered one of the most burdensome diseases globally, affecting approximately 264 million people worldwide (GBD 2017 Disease and Injury Incidence and Prevalence Collaborators, 2018)
In the NSFT experiment, feeding latency was increased [F(4,45)=20.22, P
We found that the p-Phosphatidylinositol 3kinase (PI3K), p-AKT, p-glycogen synthase kinase-3b (GSK3b), and b-catenin protein expression levels were significantly decreased after CORT exposure [F(4,10)=7.23, F (4,10)=16.28, F(4,10)=8.49, F(4,10)=8.81, P
Summary
Depression is considered one of the most burdensome diseases globally, affecting approximately 264 million people worldwide (GBD 2017 Disease and Injury Incidence and Prevalence Collaborators, 2018). Long-term exposure to CORT can induce depressive-like behaviors and cause neural deficits in the hippocampus of rodents (Alfarez et al, 2009; Morales-Medina et al, 2009), affecting neural progenitor cell differentiation, neuron survival, migration, and synaptic plasticity (Kunugi et al, 2010). Transgenic mice, with proapoptotic gene Bax deleted from neural stem cells, exhibit enhanced adult neurogenesis and resistance to depressive-like behaviors induced by CORT (Hill et al, 2015). Antidepressants can accelerate the maturation of newborn hippocampal cells and promote their survival in animal models (Wang et al, 2008; Perera et al, 2011), resulting in decrease in depressive-like behavioral symptoms
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