title: Baicalin promotes hippocampal neurogenesis via SGK1- and FKBP5-mediated glucocorticoid receptor phosphorylation in a neuroendocrine mouse model of anxiety/depression.
abstract: Antidepressants increase hippocampal neurogenesis by activating the glucocorticoid receptor (GR), but excessive GR activation impairs hippocampal neurogenesis, suggesting that normal GR function is crucial for hippocampal neurogenesis. Baicalin was reported to regulate the expression of GR and facilitate hippocampal neurogenesis, but the underlying molecular mechanisms are still unknown. In this study, we used the chronic corticosterone (CORT)-induced mouse model of anxiety/depression to assess antidepressant-like effects of baicalin and illuminate possible molecular mechanisms by which baicalin affects GR-mediated hippocampal neurogenesis. We found that oral administration of baicalin (40, 80 or 160 mg/kg) for 4 weeks alleviated several chronic CORT-induced anxiety/depression-like behaviors. Baicalin also increased Ki-67- and DCX-positive cells to restore chronic CORT-induced suppression of hippocampal neurogenesis. Moreover, baicalin normalized the chronic CORT-induced decrease in GR protein levels, the increase in GR nuclear translocation and the increase in GR phosphorylation at Ser203 and Ser211. Finally, chronic CORT exposure increased the level of FK506-binding protein 51 (FKBP5) and of phosphorylated serum- and glucocorticoid-inducible kinase 1 (SGK1) at Ser422 and Thr256, whereas baicalin normalized these changes. Together, our findings suggest that baicalin improves anxiety/depression-like behaviors and promotes hippocampal neurogenesis. We propose that baicalin may normalize GR function through SGK1- and FKBP5-mediated GR phosphorylation.
authors: Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China.
authors: Kuo
authors: K
authors: Zhang
authors: Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China.
authors: Xing
authors: X
authors: Pan
authors: Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China.
authors: Fang
authors: F
authors: Wang
authors: Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China.
authors: Jie
authors: J
authors: Ma
authors: Department of School of Functional Food And Wine, Shenyang Pharmaceutical University, 110016, Shenyang, PR China.
authors: Guangyue
authors: G
authors: Su
authors: Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China.
authors: Yingxu
authors: Y
authors: Dong
authors: Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China.
authors: Jingyu
authors: J
authors: Yang
authors: Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China.
authors: Chunfu
authors: C
authors: Wu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000633:toxicity; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D003345:Corticosterone / Q000633:toxicity; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D005419:Flavonoids / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D017874:Immediate-Early Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009490:Neurosecretory Systems / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases; D000099159:Tacrolimus Binding Protein 5
chemical_list: D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003345:Corticosterone; D000089662:Doublecortin Protein; D005419:Flavonoids; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D011965:Receptors, Glucocorticoid; D022021:Tacrolimus Binding Proteins; D000099184:Serum-Glucocorticoid Regulated Kinases; D000099159:Tacrolimus Binding Protein 5; C000714847:Dcx protein, mouse; C038044:baicalin