Z-Guggulsterone Produces Antidepressant-Like Effects in Mice through Activation of the BDNF Signaling Pathway
| Autor: | Lijuan Tong, Yibin Qin, Jili Wang, Peng Wang, Wei Zhang, Rongrong Yang, Wenfeng Hu, Fengguo Liu, Yu Gong, Zhuo Chen, Chao Huang, Bo Jiang |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Neurogenesis Z-guggulsterone Biology CREB Hippocampus 03 medical and health sciences 0302 clinical medicine Pregnenediones Neurotrophic factors Fluoxetine Internal medicine medicine Animals Pharmacology (medical) Regular Research Article CUS Cyclic AMP Response Element-Binding Protein Extracellular Signal-Regulated MAP Kinases Protein kinase B Pharmacology Brain-derived neurotrophic factor Depressive Disorder Dose-Response Relationship Drug Brain-Derived Neurotrophic Factor Tryptophan hydroxylase Antidepressive Agents Tail suspension test Mice Inbred C57BL Disease Models Animal Psychiatry and Mental health BDNF 030104 developmental biology Endocrinology biology.protein Signal transduction major depression Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | International Journal of Neuropsychopharmacology |
| ISSN: | 1469-5111 1461-1457 |
| Popis: | Background: Z-guggulsterone, an active compound extracted from the gum resin of the tree Commiphora mukul, has been shown to improve animal memory deficits via activating the brain-derived neurotrophic factor signaling pathway. Here, we investigated the antidepressant-like effect of Z-guggulsterone in a chronic unpredictable stress mouse model of depression. Methods: The effects of Z-guggulsterone were assessed in mice with the tail suspension test and forced swimming test. Z-guggulsterone was also investigated in the chronic unpredictable stress model of depression with fluoxetine as the positive control. Changes in hippocampal neurogenesis as well as the brain-derived neurotrophic factor signaling pathway after chronic unpredictable stress/Z-guggulsterone treatment were investigated. The tryptophan hydroxylase inhibitor and the tyrosine kinase B inhibitor were also used to explore the antidepressant-like mechanisms of Z-guggulsterone. Results: Z-guggulsterone (10, 30 mg/kg) administration protected the mice against the chronic unpredictable stress-induced increases in the immobile time in the tail suspension test and forced swimming test and also reversed the reduction in sucrose intake in sucrose preference experiment. Z-guggulsterone (10, 30 mg/kg) administration prevented the reductions in brain-derived neurotrophic factor protein expression levels as well as the phosphorylation levels of cAMP response element binding protein, extracellular signal-regulated kinase 1/2, and protein kinase B in the hippocampus and cortex induced by chronic unpredictable stress. Z-guggulsterone (10, 30 mg/kg) treatment also improved hippocampal neurogenesis in chronic unpredictable stress-treated mice. Blockade of the brain-derived neurotrophic factor signal, but not the monoaminergic system, attenuated the antidepressant-like effects of Z-guggulsterone. Conclusions: Z-guggulsterone exhibits antidepressant activity via activation of the brain-derived neurotrophic factor signaling pathway and upregulation of hippocampal neurogenesis. |
| Databáze: | OpenAIRE |
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