Radix Scutellariae Ameliorates Stress-Induced Depressive-Like Behaviors via Protecting Neurons through the TGFβ3-Smad2/3-Nedd9 Signaling Pathway

Chronic stress can impair hippocampal neurogenesis, increase neuronal apoptosis, and cause depressive-like behaviors. Our previous studies found that Radix Scutellariae (RS) can rescue the stress-induced neuronal injury, but the mechanism is not clear. Here, we continued to investigate the underlyin...

Full description

Saved in:
Bibliographic Details
Main Authors: Fan Zhao, Chenyiyu Zhang, Dong Xiao, Weihua Zhang, Liping Zhou, Simeng Gu, Rong Qu
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2020/8886715
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832547013078548480
author Fan Zhao
Chenyiyu Zhang
Dong Xiao
Weihua Zhang
Liping Zhou
Simeng Gu
Rong Qu
author_facet Fan Zhao
Chenyiyu Zhang
Dong Xiao
Weihua Zhang
Liping Zhou
Simeng Gu
Rong Qu
author_sort Fan Zhao
collection DOAJ
description Chronic stress can impair hippocampal neurogenesis, increase neuronal apoptosis, and cause depressive-like behaviors. Our previous studies found that Radix Scutellariae (RS) can rescue the stress-induced neuronal injury, but the mechanism is not clear. Here, we continued to investigate the underlying antidepressant mechanisms of the RS extract. A 7-week chronic unpredictable mild stress (CUMS) procedure was used to establish a murine depression model. 0.75 g/kg or 1.5 g/kg RS was administered daily to the mice during the last 4 weeks. Depressive-like behaviors were evaluated by the sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and tail suspension test (TST). The neuroprotective effect of RS was evaluated with the expression of hippocampal neuron-related markers and apoptosis-associated proteins by Nissl staining, immunohistochemistry, and western blot. Transforming growth factor-β3 (TGFβ3) pathway-related proteins were detected by western blot. Results showed that RS could ameliorate depressive-like behaviors, increase the expression of the antiapoptotic protein B-cell lymphoma 2 (BCL-2), reduce the expression of the proapoptotic protein BCL-2-associated X (BAX), and increase the number of doublecortin- (DCX-), microtubule-associated protein 2- (MAP2-), and neuronal nucleus- (NeuN-) positive cells in the hippocampus. Moreover, RS could reverse the CUMS-induced decrease of TGFβ3 protein, promote the phosphorylation of SMAD2/3, and increase the expression of downstream NEDD9 protein. These results suggest that RS could exert antidepressant effects via protecting neurons. And the molecular mechanism might be related to the regulation of the TGFβ3-SMAD2/3-NEDD9 pathway.
format Article
id doaj-art-6a2e05530713463c832918ad587792a7
institution Kabale University
issn 2090-5904
1687-5443
language English
publishDate 2020-01-01
publisher Wiley
record_format Article
series Neural Plasticity
spelling doaj-art-6a2e05530713463c832918ad587792a72025-02-03T06:46:21ZengWileyNeural Plasticity2090-59041687-54432020-01-01202010.1155/2020/88867158886715Radix Scutellariae Ameliorates Stress-Induced Depressive-Like Behaviors via Protecting Neurons through the TGFβ3-Smad2/3-Nedd9 Signaling PathwayFan Zhao0Chenyiyu Zhang1Dong Xiao2Weihua Zhang3Liping Zhou4Simeng Gu5Rong Qu6College of Chinese Medicine, College of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210046, ChinaCollege of Chinese Medicine, College of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210046, ChinaJiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210046, ChinaCollege of Chinese Medicine, College of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210046, ChinaCollege of Chinese Medicine, College of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210046, ChinaDepartment of Psychology, Jiangsu University Medical School, Zhenjiang 210023, ChinaCollege of Chinese Medicine, College of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210046, ChinaChronic stress can impair hippocampal neurogenesis, increase neuronal apoptosis, and cause depressive-like behaviors. Our previous studies found that Radix Scutellariae (RS) can rescue the stress-induced neuronal injury, but the mechanism is not clear. Here, we continued to investigate the underlying antidepressant mechanisms of the RS extract. A 7-week chronic unpredictable mild stress (CUMS) procedure was used to establish a murine depression model. 0.75 g/kg or 1.5 g/kg RS was administered daily to the mice during the last 4 weeks. Depressive-like behaviors were evaluated by the sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and tail suspension test (TST). The neuroprotective effect of RS was evaluated with the expression of hippocampal neuron-related markers and apoptosis-associated proteins by Nissl staining, immunohistochemistry, and western blot. Transforming growth factor-β3 (TGFβ3) pathway-related proteins were detected by western blot. Results showed that RS could ameliorate depressive-like behaviors, increase the expression of the antiapoptotic protein B-cell lymphoma 2 (BCL-2), reduce the expression of the proapoptotic protein BCL-2-associated X (BAX), and increase the number of doublecortin- (DCX-), microtubule-associated protein 2- (MAP2-), and neuronal nucleus- (NeuN-) positive cells in the hippocampus. Moreover, RS could reverse the CUMS-induced decrease of TGFβ3 protein, promote the phosphorylation of SMAD2/3, and increase the expression of downstream NEDD9 protein. These results suggest that RS could exert antidepressant effects via protecting neurons. And the molecular mechanism might be related to the regulation of the TGFβ3-SMAD2/3-NEDD9 pathway.http://dx.doi.org/10.1155/2020/8886715
spellingShingle Fan Zhao
Chenyiyu Zhang
Dong Xiao
Weihua Zhang
Liping Zhou
Simeng Gu
Rong Qu
Radix Scutellariae Ameliorates Stress-Induced Depressive-Like Behaviors via Protecting Neurons through the TGFβ3-Smad2/3-Nedd9 Signaling Pathway
Neural Plasticity
title Radix Scutellariae Ameliorates Stress-Induced Depressive-Like Behaviors via Protecting Neurons through the TGFβ3-Smad2/3-Nedd9 Signaling Pathway
title_full Radix Scutellariae Ameliorates Stress-Induced Depressive-Like Behaviors via Protecting Neurons through the TGFβ3-Smad2/3-Nedd9 Signaling Pathway
title_fullStr Radix Scutellariae Ameliorates Stress-Induced Depressive-Like Behaviors via Protecting Neurons through the TGFβ3-Smad2/3-Nedd9 Signaling Pathway
title_full_unstemmed Radix Scutellariae Ameliorates Stress-Induced Depressive-Like Behaviors via Protecting Neurons through the TGFβ3-Smad2/3-Nedd9 Signaling Pathway
title_short Radix Scutellariae Ameliorates Stress-Induced Depressive-Like Behaviors via Protecting Neurons through the TGFβ3-Smad2/3-Nedd9 Signaling Pathway
title_sort radix scutellariae ameliorates stress induced depressive like behaviors via protecting neurons through the tgfβ3 smad2 3 nedd9 signaling pathway
url http://dx.doi.org/10.1155/2020/8886715
work_keys_str_mv AT fanzhao radixscutellariaeamelioratesstressinduceddepressivelikebehaviorsviaprotectingneuronsthroughthetgfb3smad23nedd9signalingpathway
AT chenyiyuzhang radixscutellariaeamelioratesstressinduceddepressivelikebehaviorsviaprotectingneuronsthroughthetgfb3smad23nedd9signalingpathway
AT dongxiao radixscutellariaeamelioratesstressinduceddepressivelikebehaviorsviaprotectingneuronsthroughthetgfb3smad23nedd9signalingpathway
AT weihuazhang radixscutellariaeamelioratesstressinduceddepressivelikebehaviorsviaprotectingneuronsthroughthetgfb3smad23nedd9signalingpathway
AT lipingzhou radixscutellariaeamelioratesstressinduceddepressivelikebehaviorsviaprotectingneuronsthroughthetgfb3smad23nedd9signalingpathway
AT simenggu radixscutellariaeamelioratesstressinduceddepressivelikebehaviorsviaprotectingneuronsthroughthetgfb3smad23nedd9signalingpathway
AT rongqu radixscutellariaeamelioratesstressinduceddepressivelikebehaviorsviaprotectingneuronsthroughthetgfb3smad23nedd9signalingpathway