TY - JOUR
T1 - A natural carotenoid crocin exerts antidepressant action by promoting adult hippocampal neurogenesis through Wnt/β-catenin signaling.
AU - Tao, Weiwei
AU - Ruan, Jie
AU - Wu, Ruyan
AU - Zhao, Min
AU - Zhao, Tong
AU - Qi, Mingming
AU - Yau, Suk Yu
AU - Yau, Guangda
AU - Zhang, Hongru
AU - Hu, Yue
AU - Chen, Gang
N1 - Funding Information:
This work was supported by National Natural Science Foundation of China (81873096, 82174002, 81874374), Key research and development projects of east-west cooperation (2021BEG02040), Open Projects of the Discipline of Chinese Medicine of Nanjing University of Chinese Medicine Supported by the Subject of Academic priority discipline of Jiangsu Higher Education Institutions (NO. ZYX03KF73), and Blue Project of Middle-aged in Jiangsu province (2020).
Funding Information:
This work was supported by National Natural Science Foundation of China ( 81873096 , 82174002 , 81874374 ), Key research and development projects of east-west cooperation (2021BEG02040), Open Projects of the Discipline of Chinese Medicine of Nanjing University of Chinese Medicine Supported by the Subject of Academic priority discipline of Jiangsu Higher Education Institutions (NO. ZYX03KF73), and Blue Project of Middle-aged in Jiangsu province (2020).
Publisher Copyright:
© 2022
PY - 2023/1
Y1 - 2023/1
N2 - Introduction: Adult hippocampal neurogenesis (AHN) is acknowledged to play a critical role in depression. Emerging evidence suggests that the Wnt/β-catenin pathway can modulate hippocampal neurogenesis. Crocin, a natural carotenoid, possesses antidepressant property. Yet, how it affects neurogenesis and exerts antidepressant response remains unknown. Objective: To explore the role of AHN and Wnt/β-catenin in the antidepressant action of crocin. Methods: Depressive-related behaviors, including sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and sexual behaviors were performed following crocin treatment. Neurogenesis was characterized via immunohistochemistry, immunofluorescence, Golgi staining and electrophysiology approach. Wnt/β-catenin signaling was examined with western blot analysis. The role of AHN Wnt/β-catenin cascade in crocin's antidepressant response was assessed by conditional removal of glial fibrillary acidic protein (GFAP)-expressing newborn neural cells, temozolomide administration, microinfusion of Dkk1 or viral-mediated shRNA of Wnt3a. Results: Crocin decreased the immobility duration in TST and FST without impairing the performance in sexual behaviors. Crocin boosted the proliferation and differentiation of progenitors, and promoted dendritic maturation and functional integration of hippocampal newborn neurons. Conditional removal of GFAP-expressing neural cells or temozolomide administration impaired the antidepressant response of crocin. Additionally, Wnt/β-catenin signaling was promoted following crocin treatment. In chronic unpredictable mild stress (CUMS) murine model, crocin treatment displayed antidepressant response in SPT, FST and TST, and restored the neurogenesis levels and Wnt/β-catenin signaling impaired by CUMS. Infusion of Dickkopf-1 (DKK1) or knockdown of Wnt3a in the hippocampus impaired the antidepressant response of crocin. Conclusion: Crocin exerted antidepressant response, which was dependent on enhancement of AHN and activation of the Wnt/β-catenin pathway.
AB - Introduction: Adult hippocampal neurogenesis (AHN) is acknowledged to play a critical role in depression. Emerging evidence suggests that the Wnt/β-catenin pathway can modulate hippocampal neurogenesis. Crocin, a natural carotenoid, possesses antidepressant property. Yet, how it affects neurogenesis and exerts antidepressant response remains unknown. Objective: To explore the role of AHN and Wnt/β-catenin in the antidepressant action of crocin. Methods: Depressive-related behaviors, including sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and sexual behaviors were performed following crocin treatment. Neurogenesis was characterized via immunohistochemistry, immunofluorescence, Golgi staining and electrophysiology approach. Wnt/β-catenin signaling was examined with western blot analysis. The role of AHN Wnt/β-catenin cascade in crocin's antidepressant response was assessed by conditional removal of glial fibrillary acidic protein (GFAP)-expressing newborn neural cells, temozolomide administration, microinfusion of Dkk1 or viral-mediated shRNA of Wnt3a. Results: Crocin decreased the immobility duration in TST and FST without impairing the performance in sexual behaviors. Crocin boosted the proliferation and differentiation of progenitors, and promoted dendritic maturation and functional integration of hippocampal newborn neurons. Conditional removal of GFAP-expressing neural cells or temozolomide administration impaired the antidepressant response of crocin. Additionally, Wnt/β-catenin signaling was promoted following crocin treatment. In chronic unpredictable mild stress (CUMS) murine model, crocin treatment displayed antidepressant response in SPT, FST and TST, and restored the neurogenesis levels and Wnt/β-catenin signaling impaired by CUMS. Infusion of Dickkopf-1 (DKK1) or knockdown of Wnt3a in the hippocampus impaired the antidepressant response of crocin. Conclusion: Crocin exerted antidepressant response, which was dependent on enhancement of AHN and activation of the Wnt/β-catenin pathway.
KW - Adult hippocampal neurogenesis
KW - Crocin
KW - Depression
KW - Wnt/β-catenin
UR - http://www.scopus.com/inward/record.url?scp=85128495967&partnerID=8YFLogxK
U2 - 10.1016/j.jare.2022.02.015
DO - 10.1016/j.jare.2022.02.015
M3 - Journal article
SN - 2090-1232
VL - 43
SP - 219
EP - 231
JO - Journal of Advanced Research
JF - Journal of Advanced Research
ER -