Open AccessDopamine Burden Induced the Inactivation of Sonic Hedgehog Signaling to Cognitive Decline in Minimal Hepatic Encephalopathy
Author(s) -
Saidan Ding,
Jianjing Yang,
Xueli Huang,
Leping Liu,
Jiangnan Hu,
Zhu Xu,
Qichuan Zhuge
Publication year - 2017
Publication title -
aging and disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.808
H-Index - 54
ISSN - 2152-5250
DOI - 10.14336/ad.2016.1123
Subject(s) - cyclopamine , downregulation and upregulation , hedgehog signaling pathway , dopamine , sonic hedgehog , endocrinology , medicine , signal transduction , pharmacology , chemistry , biochemistry , gene
Minimal hepatic encephalopathy (MHE) is induced by elevated intracranial dopamine (DA). The relationship of the Shh pathway with memory loss in MHE, however, is elusive. In the current study, rats with MHE induced with DA displayed downregulation of the Shh pathway. Additionally, injection of Shh into MHE/DA-treated rats reversed downregulation of BDNF/NT3, whereas administration of cyclopamine (Cyc) enhanced the inhibition of expression of BDNF/NT3. Furthermore, naringin (Nrg) substantially prevented cognitive impairment in MHE/DA-treated rats and upregulated the Shh pathway, paralleling the elevated expression of BDNF/NT3. Overall, our results indicate that the Shh pathway can induce the expression of BDNF/NT3, and DA causes memory loss by inactivation of Shh pathway signaling to BDNF/NT3 in MHE rats, which is reversed by Nrg. Our study may provide new theory basis of pathogenesis and therapeutic target of MHE.