期刊
NATURAL PRODUCT COMMUNICATIONS
卷 17, 期 12, 页码 -出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/1934578X221141162
关键词
hyperlipidemia; high-fat diet; Curcumin-Nicotinate; amyloid-beta; BDNF/TrkB/CREB signaling; synaptogenesis; Idol/LDLR pathway
资金
- Natural Science Foundation of Hunan Province, Clinical Medical Technology Innovation Guidance Project of Hunan Province [2020JJ4553, 2020SK51908]
The study demonstrated that CurTn can alleviate synaptogenesis dysfunction in the hippocampus of high-fat diet (HFD)-induced hyperlipidemia rats by activating BDNF/TrkB/CREB signaling and modulating the Idol/LDLR pathway, which leads to the elimination of Aβ deposition.
Hyperlipidemia has been demonstrated to evoke Alzheimer disease (AD) pathologies such as Amyloid-beta (A beta) deposition and synaptogenesis dysfunction in the hippocampus. Curcumin gives protection against anti-amyloid properties and synaptogenesis dysfunction. Curcumin-Nicotinate (CurTn), a new type of curcumin derivative, ameliorates cognitive impairment by rescuing autophagic flux in the CA1 hippocampus of diabetic rats. However, whether Curtn possesses an antagonistic effect on AD-related pathologies in the hippocampus induced by hyperlipidemia remains ill-defined. The present study aims to investigate whether CurTn alleviates synaptogenesis dysfunction by promoting the activation of brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB)/cAMP-response element binding protein (CREB) signaling and whether the underlying fundamental mechanism involves the elimination of A beta deposition due to Idol/low-density lipoprotein receptor (LDLR) signaling in the hippocampus of high-fat diet (HFD)-induced hyperlipidemia rats. The results demonstrated that CurTn not only improved synaptogenesis dysfunction in the hippocampus of HFD rats, as evidenced by the increases in the expressions of synapse-related proteins postsynaptic density protein 95 (PSD-95), synapsin-1, and Glutamate receptor 1 (GluR1), but also activated BDNF/TrkB/CREB signaling, as evidenced by the elevation of the expressions of BDNF, pTrkB, and CREB. Moreover, CurTn modulated the Idol/LDLR pathway in the hippocampus of HFD rats, as evidenced by the decreased expression of Idol and the increased expression of LDLR. Furthermore, CurTn eliminated the deposition of A beta, as evidenced by the reduction in the content of A beta 40 and A beta 42. These results reveal that CurTn may attenuate synaptogenesis dysfunction by activating BDNF/TrkB/CREB signaling, as the possible result of the modulation of Idol/LDLR signaling to eliminate A beta deposition in the hippocampus of HFD rats.
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