Curcumin-Nicotinate Attenuates Hippocampal Synaptogenesis Dysfunction in Hyperlipidemia Rats by the BDNF/TrkB/CREB Pathway: Involving Idol/LDLR Signaling to Eliminate Aβ Deposition

Abstract

Hyperlipidemia has been demonstrated to evoke Alzheimer disease (AD) pathologies such as Amyloid-β (Aβ) 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 Aβ 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 Aβ, as evidenced by the reduction in the content of Aβ40 and Aβ42. 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 Aβ deposition in the hippocampus of HFD rats.