Tea O-methylated catechins, especially (−)-epigallocatechin 3-O-(3-O-methyl)gallate (EGCG3″Me), have been attracting much attention as a result of their positive health effects. The transcription regulators of O-methylated catechin biosynthesis remain elusive. In this study, the expression pattern of genes related to O-methylated catechin biosynthesis, including CsLAR, CsANS, CsDFR, CsANR, and CCoAOMT, in three tea cultivars with different contents of EGCG3″Me was investigated. Two WRKY transcription factors (TFs), designated as CsWRKY31 and CsWRKY48, belonging to groups IIb and IIc of the WRKY family, respectively, were further identified. CsWRKY31 and CsWRKY48 were nuclear-localized proteins and possessed transcriptional repression ability. Furthermore, expression of CsWRKY31 and CsWRKY48 showed negative correlation with CsLAR, CsDFR, and CCoAOMT during EGCG3″Me accumulation in tea leaves. More importantly, W-box (C/ T)TGAC(T/C) elements were located in the promoter of CsLAR, CsDFR, and CCoAOMT, and further assays revealed that CsWRKY31 and CsWRKY48 were capable of repressing the transcription of CsLAR, CsDFR, and CCoAOMT via the attachment of their promoters to the W-box elements. Collectively, our findings identify two novel negative regulators of O-methylated catechin biosynthesis in tea plants, which might provide a potential strategy to breed high-quality tea cultivar.
SCM-198 is an alkaloid found only in Herba leonuri and it has been reported to possess considerable neuroprotective effects in animal models of ischemic stroke, Parkinson’s disease and Alzheimer’s disease (AD). In this study, we demonstrated for the first time that 3-month oral SCM-198 treatment could significantly improve both recognition and spatial memory, inhibit microgliosis and promote neuronal survival in amyloid-β protein precursor and presenilin-1(AβPP/PS1) double-transgenic mice without affecting amyloid-β (Aβ) burden. In addition, decreases in cAMP-response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) phosphorylation were attenuated by SCM-198 both in vivo and in primary cortical neurons, which could be blocked by protein kinase A (PKA) inhibitors, suggesting the involvement of upstream PKA in enhancing the BDNF/TrkB/CREB signaling by SCM-198. Our results indicate that SCM-198, a drug that could promote neuronal survival and enhance BDNF/TrkB/CREB signaling, has beneficial effects on behavioral and biochemical alterations without affecting Aβ burden in AβPP/PS1 mice and might become a potential drug candidate for AD treatment in the future.
The thalamus and central dopamine signaling have been shown to play important roles in high-level cognitive processes including impulsivity. However, little is known about the role of dopamine receptors in the thalamus in decisional impulsivity. In the present study, rats were tested using a delay discounting task and divided into three groups: high impulsivity (HI), medium impulsivity (MI), and low impulsivity (LI). Subsequent in vivo voxel-based magnetic resonance imaging revealed that the HI rats displayed a markedly reduced density of gray matter in the lateral thalamus compared with the LI rats. In the MI rats, the dopamine D1 receptor antagonist SCH23390 or the D2 receptor antagonist eticlopride was microinjected into the lateral thalamus. SCH23390 significantly decreased their choice of a large, delayed reward and increased their omission of lever presses. In contrast, eticlopride increased the choice of a large, delayed reward but had no effect on the omissions. Together, our results indicate that the lateral thalamus is involved in decisional impulsivity, and dopamine D1 and D2 receptors in the lateral thalamus have distinct effects on decisional impulsive behaviors in rats. These results provide a new insight into the dopamine signaling in the lateral thalamus in decisional impulsivity.
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