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Int. J. Mol. Sci. 2015, 16(8), 18544-18563; doi:10.3390/ijms160818544

SCM-198 Ameliorates Cognitive Deficits, Promotes Neuronal Survival and Enhances CREB/BDNF/TrkB Signaling without Affecting Aβ Burden in AβPP/PS1 Mice

Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China
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Academic Editor: Chang Won Choi
Received: 15 June 2015 / Revised: 29 July 2015 / Accepted: 31 July 2015 / Published: 7 August 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

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. View Full-Text
Keywords: SCM-198; amyloid-β; Alzheimer’s disease; Morris water maze; novel object recognition; cAMP-responsive element-binding protein; brain-derived neurotrophic factor; tropomyosin-related kinase B SCM-198; amyloid-β; Alzheimer’s disease; Morris water maze; novel object recognition; cAMP-responsive element-binding protein; brain-derived neurotrophic factor; tropomyosin-related kinase B
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Hong, Z.-Y.; Yu, S.-S.; Wang, Z.-J.; Zhu, Y.-Z. SCM-198 Ameliorates Cognitive Deficits, Promotes Neuronal Survival and Enhances CREB/BDNF/TrkB Signaling without Affecting Aβ Burden in AβPP/PS1 Mice. Int. J. Mol. Sci. 2015, 16, 18544-18563.

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