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Rosmarinic acid suppresses Alzheimer's disease development by reducing amyloid ? aggregation by increasing monoamine secretion.

ABSTRACT: A new mechanism is revealed by which a polyphenol, rosmarinic acid (RA), suppresses amyloid ? (A?) accumulation in mice. Here we examined the brains of mice (Alzheimer's disease model) using DNA microarray analysis and revealed that the dopamine (DA)-signaling pathway was enhanced in the group fed RA versus controls. In the cerebral cortex, the levels of monoamines, such as norepinephrine, 3,4-dihydroxyphenylacetic acid, DA, and levodopa, increased after RA feeding. The expression of DA-degrading enzymes, such as monoamine oxidase B (Maob), was significantly downregulated in the substantia nigra and ventral tegmental area, both DA synthesis regions. Following in vitro studies showing that monoamines inhibited A? aggregation, this in vivo study, in which RA intake increased concentration of monoamine by reducing Maob gene expression, builds on that knowledge by demonstrating that monoamines suppress A? aggregation. In conclusion, RA-initiated monoamine increase in the brain may beneficially act against AD.

SUBMITTER: Hase T

PROVIDER: S-EPMC6581955 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Rosmarinic acid suppresses Alzheimer's disease development by reducing amyloid β aggregation by increasing monoamine secretion.

Hase Tomoki T Shishido Syun S Yamamoto So S Yamashita Rei R Nukima Haruka H Taira Shu S Toyoda Tsudoi T Abe Keiko K Hamaguchi Tsuyoshi T Ono Kenjiro K Noguchi-Shinohara Moeko M Yamada Masahito M Kobayashi Shoko S

Scientific reports 20190618 1

A new mechanism is revealed by which a polyphenol, rosmarinic acid (RA), suppresses amyloid β (Aβ) accumulation in mice. Here we examined the brains of mice (Alzheimer's disease model) using DNA microarray analysis and revealed that the dopamine (DA)-signaling pathway was enhanced in the group fed RA versus controls. In the cerebral cortex, the levels of monoamines, such as norepinephrine, 3,4-dihydroxyphenylacetic acid, DA, and levodopa, increased after RA feeding. The expression of DA-degradin ...[more]

PMID: 31213631

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Project description:IntroductionNeuroinflammation and metabolic dysfunction are early alterations in Alzheimer's disease (AD) brain that are thought to contribute to disease onset and progression. Glial activation due to protein deposition results in cytokine secretion and shifts in brain metabolism, which have been observed in AD patients. However, the mechanism by which this immunometabolic feedback loop can injure neurons and cause neurodegeneration remains unclear.MethodsWe used Luminex XMAP technology to quantify hippocampal cytokine concentrations in the 5xFAD mouse model of AD at milestone timepoints in disease development. We used partial least squares regression to build cytokine signatures predictive of disease progression, as compared to healthy aging in wild-type littermates. We applied the disease-defining cytokine signature to wild-type primary neuron cultures and measured downstream changes in gene expression using the NanoString nCounter system and mitochondrial function using the Seahorse Extracellular Flux live-cell analyzer.ResultsWe identified a pattern of up-regulated IFNγ, IP-10/CXCL10, and IL-9 as predictive of advanced disease. When healthy neurons were exposed to these cytokines in proportions found in diseased brain, gene expression of mitochondrial electron transport chain complexes, including ATP synthase, was suppressed. In live cells, basal and maximal mitochondrial respiration were impaired following cytokine stimulation.ConclusionsWe identify a pattern of cytokine secretion predictive of progressing amyloid-β pathology in the 5xFAD mouse model of AD that reduces expression of mitochondrial electron transport complexes and impairs mitochondrial respiration in healthy neurons. We establish a mechanistic link between disease-specific immune cues and impaired neuronal metabolism, potentially causing neuronal vulnerability and susceptibility to degeneration in AD.Supplementary informationThe online version contains supplementary material available at 10.1007/s12195-023-00782-y.

Dataset Information

Rosmarinic acid suppresses Alzheimer's disease development by reducing amyloid ? aggregation by increasing monoamine secretion.

Publications

Rosmarinic acid suppresses Alzheimer's disease development by reducing amyloid β aggregation by increasing monoamine secretion.

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