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Erinacine S, a small active component derived from Hericium erinaceus, protects oligodendrocytes and alleviates mood abnormalities in cuprizone-exposed rodents - 22/03/24

Doi : 10.1016/j.biopha.2024.116297 
Jing-Ting Fu a, Chih-Jou Yang a, Li-Ya Lee b, Wan-Ping Chen b, Yu-Wen Chen b, Chin-Chu Chen b, Yuan-Ting Sun c, Chung-Shi Yang d, Shun-Fen Tzeng a,
a Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan 
b Biotech Research Institute, Grape King Biotechnology Inc, Taoyuan, Taiwan 
c Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan 
d Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan 

Correspondence to: Department of Life Sciences, National Cheng Kung University, #1 University Road, Tainan City 70101 , Taiwan.Department of Life Sciences, National Cheng Kung University#1 University RoadTainan City70101Taiwan

Abstract

Hericium erinaceus mycelium extract (HEM), containing erinacine A (HeA) and erinacine S (HeS), has shown promise in promoting the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs), crucial for myelin production in the central nervous system (CNS). The main aim of this study was to characterize the protective effects of HEM and its components on OLs and myelin in demyelinating rodents by exposure to cuprizone (CPZ), a copper chelating agent commonly used to induce demyelination in the corpus callosum of the brain. Rats were fed by CPZ-containing diet and simultaneously orally administered HEM, HeA, or HeS on a daily basis for three weeks. We found that HEM and HeS preserved myelin and OLs in the corpus callosum of CPZ-fed rats, along with reduced microglia and astrocyte activation, and downregulated IL-1β expression. Furthermore, post-treatment with HeS, in mouse models with acute (6 weeks) or chronic (12 weeks) CPZ-induced demyelination demonstrated oral administration during the final 4 weeks (HeS4/6 or HeS4/12) effectively preserved myelin in the corpus callosum. Additionally, HeS4/6 and HeS4/12 inhibited anxious and depressive-like behaviors in CPZ-fed mice. In summary, simultaneous administration of HEM and HeS in rats during short-term CPZ intoxication preserved OLs and myelin. Furthermore, post-administration of HeS not only inhibited demyelination and gliosis but also alleviated anxiety and depression in both acute and chronic CPZ-fed mice. This study presents compelling evidence supporting the potential of HeS as a promising small active compound for protecting OLs and preserving myelin in demyelinating diseases associated with emotional disorders.

El texto completo de este artículo está disponible en PDF.

Graphical Abstract




 : 

Schematic illustration of HeS protection in myelin preservation and in the suppression of gliosis following by CPZ-intoxication. In the rat model, short-term exposure to CPZ induces OL loss/demyelination, gliosis, and cytokine upregulation (solid black arrows) in the corpus callosum, which can be significantly inhibited by daily co-treatment with HeS (indicated by the red line). In CPZ-fed mouse models with acute or chronic demyelination, HeS post-treatment can suppress CPZ-induced demyelination and astrogliosis to a lesser extent (red line). Moreover, HeS post-treatment partially mitigates CPZ-induced anxiety and depression in mice (red lines). The central or peripheral effects of HeS post-treatment in CPZ-fed mice remains to be further characterized (red dashed line). Note that gliosis and demyelination in the corpus callosum could mutually influence each other in CPZ-intoxicated rodent models (grey arrows). The figure was created with BioRender.com.


Schematic illustration of HeS protection in myelin preservation and in the suppression of gliosis following by CPZ-intoxication. In the rat model, short-term exposure to CPZ induces OL loss/demyelination, gliosis, and cytokine upregulation (solid black arrows) in the corpus callosum, which can be significantly inhibited by daily co-treatment with HeS (indicated by the red line). In CPZ-fed mouse models with acute or chronic demyelination, HeS post-treatment can suppress CPZ-induced demyelination and astrogliosis to a lesser extent (red line). Moreover, HeS post-treatment partially mitigates CPZ-induced anxiety and depression in mice (red lines). The central or peripheral effects of HeS post-treatment in CPZ-fed mice remains to be further characterized (red dashed line). Note that gliosis and demyelination in the corpus callosum could mutually influence each other in CPZ-intoxicated rodent models (grey arrows). The figure was created with BioRender.com.

El texto completo de este artículo está disponible en PDF.

Highlights

H. erinaceus mycelium extract or erinacine S prevent loss of oligodendrocytes and myelin during acute demyelination.
Post treatment with erinacine S preserves myelin amount during chronic demyelination.
Erinacine S exhibits an alleviating effect on depression and anxiety associated with chronic demyelination.

El texto completo de este artículo está disponible en PDF.

Abbreviations : APC, BBB, CNS, CPZ, CyPA, DAB, DAPI, DM, DMEM, EPM, FGF2, GFAP, HeA, HEM, HeS, Iba1, IF, IL, i.p., MBP, MS, NCBI, NSC, OL, O.P., OPC, PBS, PFA, QPCR, ROI, RRID, TNF-α

Keywords : erinacine, oligodendrocyte, demyelination, anxiety, inflammation


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© 2024  The Authors. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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