Cyclic phosphatidic acid treatment suppress cuprizone-induced demyelination and motor dysfunction in mice

Yamamoto, Shinji; Gotoh, Mari; Kawamura, Yuuki; Yamashina, Kota; Yagishita, Sosuke; Awaji, Takeo; Tanaka, Motomu; Maruyama, Kei; Murakami‐Murofushi, Kimiko; Yoshikawa, Ken

doi:10.1016/j.ejphar.2014.07.040

Cited by 33 publications

(21 citation statements)

References 59 publications

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“…We assume that the increased activation of microglia/monocytes and/or astrocytes in the white compared to the gray matter results in a higher lesion expansion. In support of this assumption is the observation that in the cuprizone model, explicit microgliosis is evident in regions of profound demyelination [62], that prevention of demyelination is paralleled by a reduced activation of microglia cells [63][64][65], and that the application of the microglia inhibitor minocycline [66] ameliorates demyelination in the cuprizone model [67]. Similar observations have been reported in the LPC model [68].…”

Section: Discussionsupporting

confidence: 64%

Lesion Expansion in Experimental Demyelination Animal Models and Multiple Sclerosis Lesions

et al. 2015

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Gray matter pathology is an important aspect of multiple sclerosis (MS) pathogenesis and disease progression. In a recent study, we were able to demonstrate that the higher myelin content in the white matter parts of the brain is an important variable in the neuroinflammatory response during demyelinating events. Whether higher white matter myelination contributes to lesion development and progression is not known. Here, we compared lesion size of intra-cortical vs. white matter MS lesions. Furthermore, dynamics of lesion development was compared in the cuprizone and lysophosphatidylcholine models. We provide clear evidence that in the human brain, white matter lesions are significantly increased in size as compared to intra-cortical gray matter lesions. In addition, studies using the cuprizone mouse model revealed that the autonomous progression of white matter lesions is more severe compared to that in the gray matter. Focal demyelination revealed that the application of equal amounts of lysophosphatidylcholine results in more severe demyelination in the white compared to the gray matter. In summary, lesion progression is most intense in myelin-rich white matter regions, irrespective of the initial lesion trigger mechanism. A better understanding of myelin debris-triggered lesion expansion will pave the way for the development of new protective strategies in the future.

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Section: Discussionsupporting

confidence: 64%

Lesion Expansion in Experimental Demyelination Animal Models and Multiple Sclerosis Lesions

et al. 2015

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“…Considering the breadth of bioactivities of this class of lipids [ 47 ], their contributions to immune responses may be diverse, particularly since they modulate nuclear function [ 48 , 49 ]. In this regard, pharmacological studies have shown that cPA analogs potently reverse experimental osteoarthritis [ 50 ], block immune-induced demyelination [ 51 ], and inhibit the growth of cancer cells [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Lipidomic analysis of immune activation in equine leptospirosis and Leptospira-vaccinated horses

et al. 2018

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Currently available diagnostic assays for leptospirosis cannot differentiate vaccine from infection serum antibody. Several leptospiral proteins that are upregulated during infection have been described, but their utility as a diagnostic marker is still unclear. In this study, we undertook a lipidomics approach to determine if there are any differences in the serum lipid profiles of horses naturally infected with pathogenic Leptospira spp. and horses vaccinated against a commercially available bacterin. Utilizing a high-resolution mass spectrometry serum lipidomics analytical platform, we demonstrate that cyclic phosphatidic acids, diacylglycerols, and hydroperoxide oxidation products of choline plasmalogens are elevated in the serum of naturally infected as well as vaccinated horses. Other lipids of interest were triacylglycerols that were only elevated in the serum of infected horses and sphingomyelins that were increased only in the serum of vaccinated horses. This is the first report looking at the equine serum lipidome during leptospiral infection and vaccination.

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“…Mice were maintained on a 12h/12h light-dark cycle and body weight was measured weekly. Mice were euthanized and tissue from the corpus callosum was collected for RNA extraction as previously reported (Yamamoto et al, 2014). Briefly, gross coronal cuts were sectioned at approximately Bregma −0.25 mm and −1.25 mm.…”

Section: Methodsmentioning

confidence: 99%

The flavonoid Baicalein attenuates cuprizone-induced demyelination via suppression of neuroinflammation

Hashimoto

Yamamoto

Iwasa

et al. 2017

Brain Research Bulletin

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Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by recurrent and progressive demyelination/remyelination cycles, neuroinflammation, oligodendrocyte loss, and axonal pathology. Baicalein isolated from the roots of Scutellaria baicalensis has been shown to exert anti-inflammatory and antioxidant effects. The cuprizone model is an established mouse model of MS and causes demyelination and motor dysfunction and induces neuroinflammation, such as glial activation and pro-inflammatory cytokine production. To determine whether Baicalein attenuates cuprizone-induced demyelination, we administrated Baicalein to cuprizone-exposed mice. Baicalein attenuated weight loss (P<0.05) and motor dysfunction (P<0.05) in the cuprizone model mice. Baicalein treatment effectively suppressed the demyelination (P<0.01) and gene expressions of CNP (P<0.05) and MBP (P<0.05). Baicalein treatment also inhibited the cuprizone-induced increase in Iba1-positive microglia (P<0.001), GFAP-positive astrocytes (P<0.001), and the gene expressions of CD11b (P<0.01), GFAP (P<0.05), TNFα (P<0.05), IL-1β (P<0.05), and iNOS (p<0.01). We found that Baicalein treatment attenuated cuprizone-induced demyelination, glial activation, pro-inflammatory cytokine expression, and motor dysfunction. Our results suggest that Baicalein may be a useful therapeutic agent in demyelinating diseases to suppress neuroinflammation.

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Cyclic phosphatidic acid treatment suppress cuprizone-induced demyelination and motor dysfunction in mice

Cited by 33 publications

References 59 publications

Lesion Expansion in Experimental Demyelination Animal Models and Multiple Sclerosis Lesions

Lesion Expansion in Experimental Demyelination Animal Models and Multiple Sclerosis Lesions

Lipidomic analysis of immune activation in equine leptospirosis and Leptospira-vaccinated horses

The flavonoid Baicalein attenuates cuprizone-induced demyelination via suppression of neuroinflammation

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