Dataset Information

Development of a Chemical Cocktail That Rescues Mouse Brain Demyelination in a Cuprizone-Induced Model.

ABSTRACT: Oligodendrocytes are glial cells located in the central nervous system (CNS) that play essential roles in the transmission of nerve signals and in the neuroprotection of myelinated neurons. The dysfunction or loss of oligodendrocytes leads to demyelinating diseases such as multiple sclerosis (MS). To treat demyelinating diseases, the development of a therapy that promotes remyelination is required. In the present study, we established an in vitro method to convert human fibroblasts into induced oligodendrocyte-like cells (iOLCs) in 3 days. The induced cells displayed morphologies and molecular signatures similar to oligodendrocytes after treatment with valproic acid and exposure to the small molecules Y27632, SU9516, and forskolin (FSK). To pursue the development of a cell-free remyelination therapy in vivo, we used a cuprizone-induced demyelinated mouse model. The small molecules (Y27632, SU9516, and FSK) were directly injected into the demyelinated corpus callosum of the mouse brain. This combination of small molecules rescued the demyelination phenotype within two weeks as observed by light and electron microscopy. These results provide a foundation for exploring the development of a treatment for demyelinating diseases via regenerative medicine.

SUBMITTER: Lai PL

PROVIDER: S-EPMC8997971 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Development of a Chemical Cocktail That Rescues Mouse Brain Demyelination in a Cuprizone-Induced Model.

Lai Pei-Lun PL Ng Chi-Hou CH Wu Chia-Hsin CH Lai Chien-Ying CY Schuyler Scott C SC Wang Vicki V Lin Hsuan H Lee Yueh-Chang YC Chuang Ming-Hsi MH Yang Chang-Huan CH Chen Wei-Ju WJ Huang Hsiao-Chun HC Lu Jean J

Cells 20220324 7

Oligodendrocytes are glial cells located in the central nervous system (CNS) that play essential roles in the transmission of nerve signals and in the neuroprotection of myelinated neurons. The dysfunction or loss of oligodendrocytes leads to demyelinating diseases such as multiple sclerosis (MS). To treat demyelinating diseases, the development of a therapy that promotes remyelination is required. In the present study, we established an in vitro method to convert human fibroblasts into induced ...[more]

PMID: 35406658

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Project description:BackgroundVarious studies by MRI exhibit that the corpus callosum (CC) is the most vulnerable to cuprizone administration, detecting the demyelination and remyelination process using different MRI parameters are, however, lacking.PurposeTo investigate the sensitivity of multiparametric MRI both in vivo and ex vivo for demyelination and remyelination.Study typeProspective.Animal modelA cuprizone mice model with an age-matched control group (n = 5), 4-week cuprizone exposure group followed by 9-week on a normal diet (n = 6), and a 13-week cuprizone exposure group (n = 6).Field strength/sequence3D gradient recalled echo, T2 -weighted, and diffusion tensor imaging (DTI) at 7.0T and 9.4T.AssessmentQuantification of DTI metrics, quantitative susceptibility mapping (QSM), and T2 -weighted imaging intensity in major white matter bundles.Statistical testsNonparametric permutation tests were used with a cluster-forming threshold as 3.09 (equivalent to P = 0.001), and the significant level as P = 0.05 with family-wise correction.ResultsIn vivo susceptibility values increased from -11.7 to -0.7 ppb (P < 0.001) in CC and from -13.7 to -5.1 ppb (P < 0.001) in the anterior commissure (AC) after the 13-week cuprizone exposure. Ex vivo susceptibility values increased from -25.4 to 7.4 ppb (P < 0.001) in CC and from -41.6 to -15.8 ppb (P < 0.001) in AC. Susceptibility values showed high variations to demyelination for in vivo studies (94.0% in CC, 62.8% in AC). Susceptibility values exhibited higher variations than radial diffusivity for ex vivo studies (129.1% vs. 28.3% in CC, 62.0% vs. 25.0% in AC). In addition to the differential susceptibility variations in different white matter tracts, intraregional demyelination variation was also present not only in CC but also in the AC area by voxel-based analysis.Data conclusionQSM is sensitive to the demyelination process of cuprizone exposure, which can be a complementary technique to conventional T2 -weighted images and DTI metrics.Level of evidence2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:1852-1865.

Dataset Information

Development of a Chemical Cocktail That Rescues Mouse Brain Demyelination in a Cuprizone-Induced Model.

Publications

Development of a Chemical Cocktail That Rescues Mouse Brain Demyelination in a Cuprizone-Induced Model.

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