Dataset Information

Changes in neurodegeneration-related miRNAs in brains from CAPN1^-/- mice.

ABSTRACT: Calpain-1 knock-out (KO) mice exhibit enhanced susceptibility to neurodegeneration due to the lack of the neuroprotective function of calpain-1. Dicer has been shown to play a fundamental role in the biogenesis of most miRNAs. Here, we identified 45 differentially expressed miRNAs (DE miRNAs) in the brain of calpain-1 KO mice, as compared to wild-type mice. In particular, among all the DE miRNAs, 7 neurodegeneration-related miRNAs were found to be down-regulated in calpain-1 KO mice. We also found that Dicer is cleaved by calpain-1 in mouse brain, which generates an active fragment of Dicer with RNAse III activity and increases miRNA formation. Levels of active Dicer were reduced in brain homogenates from calpain-1 KO mice and incubation with calpain-1 and calcium restored Dicer activity and miRNA expression. Our results indicate that calpain-1 deletion results in decreased levels of active Dicer and changes in neurodegenerative-related miRNAs. These findings could account for some of the pathological changes found in brain of various mammals, including humans, with calpain-1 mutations or down-regulation.

SUBMITTER: Su W

PROVIDER: S-EPMC8289118 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Changes in neurodegeneration-related miRNAs in brains from CAPN1<sup>-/-</sup> mice.

Su Wenyue W Bi Xiaoning X Wang Yubin Y Baudry Michel M

BBA advances 20210213

Calpain-1 knock-out (KO) mice exhibit enhanced susceptibility to neurodegeneration due to the lack of the neuroprotective function of calpain-1. Dicer has been shown to play a fundamental role in the biogenesis of most miRNAs. Here, we identified 45 differentially expressed miRNAs (DE miRNAs) in the brain of calpain-1 KO mice, as compared to wild-type mice. In particular, among all the DE miRNAs, 7 neurodegeneration-related miRNAs were found to be down-regulated in calpain-1 KO mice. We also fou ...[more]

PMID: 34286311

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Project description:Some recent studies suggest that in progressive multiple sclerosis, neurodegeneration may occur independently from inflammation. The aim of our study was to analyse the interdependence of inflammation, neurodegeneration and disease progression in various multiple sclerosis stages in relation to lesional activity and clinical course, with a particular focus on progressive multiple sclerosis. The study is based on detailed quantification of different inflammatory cells in relation to axonal injury in 67 multiple sclerosis autopsies from different disease stages and 28 controls without neurological disease or brain lesions. We found that pronounced inflammation in the brain is not only present in acute and relapsing multiple sclerosis but also in the secondary and primary progressive disease. T- and B-cell infiltrates correlated with the activity of demyelinating lesions, while plasma cell infiltrates were most pronounced in patients with secondary progressive multiple sclerosis (SPMS) and primary progressive multiple sclerosis (PPMS) and even persisted, when T- and B-cell infiltrates declined to levels seen in age matched controls. A highly significant association between inflammation and axonal injury was seen in the global multiple sclerosis population as well as in progressive multiple sclerosis alone. In older patients (median 76 years) with long-disease duration (median 372 months), inflammatory infiltrates declined to levels similar to those found in age-matched controls and the extent of axonal injury, too, was comparable with that in age-matched controls. Ongoing neurodegeneration in these patients, which exceeded the extent found in normal controls, could be attributed to confounding pathologies such as Alzheimer's or vascular disease. Our study suggests a close association between inflammation and neurodegeneration in all lesions and disease stages of multiple sclerosis. It further indicates that the disease processes of multiple sclerosis may die out in aged patients with long-standing disease.

Dataset Information

Changes in neurodegeneration-related miRNAs in brains from CAPN1^-/- mice.

Publications

Changes in neurodegeneration-related miRNAs in brains from CAPN1<sup>-/-</sup> mice.

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Dataset Information

Changes in neurodegeneration-related miRNAs in brains from CAPN1-/- mice.

Publications

Changes in neurodegeneration-related miRNAs in brains from CAPN1<sup>-/-</sup> mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Changes in neurodegeneration-related miRNAs in brains from CAPN1^-/- mice.