Dataset Information


Genetic ablation of IP3 receptor 2 increases cytokines and decreases survival of SOD1G93A mice.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease characterized by the selective death of motor neurons. Disease pathophysiology is complex and not yet fully understood. Higher gene expression of the inositol 1,4,5-trisphosphate receptor 2 gene (ITPR2), encoding the IP3 receptor 2 (IP3R2), was detected in sporadic ALS patients. Here, we demonstrate that IP3R2 gene expression was also increased in spinal cords of ALS mice. Moreover, an increase of IP3R2 expression was observed in other models of chronic and acute neurodegeneration. Upregulation of IP3R2 gene expression could be induced by lipopolysaccharide (LPS) in murine astrocytes, murine macrophages and human fibroblasts indicating that it may be a compensatory response to inflammation. Preventing this response by genetic deletion of ITPR2 from SOD1G93A mice had a dose-dependent effect on disease duration, resulting in a significantly shorter lifespan of these mice. In addition, the absence of IP3R2 led to increased innate immunity, which may contribute to the decreased survival of the SOD1G93A mice. Besides systemic inflammation, IP3R2 knockout mice also had increased IFN?, IL-6 and IL1? expression. Altogether, our data indicate that IP3R2 protects against the negative effects of inflammation, suggesting that the increase in IP3R2 expression in ALS patients is a protective response.


PROVIDER: S-EPMC5179944 | BioStudies | 2016-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2018-01-01 | S-EPMC5718158 | BioStudies
2017-01-01 | S-EPMC5625902 | BioStudies
2019-01-01 | S-EPMC6914819 | BioStudies
2018-01-01 | S-EPMC6048270 | BioStudies
2019-01-01 | S-EPMC6881366 | BioStudies
1000-01-01 | S-EPMC6065374 | BioStudies
2019-01-01 | S-EPMC6555856 | BioStudies
2014-04-22 | E-GEOD-56926 | BioStudies
2020-01-01 | S-EPMC7166237 | BioStudies
2020-01-01 | S-EPMC7200935 | BioStudies