The role of interleukin-10 in regulating neuroinflammation relevant to tauopathies

Identification: Weston, Lea


Description

The role of interleukin-10 in regulating neuroinflammation relevant to tauopathies
 
Lea L Weston1, Shanya Jiang1, Devon Chisholm1, Kiran Bhaskar1
1University of New Mexico Health Sciences Center
      
Tauopathies include a number of neurodegenerative diseases associated with pathological formations of microtubule associated protein tau (MAPT or tau) in the brain. Neuroinflammation is a common feature of tauopathies and data shows that microglia-mediated inflammation promotes tau phosphorylation, a signature of tau pathology. Given that the anti-inflammatory cytokine, interleukin-10 (IL-10), can suppress pro-inflammatory microglia responses, we hypothesize that IL-10 has a role in regulating neuroinflammation that promotes tau pathology. We used two in vivo approaches to model the effects of inflammation on tau and determine the role of IL-10 in the progression of tau pathology. First, we compared the effects of lipopolysaccharide (LPS)-induced inflammation on endogenous mouse tau in Il10-deficient versus wildtype C57BL/6 control mice. Brains were perfused and microdissected to determine neuroinflammation and tau phosphorylation using qPCR, MSD, Western blot and IHC. The Il10-deficient mice injected with LPS showed significantly enhanced tau phosphorylation within 24 h in the hippocampus compared to LPS injected wildtype mice. Interestingly, levels of total tau were significantly reduced in LPS-injected Il10-deficient mice compared to vehicle injected Il10-deficient and wildtype control mice (with or without LPS). LPS injected Il10-deficient mice had significantly elevated levels of activated p38 mitogen activated protein kinase (p38 MAPK) compared to LPS injected wildtype mice. In the second approach, we examined the effects of Il10 deficiency in our human tau (hTau) transgenic mouse model by crossing Il10-deficient mice to our hTau mice. Brains were perfused and microdissected to determine neuroinflammation and tau phosphorylation using qPCR, MSD, Western blot and IHC. Preliminary examination of our Il10-deficient hTau mice showed no significant differences in tau pathology in Il10-deficient hTau versus control hTau mice at early time points. However, several more target mice have been generated and will be added to the study. Our results suggest IL-10 plays a role in limiting inflammation-induced tau pathology in C57BL/6 mice. Currently, preliminary data on Il10-deficient hTau mice are insufficient to determine the role of IL-10 in our genomic model of tauopathy and the study is still in progress.
 

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