Contributions
Abstract: EP1493
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Neurobiology
CPI-17, encoded by the gene ppp1r14a, is a 17 kDa cytosolic protein that functions as a potent inhibitor of certain type 1 protein serine/threonine phosphatases (e.g. smooth muscle myosin light-chain phosphatase (MLCP)). In the central nervous system, CPI-17 is, besides by smooth muscle cells, specifically expressed by mature oligodendrocytes. The role of CPI-17 for oligodendrocyte physiology and pathology is not known.
The aim of this study was to examine the role of CPI-17 during experimental demyelination. CPI-17 -/- and wildtype C57/BL6J mice were fed cuprizone for 1, 3, and 5 weeks and densities of myelin (anti-PLP, LFB/PAS stain), microglia (anti-IBA1), and oligodendrocytes (anti-OLIG2) were compared. Furthermore, extent of acute axonal injury was quantified in anti-APP stained sections.
Immunohistochemical studies showed that CPI-17 is exclusively expressed in mature oligodendrocytes. CPI-17 expressing cells are lost under various demyelinating conditions including the cuprizone model. At week 1 and 3, loss of mature oligodendrocytes was more severe in CPI-17 -/- compared to wildtype mice. This was paralleled by more severe microgliosis in CPI-17 -/- mice. Surprisingly, at week 5, the peak of cuprizone induced demyelination, anti-PLP and LFB/PAS stained sections showed severe demyelination in wildtype but not CPI-17-/- mice.
In this study, we identified a novel regulator of oligodendrocyte pathology. Future studies are now needed to understand how CPI-17 regulates remyelionation.
Disclosure: nothing to disclose
Abstract: EP1493
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Neurobiology
CPI-17, encoded by the gene ppp1r14a, is a 17 kDa cytosolic protein that functions as a potent inhibitor of certain type 1 protein serine/threonine phosphatases (e.g. smooth muscle myosin light-chain phosphatase (MLCP)). In the central nervous system, CPI-17 is, besides by smooth muscle cells, specifically expressed by mature oligodendrocytes. The role of CPI-17 for oligodendrocyte physiology and pathology is not known.
The aim of this study was to examine the role of CPI-17 during experimental demyelination. CPI-17 -/- and wildtype C57/BL6J mice were fed cuprizone for 1, 3, and 5 weeks and densities of myelin (anti-PLP, LFB/PAS stain), microglia (anti-IBA1), and oligodendrocytes (anti-OLIG2) were compared. Furthermore, extent of acute axonal injury was quantified in anti-APP stained sections.
Immunohistochemical studies showed that CPI-17 is exclusively expressed in mature oligodendrocytes. CPI-17 expressing cells are lost under various demyelinating conditions including the cuprizone model. At week 1 and 3, loss of mature oligodendrocytes was more severe in CPI-17 -/- compared to wildtype mice. This was paralleled by more severe microgliosis in CPI-17 -/- mice. Surprisingly, at week 5, the peak of cuprizone induced demyelination, anti-PLP and LFB/PAS stained sections showed severe demyelination in wildtype but not CPI-17-/- mice.
In this study, we identified a novel regulator of oligodendrocyte pathology. Future studies are now needed to understand how CPI-17 regulates remyelionation.
Disclosure: nothing to disclose