Abstract
Recent studies have demonstrated that inflammatory and immune mechanisms play important roles in the progression of chronic cerebral hypoperfusion (CCH)-induced white matter lesions (WMLs). As an endogenous neuromodulator in the brain, the extracellular levels of adenosine represent a critical endogenous mechanism for the regulation of immune and inflammatory responses. Ecto-5′-nucleotidase (CD73), which dephosphorylates AMP to adenosine, is considered to catalyze the rate-limiting step in the generation of extracellular adenosine. However, the role of CD73 in the development of CCH-induced WMLs remains unclear. In the present study, we investigated the expression and activity of CD73 using immunohistochemistry, Western blot analysis and measurements of the rate of AMP hydrolysis in a mouse model of CCH via bilateral common carotid artery stenosis (BCAS) surgery. Moreover, C57BL/6-CD73 knockout (KO) and their wild-type littermates were subjected to BCAS surgery to further investigate the functional roles of CD73 in the WMLs. White matter (WM) changes, astrocyte and microglia proliferation, proinflammatory cytokine levels in the corpus callosum and cognitive function were assessed on the 30th day after BCAS. The results indicated that CD73 expression and activities significantly increased in the corpus callosum on the 30th day after BCAS. Moreover, CD73 deficiency exacerbated CCH-induced WMLs and cognitive impairment. More reactive astrocytes and microglia were observed in the corpus callosum in CD73-KO mice. CD73 deficiency significantly increased the levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the BCAS model of CCH. These findings suggest that CD73 plays a protective role in the development of CCH-induced WMLs and cognitive impairment via the regulation of glial cell activation and proinflammatory cytokine expression.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
