Adenosine A1-Receptors Modulate mTOR Signaling to Regulate White Matter Inflammatory Lesions Induced by Chronic Cerebral Hypoperfusion.
We sought to investigate the role of the adenosine A1 receptors (A1ARs) in white matter lesions under chronic cerebral hypoperfusion (CCH) and explore the potential repair mechanisms by activation of the receptors. A right unilateral common carotid artery occlusion (rUCCAO) method was used to construct a CCH model. 2-chloro-N6-cyclopentyladenosine (CCPA), a specific agonist of A1ARs, was used to explore the biological mechanisms of repair in white matter lesions under CCH. The expression of mammalian target of rapamycin (mTOR), phosphorylation of mTOR (P-mTOR), myelin basic protein (MBP, a marker of white matter myelination) were detected by Western-blot. Pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and anti-inflammatory cytokine interleukin-10 (IL-10) levels were determined by ELISA. Compared with the control groups on week 2, 4 and 6, in CCPA-treated groups, the ratio of P-mTOR/mTOR, expression of MBP and IL-10 increased markedly, while the expression of TNF-α reduced at week 6. In conclusion, A1ARs appears to reduce inflammation in white matter via the mTOR signaling pathway in the rUCCAO mice. Therefore, A1ARs may serve as a therapeutic target during the repair of white matter lesions under CCH.
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Pengfei
P
Cheng
Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
Xuzheng
X
Zuo
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Yifei
Y
Ren
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Shunjie
S
Bai
Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
Weiju
W
Tang
Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
Xiuying
X
Chen
Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
Gong
G
Wang
Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
Haoxiang
H
Wang
Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China. huang_wen2015@sina.com.
Wen
W
Huang
Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. xiepeng973@163.com.
Peng
P
Xie
D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D017536:Carotid Artery, Common / Q000473:pathology; D016893:Carotid Stenosis / Q000150:complications; D007249:Inflammation / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D056784:Leukoencephalopathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D008026:Ligation; D008297:Male; D008810:Mice, Inbred C57BL; D004676:Myelin Basic Protein / Q000378:metabolism; D010766:Phosphorylation; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004676:Myelin Basic Protein; D043682:Receptor, Adenosine A1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases
Adenosine A1-receptor; Chronic cerebral hypoperfusion; Inflammatory; White matter; mTOR
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