title: Catalpol promotes oligodendrocyte survival and oligodendrocyte progenitor differentiation via the Akt signaling pathway in rats with chronic cerebral hypoperfusion.
abstract: Chronic cerebral hypoperfusion is thought to induce white matter lesions (WMLs), which contribute to cognitive impairment. Although inflammation and oligodendrocyte apoptosis are believed to be involved in the pathogenesis of WMLs, effective therapies have not been identified yet. This study investigated whether catalpol, an iridoid glycoside, can alleviate WMLs by promoting oligodendrocyte survival and oligodendrocyte progenitor differentiation via the Akt signaling pathway in rats with chronic cerebral hypoperfusion. A rat model of chronic cerebral hypoperfusion was created through permanent occlusion of bilateral common carotid arteries. Catalpol (5mg/kg) or saline was intraperitoneally administered daily for 10 days following the operation. On the 30th day after surgery, inflammation, oligodendrocyte apoptosis, and myelin damage in the ischemic white matter were more severe and evident than in the sham control group. Treatment with catalpol significantly suppressed white matter inflammation and attenuated oligodendrocyte apoptosis and myelin damage. The expression of phosphorylated Akt (p-Akt) and the number of mature oligodendrocytes were also markedly increased by catalpol treatment, and these effects were reversed by the PI3K inhibitor LY294002. In conclusion, catalpol attenuates hypoperfusion-induced WMLs by promoting oligodendrocyte survival and oligodendrocyte progenitor differentiation through the Akt signaling pathway. Our results suggest that catalpol may be a candidate for treating cerebrovascular WMLs.
authors.affiliation: Department of Histology and Embryology, College of Basic Medicine, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Qiyan
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Department of Histology and Embryology, College of Basic Medicine, The Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhongxiang
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Histology and Embryology, College of Basic Medicine, The Third Military Medical University, Chongqing 400038, China. Electronic address: lihongli@tmmu.edu.cn.
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D017536:Carotid Artery, Common; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D002867:Chromones / Q000494:pharmacology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D057888:Iridoid Glucosides / Q000494:pharmacology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D058953:Neural Stem Cells / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009836:Oligodendroglia / Q000187:drug effects* / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D057888:Iridoid Glucosides; D009025:Morpholines; D018696:Neuroprotective Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; C078040:catalpol; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; Catalpol; Chronic cerebral hypoperfusion; Oligodendrocyte; Oligodendrocyte progenitor; White matter lesions