期刊
EUROPEAN JOURNAL OF NEUROSCIENCE
卷 54, 期 3, 页码 5000-5015出版社
WILEY
DOI: 10.1111/ejn.15363
关键词
cognitive; ERK; hippocampal NSCs; ligustilide; post-operative cognitive dysfunction
资金
- Jiangxi Province's Science and Technology Agency Support Program [20202BAB216013]
- Second Affiliated Hospital of Nanchang University's Youth Innovation Team of science and technology program [2019YNQN12009]
- Jiangxi Province's Health and Family Planning Commission Traditional Chinese Medicine Program [2018B167]
This study demonstrated that Ligustilide can promote proliferation and neurogenesis of hippocampal neural stem cells (H-NSCs), reversing cognitive impairment caused by transient global cerebral ischemia and reperfusion (tGCI/R) injury. Furthermore, Ligustilide activates ERK1/2 to promote H-NSCs proliferation and neuronal differentiation, showing potential for the prevention and treatment of post-operative cognitive dysfunction (POCD).
Ligustilide exerts potential neuroprotective effects against various cerebral ischaemic insults and neurodegenerative disorders. However, the function and mechanisms of LIG-mediated hippocampal neural stem cells (H-NSCs) activation as well as cognitive recovery in the context of post-operative cognitive dysfunction (POCD) remain elusive and need to be explored. Mice were subjected to transient global cerebral ischaemia and reperfusion (tGCI/R) injury and treated with LIG (80 mg/kg) or vehicle for 1 month. Morris water maze test and western blot were employed to assess cognitive function. Nissl staining and immunofluorescence (IF) staining were used to detect H-NSCs proliferation and neurogenesis in hippocampus. Subsequently, primary H-NSCs were treated with LIG, and the level of H-NSCs proliferation and neuronal-differentiation was examined by IF staining for Edu and beta-Tubulin III. The protein levels of ERK1/2, beta-catenin, NICD, TLR4, Akt and FoxO1 were examined using western blotting. Finally, pretreatment with the ERK agonist SCH772984 was performed to observe the change in ERK expression. LIG treatment promoted H-NSCs proliferation and neurogenesis, increased the number of neurons in the hippocampal subfields, and ultimately reversed cognitive impairment in tGCI/R injury. Furthermore, LIG also promoted primary H-NSCs proliferation and neuronal-differentiation, as well as ERK1/2 phosphorylation. Pretreatment with SCH772984 effectively reversed the ability of LIG to induce ERK1/2 phosphorylation and promote H-NSCs proliferation and neuronal-differentiation. LIG can promote cognitive recovery after tGCI/R injury by activating ERK1/2 in H-NSCs to promote their proliferation and neurogenesis in the hippocampus. Therefore, LIG has potential for use in the prevention and/or treatment of POCD.
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