Li Ying, Ren Tong, Xu Lanxi, Wang Ying, Yang Bingye, Luo Haohong, Zeng Zhen, Zhang Yanan, Du Guicheng, Zhu Maoshu, Zhou Juan
Department of Pharmacy, Xiamen Medical College.
Key Laboratory of Chiral Drugs, School of Medicine, Xiamen University.
Neuroreport. 2019 Dec 18;30(18):1299-1306. doi: 10.1097/WNR.0000000000001360.
Our previous studies showed that propane-2-sulfonic acid octadec-9-enyl-amide (N15), a novel peroxisome proliferator-activated receptors α and γ (PPARα/γ) dual agonist, protected against ischaemia-induced acute brain damage in mice and improved cognitive ability in the chronic phase of ischaemic stroke. It is well known that hippocampal neurogenesis is closely related to cognitive function. In the present study, we investigated the effect of N15 on hippocampal neurogenesis and neuroplasticity in a middle cerebral artery occlusion (MCAO) rat model. The middle cerebral artery of rats was blocked for 2 hours. Oral administration of 100 mg/kg N15 or vehicle was given once daily for days 2-13 after MCAO. The newly mature neurons were detected by staining. The expressions of synapse-related proteins were observed by qRT-PCR or western blotting. We found that N15-treated rats showed improved survival post-MCAO. In addition, N15 treatment markedly increased the newly mature neurons and enhanced the expression levels of growth-associated protein-43, synaptophysin, brain-derived neurotrophic factor and neurotrophin-3 in the hippocampus. Moreover, N15 promoted the activation of PPARα and PPARγ on day 7 and 14 after cerebral ischaemia. These results reveal that N15 may promote neurogenesis and neuroplasticity in MCAO rats through the activation of the PPARα/γ dual signal pathway.
我们之前的研究表明，新型过氧化物酶体增殖物激活受体α和γ（PPARα/γ）双重激动剂十八碳-9-烯基丙烷-2-磺酸酰胺（N15）可保护小鼠免受缺血诱导的急性脑损伤，并改善缺血性中风慢性期的认知能力。众所周知，海马神经发生与认知功能密切相关。在本研究中，我们在大脑中动脉闭塞（MCAO）大鼠模型中研究了N15对海马神经发生和神经可塑性的影响。将大鼠大脑中动脉阻断2小时。在MCAO后的第2 - 13天，每天口服给予100 mg/kg N15或赋形剂一次。通过染色检测新成熟的神经元。通过qRT-PCR或蛋白质印迹观察突触相关蛋白的表达。我们发现，经N15处理的大鼠在MCAO后存活率提高。此外，N15处理显著增加了新成熟的神经元，并增强了海马中生长相关蛋白-43、突触素、脑源性神经营养因子和神经营养因子-3的表达水平。此外，N15在脑缺血后第7天和第14天促进了PPARα和PPARγ的激活。这些结果表明，N15可能通过激活PPARα/γ双信号通路促进MCAO大鼠的神经发生和神经可塑性。
