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.
aDepartment of Pharmacy, Xiamen Medical College
bKey Laboratory of Chiral Drugs, School of Medicine, Xiamen University
cXiang’an Branch, The First Affiliated Hospital of Xiamen University
dThe Fifth Hospital of Xiamen
eDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
Received 1 September 2019 Accepted 20 September 2019
Correspondence to Juan Zhou, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361101, China., Tel: + 86 592 2139531; fax: +86 592 2317301; e-mail: email@example.com