Chronic oleoylethanolamide treatment improves spatial cognitive deficits through enhancing hippocampal neurogenesis after transient focal cerebral ischemia.
Oleoylethanolamide (OEA) has been shown to have neuroprotective effects after acute cerebral ischemic injury. The aim of this study was to investigate the effects of chronic OEA treatment on ischemia-induced spatial cognitive impairments, electrophysiology behavior and hippocampal neurogenesis. Daily treatments of 30 mg/kg OEA significantly ameliorated spatial cognitive deficits and attenuated the inhibition of long-term potentiation (LTP) in the middle cerebral artery occlusion (MCAO) rat model. Moreover, OEA administration improved cognitive function in a manner associated with enhanced neurogenesis in the hippocampus. Further study demonstrated that treatment with OEA markedly increased the expressions of brain-derived neurotrophic factor (BDNF) and peroxisome proliferator-activated receptors α (PPARα). Our data suggest that chronic OEA treatment can exert functional recovery of cognitive impairments and neuroprotective effects against cerebral ischemic insult in rats via triggering of neurogenesis in the hippocampus, which supports the therapeutic use of OEA for cerebral ischemia.
Xiamen Key Laboratory of Chiral Drugs, Medical College, Xiamen University, Xiang'an District, Xiamen 361102, China.
Li-Chao
LC
Yang
Xiamen Key Laboratory of Chiral Drugs, Medical College, Xiamen University, Xiang'an District, Xiamen 361102, China.
Han
H
Guo
Xiamen Key Laboratory of Chiral Drugs, Medical College, Xiamen University, Xiang'an District, Xiamen 361102, China.
Hao
H
Zhou
Xiamen Key Laboratory of Chiral Drugs, Medical College, Xiamen University, Xiang'an District, Xiamen 361102, China.
Da-Qin
DQ
Suo
Xiamen Key Laboratory of Chiral Drugs, Medical College, Xiamen University, Xiang'an District, Xiamen 361102, China.
Wen-Jun
WJ
Li
Xiamen Key Laboratory of Chiral Drugs, Medical College, Xiamen University, Xiang'an District, Xiamen 361102, China.
Yu
Y
Zhou
Xiamen Key Laboratory of Chiral Drugs, Medical College, Xiamen University, Xiang'an District, Xiamen 361102, China.
Yun
Y
Zhao
Department of Neurosurgery, Xiamen Traditional Chinese Medicine Hospital, Xiamen 361005, China.
Wu-Shuang
WS
Yang
Xiamen Key Laboratory of Chiral Drugs, Medical College, Xiamen University, Xiang'an District, Xiamen 361102, China. Electronic address: xinjin@xmu.edu.cn.
Xin
X
Jin
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy / Q000523:psychology*; D018891:Dentate Gyrus / Q000187:drug effects / Q000503:physiopathology; D063388:Endocannabinoids; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D055495:Neurogenesis; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009829:Oleic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D047493:PPAR alpha / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D065853:Spatial Learning / Q000187:drug effects*
D019208:Brain-Derived Neurotrophic Factor; D063388:Endocannabinoids; D009829:Oleic Acids; D047493:PPAR alpha; C488250:oleoylethanolamide
3-Aminobenzamide (PubChem CID: 1645); 3′-Azido-deoxythymidine (PubChem CID: 451515); 5-Bromo-2′-deoxyuridine (PubChem CID: 6035); Focal cerebral ischemia; Hippocampal neurogenesis; Oleoylethanolamide; Oleoylethanolamide (PubChem CID: 5283454); Rats; Spatial cognitive function