title: Effect of delta opioid receptor activation on spatial cognition and neurogenesis in cerebral ischemic rats.
abstract: This study aimed to investigate whether a selective delta opioid receptor agonist, [D-Ala2, D-Leu5]-Enkephalin (DADLE), regulates neurogenesis in the hippocampus of ischemic rats. Using an intracerebral cannula, rats were subjected to cerebral ischemia using the standard four-vessel occlusion. DADLE (2.5nmol), DADLE (2.5nmol) with naltrindole (NAL) (2.5nmol), or vehicle was administered at the onset of reperfusion. Bromodeoxyuridine (BrdU, 100mg/kg, intraperitoneal) was used to label newly formed cells from days 1 to 7 after ischemia. Immunohistochemistry was used to evaluate cell proliferation and apoptosis and differentiation 7days 28 days, respectively, after ischemia. Morris water maze test was conducted to test spatial learning and memory 23-27 days after ischemia. We found that DADLE treatment improved performance in the Morris water maze test, promoted proliferation and differentiation of newly formed neurons, and inhibited differentiation into astrocytes in a rat model of cerebral ischemia. Furthermore, the protective effects of DADLE were significantly reversed by co-administration of NAL (P<0.05), a highly potent and selective delta opioid receptor antagonist. Our findings suggest that DADLE promotes spatial cognitive function recovery and regulates neurogenesis after ischemia, which may provide a promising therapeutic strategy for cerebral ischemia.
authors.affiliation: Department of Anesthesiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
authors.forename: Shu-Yan
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, East China Normal University, Shanghai 200062, China.
authors.forename: Ya-Le
authors.initials: YL
authors.lastname: Duan
authors.affiliation: Department of Anesthesiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200062, China.
authors.forename: Xiang-Rui
authors.initials: XR
authors.lastname: Wang
authors.affiliation: Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, East China Normal University, Shanghai 200062, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China. Electronic address: zhangguangming967@163.com.
authors.forename: Guang-Ming
authors.initials: GM
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D002454:Cell Differentiation; D049109:Cell Proliferation; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D055495:Neurogenesis; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists*; D065853:Spatial Learning / Q000187:drug effects*
chemical_list: D018696:Neuroprotective Agents; D017465:Receptors, Opioid, delta; D016308:Enkephalin, Leucine-2-Alanine
keywords: Cerebral ischemia; DADLE; Delta-opioid receptor; Neurogenesis; Spatial cognition