PMID- 26424009 OWN - NLM STAT- MEDLINE DCOM- 20160725 LR - 20151001 IS - 1347-5215 (Electronic) IS - 0918-6158 (Linking) VI - 38 IP - 10 DP - 2015 TI - Osthole Upregulates BDNF to Enhance Adult Hippocampal Neurogenesis in APP/PS1 Transgenic Mice. PG - 1439-49 LID - 10.1248/bpb.b15-00013 [doi] AB - Adult hippocampal neurogenesis occurs in the dentate gyrus (DG) of the mouse hippocampus, and plays roles in learning and memory progresses. In amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice, a rodent model of Alzheimer's disease (AD), severe impairment of neurogenesis in the dentate subgranular zone (SGZ) of the DG has been reported. Osthole, an active constituent of Cnidium monnieri (L.) CUSSON, has been reported to exert neuroprotective effects and may promote neural stem cell proliferation. However, whether osthole ameliorates spatial memory deficits and improves hippocampal neurogenesis in APP/PS1 mice remains unknown. In this study we found that osthole (30 mg/kg intraperitoneally (i.p.) once daily) treatment dramatically ameliorated the cognitive impairments by Morris Water Maze test and passive avoidance test, and augmented neurogenesis in the DG of hippocampus in APP/PS1 mice. Furthermore, osthole treatment upregulated expression of brain-derived neurotrophic factor (BDNF) and enhanced activation of the BDNF receptor tyrosine receptor kinase B (TrkB) following increased phosphorylation of cyclic AMP response element-binding protein (CREB), indicating that osthole improves neurogenesis via stimulating BDNF/TrkB/CREB signaling in APP/PS1 transgenic mice. FAU - Liu, Hong AU - Liu H AD - Department of Neurology, Liaocheng Hospital. FAU - Xue, Xinhong AU - Xue X FAU - Shi, Huijian AU - Shi H FAU - Qi, Lifeng AU - Qi L FAU - Gong, Dianrong AU - Gong D LA - eng PT - Journal Article PL - Japan TA - Biol Pharm Bull JT - Biological & pharmaceutical bulletin JID - 9311984 RN - 0 (Amyloid beta-Peptides) RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Coumarins) RN - 0 (Creb1 protein, mouse) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Neuroprotective Agents) RN - 0 (Peptide Fragments) RN - 0 (Presenilin-1) RN - 0 (amyloid beta-protein (1-40)) RN - 0 (presenilin 1, mouse) RN - XH1TI1759C (osthol) SB - IM MH - Alzheimer Disease/drug therapy MH - Amyloid beta-Peptides/metabolism MH - Amyloid beta-Protein Precursor/genetics MH - Animals MH - Avoidance Learning/drug effects MH - Behavior, Animal/drug effects MH - Brain-Derived Neurotrophic Factor/biosynthesis MH - Coumarins/*pharmacology/therapeutic use MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Disease Models, Animal MH - Hippocampus/*drug effects/metabolism/physiology MH - Male MH - Maze Learning/drug effects MH - Memory/drug effects MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Neurogenesis/*drug effects MH - Neuroprotective Agents/*pharmacology/therapeutic use MH - Peptide Fragments/metabolism MH - Presenilin-1/genetics MH - Up-Regulation EDAT- 2015/10/02 06:00 MHDA- 2016/07/28 06:00 CRDT- 2015/10/02 06:00 PHST- 2015/10/02 06:00 [entrez] PHST- 2015/10/02 06:00 [pubmed] PHST- 2016/07/28 06:00 [medline] AID - 10.1248/bpb.b15-00013 [doi] PST - ppublish SO - Biol Pharm Bull. 2015;38(10):1439-49. doi: 10.1248/bpb.b15-00013.