PMID- 26976092 OWN - NLM STAT- MEDLINE DCOM- 20180209 LR - 20191114 IS - 1095-9564 (Electronic) IS - 1074-7427 (Linking) VI - 131 DP - 2016 May TI - GPR40 receptor activation leads to CREB phosphorylation and improves cognitive performance in an Alzheimer's disease mouse model. PG - 46-55 LID - S1074-7427(16)00065-4 [pii] LID - 10.1016/j.nlm.2016.03.006 [doi] AB - Alzheimer's disease (AD) is a very complex neurodegenerative disorder as neuronal loss is a prominent and initial feature of AD. This loss correlates with cognitive deficits more closely than amyloid load. GPR40 receptor belongs to the class of G-protein coupled receptors, is expressed in wide parts of the brain including the hippocampus which is involved in spatial learning and memory. Till now, there are few studies investigating the functional role of GPR40 in brain. In this study, we evaluated the functional role of GPR40 receptor in the A-beta AD mice model. Administration of Abeta1-42 (410pmol) intracerebroventricularly (i.c.v.) once at the beginning of experiment significantly impaired cognitive performance (in step-through passive test), the ability of spatial learning and memory in (Morris water maze test), working memory, attention, anxiety in (Novel object recognition test), and spatial working and reference-memory in (Hole board discrimination test) compared with the control group. The results revealed that GPR40 receptor treatment groups significantly ameliorated model mice cognitive performance. All GPR40 receptor agonist GW9508, treatment groups enhanced the learning and memory ability in Step-through passive test, Morris water maze test, Hole board discrimination test, Novel object recognition test. Furthermore, we have observed that activation of GPR40 receptor provoked the phosphorylation of the cAMP response element binding protein (CREB) and significant increase in neurotropic factors including brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), neurotrohin-4 (NT-4) in mouse hippocampal neurons and contribute to neurogenesis. These results suggest that GPR40 is a suitable therapeutic candidate for neurogenesis and neuroprotection in the treatment and prevention of AD. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Khan, Muhammad Zahid AU - Khan MZ AD - Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China. FAU - Zhuang, Xuxu AU - Zhuang X AD - Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China. FAU - He, Ling AU - He L AD - Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: heling92@hotmail.com. LA - eng PT - Journal Article DEP - 20160311 PL - United States TA - Neurobiol Learn Mem JT - Neurobiology of learning and memory JID - 9508166 RN - 0 (Amyloid beta-Peptides) RN - 0 (Ffar1 protein, mouse) RN - 0 (GW9508) RN - 0 (Methylamines) RN - 0 (Nerve Growth Factors) RN - 0 (Neuroprotective Agents) RN - 0 (Peptide Fragments) RN - 0 (Propionates) RN - 0 (Receptors, G-Protein-Coupled) RN - 0 (amyloid beta-protein (1-42)) RN - EC 2.3.1.48 (CREB-Binding Protein) RN - EC 2.3.1.48 (Crebbp protein, mouse) SB - IM MH - Alzheimer Disease/chemically induced/physiopathology/*prevention & control MH - Amyloid beta-Peptides/*pharmacology MH - Animals MH - Behavior, Animal/physiology MH - CREB-Binding Protein/*metabolism MH - Cognitive Dysfunction/chemically induced/physiopathology/*prevention & control MH - Disease Models, Animal MH - Hippocampus/*metabolism MH - Male MH - Methylamines/administration & dosage/*pharmacology MH - Mice MH - Mice, Inbred ICR MH - Nerve Growth Factors/drug effects/*metabolism MH - Neuroprotective Agents/administration & dosage/*pharmacology MH - Peptide Fragments/*pharmacology MH - Propionates/administration & dosage/*pharmacology MH - Receptors, G-Protein-Coupled/agonists/*metabolism MH - Spatial Learning/drug effects/physiology MH - Spatial Memory/drug effects/physiology OTO - NOTNLM OT - Alzheimer's disease OT - Behavioral tests OT - GPR40 receptor OT - Neurotropic factors OT - Spatial learning and memory OT - cAMP response element binding protein EDAT- 2016/03/16 06:00 MHDA- 2018/02/10 06:00 CRDT- 2016/03/16 06:00 PHST- 2015/09/22 00:00 [received] PHST- 2016/02/01 00:00 [revised] PHST- 2016/03/05 00:00 [accepted] PHST- 2016/03/16 06:00 [entrez] PHST- 2016/03/16 06:00 [pubmed] PHST- 2018/02/10 06:00 [medline] AID - S1074-7427(16)00065-4 [pii] AID - 10.1016/j.nlm.2016.03.006 [doi] PST - ppublish SO - Neurobiol Learn Mem. 2016 May;131:46-55. doi: 10.1016/j.nlm.2016.03.006. Epub 2016 Mar 11.