PMID- 25014004 OWN - NLM STAT- MEDLINE DCOM- 20150716 LR - 20191210 IS - 1872-7549 (Electronic) IS - 0166-4328 (Linking) VI - 272 DP - 2014 Oct 1 TI - An enriched environment ameliorates memory impairments in PACAP-deficient mice. PG - 269-78 LID - S0166-4328(14)00445-8 [pii] LID - 10.1016/j.bbr.2014.07.005 [doi] AB - We previously found that juvenile pituitary adenylate cyclase-activating polypeptide (PACAP)-knockout (PACAP(-/-)) mice reared in an enriched environment (EE) for 4 weeks showed attenuated hyperactivity, jumping behavior, impairments in social interaction, and depression-like behavior. The present study examined the effects of EE on memory function and memory-related protein levels in PACAP(-/-) mice. Eight-week-old PACAP(-/-) mice displayed fear memory dysfunction in a contextual fear conditioning test and cognitive impairments in a novel object recognition test. Rearing of 4-week-old PACAP(-/-) mice in an EE for 4 weeks ameliorated these memory impairments. The beneficial effects of EE were also observed 2 weeks after a return to housing in a standard environment (SE). This suggests that the effects of EE on impaired memory are long-lasting. In both wild-type and PACAP(-/-) mice, EE increased the protein levels of the NMDA receptor NR2B subunit, phospho-ERK, phospho-CaMKII, and brain-derived neurotrophic factor (BDNF) in the hippocampus, and decreased neurotrophin-3 levels, whereas it did not affect nerve growth factor and glial cell-derived neurotrophic factor levels. Increased levels of NR2B, phospho-ERK, phospho-CaMKII and BDNF were not observed 2 weeks after a return to housing in a SE. These findings suggest that living in an EE engenders long-lasting reductions in memory impairments in PACAP(-/-) mice. The present study also implies that increases in hippocampal memory-related protein and BDNF levels are responsible for the beneficial effects of an EE, but not for the maintenance of these effects. CI - Copyright (c) 2014 Elsevier B.V. All rights reserved. FAU - Takuma, Kazuhiro AU - Takuma K AD - Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita 565-0871, Osaka, Japan. FAU - Maeda, Yuko AU - Maeda Y AD - Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita 565-0871, Osaka, Japan. FAU - Ago, Yukio AU - Ago Y AD - Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita 565-0871, Osaka, Japan. FAU - Ishihama, Toshihiro AU - Ishihama T AD - Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita 565-0871, Osaka, Japan. FAU - Takemoto, Kosuke AU - Takemoto K AD - Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita 565-0871, Osaka, Japan. FAU - Nakagawa, Akira AU - Nakagawa A AD - Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita 565-0871, Osaka, Japan. FAU - Shintani, Norihito AU - Shintani N AD - Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita 565-0871, Osaka, Japan. FAU - Hashimoto, Hitoshi AU - Hashimoto H AD - Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita 565-0871, Osaka, Japan; United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, 2-2 Yamada-oka, Suita 565-0871, Osaka, Japan. FAU - Baba, Akemichi AU - Baba A AD - Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita 565-0871, Osaka, Japan; Hyogo University of Health Science, Kobe 650-8530, Japan. FAU - Matsuda, Toshio AU - Matsuda T AD - Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita 565-0871, Osaka, Japan; United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, 2-2 Yamada-oka, Suita 565-0871, Osaka, Japan. Electronic address: matsuda@phs.osaka-u.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140709 PL - Netherlands TA - Behav Brain Res JT - Behavioural brain research JID - 8004872 RN - 0 (Adcyap1 protein, mouse) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (NR2B NMDA receptor) RN - 0 (Neurotrophin 3) RN - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 9061-61-4 (Nerve Growth Factor) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism MH - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism MH - Conditioning, Psychological/physiology MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Fear/physiology MH - Glial Cell Line-Derived Neurotrophic Factor/metabolism MH - Hippocampus/growth & development/*physiopathology MH - *Housing, Animal MH - Male MH - Memory Disorders/*physiopathology/*therapy MH - Mice, Inbred ICR MH - Mice, Knockout MH - Nerve Growth Factor/metabolism MH - Neurotrophin 3/metabolism MH - Phosphorylation MH - Pituitary Adenylate Cyclase-Activating Polypeptide/*deficiency/genetics MH - Random Allocation MH - Receptors, N-Methyl-D-Aspartate/metabolism MH - Recognition, Psychology/physiology OTO - NOTNLM OT - Cognitive impairment OT - Enriched environment OT - Fear memory dysfunction OT - Neurotrophin OT - PACAP EDAT- 2014/07/12 06:00 MHDA- 2015/07/17 06:00 CRDT- 2014/07/12 06:00 PHST- 2014/04/03 00:00 [received] PHST- 2014/06/30 00:00 [revised] PHST- 2014/07/02 00:00 [accepted] PHST- 2014/07/12 06:00 [entrez] PHST- 2014/07/12 06:00 [pubmed] PHST- 2015/07/17 06:00 [medline] AID - S0166-4328(14)00445-8 [pii] AID - 10.1016/j.bbr.2014.07.005 [doi] PST - ppublish SO - Behav Brain Res. 2014 Oct 1;272:269-78. doi: 10.1016/j.bbr.2014.07.005. Epub 2014 Jul 9.