An enriched environment ameliorates memory impairments in PACAP-deficient mice.
An enriched environment ameliorates memory impairments in PACAP-deficient mice.
复制标题
丰富的环境可改善 PACAP 缺陷小鼠的记忆障碍。
DOI：
10.1016/j.bbr.2014.07.005
复制
发表时间：
2014
期刊：
影响因子：
2.7
通讯作者：
Matsuda T
中科院分区：
文献类型：
--
作者：
Takuma K;Maeda Y;Ago Y;Ishihama T;Takemoto K;Nakagawa A;Shintani N;Hashimoto H;Baba A;Matsuda T
我们以前发现，幼年垂体腺苷酸环化酶激活多肽（PACAP）敲除（PACAP−/−）小鼠在丰富的环境（EE）中饲养4周，表现出减弱的多动，跳跃行为，社会互动障碍和抑郁样行为。本研究考察了EE对PACAP−/−小鼠记忆功能和记忆相关蛋白水平的影响。八周龄的PACAP−/−小鼠在情境恐惧条件反射测试中表现出恐惧记忆功能障碍，在新物体识别测试中表现出认知障碍。将4周龄的PACAP−/−小鼠在EE中饲养4周可改善这些记忆障碍。在返回标准环境（SE）中的住房后2周，也观察到EE的有益效果。这表明EE对记忆受损的影响是持久的。在野生型和PACAP−/−小鼠中，EE增加了海马中NMDA受体NR 2B亚基、磷酸化ERK、磷酸化CaMKII和脑源性神经营养因子（BDNF）的蛋白水平，并降低了神经营养因子-3水平，但不影响神经生长因子和胶质细胞源性神经营养因子水平。在返回SE住房后2周，未观察到NR 2B、磷酸化ERK、磷酸化CaMKII和BDNF水平升高。这些发现表明，生活在EE中会导致PACAP−/−小鼠记忆障碍的长期减少。本研究还表明，海马记忆相关蛋白和脑源性神经营养因子水平的增加是EE的有益作用的原因，但不是维持这些作用的原因。
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.