Hashikawa Naoya, Ogawa Takumi, Sakamoto Yusuke, Ogawa Mami, Matsuo Yumi, Zamami Yoshito, Hashikawa-Hobara Narumi
Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama, 700-0005, Japan.
Cell Mol Neurobiol. 2015 Aug;35(6):807-17. doi: 10.1007/s10571-015-0174-x. Epub 2015 Mar 28.
Stress is known to affect neurotrophic factor expression, which induces depression-like behavior. However, whether there are time-dependent changes in neurotrophic factor mRNA expression following stress remains unclear. In the present study, we tested whether chronic stress exposure induces long-term changes in depression-related behavior, serum corticosterone, and hippocampal proliferation as well as neurotrophic factor family mRNA levels, such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and ciliary neurotrophic factor (CNTF), in the mouse hippocampus. The mRNA level of neurotrophic factors (BDNF, NGF, NT-3, and CNTF) was measured using the real-time PCR. The serum corticosterone level was evaluated by enzyme-linked immunosorbent assay, and, for each subject, the hippocampal proliferation was examined by 5-bromo-2-deoxyuridine immunostaining. Mice exhibited depression-like behavior in the forced-swim test (FST) and decreased BDNF mRNA and hippocampal proliferation in the middle of the stress exposure. After 15 days of stress exposure, we observed increased immobility in the FST, serum corticosterone levels, and BDNF mRNA levels and degenerated hippocampal proliferation, maintained for at least 2 weeks. Anhedonia-like behavior in the sucrose preference test and NGF mRNA levels were decreased following 15 days of stress. NGF mRNA levels were significantly higher 1 week after stress exposure. The current data demonstrate that chronic stress exposure induces prolonged BDNF and NGF mRNA changes and increases corticosterone levels and depression-like behavior in the FST, but does not alter other neurotrophic factors or performance in the sucrose preference test.
已知应激会影响神经营养因子的表达，进而诱发类似抑郁的行为。然而，应激后神经营养因子mRNA表达是否存在时间依赖性变化仍不清楚。在本研究中，我们测试了慢性应激暴露是否会在小鼠海马体中诱导与抑郁相关行为、血清皮质酮、海马体增殖以及神经营养因子家族mRNA水平（如脑源性神经营养因子（BDNF）、神经生长因子（NGF）、神经营养因子-3（NT-3）和睫状神经营养因子（CNTF））的长期变化。使用实时PCR测量神经营养因子（BDNF、NGF、NT-3和CNTF）的mRNA水平。通过酶联免疫吸附测定法评估血清皮质酮水平，并且对每个受试者，通过5-溴-2-脱氧尿苷免疫染色检查海马体增殖情况。在应激暴露中期，小鼠在强迫游泳试验（FST）中表现出类似抑郁的行为，BDNF mRNA和海马体增殖减少。应激暴露15天后，我们观察到FST中的不动时间增加、血清皮质酮水平和BDNF mRNA水平升高以及海马体增殖退化，这种情况持续至少2周。应激15天后，蔗糖偏好试验中的快感缺失样行为和NGF mRNA水平降低。应激暴露1周后，NGF mRNA水平显著更高。目前的数据表明，慢性应激暴露会诱导BDNF和NGF mRNA的长期变化，并增加皮质酮水平以及FST中的类似抑郁行为，但不会改变其他神经营养因子或蔗糖偏好试验中的表现。
