Comprehensive Behavioral Analysis of Activating Transcription Factor 5-Deficient Mice.
Comprehensive Behavioral Analysis of Activating Transcription Factor 5-Deficient Mice.
复制标题
DOI：
10.3389/fnbeh.2017.00125
复制
发表时间：
2017
影响因子：
3
通讯作者：
Takahashi Y
中科院分区：
文献类型：
--
作者：
Umemura M;Ogura T;Matsuzaki A;Nakano H;Takao K;Miyakawa T;Takahashi Y
转录激活因子5（ATF 5）是CREB/ATF碱性亮氨酸拉链转录因子家族的成员。我们以前报道过，ATF 5-/-小鼠表现出异常的嗅球发育，由于受损的中间神经元供应。此外，ATF 5-/-小鼠的攻击性低于ATF 5 +/+小鼠。尽管ATF 5在脑中广泛表达，并参与调节神经元的增殖和发育，但其在高级脑中的生理作用尚不清楚。我们的目的是研究ATF 5在高级脑中的生理作用。我们使用ATF 5-/-小鼠和野生型同窝仔进行了全面的行为分析。在旷场试验中，ATF 5-/-小鼠表现出异常的运动活动。在光暗转换试验和旷场试验中，它们也表现出异常的焦虑样行为。此外，与野生型相比，ATF 5-/-小鼠在Crawley社会互动测试中显示出减少的社会互动，在热板测试中显示出增加的疼痛敏感性。最后，与野生型相比，ATF 5-/-小鼠在T-迷宫测试中的行为灵活性降低。此外，我们证明了ATF 5-/-小鼠在几个脑区显示单胺神经递质水平的紊乱。提示ATF 5缺乏可引起行为异常和脑内单胺类神经递质水平的紊乱。ATF 5-/-小鼠的行为异常可能是由于单胺水平的紊乱。总之，这些发现表明，ATF 5-/-小鼠可能是一些精神疾病的独特动物模型。
Activating transcription factor 5 (ATF5) is a member of the CREB/ATF family of basic leucine zipper transcription factors. We previously reported that ATF5-deficient (ATF5-/-) mice demonstrated abnormal olfactory bulb development due to impaired interneuron supply. Furthermore, ATF5-/- mice were less aggressive than ATF5+/+ mice. Although ATF5 is widely expressed in the brain, and involved in the regulation of proliferation and development of neurons, the physiological role of ATF5 in the higher brain remains unknown. Our objective was to investigate the physiological role of ATF5 in the higher brain. We performed a comprehensive behavioral analysis using ATF5-/- mice and wild type littermates. ATF5-/- mice exhibited abnormal locomotor activity in the open field test. They also exhibited abnormal anxiety-like behavior in the light/dark transition test and open field test. Furthermore, ATF5-/- mice displayed reduced social interaction in the Crawley’s social interaction test and increased pain sensitivity in the hot plate test compared with wild type. Finally, behavioral flexibility was reduced in the T-maze test in ATF5-/- mice compared with wild type. In addition, we demonstrated that ATF5-/- mice display disturbances of monoamine neurotransmitter levels in several brain regions. These results indicate that ATF5 deficiency elicits abnormal behaviors and the disturbance of monoamine neurotransmitter levels in the brain. The behavioral abnormalities of ATF5-/- mice may be due to the disturbance of monoamine levels. Taken together, these findings suggest that ATF5-/- mice may be a unique animal model of some psychiatric disorders.
登录
查看更多内容
影响因子：
6.2
作者：
Kumazaki H;Muramatsu T;Fujisawa TX;Miyao M;Matsuura E;Okada K;Kosaka H;Tomoda A;Mimura M
通讯作者：
Mimura M
影响因子：
168.9
作者：
Levy, Susan E.;Mandell, David S.;Schultz, Robert T.
通讯作者：
Schultz, Robert T.
影响因子：
64.8
作者：
Chamero, Pablo;Marton, Tobias F.;Stowers, Lisa
通讯作者：
Stowers, Lisa
DOI：
10.1158/1541-7786.mcr-08-0365
发表时间：
2009-06
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Li G;Li W;Angelastro JM;Greene LA;Liu DX
通讯作者：
Liu DX
DOI：
10.3791/1088
发表时间：
2008-12-22
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Komada, Munekazu;Takao, Keizo;Miyakawa, Tsuyoshi
通讯作者：
Miyakawa, Tsuyoshi