Otsuka Shintaro, Ohkido Taro, Itakura Makoto, Watanabe Shigeru, Yamamori Saori, Iida Yuuki, Saito Masanori, Miyaoka Hitoshi, Takahashi Masami
Kitasato University Graduate School of Medical Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa 252-0374, Japan.
Department of Biochemistry, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara-shi, Kanagawa 252-0374, Japan.
Epilepsy Res. 2016 Jul;123:55-67. doi: 10.1016/j.eplepsyres.2016.04.007. Epub 2016 Apr 25.
A mouse model of epilepsy was generated by inducing status epilepticus (SE) for either 1.5 or 4.5h with pilocarpine to study anxiety-related behaviors, changes in the electroencephalogram of the cerebral cortex and hippocampus, and expression of hippocampal proteins. The viability and rate of success of SE induction were high in C57BL/6N mice but not in C57BL/6J mice. C57BL/6N mice were immotile during the first 2days after SE; however, by the third day, most mice were recovered and exhibited strong anxiety-related behaviors in response to the light/dark preference test and open field test. There was a striking difference in the temporal appearance of anxiety-related behavior between the two SE durations: 1.5h SE mice exhibited strong anxiety-related behavior 3days after SE that gradually attenuated over the next few weeks, whereas 4.5h SE mice exhibited strong anxiety-related behavior 3days after SE that persisted even at nearly 1year after SE. Mice receiving both SE durations exhibited generalized seizures (GS) after SE; however, there was a marked difference in the timing and duration of GS appearance. Mice in the 4.5h SE group exhibited spontaneous GS from 4days to at least 96days after SE. In contrast, mice in the 1.5h SE group exhibited GS only within the first several days after SE; however, epileptic spike clusters continuously appeared in the cerebral cortex and hippocampus for up to twelve days after SE. Among the hippocampal proteins tested, only brain derived-neurotrophic factor (BDNF) exhibited altered expression in parallel with anxiety-related behavior. These results showed the possibility that BDNF expression in the hippocampus might cause anxiety-related behavior in adulthood.
通过用毛果芸香碱诱导癫痫持续状态（SE）1.5小时或4.5小时，建立癫痫小鼠模型，以研究焦虑相关行为、大脑皮层和海马体脑电图的变化以及海马体蛋白的表达。C57BL/6N小鼠中SE诱导的存活率和成功率较高，但C57BL/6J小鼠中则不然。C57BL/6N小鼠在SE后的头两天内活动减少；然而，到第三天，大多数小鼠恢复，并在明暗偏好试验和旷场试验中表现出强烈的焦虑相关行为。两种SE持续时间之间焦虑相关行为的出现时间存在显著差异：1.5小时SE组小鼠在SE后3天表现出强烈的焦虑相关行为，在接下来的几周内逐渐减弱，而4.5小时SE组小鼠在SE后3天表现出强烈的焦虑相关行为，甚至在SE后近1年仍持续存在。接受两种SE持续时间的小鼠在SE后均出现全身性惊厥（GS）；然而，GS出现的时间和持续时间存在明显差异。4.5小时SE组小鼠在SE后4天至至少96天出现自发性GS。相比之下，1.5小时SE组小鼠仅在SE后的头几天内出现GS；然而，癫痫棘波簇在SE后长达12天持续出现在大脑皮层和海马体中。在所测试的海马体蛋白中，只有脑源性神经营养因子（BDNF）的表达变化与焦虑相关行为平行。这些结果表明，海马体中BDNF的表达可能在成年期引起焦虑相关行为。
