Alteration in Anxiety with Relation to the Volume of the Locus Ceruleus in Progranulin-Deficient Mice
Alteration in Anxiety with Relation to the Volume of the Locus Ceruleus in Progranulin-Deficient Mice
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DOI：
10.1262/jrd.20239
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发表时间：
2009-10-01
影响因子：
1.8
通讯作者：
Nishihara, Masugi
中科院分区：
文献类型：
--
作者：
Chiba, Shuichi;Matsuwaki, Takashi;Nishihara, Masugi
哺乳动物的大脑在结构和功能方面表现出性别差异。在我们之前的报告中，我们发现颗粒体蛋白前体（PGRN）缺陷（pgrn（-/-））小鼠表现出雄性行为的改变，包括射精频率降低以及攻击性和焦虑水平升高。本研究的目的是阐明 PGRN 在焦虑性别差异中的作用。在高架十字迷宫中，野生型 (pgrn(+/+)) 雌性小鼠比 pgrn(+/+) 雄性小鼠在闭合臂中花费的时间更长，这表明雌性小鼠的焦虑水平高于雄性。另一方面，pgrn(-/-)小鼠没有观察到性别差异，它们的焦虑水平几乎与pgrn(+/+)雌性小鼠相同。为了阐明睾酮对雄性焦虑的影响，雄性小鼠在 5 周龄时被阉割，然后将充满睾酮或胆固醇的硅橡胶管植入其中一周。尽管 pgrn(-/-) 雄性比 pgrn(+/+) 雄性表现出更高的焦虑，但这些治疗并未影响任一基因型的开放视野中的焦虑。接下来，我们测量了室旁核 (PVN) 和蓝斑 (LC) 的体积，因为这些是与焦虑/压力相关的核，已知其结构存在性别差异。在 pgrn(+/+) 小鼠中，雄性小鼠的 LC 体积有比雌性更大的趋势。此外，尽管没有观察到性别差异，但 pgrn(-/-) 小鼠的 LC 体积比 pgrn(+/+) 小鼠更大。 pgrn(-/-)小鼠LC中的细胞数量也比pgrn(+/+)小鼠多。在基因型或性别之间没有观察到 PVN 体积的显着差异。这些结果表明 PGRN 在 LC 的组织中发挥作用，最终调节新环境中的焦虑。
The mammalian brain exhibits sex differences with respect to structure and function. In our previous report, we found that progranulin (PGRN)-deficient (pgrn(-/-)) mice displayed an alteration in male-type behaviors, including reduced frequency of ejaculation and elevated levels of aggression and anxiety. The aim of the present study was to elucidate the role of PGRN in sex differences in anxiety. In the elevated plus maze, wild-type (pgrn(+/+)) female mice spent more time in the closed arms than the pgrn(+/+) males, suggesting that the level of anxiety was higher in females than males. On the other hand, no sex difference was observed in the pgrn(-/-) mice, and their anxiety levels were almost the same as those of the pgrn(+/+) females. To elucidate the effect of testosterone on male anxiety, male mice were castrated at 5 weeks of age and silastic tubes filled with either testosterone or cholesterol were then implanted into them for one week. These treatments did not affect anxiety in the open field in either genotypes, although the pgrn(-/-) males exhibited higher anxiety than pgrn(+/+) males. Next, we measured the volume of the paraventricular nucleus (PVN) and the locus ceruleus (LC), as these are anxiety/stress-related nuclei that are known to have sex differences in their structures. In the pgrn(+/+) mice, there was a tendency for the volume of the LC to be larger in males than females. In addition, the pgrn(-/-) mice had a larger volume of LC than the pgrn(+/+) mice, although no sexual differences were observed. The number of cells in the LC was also larger in the pgrn(-/-) than in the pgrn(+/+) mice. No significant differences in the volumes of the PVN were observed between genotypes or sexes. These results suggest that PGRN plays a role in organization of the LC, which eventually modulates anxiety in novel environments.