Mechanism for sex difference in pain responses (1) Mapping of and time course of the exression of phosphorylated CREB induced by formalin

疼痛反应性别差异的机制（1）福尔马林诱导磷酸化CREB表达的图谱和时程

• 批准号: 17590208
• 负责人: TANAKA Fukuko
• 金额: $ 2.18万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590208/
• 关键词: sex difference; CREB; Formalin test; nociceptive stimuli; sexual differentiatin; bed nucleus of the stria terminalis; DARPP32; rat; 脳・神経; 側座核

Formalin injection induces two phases of nociceptive responses separated by interphase, a brief quiescent period. This pattern was similar in both sexes, but there was a prominent increase in nociceptive response during interphase in female rats. Next, the expression of phosphorylated CREB (pCREB) was immunohistochemically examined during various times after formalin injection. We found that the number of pCREB-immunoreactive cells (pCREB cells) in the bilateral dorsolateral divisions of the bed nucleus of the stria terminalis (BSTLD) was significantly increased by formalin injection in females, but not in males. These changes were observed selectively 5-10 min after formalin injection, a period corresponding to behavioral interphase, and were specific to formalin injection. These data indicate that the CREB in the BSTLD is phosphorylated in a female-specific manner in association with the sex difference in the formalin test. We next examined the effects of castration and testosterone or 17β-estradiol replacement Behavioral data indicated the involvement of estrogen in interphase. In parallel with the behavioral data, there were no changes in the number of pCREB cells in the BSTLD of orchidectomized rats 5-10 min (interphase) after formalin injection irrespective of steroid replacement. In ovariectomized rats, however, the number of pCREB cells in the testosterone or estrogen replaced groups injected with formalin was significantly greater than in the saline injected rats. Furthermore, formalin injection failed to increase the pCREB expression in ovariectomized rats without steroid replacement. These results indicate that the changes in both behavioral and pCREB responses observed during interphase are gonadal steroid-dependent in female rats.

注射福尔马林会引起两个阶段的伤害性反应，分为两个阶段，即短暂的静止期。这种模式在两性中都是相似的，但雌性大鼠在间期伤害性反应显著增加。用免疫组织化学方法检测福尔马林注射后不同时间磷酸化CREB(PCREB)的表达。结果发现，注射福尔马林后，雌性大鼠双侧终纹床核背外侧区(BSTLD)的pCREB免疫反应阳性细胞(pCREB细胞)数量显著增加，而雄性则无明显变化。这些变化是在福尔马林注射后5~10min选择性地观察到的，这段时间对应于行为间期，并且是福尔马林注射所特有的。这些数据表明，BSTLD中的CREB以一种女性特有的方式被磷酸化，这与福尔马林试验中的性别差异有关。接下来，我们研究了去势和睾酮或17β-雌二醇替代的效果。行为数据表明，雌激素参与了间期。注射福尔马林后5~10min(间期)，去大鼠BSTLD内pCREB细胞的数量与行为学数据平行，但与激素替代无关。然而，在去卵巢的大鼠中，注射福尔马林的睾酮或雌激素替代组的pCREB细胞数量明显多于注射生理盐水的大鼠。此外，注射福尔马林不能增加去卵巢大鼠不补充类固醇的pCREB的表达。这些结果表明，雌性大鼠在间期观察到的行为反应和pCREB反应的变化是性腺激素依赖的。

项目成果

「研究成果報告書概要(欧文)」より

摘自《研究结果报告摘要（欧洲）》

• 发表时间: 2006
• 期刊: Seibutsu Butsuri 46(1)
• 作者: Yasushi Shigeri;Keiko Shimamoto
• 通讯作者: Keiko Shimamoto

Gonadal steroid hormones maintain the stress-induced acetylcholine release in the hippocampus : simultaneous measurements of the extracellular acethylcholine and serum corticosterone levels in the same subjects

性腺类固醇激素维持海马中应激诱导的乙酰胆碱释放：同时测量同一受试者的细胞外乙酰胆碱和血清皮质酮水平

• 发表时间: 2008
• 期刊: Endocrinology 149
• 作者: Mitsushima D;Takase K;Funabashi T;Kimura F.
• 通讯作者: Kimura F.

Bisphenol A induces transforming growth factor-beta3 mRNA in the preoptic area : a cDNA expression array and Northern blot study

双酚 A 在视前区诱导转化生长因子-β3 mRNA：cDNA 表达阵列和 Northern 印迹研究

• 发表时间: 2007
• 期刊: Neurosci Lett 411(1)
• 作者: Fukushima A;Funabashi T;Kawaguchi M;Mitsushima D;Kimura F.
• 通讯作者: Kimura F.

Effects of p-Nonylphenol and 4-tert-Octylphenol on the Anterior Pituitary Functions in Adult Ovariectomized Rats

• DOI: 10.1159/000096093
• 发表时间: 2006-12
• 期刊: Neuroendocrinology
• 影响因子: 4.1
• 作者: Miyako Furuta;T. Funabashi;M. Kawaguchi;Takahiro J. Nakamura;D. Mitsushima;F. Kimura

面白いほどよくわかる!脳とこころのしくみ

越有趣，您就越了解大脑和思维的工作原理！

• 发表时间: 2007
• 作者: Kato;G. et al.;田中 冨久子
• 通讯作者: 田中 冨久子