Brain Mechanism of Aggression

攻击性的大脑机制

• 批准号: 17330151
• 负责人: OGAWA Sonoko
• 金额: $ 9.92万
• 依托单位: UNIVERSITY of TSUKUBA
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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/grant/KAKENHI-PROJECT-17330151/
• 关键词: Aggressive Behavior; Estrogen Receptors; Activity; Emotionality; Social Investigation; Anxiety-Related Behavior; Serotonin

During the funding period, we have worked to determine the role of estrogen receptor β (ER-β) in the regulation of aggressive behavior in mice in relation to the levels of anxiety levels, social recognition and stress responsiveness.(1) In the first set of the studies, we tested the effects of estrogen replacement on the levels of anxiety in gonadectomized male mice of ER-b knockout (βERKO) as well as wild-type (WT). The levels of anxiety measured during the light-dark transition tests significantly decreased by estrogen treatment in WT, but not in βERKO, male mice. We also measured the mRNA levels of serotonin transporter (SERT) in ER-β rich midbrain dorsal raphe nuclei. Again, estrogen increased SERT mRNA levels in WT mice but it failed to do so in βERKO mice.(2) Aggressive behavior of male mice is known to first appear around the time of puberty onset at 5-6weeks of age. In our previous studies, we found an increase of aggression in PERKO mice at the pubertal age suggesting disruption of inhibitory brain system. In the second set of studies, we studied the effects of stress loading on the onset of aggressive behavior around the puberty age. Aggressive behavior measured at 5weeks of age was greatly decreased in mice those separated from their mothers during neonatal period. Decreased levels and a delayed onset of aggression at pubertal age were particularly pronounced in βERKO male mice compared to WT mice. Therefore, we concluded that ER-β might be involved in the development of stress responsiveness around the time of pubertal onset of aggression.

在资助期间，我们致力于确定雌激素受体β（ER-β）在调节小鼠攻击行为中的作用，这些行为与焦虑水平，社会认知和压力反应水平有关。(1)在第一组研究中，我们测试了雌激素替代对ER-b基因敲除（βERKO）和野生型（WT）的性腺切除雄性小鼠焦虑水平的影响。雌激素处理可显著降低WT雄性小鼠在明暗过渡试验中测量的焦虑水平，但βERKO雄性小鼠中未出现这种情况。我们还测定了富含ER-β的中脑中缝背核中5-羟色胺转运体（SERT）的mRNA水平。同样，雌激素增加了WT小鼠中的SERT mRNA水平，但在βERKO小鼠中没有这样做。(2)雄性小鼠的攻击行为已知在5- 6周龄的青春期开始时首次出现。在我们以前的研究中，我们发现PERKO小鼠在青春期的攻击性增加，这表明抑制性脑系统的破坏。在第二组研究中，我们研究了压力负荷对青春期前后攻击行为发生的影响。在新生期与母亲分离的小鼠在5周龄时测量的攻击行为大大减少。与WT小鼠相比，βERKO雄性小鼠中青春期攻击性水平降低和延迟发作尤其明显。因此，我们认为ER-β可能参与了青春期攻击性发生前后应激反应的发展。

项目成果

Gene Therapy of the Central Nervous System : From Bench to Bedside.

中枢神经系统的基因治疗：从实验室到临床。

• 发表时间: 2005
• 作者: Musatov;S.A.;Pfaff;D.W.;Kaplitt;M.;Ogawa;S.
• 通讯作者: S.

Abolition of sex-dependent effects of prenatal exposure to diethylstilbestrol on emotional behavior in estrogen receptor α knockout mice.

消除产前接触己烯雌酚对雌激素受体α基因敲除小鼠情绪行为的性别依赖性影响。

• 发表时间: 2006
• 期刊: Neuroreport 17
• 作者: Tomihara;K.;Kaitsuka;T.;Soga;T.;Korach;K.S.;Pfaff;D.W.;Takahama;K.;Ogawa;S.
• 通讯作者: S.

Knockdown of estrogen receptor α using viral-mediated RNA interference abolishes female sexual behavior.

使用病毒介导的 RNA 干扰敲低雌激素受体 α，可以消除女性的性行为。

• 发表时间: 2006
• 期刊: Proceedings of the National Academy of Sciences, U.S.A. 103
• 作者: Musatov;S.A.;Chen;W.;Pfaff;D.W.;Kaplitt;M.;Ogawa;S.
• 通讯作者: S.

Biology of aggression

• DOI: 10.1093/acprof:oso/9780195168761.001.0001
• 发表时间: 2005-09
• 作者: R. Nelson

Involvement of estrogen receptor receptor α,β, and oxytocin in social discrimination : a detailed behavioral analysis with knockout female mice.

雌激素受体α、β和催产素参与社会歧视：对基因敲除雌性小鼠的详细行为分析。

• 发表时间: 2006
• 期刊: Genes, Brain and Behavior 5
• 作者: Choleris;E.;Ogawa;S.;Kavaliers;M.;Gustafsson;J-A.;Korach;K.S.;Muglia;L.J.;Pfaff;D.W.
• 通讯作者: D.W.