Brain Mechanism 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，涉及焦虑水平、社会认可和应激反应。(1)在第一组研究中，我们测试了雌激素替代对去势雄性ER-b基因敲除小鼠(βERKO)以及野生型(WT)小鼠焦虑水平的影响。在明暗转换测试中测量到的焦虑水平在WT中被雌激素治疗显著降低，但在βerko雄性小鼠中没有。我们还检测了富含ER-β的中缝背核中5-羟色胺转运体的基因表达水平。同样，雌激素增加了WT小鼠的SERT mRNA水平，但在βERKO小鼠中却没有做到这一点。(2)已知雄性小鼠的攻击行为最早出现在5-6周大的青春期开始时间。在我们之前的研究中，我们发现Perko小鼠在青春期的攻击性增加，这表明抑制大脑系统的破坏。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开始的影响。那些在新生期与母亲分离的小鼠在5周龄时测量到的攻击行为大大减少。与WT小鼠相比，βERKO雄性小鼠青春期水平降低和攻击开始延迟尤为明显。因此，我们得出结论，ER-β可能参与青春期攻击性发作前后应激反应的发展。

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.