Jyotika Jigyasa, McCutcheon Jill, Laroche Julie, Blaustein Jeffrey D, Forger Nancy G
Department of Psychology and Neuroscience and Behavior Program, University of Massachusetts, Amherst, Massachusetts 01003, USA.
Dev Neurobiol. 2007 Sep 15;67(11):1511-9. doi: 10.1002/dneu.20525.
Cell death is a nearly ubiquitous feature of the developing nervous system, and differential death in males and females contributes to several well studied sex differences in neuron number. Nonetheless, the functional importance of neuronal cell death has been subjected to few direct tests. Bax, a pro-apoptotic protein, is required for cell death in many neural regions. Deletion of the Bax gene in mice increases neuron number in several areas and eliminates sex differences in cell number in the brain and spinal cord. Here, sexual and motor behaviors were examined in Bax-/- mice and their wild-type siblings to test the functional consequences of preventing Bax-dependent cell death. Animals were gonadectomized in adulthood and provided with ovarian hormones or with testosterone for tests of feminine and masculine sexual behaviors, respectively. Wild-type mice exhibited a sex difference in feminine sexual behavior, with high lordosis scores in females and low scores in males. This sex difference was eliminated by Bax deletion, with very low receptivity exhibited by both male and female Bax-/- mice. Masculine sexual behavior was not sexually dimorphic among wild-type mice, but mounts and pelvic thrusts were nearly eliminated in Bax-/- mice of both sexes. Motor strength and performance at low speeds on a RotaRod apparatus did not differ by sex or Bax gene status. However, Bax-/- animals exhibited impairments on the RotaRod at higher speeds. Thus, developmental cell death may be required for masculine and feminine sexual behaviors and the fine tuning of motor coordination.
细胞死亡是发育中的神经系统几乎普遍存在的特征，雄性和雌性的差异性死亡导致了神经元数量上一些已被充分研究的性别差异。尽管如此，神经元细胞死亡的功能重要性很少受到直接测试。Bax是一种促凋亡蛋白，在许多神经区域的细胞死亡中是必需的。在小鼠中删除Bax基因会增加几个区域的神经元数量，并消除大脑和脊髓中细胞数量的性别差异。在此，对Bax基因敲除小鼠及其野生型同窝小鼠的性行为和运动行为进行了检查，以测试阻止Bax依赖性细胞死亡的功能后果。动物在成年后进行性腺切除，分别给予卵巢激素或睾酮以测试雌性和雄性的性行为。野生型小鼠在雌性性行为上表现出性别差异，雌性的脊柱前凸得分高，雄性得分低。这种性别差异通过删除Bax而消除，雄性和雌性Bax基因敲除小鼠的接受性都非常低。野生型小鼠的雄性性行为没有性别差异，但两性的Bax基因敲除小鼠的爬跨和骨盆推力几乎都消失了。在RotaRod装置上，运动强度和低速表现不因性别或Bax基因状态而有所不同。然而，Bax基因敲除动物在较高速度下在RotaRod上表现出损伤。因此，发育性细胞死亡可能是雄性和雌性性行为以及运动协调精细调节所必需的。
