Breeding status and delayed motoneuron maturation in a eusocial mammal

真社会性哺乳动物的繁殖状况和运动神经元成熟延迟

• 批准号: 7348350
• 负责人: Marianne L Seney
• 金额: $ 2.69万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7348350
• 关键词: Address; Adult; Amyotrophic Lateral Sclerosis; Androgens; Animals; Atrophic; Axon; Behavior; Behavioral; Birth; Breeding; Caring; Cell Death; Cell Nucleus; Cells; Complex; Degenerative Disorder; Exhibits; Female; Floods; Gonadal Hormones; Gonadal Steroid Hormones; Heterocephalus; Homologous Gene; Hormones; Individual; Injection of therapeutic agent; Interneurons; Investigation; Label; Life; Link; Maintenance; Mammals; Mole Rats; Motor Neurons; Muscle; Nervous System Physiology; Neuronal Plasticity; Neurons; Numbers; Partner in relationship; Pattern; Phenotype; Physiological; Population; Recruitment Activity; Reproduction; Sex Characteristics; Signal Transduction; Skeletal muscle structure of perineum; Social status; Societies; Spinal; Spinal Cord; Structure; Testing; Testosterone; Tracer; Undifferentiated; Urethra; Vulva; animal breeding; behavior influence; cell type; cohort; immunocytochemistry; levator ani muscle; life history; male; nerve stem cell; nerve supply; neurochemistry; neuromuscular system; reproductive; sex; size; social; social organization

DESCRIPTION (provided by applicant): In animals with complex societies, social signals can profoundly influence behavior, physiology, and the nervous system. Naked mole-rats exhibit a strict hierarchical social organization in which breeders are dominant to all non-breeders. Recently, a change in social status has been linked to what appears to be late differentiation of spinal motoneurons. Naked mole-rats live in large colonies consisting of a single breeding female (the queen), one to three breeding males, and a large cohort of reproductively suppressed subordinates. Over 95% of subordinates will remain reproductively inactive for their entire lives. A subordinate can become reproductive, however, if a breeding animal dies or if it is removed from the colony and paired with an opposite-sex mate. This change in social status causes an increase in the number of motoneurons innervating perineal muscles. This project will: 1) determine which factors trigger the changes observed in the spinal cord by independently manipulating gonadal hormones and social status, 2) establish the neurochemical identity of cells within the spinal cord that become large motoneurons in breeders using immunocytochemistry for cell-type markers, and 3) determine the targets of the large motoneurons recruited in breeders by retrograde tract-tracing. The unique social structure and life history of naked mole-rats give us the opportunity to examine neural plasticity in an adult mammal, including the late differentiation or re-specification of neuron subtype in the spinal cord. This information could be used to develop treatments for degenerative diseases characterized by loss or atrophy of motoneurons, such as amyotrophic lateral sclerosis (ALS).

描述（由申请人提供）：在具有复杂社会的动物中，社会信号可以深刻地影响行为、生理和神经系统。裸鼹鼠表现出严格的等级社会组织，其中繁殖者对所有非繁殖者都占主导地位。最近，社会地位的变化与脊髓运动神经元的晚期分化有关。裸鼹鼠生活在由一只正在繁殖的雌性（蚁后）、一到三只正在繁殖的雄性以及一大群生殖受到抑制的下属组成的大型群体中。超过95%的下属将终生保持生殖不活跃状态。然而，如果繁殖动物死亡或者它被从群体中移出并与异性配偶配对，则下属可以具有繁殖能力。这种社会地位的变化导致支配会阴肌肉的运动神经元数量增加。该项目将：1）通过独立操纵性腺激素和社会地位来确定哪些因素触发脊髓中观察到的变化，2）使用细胞类型标记的免疫细胞化学确定脊髓内细胞的神经化学特性，这些细胞在种鸡中成为大运动神经元，3）通过逆行束追踪确定在种鸡中招募的大运动神经元的目标。裸鼹鼠独特的社会结构和生活史使我们有机会检查成年哺乳动物的神经可塑性，包括脊髓中神经元亚型的晚期分化或重新特化。这些信息可用于开发以运动神经元丢失或萎缩为特征的退行性疾病的治疗方法，例如肌萎缩侧索硬化症（ALS）。