Role of androgens and activity in axon regeneration

雄激素和活性在轴突再生中的作用

基本信息

批准号：
9025810
负责人：
Patricia J Ward
金额：
$ 5.8万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9025810
关键词：
Accounting Afferent Neurons Aging Androgen Receptor Androgen Therapy Androgens Astrocytes Axon Basic Science Brain-Derived Neurotrophic Factor Cations Cell Separation Cells Centrifugation Child Electric Stimulation Enzymes Exercise Female Genetic Health Individual Intervention Knock-out Knockout Mice Knowledge Ligands Light Limb structure LoxP-flanked allele Measures Mediating Medical Messenger RNA Microglia Motor Motor Neurons Movement Mus Muscle Natural regeneration Nerve Neurodegenerative Disorders Neuroglia Neurons Oligodendroglia Operative Surgical Procedures Optics Outcome Measure Patients Peripheral nerve injury Physical therapy Play Population Population Heterogeneity Production Proteins Radioimmunoassay Receptor Gene Reporter Research Rhodopsin Role Sensory Signal Transduction Site Source Speed Steroids Surgical sutures Technology Woman Work androgenic axon regeneration base cell type functional outcomes injured innovation male men nerve injury nerve transection novel optogenetics peripheral nerve regeneration peripheral nerve transection promoter receptor recombinase-mediated cassette exchange reinnervation research study response sciatic nerve

项目摘要

DESCRIPTION (provided by applicant): More than 200,000 patients are treated every year for peripheral nerve injury. Approximately 90% of patients never recover full movement of an injured limb. Slow axon regeneration and/or misdirected axon targeting are most often blamed for these poor functional outcomes. Increased neuronal activity, such as through exercise or electrical stimulation, enhances axon regeneration following peripheral nerve injury. We have shown that brain derived neurotrophic factor (BDNF) expression in the neurons whose axons are regenerating is required for this enhancement, but also that signaling through androgen receptors is required in both males and females. The source of the ligands for these receptors, androgens, is not known, especially in females. We hypothesize that their availability could be altered by the effects of neuronal activity on steroid converting enzymes. By measuring the expression of these enzymes in both neuronal and non-neuronal cells in response to increased neuronal activity, we anticipate that we can identify the sources of androgen that promote enhanced axon regeneration. The targets of androgenic activity required to promote axon regeneration also are poorly known. By evaluating the effects of increased neuronal activity on axon regeneration in mice in which the androgen receptor gene is knocked out in a cell-type specific manner, we will be able to identify the cellular requirements for androgen receptor-mediated enhancement of axon regeneration. In this proposed study, we will use a combination of newly available technologies to investigate these roles. Clinically, androgen therapy is already in use. Knowledge of androgen production and signaling is needed to tailor this potential therapy for peripheral nerve regeneration and could be applied to other neurodegenerative diseases.

描述（由申请人提供）：每年有20万多名患者因周围神经损伤而受到治疗。大约90％的患者从未恢复受伤的肢体的全部运动。慢速轴突再生和/或误导轴突靶向最常归咎于这些功能不佳的结果。神经元活性的增加，例如通过运动或电刺激，可以增强周围神经损伤后的轴突再生。我们已经表明，这种增强需要轴突重生的神经元中脑衍生的神经营养因子（BDNF）表达，但在男性和女性中都需要通过雄激素受体的信号传导。这些受体的配体的来源，雄激素尚不清楚，尤其是在女性中。我们假设神经元活性对类固醇转化酶的影响可以改变它们的可用性。通过测量这些酶在神经元细胞和非神经元细胞中的表达，响应于神经元活性的增加，我们预计我们可以鉴定雄激素的来源，从而促进增强的轴突再生。促进轴突再生所需的雄激素活性的靶标也鲜为人知。通过评估神经元活性增加对以细胞类型特异性敲除雄激素受体基因的小鼠的轴突再生的影响，我们将能够鉴定出对雄激素受体介导的轴突再生增强的细胞需求。在这项拟议的研究中，我们将使用新近可用的技术的组合来研究这些角色。临床上，雄激素疗法已经在使用。需要了解雄激素的产生和信号传导来量身定制这种潜在的治疗外周神经再生，并可以应用于其他神经退行性疾病。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

HIF1a and angiogenesis are critical for the regenerative effects of exercise.

HIF1a 和血管生成对于运动的再生作用至关重要。

DOI：
发表时间：
2022
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
0
作者：
Ward,Patricia;Wariyar,Supriya;Tian,Tina;Pottorf,Tana;Brown,Alden
通讯作者：
Brown,Alden