Identifying mechanisms underlying sex differences in motoneuron discharge

识别运动神经元放电性别差异的机制

基本信息

批准号：
10751793
负责人：
Sophia Theresa Jenz
金额：
$ 4.35万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10751793
关键词：
Address Animals Ankle Biological Brain Stem Brain region Cell Nucleus Cognition Contraceptive methods Disease Disease Progression Electromyography Emotions Equity Esthesia Estradiol Estradiol Receptors Estrogens Exclusion Exhibits Fatigue Female Gonadal Steroid Hormones Health Hormonal Hormones Human Human body Individual Isometric Contraction Knowledge Luteal Phase Mediating Menstrual cycle Menstruation Methods Motor Motor Neurons Movement Muscle Fibers Nervous System Nervous System Physiology Neurons Neurosciences Norepinephrine Oral Oral Contraceptives Output Pain Participant Pattern Performance Physiological Physiology Positioning Attribute Process Progesterone Progesterone Receptors Progestins Property Research Resistance Serotonin Sex Differences Signal Transduction Spinal Cord Surface System Testing Time Underrepresented Populations Work biophysical properties insight male monoamine motor control nervous system disorder neuromuscular neurophysiology neuroregulation sex sex cycle young adult

项目摘要

Project Summary Studies in neurophysiology have historically excluded female participants. This has resulted in a well encompassing understanding of the neural control of movement in males, and a poor understanding of mechanisms underlying motor control differences in females. There is great need to study female motor physiology, as many neurological diseases progress differently between the sexes. In recent years, studies that have included adequate numbers of female participants have found motoneuronal discharge patterns and neuromuscular fatigue differ between the sexes but the mechanisms underlying these differences are unknown. Descending monoaminergic input from brainstem nuclei provide and modify motoneuronal discharge and is broadly understudied in the motor system. Our lab, however, has developed robust methods to quantify these monoaminergic influences on motoneuron discharge in humans. Thus, to understand if monoaminergic input is responsible for sex differences in motoneuron properties, I will indirectly quantify the amount of monoaminergic input to motoneurons in females and males. Motor commands consist of excitation, inhibition, and a lesser known neuromodulatory component that result in their subsequent discharge and activation of innervated muscle fibers. Neuromodulation is induced by release of two monoamines, serotonin and norepinephrine, from the brainstem to the spinal cord, which substantially alter discharge patterns of motoneurons. Sex hormones have extensive effects on many physiological systems in the human body and differ between the sexes. Females have levels of estradiol and progesterone that fluctuate regularly across the menstrual cycle and these fluctuations are associated with aspects motor control, including motoneuron discharge rates and fatigue. Additionally, neurons throughout the body, including the brainstem and spinal cord, contain estradiol and progesterone receptors. This suggests that fluctuating sex hormones may impact motoneuron function, but, again, underlying mechanisms have not been studied. Thus, to accurately assess sex differences in motoneuron discharge, hormonal cycles must be considered. I will use surface EMG arrays to quantify motoneuron discharge patterns during voluntary isometric contractions to determine 1) if monoaminergic input to motoneurons differs between males and females, and 2) whether motoneuron discharge patterns fluctuate across the menstrual cycle in females. This study will assess whether the amount of monoaminergic input motoneurons receive differs between the sexes to test a possible explanation for known sex differences, while also assessing other aspects of motoneuron discharge. Whether or not these studies identify sex-differences, findings from this work will not only further the scientific knowledge of how these sex hormones influence nervous system function but will highlight the critical importance for additional studies focusing on female participants out of need, necessity, and equity.

项目摘要从历史上看，神经生理学的研究排除了女性参与者。这导致了一口井包括对男性运动的神经控制的理解，以及对女性运动控制差异的基础机制。迫切需要研究女性电动机生理学，由于男女之间的许多神经疾病的发展不同。近年来，研究包括足够数量的女性参与者发现了运动神经元排出模式，并且性别之间的神经肌肉疲劳不同，但是这些差异的基础机制尚不清楚。来自脑干核的降胺能输入提供并修改运动神经元放电，IS 在电机系统中进行了广泛研究。但是，我们的实验室已经开发了可靠的方法来量化这些方法单胺能对人类运动神经元排出的影响。因此，了解单胺能输入是否是负责运动神经元特性的性别差异，我将间接量化单胺能的量女性和男性运动神经元的输入。电机命令包括激发，抑制和鲜为人知的神经调节成分在随后的释放和神经纤维的激活中。神经调节是通过释放诱导的从脑干到脊髓的两个单胺，5-羟色胺和去甲肾上腺素改变运动神经元的放电模式。性激素对许多生理系统都有广泛的影响在人体中，性别之间有所不同。雌性具有波动的雌二醇和孕酮水平经常跨月经周期，这些波动与运动控制方面有关，包括运动神经元的放电率和疲劳。此外，整个身体的神经元，包括脑干和脊髓，含有雌二醇和孕酮受体。这表明波动的性激素可能影响运动神经元的功能，但尚未研究基本机制。因此，准确评估运动神经元排出的性别差异，必须考虑荷尔蒙周期。我将使用表面EMG 在自愿等轴测收缩期间量化运动神经元排出模式以确定1）男性和女性之间的单胺能输入与运动神经元不同，2）运动神经元是否排出模式在女性的月经周期中波动。这项研究将评估单胺能输入运动神经元的量是否在性别来测试已知性别差异的可能解释，同时还评估了运动神经元的其他方面释放。这些研究是否确定性别差异，这项工作的发现不仅会进一步关于这些性激素如何影响神经系统功能的科学知识，但会突出关键对于出于需求，必要性和公平性而集中于女性参与者的其他研究的重要性。