Identifying mechanisms underlying sex differences in motoneuron discharge

识别运动神经元放电性别差异的机制

• 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
• 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

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 神经生理学的研究历来排除女性参与者。这导致了一口井 包括对男性运动神经控制的理解，以及对 女性运动控制差异的潜在机制。研究女性运动的必要性很大 生理学，因为许多神经疾病的进展在性别之间是不同的。近年来，研究表明， 包括足够数量的女性参与者，发现了运动神经元放电模式， 神经肌肉疲劳在两性之间存在差异，但这些差异背后的机制尚不清楚。 来自脑干核团的下行单胺能输入提供并改变运动神经元放电， 在运动系统中被广泛研究。然而，我们的实验室已经开发出强大的方法来量化这些 单胺能对人类运动神经元放电的影响。因此，为了了解单胺能输入是否 负责运动神经元特性的性别差异，我将间接量化单胺能神经元的数量。 输入到运动神经元中。 运动指令包括兴奋、抑制和一种鲜为人知的神经调节成分， 在其随后的神经支配的肌肉纤维的放电和激活中。神经调节是由释放 两种单胺，血清素和去甲肾上腺素，从脑干到脊髓， 改变运动神经元的放电模式。性激素对许多生理系统有广泛的影响 在人体内，不同性别之间的差异。女性体内的雌二醇和孕酮水平 这些波动与运动控制有关，包括 运动神经元放电率和疲劳。此外，全身的神经元，包括脑干和 脊髓，含有雌二醇和孕酮受体。这表明性激素的波动可能 影响运动神经元的功能，但是，同样，根本的机制还没有研究。因此，为了准确地 评估运动神经元放电的性别差异，必须考虑激素周期。我会用表面肌电图 阵列来量化自主等长收缩期间的运动神经元放电模式，以确定1）是否 运动神经元的单胺能输入在男性和女性之间存在差异，以及2）运动神经元是否放电 在女性的月经周期中会有波动。 本研究将评估运动神经元接受的单胺能输入的量是否在不同的运动神经元之间存在差异。 性别，以测试已知的性别差异的可能解释，同时也评估运动神经元的其他方面， 放电无论这些研究是否确定了性别差异，这项工作的发现不仅将进一步促进 关于这些性激素如何影响神经系统功能的科学知识，但将强调关键 出于需要、必要性和公平，必须开展更多的研究，重点关注女性参与者。