Department of Biophysics, International School of Medicine, University of Health Sciences, Istanbul, Turkey, 34668.
Hamidiye School of Medicine, University of Health Sciences, Istanbul, Turkey, 34668.
ACS Chem Neurosci. 2023 Feb 15;14(4):527-553. doi: 10.1021/acschemneuro.2c00589. Epub 2023 Feb 1.
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS). Although emerging evidence has shown that changes in neurotransmitter levels in the synaptic gap may contribute to the pathophysiology of MS, their specific role has not been elucidated yet. In this review, we aim to analyze preclinical and clinical evidence on the structural and functional changes in neurotransmitters in MS and critically discuss their potential role in MS pathophysiology. Preclinical studies have demonstrated that alterations in glutamate metabolism may contribute to MS pathophysiology, by causing excitotoxic neuronal damage. Dysregulated interaction between glutamate and GABA results in synaptic loss. The GABAergic system also plays an important role, by regulating the activity and plasticity of neural networks. Targeting GABAergic/glutamatergic transmission may be effective in fatigue and cognitive impairment in MS. Acetylcholine (ACh) and dopamine can also affect the T-mediated inflammatory responses, thereby being implicated in MS-related neuroinflammation. Also, melatonin might affect the frequency of relapses in MS, by regulating the sleep-wake cycle. Increased levels of nitric oxide in inflammatory lesions of MS patients may be also associated with axonal neuronal degeneration. Therefore, neurotransmitter imbalance may be critically implicated in MS pathophysiology, and future studies are needed for our deeper understanding of their role in MS.
多发性硬化症（MS）是一种中枢神经系统（CNS）的慢性炎症性和神经退行性疾病。尽管新出现的证据表明，突触间隙神经递质水平的变化可能有助于 MS 的病理生理学，但它们的具体作用尚未阐明。在这篇综述中，我们旨在分析 MS 中神经递质的结构和功能变化的临床前和临床证据，并批判性地讨论它们在 MS 病理生理学中的潜在作用。临床前研究表明，谷氨酸代谢的改变可能通过引起兴奋性神经元损伤而导致 MS 的病理生理学改变。谷氨酸和 GABA 之间的调节异常导致突触丧失。γ-氨基丁酸（GABA）能系统也起着重要的作用，通过调节神经网络的活动和可塑性。靶向 GABA 能/谷氨酸能传递可能对 MS 中的疲劳和认知障碍有效。乙酰胆碱（ACh）和多巴胺也可以影响 T 介导的炎症反应，从而与 MS 相关的神经炎症有关。此外，褪黑素可能通过调节睡眠-觉醒周期来影响 MS 中的复发频率。MS 患者炎症病变中一氧化氮水平的升高也可能与轴突神经元变性有关。因此，神经递质失衡可能与 MS 的病理生理学密切相关，需要进一步的研究来加深我们对其在 MS 中的作用的理解。
