The Role of Glutamate in the Pathogenesis of Multiple Sclerosis

Kuzmina, U. Sh.; Зайнуллина, Л. Ф.; Вахитов, В. А.; Bakhtiyarova, K. Z.; Vakhitova, Yu. V.

doi:10.1007/s11055-020-00953-8

Cited by 8 publications

(8 citation statements)

References 57 publications

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“…Evidence suggests that the neuroprotective mechanisms of CB1 activation, demonstrated in EAE, against excitotoxic neurodegeneration involve countering the effects of IL-1β on glutamate release from presynaptic nerve terminals, in addition to reversing the enhancing effects of TNF-α on postsynaptic glutamate receptor expression and function [180,201,202]. This abrogation of glutamate-induced cell injury could have therapeutic effects in MS since excess glutamate has been shown to play a role in the pathogenesis of MS [203].…”

Section: Mechanisms That Would Provide Neuroprotection and Stimulate ...mentioning

confidence: 99%

Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination

et al. 2022

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Despite current therapeutic strategies for immunomodulation and relief of symptoms in multiple sclerosis (MS), remyelination falls short due to dynamic neuropathologic deterioration and relapses, leading to accrual of disability and associated patient dissatisfaction. The potential of cannabinoids includes add-on immunosuppressive, analgesic, neuroprotective, and remyelinative effects. This study evaluates the efficacy of medical marijuana in MS and its experimental animal models. A systematic review was conducted by a literature search through PubMed, ProQuest, and EBSCO electronic databases for studies reported since 2007 on the use of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) in MS and in experimental autoimmune encephalomyelitis (EAE), Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), and toxin-induced demyelination models. Study selection and data extraction were performed by 3 reviewers, and 28 studies were selected for inclusion. The certainty of evidence was appraised using the Cochrane GRADE approach. In clinical studies, there was low- and moderate-quality evidence that treatment with ~1:1 CBD/THC mixtures as a nabiximols (Sativex®) oromucosal spray reduced numerical rating scale (NRS) scores for spasticity, pain, and sleep disturbance, diminished bladder overactivity, and decreased proinflammatory cytokine and transcription factor expression levels. Preclinical studies demonstrated decreases in disease severity, hindlimb stiffness, motor function, neuroinflammation, and demyelination. Other experimental systems showed the capacity of cannabinoids to promote remyelination in vitro and by electron microscopy. Modest short-term benefits were realized in MS responders to adjunctive therapy with CBD/THC mixtures. Future studies are recommended to investigate the cellular and molecular mechanisms of cannabinoid effects on MS lesions and to evaluate whether medical marijuana can accelerate remyelination and retard the accrual of disability over the long term.

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Section: Mechanisms That Would Provide Neuroprotection and Stimulate ...mentioning

confidence: 99%

Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination

et al. 2022

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“…This glutamate-mediated excitotoxicity can be triggered by energy deficiency, oxidative stress, mitochondrial dysfunction, and calcium overload. 205 Thus, targeting glutamate signaling and its receptors is important for future studies in MS treatment. Amantadine and memantine, which are NMDA receptor antagonists, inhibit the pro-inflammatory response in EAE model rats.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Role of Neurotransmitters in Multiple Sclerosis: An Expanded Review

Akyüz

Celik

Aslan

et al. 2023

ACS Chem. Neurosci.

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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.

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“…Limitations are the cross-sectional design, unequal group sizes, lack of physical disability readouts besides EDSS, and lack of imaging data. Our work primarily focused on excitatory circuits because MS has been associated with alterations in the glutamatergic network [33,34] and since QPS has been shown to specifically modulate excitatory circuits and to leave inhibitory circuits unchanged [31]. However, inhibitory circuits can be altered in MS as well [54].…”

Section: Discussionmentioning

confidence: 99%

“…QPS has been shown to selectively modulate the excitatory glutamatergic cortical neuronal network, whereas other TMS protocols also modulate inhibitory GABA-ergic networks [31,32]. Since the glutamatergic network presumably plays an important role in the pathophysiology of MS [33,34], QPS may represent a more reliable method to measure cortical plasticity in MS than other TMS protocols.…”

Section: Introductionmentioning

confidence: 99%

The degree of cortical plasticity correlates with cognitive performance in patients with Multiple Sclerosis

Balloff

Penner

et al. 2022

Brain Stimulation

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The Role of Glutamate in the Pathogenesis of Multiple Sclerosis

Cited by 8 publications

References 57 publications

Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination

Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination

Exploring the Role of Neurotransmitters in Multiple Sclerosis: An Expanded Review

The degree of cortical plasticity correlates with cognitive performance in patients with Multiple Sclerosis

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