Serotoninergic system targeting in multiple sclerosis: the prospective for pathogenetic therapy.

Melnikov, Mikhail; Sviridova, Anastasiya; Rogovskii, Vladimir; Oleskin, Alexander V.; Boziki, Marina; Bakirtzis, Christos; Kesidou, Evangelia; Grigoriadis, Nikolaos; Boyко, Alexey

doi:10.1016/j.msard.2021.102888

Cited by 19 publications

(19 citation statements)

References 128 publications

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“…Serotoninergic routes are highly responsible for modulating both our autonomic and neuroendocrine reactions to stressful stimuli, as serotonin constitutes a major HPA axis modulator ( 16 , 17 ). In patients suffering from depression or anxiety, the serotoninergic network is significantly altered by accumulating stress, thereby severely impacting HPA axis function ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Antidepressants on Multiple Sclerosis: A Review of In Vitro and In Vivo Models

et al. 2021

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BackgroundIncreased prevalence of depression has been observed among patients with multiple sclerosis (MS) and correlated with the elevated levels of proinflammatory cytokines and the overall deregulation of monoaminergic neurotransmitters that these patients exhibit. Antidepressants have proved effective not only in treating depression comorbid to MS, but also in alleviating numerous MS symptoms and even minimizing stress-related relapses. Therefore, these agents could prospectively prove beneficial as a complementary MS therapy.ObjectiveThis review aims at illustrating the underlying mechanisms involved in the beneficial clinical effects of antidepressants observed in MS patients.MethodsThrough a literature search we screened and comparatively assessed papers on the effects of antidepressant use both in vitro and in vivo MS models, taking into account a number of inclusion and exclusion criteria.ResultsIn vitro studies indicated that antidepressants promote neural and glial cell viability and differentiation, reduce proinflammatory cytokines and exert neuroprotective activity by eliminating axonal loss. In vivo studies confirmed that antidepressants delayed disease onset and alleviated symptoms in Experimental Autoimmune Encephalomyelitis (EAE), the most prevalent animal model of MS. Further, antidepressant agents suppressed inflammation and restrained demyelination by decreasing immune cell infiltration of the CNS.ConclusionAntidepressants were efficient in tackling numerous aspects of disease pathophysiology both in vitro and in vivo models. Given that several antidepressants have already proved effective in clinical trials on MS patients, the inclusion of such agents in the therapeutic arsenal of MS should be seriously considered, following an individualized approach to minimize the adverse events of antidepressants in MS patients.

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Section: Introductionmentioning

confidence: 99%

Antidepressants on Multiple Sclerosis: A Review of In Vitro and In Vivo Models

et al. 2021

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“…It is important to note that depression is one of the most common symptoms in MS and may aggravate its course, which could be explained by similar pathogenetic mechanisms of MS and depression, including an enhanced Th17 immune response [ 18 , 19 ]. Conversely, the clinical efficacy of “controlled stress” therapies, such as treatment with antidepressants, lifestyle modification, and coping strategies in MS, was shown [ 10 , 20 , 21 ].…”

Section: The Involvement Of Dopamine In the Development Of Clinical Symptoms In Msmentioning

confidence: 99%

“…In addition, autocrine regulatory effects of dopamine on immune cells were demonstrated [ 7 ]. The data on the influence of dopamine, norepinephrine, and serotonin on experimental autoimmune encephalomyelitis (EAE) and MS course allow one to propose the therapeutic prospective of their receptor targeting in MS [ 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Dopaminergic Receptor Targeting in Multiple Sclerosis: Is There Therapeutic Potential?

Melnikov

Pashenkov

Boyко

2021

IJMS

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Dopamine is a neurotransmitter that mediates neuropsychological functions of the central nervous system (CNS). Recent studies have shown the modulatory effect of dopamine on the cells of innate and adaptive immune systems, including Th17 cells, which play a critical role in inflammatory diseases of the CNS. This article reviews the literature data on the role of dopamine in the regulation of neuroinflammation in multiple sclerosis (MS). The influence of dopaminergic receptor targeting on experimental autoimmune encephalomyelitis (EAE) and MS pathogenesis, as well as the therapeutic potential of dopaminergic drugs as add-on pathogenetic therapy of MS, is discussed.

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“…On the other hand, 5-HT may regulate the ≪gut-brain≫ axis and modulate immune cell activity and cytokine production (2, 3). It is known that immune cells of both the innate and adaptive immune systems express serotonergic receptors (3). Furthermore, according to some studies, several immune cells may produce 5-HT, which suggests serotonergic autoregulation of immune cell function (4).…”

Section: Introductionmentioning

confidence: 99%

Serotonergic drug repurposing in multiple sclerosis: A new possibility for disease-modifying therapy

et al. 2022

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Investigation of neuroimmune interactions is one of the most developing areas in the study of multiple sclerosis pathogenesis. Recent evidence suggests the possibility of modulating neuroinflammation by targeting biogenic amine receptors. It has been shown that selective serotonin reuptake inhibitor fluoxetine modulates innate and adaptive immune system cells' function and can reduce experimental autoimmune encephalomyelitis and multiple sclerosis severity. This brief report discusses the immune mechanisms underlying the multiple sclerosis pathogenesis and the influence of fluoxetine on them. The retrospective data on the impact of fluoxetine treatment on the course of multiple sclerosis are also presented. The results of this and other studies suggest that fluoxetine could be considered an additional therapy to the standard first-line disease-modifying treatment for relapsing–remitting multiple sclerosis.

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Serotoninergic system targeting in multiple sclerosis: the prospective for pathogenetic therapy.

Cited by 19 publications

References 128 publications

Antidepressants on Multiple Sclerosis: A Review of In Vitro and In Vivo Models

Antidepressants on Multiple Sclerosis: A Review of In Vitro and In Vivo Models

Dopaminergic Receptor Targeting in Multiple Sclerosis: Is There Therapeutic Potential?

Serotonergic drug repurposing in multiple sclerosis: A new possibility for disease-modifying therapy

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