Bromocriptine Therapy in Multiple Sclerosis

Bissay, Véronique; Klippel, Nina De; Herroelen, Luc; Schmedding, Eric; Buisseret, T; Ebinger, Guy; Keyser, Jacques De

doi:10.1097/00002826-199410000-00011

Cited by 40 publications

(20 citation statements)

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“…When lower levels of DA are released likely the main activation is D3Rs in T cells, which could lead to T cell migration, while higher levels of DA could activate D5Rs instead and as a consequence inhibition of the T cell function [129]. Despite the potential role of DA in MS, a pilot study in MS patients treated with D2Rs agonist after a year of treatment no changes were observed in the progression of this disease [211]. It's important to mention that other catecholamines are also participating such as -adrenergic receptors (AR) and balance between DA and -AR inhibitory and stimulatory effects play an important role in the lymphocytes activation.…”

Section: Multiple Sclerosis and Da Receptorsmentioning

confidence: 98%

Dopamine Receptors and Neurodegeneration

Rangel‐Barajas¹,

Coronel²,

Florán³

2015

Aging and disease

187

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Dopamine (DA) is one of the major neurotransmitters and participates in a number of functions such as motor coordination, emotions, memory, reward mechanism, neuroendocrine regulation etc. DA exerts its effects through five DA receptors that are subdivided in 2 families: D1-like DA receptors (D1 and D5) and the D2-like (D2, D3 and D4). All DA receptors are widely expressed in the central nervous system (CNS) and play an important role in not only in physiological conditions but also pathological scenarios. Abnormalities in the DAergic system and its receptors in the basal ganglia structures are the basis Parkinson's disease (PD), however DA also participates in other neurodegenerative disorders such as Huntington disease (HD) and multiple sclerosis (MS). Under pathological conditions reorganization of DAergic system has been observed and most of the times, those changes occur as a mechanism of compensation, but in some cases contributes to worsening the alterations. Here we review the changes that occur on DA transmission and DA receptors (DARs) at both levels expression and signals transduction pathways as a result of neurotoxicity, inflammation and in neurodegenerative processes. The better understanding of the role of DA receptors in neuropathological conditions is crucial for development of novel therapeutic approaches to treat alterations related to neurodegenerative diseases.

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Section: Multiple Sclerosis and Da Receptorsmentioning

confidence: 98%

Dopamine Receptors and Neurodegeneration

Rangel‐Barajas¹,

Coronel²,

Florán³

2015

Aging and disease

187

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“…Another study has found a positive correlation between PRL serum levels and the number of anti-MOG antibody secreting cells [90]. When BCR treatment has been applied to human MS, an open label study reported no efficacy in reducing disease activity [91], while a single case report has described the control of paroxystic symptoms [92]. On the whole, these data did not allow drawing a definite conclusion on the role of PRL in CNS autoimmunity.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Prolactin: A versatile regulator of inflammation and autoimmune pathology

Costanza¹,

Binart

Steinman

et al. 2015

Autoimmunity Reviews

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“…Stimulation of β 2 -AR and DR D5 in human lymphocytes results in a pattern of effects which overall are beneficial for MS [23,24,47,48,49,50], while stimulation of DR D5 in Treg results in a decreased regulatory function of these cells [29], which in turn may be harmful for MS. Although initial studies showed that experimental autoimmune encephalomyelitis usually benefits from drugs acting on AR [51,52,53] as well as on DR [54], only limited results were subsequently obtained in MS patients [51,55]. According to the overall picture now available, a likely explanation could be that in untreated MS patients β 2 -AR- and DR D5-operated pathways in lymphocytes are nonresponsive (or hyperresponsive as in the case of dopaminergic pathways in Treg, possibly leading to detrimental effects).…”

Section: Discussionmentioning

confidence: 99%

Dopaminergic Modulation of CD4+CD25<sup>high</sup> Regulatory T Lymphocytes in Multiple Sclerosis Patients during Interferon-β Therapy

Cosentino

Zaffaroni²,

Trojano

et al. 2012

Neuroimmunomodulation

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Objective: We investigated dopaminergic inhibition of CD4+CD25^high regulatory T lymphocytes (Treg) in relapsing-remitting multiple sclerosis (MS) patients treated with interferon (IFN)-β. Methods: MS patients were prospectively studied at baseline and during 1 year of IFN-β, and compared with healthy controls (HCs). Treg were separated by immunomagnetic sorting and the effect of dopamine (DA) on Treg was assessed in coculture experiments with homologous effector T lymphocytes (Teff). Tyrosine hydroxylase (TH), dopaminergic receptors (DR) D3 and D5, and forkhead box protein P3 (FoxP3) mRNA were assessed by real-time PCR. Circulating CD4+ T cell subsets were assessed by flow cytometry. Results: In coculture experiments, Treg inhibition of Teff proliferation was reduced by DA in HCs and completely abolished in MS patients at baseline. However, in patients after 12 months of IFN-β, Teff proliferation was impaired and DA had no more effect on Treg. In comparison to cells from HCs, Treg from MS patients at baseline had increased mRNA for DR D5 and TH (but not for DR D3). During treatment with IFN-β, both DR D5 and TH mRNA decreased down to values lower than those of cells from HCs. In comparison to HCs, MS patients had a higher frequency of circulating Treg, both at baseline and after IFN-β, while FoxP3 mRNA levels in Treg were similar in patients and HCs and did not show major changes during IFN-β. Conclusions: Dopaminergic inhibition of Treg in MS patients is suppressed during IFN-β treatment. Treg play a key role in the suppression of autoimmunity, thus the effect may have a therapeutic repercussion.

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Bromocriptine Therapy in Multiple Sclerosis

Cited by 40 publications

References 0 publications

Dopamine Receptors and Neurodegeneration

Dopamine Receptors and Neurodegeneration

Prolactin: A versatile regulator of inflammation and autoimmune pathology

Dopaminergic Modulation of CD4+CD25<sup>high</sup> Regulatory T Lymphocytes in Multiple Sclerosis Patients during Interferon-β Therapy

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