Serotonin stimulates Echinococcus multilocularis larval development

Abstract Background Serotonin is a phylogenetically ancient molecule that is widely distributed in most metazoans, including flatworms. In addition to its role as a neurotransmitter, serotonin acts as a morphogen and regulates developmental processes. Although several studies have focused on the serotonergic nervous system in parasitic flatworms, little is known on the role of serotonin in flatworm development. Methods To study the effects of serotonin on proliferation and development of the cestode Echinococcus multilocularis, we cloned the genes encoding the E. multilocularis serotonin transporter (SERT) and tryptophan hydroxylase (TPH), analyzed gene expression by transcriptome analysis and whole mount in situ hybridization (WMISH) and performed cell culture experiments. Results We first characterized orthologues encoding the SERT and TPH, the rate-limiting enzyme in serotonin biosynthesis. WMISH and transcriptomic analyses indicated that the genes for both SERT and TPH are expressed in the parasite nervous system. Long-term treatment of parasite stem cell cultures with serotonin stimulated development towards the parasite metacestode stage. Mature metacestode vesicles treated with serotonin showed increased rates of incorporation of the thymidine analogue 5-ethynyl-2′-deoxyuridine (EdU), indicating stimulated cell proliferation. In contrast, treatment with the selective serotonin reuptake inhibitor paroxetine strongly affected the viability of parasite cells. Paroxetine also caused structural damage in metacestode vesicles, suggesting that serotonin transport is crucial for the integrity of parasite vesicles. Conclusions Our results indicate that serotonin plays an important role in E. multilocularis development and proliferation, providing evidence that the E. multilocularis SERT and TPH are expressed in the nervous system of the protoscolex. Our results further suggest that the E. multilocularis SERT has a secondary role outside the nervous system that is essential for parasite integrity and survival. Since serotonin stimulated E. multilocularis metacestode development and proliferation, serotonin might also contribute to the formation and growth of the parasite in the liver.

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Serotoninergic but not noradrenergic neurons in rat central nervous system adapt to long-term treatment with monoamine oxidase inhibitors

Neuroscience ◽

10.1016/0306-4522(85)90107-1 ◽

1985 ◽

Vol 16 (4) ◽

pp. 949-955 ◽

Cited By ~ 96

Author(s):

P. Blier ◽

C. de Montigny

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Monoamine Oxidase ◽

Term Treatment ◽

Monoamine Oxidase Inhibitors ◽

Noradrenergic Neurons ◽

Long Term Treatment

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Long-term management of gout

10.1093/med/9780199668847.003.0046 ◽

2016 ◽

Author(s):

Fernando Perez-Ruiz ◽

Irati Urionagüena ◽

Sandra P. Chinchilla

Keyword(s):

Structural Damage ◽

Serum Urate ◽

Term Treatment ◽

Lifestyle Changes ◽

Long Term Treatment ◽

Patient Reported ◽

Concomitant Medications ◽

Urate Lowering Treatment ◽

Term Management

Long-term management of gout comprises several aspects. Although in the short term, prophylaxis and treatment of acute episodes of inflammation are of great importance, the milestone for the long-term management of gout is targeted, sustained, and long-term control of hyperuricaemia. Treating to target subsaturating serum urate (SUA) levels, which may be initially dependent on the severity of the disease in the individual patient, is associated with a progressive reduction to no episodes of acute inflammation, regression and disappearance of subcutaneous and articular monosodium urate deposits and associated chronic inflammation, and improvement in patient-reported, health-related quality of life. Early and effective urate-lowering treatment to target levels will also prevent the development of structural damage. Urate-lowering treatment includes any measure intending to reduce SUA levels to target: lifestyle changes, modifications of concomitant medications favouring hyperuricaemia, and urate-lowering medications (ULMs). Availability of ULMs is variable worldwide, and prescription should be judicious, according to approved labels, and always considering associated health conditions and concomitant medications. Effectiveness and safety should be periodically monitored. Long-term treatment of gout still remains suboptimal in the twenty-first century. As practising clinicians, we cannot afford to neglect a ‘curable disease’.

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Isolated angiitis of the central nervous system: Lack of inflammation after long-term treatment

Neurology ◽

10.1212/wnl.52.1.196 ◽

1999 ◽

Vol 52 (1) ◽

pp. 196-196 ◽

Cited By ~ 13

Author(s):

G. Riemer ◽

K. Lamszus ◽

R. Zschaber ◽

H. J. Freitag ◽

C. Eggers ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Term Treatment ◽

Long Term Treatment ◽

The Central Nervous System

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GCT-41. RESPONSE-BASED RADIATION THERAPY IN PATIENTS WITH NEWLY DIAGNOSED CENTRAL NERVOUS SYSTEM LOCALIZED GERMINOMA: A CHILDREN’S ONCOLOGY GROUP (COG) PROSPECTIVE PHASE 2 CLINICAL TRIAL

Neuro-Oncology ◽

10.1093/neuonc/noaa222.259 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii336-iii336

Author(s):

Ute Bartels ◽

Jason Fangusaro ◽

Dennis Shaw ◽

Aashim Bhatia ◽

Arzu Omar-Thomas ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Mature Teratoma ◽

Progression Free Survival ◽

Complete Response ◽

Term Treatment ◽

Term Survival ◽

Tumor Bed ◽

Long Term Treatment

Abstract BACKGROUND The objective of stratum 2 of COG ACNS1123 was to evaluate children and young adults (3–21 years) with localized central nervous system (CNS) germinoma and investigate whether simplified pre-irradiation chemotherapy followed by response based dose-reduced whole ventricular irradiation (WVI) would maintain a high progression-free survival (PFS) while reducing long term treatment burden. METHODS Pre-irradiation chemotherapy consisted of 4 cycles of carboplatin and etoposide every 21 days followed by response-based irradiation (XRT). Patients with a complete response (CR) to pre-XRT chemotherapy received 18Gy WVI + 12Gy boost to the tumor bed. Patients with partial response (PR) but less than 1.5 cm residual proceeded to 24Gy WVI + 12Gy boost. All patients were also enrolled on COG ALTE07C1 to prospectively evaluate and longitudinally model the cognitive, social and behavioral functioning. RESULTS During a total accrual time of 45.5 months from 05/2012 to 06/2018, 137 eligible patients were enrolled. Median age was 14.09 years (4.95–21.46), 73% were male, and 45.26% had elevated βhCG in serum and/or cerebrospinal fluid. Twenty-nine patients (21.17%) did not have tissue biopsy. Eleven patients underwent second-look surgery; 7 had mature teratoma and 4 had non-viable tumor. Eighty-one patients (59.13%) had a CR. There were 4 relapses in patients receiving 18Gy WVI + boost, but no deaths. No unexpected treatment-related events were observed. The estimated 3-year PFS was 94.4 ±2.7% among 74 evaluable subjects. CONCLUSION This study shows promise in XRT reduction for patients with localized CNS germinoma and CR. Long-term survival outcomes and ALTE07C1 data are being evaluated.

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