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      Serotonin Levels in the Serum of Persons with Onchocerciasis-Associated Epilepsy: A Case-Control Study

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          Abstract

          Onchocerciasis-associated epilepsy (OAE) is a devastating childhood disorder occurring in areas with high Onchocerca volvulus transmission. Despite epidemiological evidence showing the association between O. volvulus and epilepsy, the underlying mechanism remains unknown. Since high levels of serotonin are known to induce seizures, we investigated serotonin levels in persons with OAE and controls selected from the Democratic Republic of Congo. Serum serotonin levels were determined by ELISA in 19 persons with OAE, 32 persons with epilepsy without O. volvulus infection, 18 with O. volvulus infection but without epilepsy, and 35 with neither O. volvulus infection nor epilepsy. O. volvulus infection was diagnosed by skin snip testing and/or OV16 antibody detection. Serum serotonin levels were significantly decreased in persons with OAE compared to persons with O. volvulus infection and no epilepsy. In conclusion, an increased serotonin level is unable to explain the pathogenesis of OAE. Other hypotheses to identify the causal mechanism of OAE will need to be investigated.

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          Differences between males and females in rates of serotonin synthesis in human brain.

          M Diksic, Ana C. A. X. De-Oliveira, P. Blier … (1997)
          Rates of serotonin synthesis were measured in the human brain using positron emission tomography. The sensitivity of the method is indicated by the fact that measurements are possible even after a substantial lowering of synthesis induced by acute tryptophan depletion. Unlike serotonin levels in human brain, which vary greatly in different brain areas, rates of synthesis of the indolamine are rather uniform throughout the brain. The mean rate of synthesis in normal males was found to be 52% higher than in normal females; this marked difference may be a factor relevant to the lower incidence of major unipolar depression in males.
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            Platelets release pathogenic serotonin and return to circulation after immune complex-mediated sequestration

            Nathalie Cloutier, Isabelle Allaeys, Geneviève Marcoux … (2018)
            Immune complexes (ICs) form when antibodies encounter their antigens. ICs are present in blood in multiple pathological conditions. Given the abundance of platelets in blood and that they express a receptor for ICs, called Fcγ receptor IIA (FcγRIIA), we examined the impact of ICs in blood in a mouse model. We found that circulating ICs induced systemic shock, characterized by loss of consciousness, by activating platelet FcγRIIA. Shock was mediated by the liberation of serotonin, a molecule better known for its role in the brain, from platelet granules. During shock, platelets were sequestered in the lungs and brain and returned to the blood circulation after their degranulation. Platelets are thus crucial in response to ICs. There is a growing appreciation for the contribution of platelets to immunity; however, our knowledge mostly relies on platelet functions associated with vascular injury and the prevention of bleeding. Circulating immune complexes (ICs) contribute to both chronic and acute inflammation in a multitude of clinical conditions. Herein, we scrutinized platelet responses to systemic ICs in the absence of tissue and endothelial wall injury. Platelet activation by circulating ICs through a mechanism requiring expression of platelet Fcγ receptor IIA resulted in the induction of systemic shock. IC-driven shock was dependent on release of serotonin from platelet-dense granules secondary to platelet outside-in signaling by αIIbβ3 and its ligand fibrinogen. While activated platelets sequestered in the lungs and leaky vasculature of the blood–brain barrier, platelets also sequestered in the absence of shock in mice lacking peripheral serotonin. Unexpectedly, platelets returned to the blood circulation with emptied granules and were thereby ineffective at promoting subsequent systemic shock, although they still underwent sequestration. We propose that in response to circulating ICs, platelets are a crucial mediator of the inflammatory response highly relevant to sepsis, viremia, and anaphylaxis. In addition, platelets recirculate after degranulation and sequestration, demonstrating that in adaptive immunity implicating antibody responses, activated platelets are longer lived than anticipated and may explain platelet count fluctuations in IC-driven diseases.
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              The temporal relationship between onchocerciasis and epilepsy: a population-based cohort study

              Cédric B Chesnais, Hugues C. Nana-Djeunga, Alfred Njamnshi … (2018)
              Many studies have suggested that onchocerciasis might be associated with epilepsy. Therefore, we did a cohort study to assess the incidence of epilepsy relative to Onchocerca volvulus skin microfilarial density (MFD) measured during childhood and to assess the possibility of a temporal relationship.
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                Author and article information

                Contributors
                Fabrizio Bruschi: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Pathogens
                Journal ID (iso-abbrev): Pathogens
                Journal ID (publisher-id): pathogens
                Title: Pathogens
                Publisher: MDPI
                ISSN (Electronic): 2076-0817
                Publication date (Electronic): 08 June 2021
                Publication date Collection: June 2021
                Volume: 10
                Issue: 6
                Electronic Location Identifier: 720
                Affiliations
                [1 ]Global Health Institute, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium; Alfred.dusabimana@ 123456uantwerpen.be (A.D.); robert.colebunders@ 123456uantwerpen.be (R.C.)
                [2 ]Global Health Institute, Gouverneur Kinsbergencentrum, University of Antwerp, Doornstraat 331, 2610 Wilrijk, Belgium
                [3 ]Molecular Pathology Group, Laboratory of Cell Biology & Histology, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium; samir.kumarsingh@ 123456uantwerpen.be
                [4 ]Provincial Health Division Ituri, Ministry of Health, P.O. Box 57 Bunia, Democratic Republic of the Congo; michel.mandro@ 123456student.uantwerpen.be
                [5 ]Brain Research Africa Initiative (BRAIN), Yaoundé P.O. Box 25625, Cameroon; JosephNeson.SieweFodjo@ 123456uantwerpen.be
                [6 ]Centre de Recherche en Maladies Tropicales, Rethy, P.O. Box 143 Bunia, Democratic Republic of the Congo; fnyisi@ 123456gmail.com
                [7 ]Centre Neuro-Psycho Pathologique, University of Kinshasa, P.O. Box 127 Kinshasa, Democratic Republic of the Congo; debymukendi@ 123456yahoo.fr
                [8 ]Department of Mathematics and Statistics, University of Limerick, V94 T9PX Limerick, Ireland; joweygwatsv@ 123456gmail.com
                Author notes
                [* ]Correspondence: krizia.vieri@ 123456uantwerpen.be (M.K.V.); an.hotterbeekx@ 123456uantwerpen.be (A.H.); Tel.: +32-3-265-25-52 (M.K.V.); +32-3-265-27-52 (A.H.)
                Author information
                https://orcid.org/0000-0003-3967-4945
                https://orcid.org/0000-0003-3356-4032
                https://orcid.org/0000-0003-2660-880X
                https://orcid.org/0000-0002-4024-2181
                https://orcid.org/0000-0002-1919-1340
                Article
                Publisher ID: pathogens-10-00720
                DOI: 10.3390/pathogens10060720
                PMC ID: 8226745
                PubMed ID: 34201076
                SO-VID: 4ad76851-a677-44c1-9ade-ab9258adb2a0
                Copyright © © 2021 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 19 May 2021
                Date accepted : 04 June 2021
                Categories
                Subject: Article

                Keywords: epilepsy,nodding syndrome,onchocerciasis,onchocerca volvulus,serotonin,pathogenesis
                Data availability:
                Keywords: epilepsy, nodding syndrome, onchocerciasis, onchocerca volvulus, serotonin, pathogenesis

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