title: Increased synapsin I expression in cerebral malaria.
abstract: Synapsin I is a neuronal phosphoprotein contained in the synaptic vesicles of mammalian central and peripheral nervous systems. It regulates both neurotransmitter release and synaptic formation. Variations in synapsin I expression in the brain have been reported to cause brain malfunction. In severe malaria, neurological complications, such as convulsion, delirium and coma, suggest abnormalities in the release of neurotransmitters. This study evaluated synapsin I expression in cerebral malaria (CM). An immunohistochemical method was used to study the semi-quantitative and qualitative expression of synapsin I in the brain of CM patients (10 cases) who died with Plasmodium falciparum, compared with non-cerebral malaria (NCM) (4 cases), and control brain tissues (5). Synapsin I was expressed in the gray matter of the cerebral cortex and the molecular layer of the cerebellum, as a diffusely dense precipitate pattern in the neuropil, with no immunoreactivity in the neurons, neuronal dendrites, glial cells, endothelial cells, and Purkinje cells. The findings were similarly demonstrated in CM, NCM, and control brain tissues. However, in the granular layer of the cerebellum, a significant increase in synapsin I expression was observed in the granule cells, and the glomerular synaptic complex, from the CM group, compared with the NCM, and control brain tissues (all P < 0.05). Parasitemia showed a positive correlation with synapsin I expression in the granule cells (on admission: Spearman's ρ = 0.600, P = 0.023) (before death: Spearman's ρ = 0.678, P = 0.008), and glomerular synaptic complex (before death: Spearman's ρ = 0.571, P = 0.033). It was hypothesized that CM causes pre-synaptic excitation and eventually activation of synapsin I, leading to increased neurotransmitter release. Synapsin I inhibitor should be investigated further as a target for a therapeutic intervention to alleviate neurological symptoms in severe malaria.
authors.affiliation: Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University Bangkok 10400, Thailand.
authors.forename: Klairoong
authors.initials: K
authors.lastname: Thonsranoi
authors.affiliation: Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University Bangkok 10400, Thailand.
authors.forename: Supattra
authors.initials: S
authors.lastname: Glaharn
authors.affiliation: School of Medicine, Walailak University Nakhon Si Thammarat 80161, Thailand.
authors.forename: Chuchard
authors.initials: C
authors.lastname: Punsawad
authors.affiliation: Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University Bangkok 10400, Thailand.
authors.forename: Urai
authors.initials: U
authors.lastname: Chaisri
authors.affiliation: Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University Bangkok 10400, Thailand.
authors.forename: Srivicha
authors.initials: S
authors.lastname: Krudsood
authors.affiliation: Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol UniversityBangkok 10400, Thailand; Center for Emerging and Neglected Infectious Diseases, Mahidol UniversitySalaya, Nakhon Pathom 73170, Thailand.
authors.forename: Parnpen
authors.initials: P
authors.lastname: Viriyavejakul
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016779:Malaria, Cerebral / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D016778:Malaria, Falciparum / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D018512:Parasitemia / Q000378:metabolism / Q000473:pathology; D010963:Plasmodium falciparum / Q000302:isolation & purification; D016704:Synapsins / Q000032:analysis*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016704:Synapsins
keywords: Malaria; Plasmodium falciparum; cerebral malaria; immunohistochemistry; synapsin I
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