Division of Cell Biology, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Neuroscience Institute, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Division of Cell Biology, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Neuroscience Institute, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Joshua S Selfe
Division of Cell Biology, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Neuroscience Institute, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Ulrich Fabien Prodjinotho
Center for Global Health, TUM School of Medicine, Technical University of Munich, Munich, Germany
Matthijs B Verhoog
Division of Cell Biology, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Neuroscience Institute, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Siddhartha Mahanty
Department of Medicine, The Peter Doherty Institute for Infection and Immunity and the Victorian Infectious Diseases Service, University of Melbourne, Melbourne, Australia
Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; School of Biosciences, Cardiff University, Cardiff, United Kingdom
William Horsnell
Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom; Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, Orleans, France
Chummy Sikasunge
School of Veterinary Medicine, Department of Paraclinicals, University of Zambia, Lusaka, Zambia
Clarissa Prazeres da Costa
Center for Global Health, TUM School of Medicine, Technical University of Munich, Munich, Germany
Division of Cell Biology, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Neuroscience Institute, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
Neurocysticercosis (NCC) is caused by infection of the brain by larvae of the parasitic cestode Taenia solium. It is the most prevalent parasitic infection of the central nervous system and one of the leading causes of adult-acquired epilepsy worldwide. However, little is known about how cestode larvae affect neurons directly. To address this, we used whole-cell patch-clamp electrophysiology and calcium imaging in rodent and human brain slices to identify direct effects of cestode larval products on neuronal activity. We found that both whole cyst homogenate and excretory/secretory products of cestode larvae have an acute excitatory effect on neurons, which can trigger seizure-like events in vitro. This effect was mediated by glutamate receptor activation but not by nicotinic acetylcholine receptors, acid-sensing ion channels, or Substance P. Glutamate-sensing fluorescent reporters (iGluSnFR) and amino acid assays revealed that the larval homogenate of the cestodes Taenia crassiceps and Taenia solium contained high concentrations of the amino acids glutamate and aspartate. Furthermore, we found that larvae of both species consistently produce and release these excitatory amino acids into their immediate environment. Our findings suggest that perturbations in glutamatergic signalling may play a role in seizure generation in NCC.
