de Lange, Anja, Tomes, Hayley, Selfe, Joshua, Prodjinotho, Ulrich Fabien, Verhoog, Matthijs Bernard, Mahanty, Siddhartha, Smith, Katherine ORCID: https://orcid.org/0000-0001-8150-5702, Horsnell, William, Sikasunge, Chummy, Prazeres da Costa, Clarissa and Raimondo, Joseph Valentino 2023. Cestode larvae excite host neuronal circuits via glutamatergic signaling. eLife 2023 , 88174.1. 10.7554/eLife.88174.1 |
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Abstract
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. Underlying this effect was cestode-induced neuronal depolarization, which was mediated by glutamate receptor activation but not by nicotinic acetylcholine receptors, acid-sensing ion channels nor 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 acid’s 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 signaling may play a role in seizure generation in NCC.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Biosciences |
Publisher: | eLife Sciences Publications |
ISSN: | 2050-084X |
Date of First Compliant Deposit: | 25 April 2024 |
Date of Acceptance: | 13 July 2023 |
Last Modified: | 21 May 2024 09:15 |
URI: | https://orca.cardiff.ac.uk/id/eprint/168379 |
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