Cestode larvae excite host neuronal circuits via glutamatergic signaling

Abstract

AbstractNeurocysticercosis (NCC) is caused by the presence of Taenia solium larvae in the brain and is the leading cause of adult-acquired epilepsy worldwide. However, little is known about how seizures emerge in NCC. To address this knowledge gap we used whole-cell patch-clamp electrophysiology and calcium imaging in rodent hippocampal organotypic slice cultures to identify direct effects of cestode larval products on neuronal activity. We found both whole cyst homogenate and excretory/secretory (E/S) products of Taenia larvae have an acute excitatory effect on neurons, which trigger seizure-like events in vitro. Underlying this effect was Taenia-induced neuronal depolarization, which was mediated by glutamate receptor activation but not by nicotinic acetylcholine receptors, acid-sensing ion channels nor Substance P. Glutamate assays revealed the homogenate of both Taenia crassiceps and Taenia solium larvae contained high concentrations of glutamate and that larvae of both species consistently produce and release this excitatory neurotransmitter into their immediate environment. These findings contribute towards the understanding of seizure generation in NCC.Author summaryBrain infection by larvae of the tapeworm Taenia solium (neurocysticercosis or NCC) is the leading cause of acquired epilepsy in adulthood. Little is understood about the mechanisms by which larvae cause seizures. To address this, we used electrophysiological and imaging techniques in rodent brain slices to investigate how tapeworm larvae directly impact neuronal function. We discovered that both the homogenate and secretory products of tapeworm larvae excite neurons and can trigger seizure-like events in brain slices. This effect was caused by the activation of glutamate receptors and not by activating other types of receptors in the brain. Finally, we observed that tapeworm larvae both contain and release the neurotransmitter glutamate into their immediate environment. These findings are relevant for understanding how tapeworm larvae cause seizures in NCC.