Author response: Cestode larvae excite host neuronal circuits via glutamatergic signalling

Résumé fourni par la source

One of the main causes of epilepsy in adults – particularly in developing countries – is a parasitic brain infection called neurocysticercosis. This can happen when people swallow tapeworm eggs, which hatch into larvae and migrate throughout the body. When these larvae infect the brain, they form structures called cysts, which can cause seizures. It is thought that inflammation in the brain contributes to the development of seizures in neurocysticercosis, but how this might work is still poorly understood. The larvae produce chemicals that can interact with nearby cells in the body, including the defensive cells of our immune system. However, it remains unknown whether those chemicals also interact with brain cells. De Lange, Tomes et al. set out to determine if tapeworm larvae produced any specific chemicals that affect the activity of brain cells, and if they might play a role in epileptic seizures. To do this, the researchers collected materials from tapeworm larvae, which included both the substances they naturally released and a mixture made from crushed whole larvae. They then applied these substances to brain tissue grown in cell culture while recording the electrical activity of individual brain cells. Experiments using brain tissue derived from rats, mice and humans revealed that the larval products made brain cells more excited and led to them firing more electrical signals than normal. This excitation was strong enough to trigger larger patterns of activity across the brain tissue that mimicked the effect of an epileptic seizure. Further biochemical analysis of the larval products and the larvae themselves revealed that tapeworm larvae continuously release a chemical called glutamate, which is known to excite brain cells. These results suggested that tapeworm larvae might cause epilepsy by producing excess glutamate and overexciting brain cells – a mechanism similar to the way that other brain conditions, like tumors, also trigger seizures. This work has revealed a new mechanism for how tapeworm larvae might cause seizures in neurocysticercosis. The next step will be understanding how the larvae release glutamate into the brain, for example, if they actively produce it, or if it is passively released when they die. In the future, de Lange et al. hope this knowledge will help develop new treatments that help prevent seizures in people with neurocysticercosis.

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