Excitable brain worms - the story we didn't know we needed
Illustrated by Ashleigh Campsall for The Scientist article, Feb 1 2024.
A research article quietly published in the eLife journal roughly a year ago has been steadily gathering momentum in the popular science sphere. This follows a notable rise in public interest in parasitic infections, perhaps popularised by the recent popular HBO series 'The Last of Us.' Additionally, a rise in cases of parasitic and fungal infections, reportedly due to to climate change, may be capturing the public's fascination - parasites adapting to tolerate hotter temperatures, making humans more susceptible to infection (as our body temperature becomes less of a deterrant). Whatever the reason, the public want to know more and an unsuspecting paper on tapeworm and epilepsy seemed to satisfy this hunger for knowledge.
The research article, entitled 'Cestode larvae excite host neuronal circuits via glutamatergic signalling,' details work done in the lab of Joseph Raimondo (Neuroscience Institute & Human Biology Department, UCT) and was most recently featured as a podcast episode produced by The Naked Scientists (Cambridge University) as part of the eLife podcast series. Dr Chris Smith, the host, introduced the research as follows:
'One cause of the seizure condition epilepsy is the disease known as cysticercosis. This is the result of ingesting the eggs of the pork tapeworm Taenia solium. These eggs hatch into larvae that migrate throughout the body and then form tissue cysts, which often crop up in the brain where they're known to trigger 'fits' - although we weren't sure exactly why. But now, thanks to Hayley Tomes and Anja De Lange from the University of Cape Town we have a much clearer picture of what might be going on.'
Listen to the episode here (from 24min5sec) to hear our researchers discuss the experiments and their findings.
As described by the 'eLife digest' article (a short, plain-language summary of the research), 'researcher's Dr Anja De Lange and Dr Hayley Tomes 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.'
There is something grotesquely fascinating about how these parasites are able to find their way into a human brain, hunker down and quietly release excitatory chemicals for, sometimes, years before a person might ever experience a seizure. Truly a wonder, or horror, of evolution, depending of course on whether you are the tapeworm or the human. Another article about this work published by The Scientist, further describes how De Lange et al. confirmed that the excitatory chemical released and contained by the larvae was glutamate and how this adds much needed basic science evidence to explain the clinical phenomenon seen in neurocysticercosis.
Whilst not exactly accurate, the following wonderful illustration by Ashleigh Campsall (for The Scientist) perfectly captures what most people picture when they learn that tapeworm can infest a brain and lead to seizures. And as such might also capture what makes this research so intellectually appealing and, pun intended, engrossing.