“Glioma: How it Intercepts Neural Impulses and Impairs Cognitive Abilities”

Glioma causes its neurons to intercept other people’s impulses – they help cancer cells grow.

Brain cancer inevitably affects the mental state of patients, and the weakening of cognitive abilities is one of the most common symptoms. The question is what exactly happens in the brain.

First, the most obvious mechanism is that when a tumor grows in the brain, it simply physically presses on the surrounding tissue. Neurons and neural circuits feel pressure and therefore work worse. Secondly, the tumor breaks neural connections, growing into different areas of the brain. Thirdly, the presence of a tumor disrupts the physiology of the surrounding tissue, edema occurs in it, and for neurons, swelling does not disappear without a trace. Fourth, tumors can rearrange their vasculature to receive more nutrients. But if the tumor receives more of them, then the neighboring tissues receive less of them, with all the ensuing consequences.

In an article in Nature Researchers at the University of California at San Francisco describe another reason why a brain with a tumor begins to work worse – the tumor, as it turned out, directly rebuilds neural circuits. Moreover, she rebuilds them so that the part of the brain where the tumor is located receives neural impulses that normally do not touch it. Why does cancer need it? Then, that he receives certain advantages from neural signals.

In this case, we are talking about glioma – a tumor that is formed by degenerated service cells of the nervous tissue. They are called by the general word glia, or neuroglia, hence the name of cancer. We wrote a lot about the fact that gliomas literally parasitize neurons, and the more active the neurons work, the more actively the tumor develops. For example, we talked about how glioma cells intercept neurotransmitters from neurons that help cancer cells multiply and spread throughout the brain. Glioma can even specifically influence the surrounding neurons so that they give it the necessary neurotransmitter molecules. Last year and the year before Nature articles appeared that described how gliomas literally grow on neural signals, only then they talked about sensory signals that run along the visual and olfactory neural pathways.

The new study is no longer talking about unintentional sensory signals, but about “higher thoughts”, if you can call them that – that is, about the signals that accompany language processes. Patients with gliomas who underwent brain surgery remained conscious during the operation, they were shown different pictures and asked to name what they depicted. Naturally, the language zones in the brain were activated, but at the same time, those areas where there were glioma islands were activated – moreover, the areas with gliomas had nothing to do with speech and language. That is, zones with gliomas were connected to the language network. Moreover, there was no evidence in favor of the fact that ordinary language areas begin to work better from this – tumor areas did not add new “computing power”.

Further experiments showed that among the glioma zones there are different ones: some are sensitive to activity in other parts of the brain, while others, on the contrary, are relatively indifferent to extraneous activity. The difference in activity means a difference in connectivity, in the interneuronal connections that link the glioma area to others. That is, in one case, the part of the brain with the tumor clearly made more connections to other neuronal centers. It turned out that in such “overconnected” glioma zones, a particularly large amount of thrombospondin-1 (TSP-1) protein, which is needed for the formation of synapses, is synthesized. In a healthy brain, it is secreted by glial cells called astrocytes, helping neurons form new synapses and new neuronal circuits. Glioma cells synthesize TSP-1 beyond measure, forcing neurons to connect to different neural circuits that they generally do not need.

With the help of TSP-1, the glioma can connect with neurons in some other area of ​​the brain where it will be transplanted. This has been shown in experiments with brain organoids – three-dimensional cellular structures that grow in a nutrient medium, imitating a piece of brain tissue. The organelles were grown together with glioma cells, and if such an organoid also had a lot of TSP-1, it could easily be transplanted into the mouse brain – there glioma neurons easily formed synapses with local neurons. (Just in case, let us clarify once again that tumor cells do not belong to neurons, but to auxiliary glial cells, however, those neurons that grow surrounded by glioma cells are forced to listen to their molecular signals.)

Those gliomas that force their neurons to form more synapses grow more actively and actively invade new territories. Since they studied the connection of gliomas with higher – linguistic – nervous activity, it can be said that brain cancer literally feeds on thoughts. By forcing their neurons to collect other people’s impulses, gliomas mess up the work of neural networks. To the deterioration of cognitive abilities, epileptic seizures can be added here, from which patients with gliomas also suffer. Observations on humans and experiments with mice suggest that the more actively a glioma connects to other areas of the brain, the more it forces its neurons to form more and more new synapses, the worse the clinical prognosis – that is, the more cognitive problems the patient will have and the more less likely to live longer.

But if the glioma is treated with gabapentin, then it will begin to grow more slowly. Gabapentin is an anticonvulsant drug prescribed for epilepsy and some other neurological disorders. The mechanism of its action is not entirely clear, in general, as you might guess, it regulates the activity of neurons. Among other things, it is known that it suppresses the work of the TSP-1 protein, which is so important for gliomas; this is obviously why gabapentin inhibits tumor growth. Experiments with gabapentin were performed on mice that were transplanted with aggressive gliomas that provoke neurons to extra synapses. It is possible that in the near future the antiglioma effect of gabapentin will be tested in clinical trials, and if it turns out to be effective enough, then it can be connected to the treatment of human gliomas.