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(the cover image is generated by AI and does not represent the real situation. Source: Bing image creator) A little eavesdropping on the "whispers" of the brain and tumors.

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Thanks to the sophisticated brain, we can perceive the world and interact with it. 86 billion neurons in our brain are woven into complex networks with the help of glial cells, echoing each other, playing all the stories between us and the outside world.

However, the tumor in the brain is like a sudden burst of discordant notes in this performance, making this beautiful concert unlucky. Glioma (gliomas) is one of many brain tumors that disrupt brain function and cause cognitive impairment. Gliomas arise from the canceration of glial cells, and the cognitive abilities of most glioma patients gradually decline in the last few months of their lives, such as aphasia (aphasia) or visual-spatial memory impairment in some patients. These cognitive impairment can affect the normal life of patients, and many people suffer from depression at the same time, which makes it difficult for them to bid farewell to the world in peace.

For many years, scientists have been trying to find the mechanism behind glioma affecting brain cognition, in order to find a treatment. They put forward many hypotheses, such as gliomas squeeze brain regions, disrupt brain physiological function, and compete with the brain for energy, but a new study provides a new idea: malignant gliomas can access the brain's neural circuits. and engulf the energy of neurons continue to grow, eventually bringing the host to death. The paper was published in Nature on March 23.

Is the tumor thinking? At first, the researchers found that similar neural signals indicating "the brain is thinking" could also be detected in glioma areas. The researchers showed some pictures or words to some glioma patients, asked the patients to say the words corresponding to the pictures or words, and monitored the brain neural activity of the patients in the process. Although these gliomas are located in areas of the cerebral cortex that are not responsible for language-related neural activity, neural signals indicating "task-related neural activity" (task-relevant neural activity) appear in these areas when the patient says a word.

The word or picture hint received by the patient (Krishna et al, 2023) indicates that there may be nerves in the glioma area, and when the language-related nerves in the brain are excited, the nerves in these glioma areas are excited together, as if the tumor and the brain are "thinking" together. The researchers believe that this may be because the tumor changes the brain's neural circuits, connecting the language-related neural activity in the cerebral cortex to the neural activity in the glioma area, forming a neural "functional connection" (functional connectivity).

So is the tumor really helping the brain think?

Maybe not, but if there is, it's not much. In general, when patients recognize and speak infrequently used words, they need more neural activity than to recognize commonly used words, so there are significant differences in neural signals. In the above experiment, although there was neural activity in the glioma area when patients identified uncommonly used words, there was no significant difference in neural signals between patients and patients when they said common words. This suggests that the neural activity of gliomas makes no additional contribution to the decoding of less commonly used words in the brain.

When speaking high-frequency and low-frequency words, the neural signals of tumor area and non-tumor area were compared. (Krishna et al, 2023) nerve growth into the tumor area although the above test detected neural activity in the glioma area, more evidence is needed to confirm the existence of nerve growth activity in the glioma.

When these patients removed brain gliomas, the researchers used magnetoencephalography (MEG, which measures the magnetic field generated by neural activity currents in the brain to observe and study brain function). It was observed that there were specific areas with rich neural "functional connections" in these gliomas, known as the "high functional connectivity" (HFC) areas of gliomas.

The researchers found that the expression of several genes associated with synaptic formation increased significantly in these HFC regions. This is consistent with previous studies that some gliomas can alter the brain's neural circuits by secreting signaling factors that promote synaptic formation. Subsequently, the researchers did observe more synaptic growth activity (compared to non-HFC regions) in sections of the HFC regions of these gliomas.

Later in vitro experiments also confirmed this. When the tumor tissue in the HFC region of glioma was co-cultured with mouse hippocampal neurons (hippocampal neurons) in vitro, a significant increase in synaptic activity was also observed. Then, after co-culture of HFC tumor tissue and human nerve tissue in vitro for 48 hours, the neural activity detected in the nerve tissue also increased significantly.

When the glioma (red) was co-cultured with the nerve organ (green), the tumor tissue in the HFC region of the glioma was quickly connected to the nervous system (tumor tissue in the glioma HFC region on the left and non-HFC region on the right) (Krishna et al, 2023). Then, the researchers implanted human HFC glioma tissue directly into the brain of mice for a period of time. There are many synaptic connections between nerves and gliomas in the cerebral cortex of mice where the tumor is located. These experimental results show that the HFC region of glioma can promote synaptic formation, thus changing the neural pathway of the brain.

Tumors connected to the nerves grow faster. What is the attempt of gliomas to connect themselves to the neural pathways of the brain? do they want to communicate with the brain?

Rather than "communicating" with the brain through nerves, it behaves more like a "mind that engulfs the brain". As we mentioned earlier, for the normal thinking activity of the brain (patients say the words corresponding to pictures or words), the nerves in the glioma area contribute very little to thinking. However, for gliomas, there is a lot of profit after being connected to the brain nerve.

First of all, gliomas are growing faster. The researchers co-cultured the glioma HFC region with mouse hippocampal nerve cells, and the HFC tumor tissue grew fivefold in one night. In the non-HFC region, the tumor growth rate was the same with or without co-culture of mouse hippocampal neurons. In addition, another experiment showed that the invasiveness of tumors in HFC regions was significantly higher than that in non-HFC regions.

To sum up, nerves make tumors grow faster and more easily invade normal areas, as if gliomas are using normal neural activity to make themselves grow. The survival time of mice implanted with human glioma HFC region tissue was significantly lower than that of mice implanted in non-HFC regions. The same is true for human patients: according to the study data, human patients with HFC regions in gliomas survived significantly less than those without HFC regions. This suggests that nerve access makes tumors grow faster and makes patients have a shorter life expectancy.

New treatment ideas although the news that gliomas can accelerate the growth of brain nerves is frustrating, on the other hand, this study also brings new ideas for the treatment of gliomas. Researchers also began to think about whether they could inhibit this ability of gliomas, which in turn inhibit their growth.

So the researchers used gene knockdown technology to suppress synaptic formation-related genes in HFC tumor tissues and found that their invasiveness decreased to the same level as non-HFC tumor tissues. The researchers then added a drug, gabapentin (gabapentin), to the neuro-glioma co-culture, which inhibits synaptic formation. After the addition of gabapentin for 24 h to 48 h, the neural activity observed in glioma decreased significantly. When gabapentin was used in mice implanted with human glioma HFC, the growth rate of glioma was also significantly reduced. It is hoped that gabapentin's treatment of gliomas will soon be applied to human patients.

Gabapentin can inhibit the effect of thrombospondin receptor (thrombospondin receptor) α 2 δ-1, thus inhibiting the effect of TSP-1, a signal molecule that promotes synaptic formation. TSP-1 is a signal molecule in glioma HFC region that plays a major role in promoting synaptic formation. (photo source: Wikipedia) of course, there is still a long way to go for related research. Finally, a quote from an article in Nature news reporting on the study ended: "two ghosts, thoughts and tumors, are whispering to each other in the dark corners of the brain. New ways to improve the lives of brain tumor patients may be hidden in their conversations, so please feel free to eavesdrop."

Reference link:

Https://www.nature.com/articles/s41586-023-06036-1#MOESM6

Https://www.nature.com/articles/d41586-023-01387-1#ref-CR1

Https://www.nature.com/articles/s41586-019-1564-x

Https://www.nature.com/articles/s41586-019-1563-y

Https://europepmc.org/article/MED/35802914

Https://pubmed.ncbi.nlm.nih.gov/20878206/

Https://pubmed.ncbi.nlm.nih.gov/32626582/

Https://www.nature.com/articles/d41586-019-02746-7

This article comes from the official account of Wechat: global Science (ID:huanqiukexue)

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