June 16, 2024

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Subversive discovery: Brain thinking promotes tumor growth!

Subversive discovery: Brain thinking promotes tumor growth!



Subversive discovery: Brain thinking promotes tumor growth! Glioma affects cognition and survival by hijacking neurons.

Glioblastoma (glioblastoma) is a common intracranial malignant tumor originating from glial cells in the brain.

This type of tumor is extremely aggressive and has almost no possibility of cure. Remarkably, this type of tumor is only found in the central nervous system, but scientists still don’t know if there is an interaction between glioblastoma cells and the 86 billion neurons in the human brain.


Exploring this interaction is particularly important for improving patient outcomes, as most glioma patients experience symptoms such as headaches, seizures, visual disturbances, and incontinence in the last few months of life, as well as cognitive impairment. Gradually declined, seriously affecting the quality of life of patients.


Recently, researchers from the University of California, San Francisco published a research paper entitled: Glioblastoma remodeling of human neural circuits decreases survival in the journal Nature .


The study shows that gliomas can grow recklessly by altering the brain’s neural circuits, and can deprive the host of cognitive functions and eventually lead to the death of the host. These new findings may lead to new approaches to glioma treatment and offer some ways to delay cognitive decline in glioma patients.


The study proposes a disruptive new concept— glioma cells can “communicately hijack” brain neural circuits , occupying brain computing power and sacrificing cognitive functions, thereby promoting tumor growth.

Even more striking, conscious thought, as well as mental activity through the mechanism of language, appears to contribute to the development of gliomas.


Subversive discovery: Brain thinking promotes tumor growth! Glioma affects cognition and survival by hijacking neurons.


Glioma and Neuronal Networks


The human brain is a rather complex system, and a large-scale neural network is constructed through highly coordinated interactions among various neuron cell groups. The dynamics and malleability of these neural networks, often referred to as neuroplasticity, underlie development and learning, in addition to repairing brain damage.


The most basic unit of neuroplasticity is the junction between two neurons, called a synapse, which allows information to travel within the brain and to the rest of the body. In fact, all human thoughts, actions, emotions, and memories exist in a network of electrochemical signals mediated by neural synapses.


Previously, scientists generally believed that gliomas impair neurological and cognitive function in one of several ways: 1) by infiltrating and affecting brain tissue; 2) by squeezing adjacent tissue; 3) by inducing swelling around the tumor; 4) Or possibly competition for blood supply through “vessel stealing”.


Numerous convincing studies have shown that neural activity can promote glioma growth . It has been previously reported that synapses with electrophysiological functions can be formed between neurons and glioma cells, and the depolarization current triggered by synaptic activity is the basis of neuronal activation and information flow in the brain, which can promote glial Intense proliferation of tumors. Additionally, studies have shown that neuronal activity in the visual pathway appears to contribute to tumor development.



Glioma hijacks neuroplasticity


In the new study, published in Nature , the research team uncovered a previously unknown mechanism: Gliomas hijack neuroplasticity to suit their own needs through synaptic remodeling, actively changing brain structure, and exploiting this induced neuroplasticity. The capacity for plasticity allows gliomas to receive additional neuronal signals to proliferate rapidly.

Even more “horrifying” is that conscious thinking, as well as mental activities through language mechanisms, seem to promote the development of gliomas.


Subversive discovery: Brain thinking promotes tumor growth! Glioma affects cognition and survival by hijacking neurons.Gliomas can remodel the brain’s remote functional neural circuits


To demonstrate this, the research team performed a multiscale analysis – linking synapse formation to large-scale neural networks in the brain. The researchers used magnetoencephalography (MEG) techniques to detect small magnetic fields generated by the electrical activity of large numbers of neurons, and brain regions that exhibit correlated fluctuations in these fields are thought to be functionally connected.


By studying the correlation of MEG signals from different regions of tumor-infiltrated brain tissue with other brain regions, they assessed the connectivity between different subregions of glioma, some of which were classified as regions with high or low functional connectivity ( HFC or LFC) .


Subversive discovery: Brain thinking promotes tumor growth! Glioma affects cognition and survival by hijacking neurons.Tumor-infiltrating brain tissue exhibits areas of synaptic remodeling characterized by expression of synaptogenetic factors by glioma cells


In the HFC region, genes involved in the remodeling of neural circuits, such as the gene encoding the protein TSP-1 , were expressed higher than usual. TSP-1 is a protein involved in synapse formation that is normally secreted by healthy cells called astrocytes.

Regions where gliomas caused synaptic changes at the molecular level showed altered connectivity with the entire brain.




Glioma cells promote synapse formation


To study the formation of synapses in the HFC region in more detail, the research team performed a series of experiments, including using 3D organoids containing glioma cells.

Cells from the HFC area of ​​gliomas better integrated with co-cultured neurons and exhibited more electrical activity than those from the LFC area.

These findings help to understand associated symptoms in glioma patients, such as seizures, which may be triggered by upregulation of synapse formation between glioma cells and neuronal cells.


Subversive discovery: Brain thinking promotes tumor growth! Glioma affects cognition and survival by hijacking neurons.Gliomas exhibit bidirectional interactions with HFC brain regions


Consistent with the authors’ hypothesis, TSP-1 plays a key role in glioma-mediated synapse formation: when TSP-1 was added to the LFC region of glioma co-cultured with neurons, its behavior pattern was similar to that of tumor Organoid models of co-culture of cells from the HFC region are similar.


In contrast, glioma proliferation was reduced when the TSP-1 inhibitor gabapentin was added to the co-cultures . Furthermore, in vivo transplantation of TSP-1-enriched glioma-infiltrated brain tissue into the hippocampus of mice also resulted in the formation of new synapses.



Intratumoral connectivity correlates with survival and TSP-1 in glioma patients


Not only that, but when exposed to media soaked in neural samples, HFC glioma cells showed greater invasiveness and developed extracellular structures called tumor microtubules that link tumor cells together.

These microtubules may amplify the effects of incoming currents from neural activity.

This finding has profound implications for the treatment of glioma, as glioma cells with microtubule junctions are resistant to cell death induced by radiation therapy.



Glioma affects host cognition


Notably, gliomas enriched in functional connectivity are generally associated with poorer survival and cognitive decline in both mice and humans.

In this regard, the research team explored the mechanism behind it through language tasks: In language tasks, people who are still awake while undergoing brain surgery are asked to perform vocabulary retrieval language tasks, such as naming objects in pictures and recording their Cerebral cortex activity.


Combining site-specific tumor biopsies and cell biology experiments, the researchers found that gliomas remodel functional neural circuits such that task-related neural responses activate the tumor-infiltrated cerebral cortex far beyond normal cortical regions activated in healthy brains.


Schematic diagram of how brain tumors affect the host’s cognitive abilities


These findings suggest that brain-infiltrating gliomas hijack the plasticity of neural networks and occupy a large amount of computing power in the host brain, thus promoting their own crazy proliferation at the expense of cognitive function. Therefore, cognitive decline in glioma patients may be an independent predictor of poor survival.





The “communication hijacking” between glioma cells and neural circuits is undoubtedly a shocking new concept, just like in a spy movie, an intelligence agency deciphers the opponent’s communication code to obtain all its strategic intelligence. Through this hijacking of communication, gliomas exhibit a unique form of neuroplasticity that may only exist in tumors within the brain.


Altogether, the study, published in Nature , shows that gliomas that infiltrate the brain can form synaptic connections with neurons in the brain, hijacking and remodeling neural circuits in a process that both promotes tumor progression and impairs Cognitive ability of patients, thus revealing how malignant glioma cells affect cognitive ability and survival time of patients through interactions with neurons.












References :

Subversive discovery: Brain thinking promotes tumor growth! Glioma affects cognition and survival by hijacking neurons.

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