Nature: brain tumor deterioration accompanied by neural network remodeling

January 31, 2020 / Biovalley / recently, scientists from Baylor Medical College discovered a new mechanism of glioma deterioration: it accelerated the vicious circle by changing the activity of peripheral neurons, and promoted the development of epilepsy related to tumor deterioration Their findings, published in nature, suggest that mutations in the PIK3CA gene drive tumor progression, two of which significantly alter the expression of synaptic related genes in neurons The initial goal of the study was to develop an experimental system that would allow researchers to identify new cancer genes in mouse models of brain tumors In order to achieve this goal, Dr deneen laboratory and Dr Kenneth L Scott began to cooperate Based on the mouse model of glioma, they established a novel high-throughput screening platform to identify these PIK3CA variants Later, the researchers found a variety of mutations in the PIK3CA that drive glioma development Two of the PIK3CA mutations, c420r and h1047r, respectively, significantly drive tumor development In addition, some genes specifically expressed in glioma with c420r and h1047r gene mutations are involved in synaptic formation, which indicates that these tumor cells may affect synaptic formation of adjacent neurons "Because the above mutations of PIK3CA lead to different conformations of its proteins, these mutations may drive the development of glioma through different mechanisms." To study these different mechanisms, denien and his colleagues focused on synaptic genetic markers, says denien "It is well known that the destruction of synaptic structure will lead to changes in the connectivity and activity of neural networks, and in some cases, lead to seizures." Their research shows that c420r and h1047r mutations, which lead to the deterioration of glioma, do promote the excitability of neurons around the tumor, and reshape the neural network by inducing synapse formation Mice with these tumors had seizures much earlier than mice with other PIK3CA mutations The researchers studied the mechanism of c420r and h1047r glioma on their microenvironment, and found that these glioma can secrete several molecules of the glycocan (GPC) family, in which GPC3 protein drives the effect of hyperactivity and synaptic remodeling In addition, they found that GPC3 itself drives glioma formation These findings provide strong evidence for the influence of glioma on neuronal microenvironment for the first time Origin of information: brain tumors remote neural synapses to promote growth origin: PIK3CA variants selectively initiate brain hyperactivity during gliomagenesis, nature (2020) Doi: 10.1038/s41586-020-1952-2