Nature: Neuronal activity promotes tumor growth, which is actually related to it

Neurofibromatosis type 1 (NF1) is a genetic disease that can cause brown spots on the skin and abnormal growth of nerves, caused by mutations in the same name gene NF1.

About 15% of patients with neurofibromatosis type 1 (NF1) develop poorly differentiated optic neuromas (called optic gliomas, OPG) in early childhood.

On May 26, 2021, Michelle Monje of the Department of Neurology and Neuroscience of Stanford University and David H.

In order to study the effect of neuronal activity on the growth of low-grade glioma and the formation of glioma, they used a type of Nf1-OPG transgenic mice called poorly differentiated optic neuroma, which has a high tumor incidence.

The formation of mouse Nf1 optic glioma requires two conditions to be met at the same time: somatic Nf1 in neural progenitor cells is lack of function; heterozygous Nf1 mutations also exist in non-neoplastic (stromal) cells, similar to NF1 cancer susceptibility syndrome Of patients.

They injected optogenetic virus into RGC of Nf1-OPG transgenic mice, and assessed the tumor growth rate at 12 weeks after activating RGC at 6 weeks of age.

Dark environment inhibits tumor growth

More interestingly, sunlight affects the growth of tumors in Nf1-OPG transgenic mice: tumors grow faster under full light (24 hours of light), but tumors grow slowly in total darkness (24 hours of darkness).

Previous studies have found that cortical neuronal activity drives the growth of well-differentiated tumors through paracrine BDNF and synaptoadhesin NLGN3.

Researchers found that light-activated RGC can indeed cause the levels of BDNF and NLGN3 to increase, and incubating NLGN3 in vitro can also promote the growth of poorly differentiated optic neuroma.

Knockout of NLGN3 inhibits tumor growth

After knocking out NLGN3, the tumor growth of Nf1-OPG transgenic mice seemed to be paused: the volume of the optic nerve was no different from normal, and the proliferation of tumor cells was significantly reduced.

After the researchers injected tetrodotoxin into the vitreous body to inhibit neuronal activity, the expression of NLGN3 secreted by the optic nerve was significantly reduced.

Completely in the dark environment does not affect the secretion of NLGN3 in normal mice.

Disintegrin and metalloprotease 10 (ADAM10) is a "sheddase" that can hydrolyze more than 30 transmembrane proteins.

Nature also distributed commentary articles by Varun Venkataramani and Frank Winkler from the Department of Neurology of the German Cancer Research Center and the Affiliated Hospital of Heidelberg University in Germany.

They said that this is an exciting study.

So, what is the clinical significance of this research? Should NF1 patients be told that they need to wear sunglasses or cover their eyes? Should somehow reduce the overall neuronal activity of cancer patients?

Original source:

Pan, Y.