Michelle Monje, MD, PhD

Nerve activity can initiate the formation of tumors and foster their growth in neurofibromatosis

By Christopher Vaughan

Researchers at the institute have shown, for the first time, that nerve activity is required for the formation of a particular kind of brain tumor in a genetically susceptible population. Institute researcher Michelle Monje, MD, PhD and her colleagues have shown that in a mouse model that carried a mutation in the neurofibromatosis gene NF1, nerve activity along optic nerves could initiate the formation of an optic glioma. The researchers also showed how the development and growth of the glioma could be controlled by controlling the activity of this nerve activity. Their research was published in the journal Nature.

Neurofibromatosis is a genetic disease that carries with it a significant risk that children with this disorder will form gliomas--cancerous tumors in the brain. Gliomas in the optic nerve are particularly common in children with NF1, affecting one in 6 children with the genetic syndrome. Monje, along with colleague David Gutmann at Washington University in St. Louis, studied how nerve activity affected the development and growth of tumors in a mouse model of the disease. 

Activity in the optic nerve can be affected simply by regulating a mouse’s exposure to light, which makes it to manipulate through controlled light exposure. “We found that tumors didn’t form within the optic nerve when mice with predisposed to NF1-associated optic gliomas were not exposed to light during the critical period when these tumors develop,” Monje said. “We were really surprised that tumor initiation was so dependent on optic nerve activity, despite a strong genetic predisposition to tumor formation in these mice.”

The Monje lab had previously shown that the growth of another class of glioma (high-grade gliomas, including glioblastoma and diffuse intrinsic pontine glioma) was fostered by nerve activity. In this research, Monje and her colleagues showed that the growth of gliomas resulting from the presence of the NF1 gene mutation, which are low-grade gliomas, was also fostered by nerve activity. 

The research has implications for the potential treatment of tumors associated with neurofibromatosis.. “These findings give us a new avenue to explore possible therapeutic interventions for these debilitating optic gliomas. We have a lot more work to do.”

One possibility is to use pharmacological intervention to stop tumor initiation or growth. The Monje lab has previously shown that glioma growth is associated with the activity of a molecule called neuroligin-3 (NL3). “If we block neuroligin-3 signaling in mice, we see smaller tumors, but also fewer tumors,” Monje said.