Role of satellite glia cells in chemotherapy-induced neuropathy

2020 Pilot Project Read More

Investigators

Principal Investigator: Stefanie Geisler (WashU Neurology)
Collaborator: Valeria Cavalli (WashU Dept. of Neuroscience)

Description

Neurodegeneration has classically focused on neurons, however major recent breakthroughs led to the realization that glial cells in the brain also play an essential role in the development and progression of neurodegenerative diseases. In the peripheral nervous system, neurons are also closely surrounded by glial cells, but less is known about the peripheral neuron-glia interactions and the involvement of peripheral glia in neurodegenerative diseases. We propose to fill this major gap in knowledge by identifying the molecular signature of a specialized peripheral glia, i.e., satellite glia cells, which completely surround sensory neurons, in a mouse model of peripheral neuropathy. Peripheral neuropathies are the most common neurodegenerative diseases affecting more than 20 million people in the USA alone. Chemotherapy, including treatment with the highly effective drug bortezomib (BTZ), is a frequent cause of peripheral neuropathy. BTZ-induced neurotoxicity stands out among different types of chemotherapy-induced neuropathy as it can be extremely painful. This pain can last long after treatment has ended and significantly reduce the quality of life of patients. Pain is frequently associated with degeneration of intraepidermal nerve fibers. However, surprisingly, such loss has not been observed in most patients treated with BTZ or in our BTZ-induced neuropathy mouse model. Rather, our preliminary data suggest that satellite glia cells surrounding sensory neurons respond to BTZ treatment by increasing expression of a gene that reflect their activation state. We know that satellite glia cells contribute to pain in several injury models by impacting neuronal excitability and, thus, nociceptive threshold. But whether and how satellite glia contribute to pain in peripheral neuropathies has not been explored. Here, we aim to understand how SGC respond to BTZ treatment with the goal to establish mechanistic insights that can be exploited therapeutically to alleviate pain and other sensory abnormalities.

Investigators

Pilot project teams include Hope Center faculty members and others. For more about Hope Center faculty on this team, click below.

Stefanie Geisler

Valeria Cavalli