Investigating the role of NG2-glia in the development of epilepsy

Project Summary
According to the CDC, there are more than 3 million people with active epilepsy in the US. It is estimated that
up to 50% of all epilepsy cases are initiated by a neurological insult and are called acquired epilepsy. Brain
infections and traumatic brain injury are two major examples of common brain injuries that can lead to the
development of acquired epilepsy. Although there is diversity in the etiology and the severity of the disorder,
understanding the cellular and molecular mechanisms by which seizures develop will aid in uncovering novel
ways to prevent epilepsy following high-risk CNS injuries.
Evidence has accumulated indicating that glial cells play an important role in the initiation and maintenance of
the prolonged neuroplasticity changes underlying the development of epilepsy. NG2-glia are commonly known
as oligodendrocyte progenitor cells (OPCs). However, a growing body of evidence has led to their classification
as a major glial cell-type in their own right. Recent evidence suggests that these cells play important roles in
maintaining environmental homeostasis, and disruptions to NG2-glia function have now been highly implicated
in the development and progression of neurologic disease.
To investigate whether NG2-glia are involved in epilepsy development, in Aim 1, NG2-glia morphology, structural
organization, and protein expression were evaluated in a viral infection-induced mouse model of acquired
epilepsy. The analysis identified that NG2-glia have highly reactive morphology, increased proliferation, and are
involved in scar formation both during viral infection and following viral clearance. These NG2-glia responses
are also highly localized to the hippocampus, the site of active infection and the origin site of seizures. This is
significant because, while likely triggered by the initiating infection, the NG2-glia reaction may continue to play
an important role in long-term neuroplasticity deficits that lead to epilepsy.
Preliminary experiments in Aim 2 demonstrate that extracellular purines (damage signals that are heavily
produced in the hippocampus following viral infection) induce robust elevations in intracellular calcium in NG2-
glia. This finding is important because calcium can be used as a functional readout to better understand the real-
time dynamics and the environmental signals initiating the NG2-glia reaction to injury and infection. Future work
aims to use calcium signaling as a functional readout combined with morphological changes to better understand
the intracellular and intercellular communication that occurs between glial cells during injury and disease. This
study is the first to analyze calcium signaling in NG2-glia during infection and epilepsy development, and may
lead to novel cellular and molecular targets to restore homeostasis and prevent the development of epilepsy
following a high-risk insult to the central nervous system.

Grant Number: 5K00NS125773-05
NIH Institute/Center: NIH
Principal Investigator: Laura Bell