# Targeting Neuron-Microglia Interactions at the Margin of Glioma

> **NIH NIH F30** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $53,974

## Abstract

PROJECT SUMMARY/ABSTRACT
 Recent studies have revealed that crosstalk between glioma cells and the brain microenvironment is a
crucial regulator of cancer initiation and progression. A vast majority of glioma patients suffer from seizures, and
this pathological neuronal activity has been proposed to contribute to increased glioma growth and proliferation.
While some have hypothesized that neurons may be directly altering glioma cell activity, this proposal
investigates whether a more prominent consequence of pathological neuronal activity is to cause activation of
microglia, whose pro-inflammatory response contributes to glioma growth. This proposal will investigate
glioma-induced changes in neuronal and microglial activity and whether neuronal activity, microglia,
and glioma cells are mechanistically linked in driving cancer progression. Microglia have been separately
implicated in both epileptogenesis and glioma growth. Neurons communicate directly with microglia through
secreted purines, such as ATP, acting on microglial purinergic receptors. This ATP binding causes microglial
activation, and activated microglia have been shown to stimulate glioma cell growth, enhance invasiveness and
migration of glioma cells, and cause angiogenesis. P2RX7 is a well-studied purinergic receptor present on
microglia, shown in preliminary data to be highly expressed in the tumor microenvironment. In aim 1, I will use
whisker stimulation with simultaneous in-vivo imaging of neuronal and microglial calcium activity to determine if
the presence of glioma causes pathological stimulus-evoked responses in neurons and microglia. In aim 2, I will
utilize electroconvulsive seizure (ECS) induction to determine the effect of seizures, a known instance of
pathological neuronal activity, on microglial expression of inflammatory cytokines as well as on glioma growth.
In both aims I will administer Brilliant Blue G (BBG), a selective P2RX7 inhibitor with known CNS penetrance to
interrogate if these effects are mediated through purinergic signaling between neurons and microglia.

## Key facts

- **NIH application ID:** 10875397
- **Project number:** 5F30CA257768-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Alexander Goldberg
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 5
- **Project period:** 2021-06-15 → 2025-06-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10875397

## Citation

> US National Institutes of Health, RePORTER application 10875397, Targeting Neuron-Microglia Interactions at the Margin of Glioma (5F30CA257768-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10875397. Licensed CC0.

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