# Neurogranin and Traumatic Brain Injury

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2022 · —

## Abstract

Deployed and nondeployed military personnel are at higher risk of traumatic brain injury (TBI) than
civilians. TBI of all severities can result in chronic disturbances of cognitive, behavioral, emotional, and physical
functioning. Learning, memory and attention are especially vulnerable across the spectrum of TBI injury severity
and symptoms may persist years to decades. While most TBIs experienced by Veteran’s are mild, enduring a
severe TBI produces significant personal, societal and economic burden. TBIs that require hospitalization
account for approximately 90% of total TBI medical costs. There are currently no FDA-approved
pharmacotherapies to treat TBI. Thus, research to develop new pharmacotherapies for TBI will benefit Veterans
with persistent posttraumatic neurocognitive disabilities. These impairments have been recapitulated in pre-
clinical TBI models. Animals demonstrate poor performance on cognitive tasks along with associated
pathological synaptic communication on molecular, anatomical and electrophysiological scales. Furthermore,
these models for the investigation of underlying cellular mechanisms and potential therapeutic targets of TBI
associated impairments.
 Synaptic strength and plasticity are believed to underlie learning and memory behaviors. Dysfunction of
synapses is one of the earliest and most common abnormalities preceding neuronal death in neurodegenerative
diseases and has been reported in several animal models of TBI. Neurogranin (Ng), a post-synaptic protein
localized to post-synaptic dendritic spines, notably regulates synaptic plasticity through calcium-dependent
temporal and spatial regulation of calmodulin (CaM). Synaptic activity leads to precisely timed changes in Ng
phosphorylation by protein kinase C (PKC). This is synchronized with Ca2+-CaM downstream signaling and
Calcium-Calmodulin Kinase II (CaMKII) activation via autophosphorylation. Ng modulates synaptic excitability
through these pathways. CSF and blood levels of Ng have also been used as biofluid biomarkers of synaptic
neurodegeneration in Alzheimer’s disease and other neurodegenerative syndromes, as well as in acute TBI.
Recently, chronic decreases in plasma exosome levels of Ng was seen in combat-deployment-related mild TBI.
Our recent findings showed significantly reduced Ng protein expression in the rat cortex and hippocampus up to
two weeks after controlled cortical impact, particularly in the CA1 and CA3 of the hippocampus. This evidence
suggests Ng’s potential involvement in pathological mechanisms of learning and memory difficulties after TBI.
 The overall hypothesis is that decreased Ng expression contributes to dysfunctional synaptic plasticity
and cognition after TBI. Specific Aim 1 will examine the effects of TBI on Ng signaling, associated synaptic
proteins and dendritic morphology. Preliminary data shows Ng is detectable in serum in sham and CCI-injured
animals at two weeks post-injury. Thus, for the first time, an experimental model ca...

## Key facts

- **NIH application ID:** 10254474
- **Project number:** 1I01BX005291-01A1
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** C EDWARD DIXON
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-10-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10254474

## Citation

> US National Institutes of Health, RePORTER application 10254474, Neurogranin and Traumatic Brain Injury (1I01BX005291-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10254474. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*