# Project 3

> **NIH NIH P20** · UNIVERSITY OF NORTH DAKOTA · 2020 · $292,513

## Abstract

PROJECT SUMMARY 
Lyme disease is the most prevalent arthropod-borne disease in the US with more that 30,000 cases reported 
to the Centers for Disease Control and Prevention in 2010. The causative agent of the disease is Borrelia 
burgdorferi (Bb) and is transmitted to humans by the bite of infected ticks. Treatment with antibiotics during the 
initial stage of the disease is effective, although about 25% of the patients treated with antibiotics continue to 
suffer from arthritis and other post- Lyme disease syndromes; of those patients treated for neuroborreliosis, 
many experience lingering symptoms including memory impairment and changes in cognition. Recently, our 
laboratory has demonstrated that 1) Bb can be detected in the brains of infected rats; 2) Bb can cause 
neuroinflammatory changes in the brain that recapitulate those seen in human patients and nonhuman primate 
models; and 3) antibiotic-killed Bb can induce an inflammatory response in the brain, suggesting that dead 
microorganisms and spirochetal debris that remain after antibiotic treatment can contribute to neural pathology. 
Our central hypothesis is that Lyme neuroborreliosis results from a sustained Bb-induced 
neuroinflammatory response in the absence of live microorganisms. We believe that the inflammation 
and lingering symptoms of neuroborreliosis are due to the persistence of bacterial debris following antibiotic 
treatment. 
 We have generated several reagents and methodologies to test this hypothesis with 3 Specific Aims. In 
Specific Aim 1 we will characterize the extent of antibiotic-killed Bb-induced inflammation and persistence of 
spirochetal debris in the brains of rats. In the second Specific Aim we will quantify neuronal apoptosis and 
cognitive deficits caused by antibiotic-killed Bb. Finally, in Specific Aim 3 we will determine the signaling 
pathways mediating Bb-induced neuroinflammation and apoptosis. Our findings will contribute to the 
knowledge base necessary for the development of intervention strategies for prevention and potentially 
treatment of post-Lyme disease neurological syndromes.

## Key facts

- **NIH application ID:** 9924574
- **Project number:** 5P20GM113123-05
- **Recipient organization:** UNIVERSITY OF NORTH DAKOTA
- **Principal Investigator:** Catherine Ayn Brissette
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $292,513
- **Award type:** 5
- **Project period:** — → 2021-08-04

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9924574

## Citation

> US National Institutes of Health, RePORTER application 9924574, Project 3 (5P20GM113123-05). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/9924574. Licensed CC0.

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