Date of Award
Winter 1-9-2026
Degree Type
Thesis
Degree Name
Master of Science (MS)
Department
Neuroscience
First Advisor
Gonzalo Torres
Abstract
Nucleotide-binding oligomerization domain-2 (NOD2) is a cytosolic receptor, activated by bacterial peptides that initiates innate immune responses through nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and Caspase-1 pathways. While the role of NOD2 in inflammation outside the central nervous system (CNS) is well-established, especially in the gastrointestinal system, its expression and function in the brain remain poorly defined. Previous genetic studies suggest a link between NOD2 and neurological and psychiatric conditions, including stroke, Parkinson’s disease, and schizophrenia. However, information regarding NOD2 expression, localization, and function in the CNS is limited. In this work, we investigated NOD2 expression, localization, and regulation across multiple cell types in the cerebral cortex, hippocampus, and striatum of rats. We identified NOD2 expression primarily in neurons, with consistent distribution across these brain regions with RNAscope in situ hybridization (ISH). To further quantify expression, we employed RT-qPCR and western blot, which confirmed NOD2 mRNA and protein expression was consistent between brain regions. Given its established role in inflammation in the gastrointestinal system, we hypothesized that NOD2 contributes to the acute phase of neuroinflammatory processes. We therefore assessed NOD2 expression levels in two rodent models of acute neuroinflammation: traumatic brain injury (TBI) and methamphetamine (METH) administration. In the TBI model, NOD2 expression was acutely upregulated but declined two weeks post-injury, which suggests dynamic temporal regulation. In METH-treated rats, NOD2 expression was increased in the striatum and cortex which further supports its involvement in injury- and drug-induced neuroinflammatory responses. These findings provide evidence that NOD2 is primarily expressed in neurons of the brain and demonstrate that its expression is modulated under neuroinflammatory conditions. Collectively, this work identifies NOD2 as a potential mediator of neuroinflammation and highlights a potential pathway that could represent a target for therapeutic intervention in conditions of acute neuroinflammation.
Recommended Citation
Smyth, Julia, "The Bacterial Sensing Nuclear-Oligomerization Domain 2 Receptor in the Brain: Location and Potential Function" (2026). Dissertations. 4297.
https://ecommons.luc.edu/luc_diss/4297
