Spatial Proteomic Analysis of Neuroinflammatory Pathways in Wildtype and Alpha7*nAChR Knockout Mice in a PTZ-Induced Epilepsy Model
Graduation Year
2026
Document Type
Master's Thesis
Degree
Master of Science
Program
Biological Science
Partner Organization
BioMarin Phamaceuticals Inc.
Program Director
Patti Culross, MD, MPH
First Reader
Danielle Tan, PhD
Second Reader
Kerui Gong
Abstract
Alpha7-containing nicotinic acetylcholine receptors (α7*nAChRs) engage in modulatory signaling in the central and peripheral nervous systems and the immune system. Dysregulation of α7*nAChRs can lead to several neurodegenerative diseases, including Alzheimer’s disease, autism, and epilepsy. Temporal lobe epilepsy (TLE)— a common form of drug-resistant epilepsy— has been linked to a lack of α7*nAChRs. However, how neuronal and glial subtypes interact to trigger neuroinflammatory pathways in TLE is unclear. This study focused on the effects of α7*nAChR deletion in a chronic pentylenetetrazol (PTZ)-induced seizure model to investigate cell-specific responses. We hypothesized that there would be increased neuroinflammatory activation in the α7*nAChR knockout brains following seizure. We used high-plex spatial proteomics to spatially visualize and quantify neuroimmune and neural cell types in the hippocampus of the α7*nAChR knockout mouse model. Seizure induction increased c-Fos expression and DNA damage in neurons, with greater neuronal activation observed in the α7*nAChR knockout. Microglial morphology showed changes in the α7*nAChR knockout following seizure, suggesting partial activation. These findings suggest that α7*nAChRs regulate seizure-induced neuronal excitability and respond to cellular stress following chronic seizure. α7*nAChRs may regulate microglial responses during seizure. This work demonstrates the value of spatial analysis of cellular phenotypic changes and interactions relevant to neuroimmune mechanisms in epilepsy.