To identify brain regions whose neural activity is susceptible to acute systemic inflammation

Understanding the interplay between Alzheimer's Disease (AD) pathology, such as amyloid and tau, and acute systemic inflammation is crucial for elucidating the mechanisms underlying acute disorders of cognition such as delirium. We therefore investigated the effects of systemic inflammation on neuronal activity across the brain in transgenic AD mouse models.

We studied 5xFAD transgenic mice overexpressing amyloid, PS19 transgenic mice expressing mutant tau, and their wild-type (WT) siblings. Intraperitoneal injections of lipopolysaccharides (LPS) from E. coli (0.5 mg/kg) were used to induce systemic inflammation, while other mice received saline injections. Three hours after injection mice were euthanized and perfused. To identify active neurons, we used immunohistochemical staining for c-Fos, an immediate early gene. We quantified the density of c-Fos positives cells within different brain regions using automated cell identification (Qpath) registered to a canonical brain atlas (Allen Brain Atlas).

We studied mice split into groups based on genotype and treatment (LPS vs saline). LPS caused a significant decrease in c-Fos expression in primary visual cortex and a significant increase in the hypothalamus. 5xFAD genotype had no significant effects in c-Fos cell density across areas. Further analysis is ongoing to evaluate the role of tau-related pathology (PS19 transgenic mice) in neural responses to systemic inflammation.

LPS may decrease neural activity in cortical regions but increase neural activity in regions involved in internal homeostasis, such as the hypothalamus. This suggests that acute systemic inflammation may shift the balance of neural activity from cortical regions associated with cognition to evolutionarily older brain areas responsible for internal homeostasis. The relationship between Alzheimer’s pathology and neural responses to systemic inflammation remains to be determined.