Schedule of Events | Symposia

Exploring Microglial Morphology and PFKFB3 Oxidative Stress in Depressive-like Behavior

Poster Session D - Monday, March 31, 2025, 8:00 – 10:00 am EDT, Back Bay Ballroom/Republic Ballroom

Courtney M. Chochol¹ (courtney.chochol@quinnipiac.edu), Colleen D. Ford¹, Kezzia Jones¹, Courtney Whitelock¹, Adrienne J. Betz¹, Martine M. Mirrione¹; ¹Quinnipiac University

Glial dysfunction is thought to contribute to disrupted neuronal circuits in mood disorders. Here, we explore microglia morphology and neuronal metabolism, using the Chronic Unpredictable Stress (CUS) and Maternal Separation (MS) rat models. We hypothesized that increased microglia activation and proliferation would be evident in the brain following CUS or MS compared to controls, and these increases would correlate with metabolic damage in neurons measured using the marker 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). This glycolytic enzyme is thought to accumulate with excitotoxicity, possibly contributing to oxidative stress and cell death. Following CUS and MS behavioral testing, brains were fixed and sectioned prior to immunofluorescence and confocal microscopy. Microglia number and morphology were quantified within the amygdala, hypothalamus, retrosplenial cortex, and dorsal and ventral hippocampus using ionized calcium-binding adapter molecule 1 (Iba1), along with markers for PFKFB3, and neuronal nuclei (NeuN). In CUS, we measured an increase in PFKFB3 in the ventral hippocampus CA1 and a decrease in cell body size of microglia, but no change in total counts of microglia. In MS males, our results reveal that the ventral hippocampus is more vulnerable than the dorsal hippocampus due to higher levels of phagocytic microglia. In MS females we found phagocytic microglia in the dorsal hippocampus. PFKFB3 was found to be relatively higher in the hypothalamus and amygdala compared to cortex and hippocampus. Together our data suggests evidence of early stages of neuronal dysfunction resulting from CUS and MS exposure in adolescent animals, which may be associated with altered microglia function.

Topic Area: EMOTION & SOCIAL: Other