Mitochondria are not only the powerhouse of the cell, but also signaling organelles that control cell fate and function. Previous research demonstrates that mitochondrial tricarboxylic acid (TCA) cycle intermediates such as alpha-ketoglutarate (AKG), succinate, and fumarate can regulate differentiation in highly proliferative cell types via AKG-dependent dioxygenases. However, it remains unknown to what extent mitochondrial signaling metabolites play a role in less proliferative and electrically excitable cell types like neurons. To address this, we interrogated cellular metabolism throughout neuronal development. Rat embryonic cortical neurons were cultured for 23 days in vitro (DIV) with 13C glucose or 13C glutamine for 24 hours before each extraction, and metabolite abundance and enrichment were analyzed using gas chromatography-mass spectrometry. In other cell types, increasing AKG:succinate and AKG:fumarate accompany differentiation, leading us to hypothesize these ratios would increase from DIV 2-23. Our preliminary data show the AKG:fumarate ratio is highest at DIV 2, while the AKG:succinate ratio peaks at DIV 9 and declines by DIV 23. We also observed that neurons preferred glucose relative to glutamine across all time points. Despite observing the opposite of our expected AKG-ratio trends, our findings demonstrate meaningful changes in mitochondrial signaling metabolites during neuron development, warranting further investigation into a novel role for mitochondria in neuron fate.

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by neuroinflammation and neurodegeneration, with the thalamus serving as an early indicator of disease progression. Sex differences have been observed in MS, with higher susceptibility in women and greater disability progression in men. Microglia, the resident immune cells of the central nervous system, play a key role in neuroinflammatory responses in MS. Genetic factors such as apolipoprotein E (APOE) are associated with worse outcomes in MS and increased microglial activation. In this study, we examined how APOE genotypes and sex differences influence thalamic microglial activation in the murine model of MS, experimental autoimmune encephalomyelitis (EAE). Male and female EAE and control mice expressing humanized APOE genotypes (APOE2, APOE3, APOE4) were analyzed. Thalamic sections were immunostained for IBA1 and MHCII to quantify activated microglia and assess colocalization across sex, disease status, and genotype. Significant disease-associated increases in activated microglia were observed in males across all APOE genotypes compared to controls, while no comparable differences were detected in females. This may reflect a “ceiling effect” in which females, particularly those expressing APOE4, exhibit elevated baseline microglial activation. These findings suggest that APOE genotype and sex contribute to differential microglial responses during neuroinflammation and may provide insight into MS progression and potential therapeutic targets.

Fundamental to social cohesion, prosocial behavior is frequently dysregulated in neuropsychiatric disorders. Mice exhibit prosociality through allogrooming, a comforting of distressed partners. Prior research has reported a positive correlation between slow-wave sleep and prosocial preferences, but it remains unclear whether sleep regulatory mechanisms are important for prosocial behaviors. This study investigated whether allogrooming is influenced by time of day (dark/active vs. light/inactive phase). We hypothesize that mice will exhibit reduced allogrooming during the light phase. Pairs of male mice housed in a 12h light:12h dark cycle were designated as allogroomer or partner. The partner was subjected to 20 minutes of restraint stress, either 6h after the onset of the light phase or 6h after the onset of the dark phase. The allogroomer’s behaviors were then video recorded and scored with custom software. Allogrooming mice exhibited significant increases in investigation following partner stress (light: p=0.008, dark: p=0.003) and heightened self-grooming (p=0.019) during the light phase. We also observed a trend towards more allogrooming during the light phase that did not reach statistical significance (p=0.106). These results suggest that prosocial behavior is more prominent during the inactive period, contrary to our hypothesis. Since circadian mechanisms likely underlie time-of-day effects on behavior, this work supports the link between sleep/circadian regulatory mechanisms and healthy prosocial behavior.

A key part of all science fields, and especially life sciences, is being able to convert qualitative descriptions into quantitative data. Neurons are the basic units of information processing in the brain, having many measurable morphological traits, including dendrite and axon length, thickness, soma radius, and more. Through the online conversion and creation of SWC files, neurons are able to be reconstructed, creating a digital representation with lines and 3D coordinates, based on microscopic image scans of the mouse brain and spinal cord. In the dry lab team of Dr. Dong’s lab, we focus on reconstructing neurons that are present in the images produced by the wet lab team, using software called the Fast Neurite Tracer (FNT). After reconstruction and conversion from an image to a SWC file, the next stage is analysis. One such analysis tool is Trees Toolbox, which allows users not only to extract quantitative data from SWC files but also to model and simulate changes based on the characteristics of the neurons. This poster specifically analyzes the Brainstem region, with the goal of identifying standard characteristics like the average branch length, angle between branches, and the soma size. Analysis will reveal that the morphological properties of neurons are correlated with their location and function within the brain, which can be extended into developing further hypotheses about how neurons develop.

Ataxia Telangiectasia (A-T) is a rare autosomal recessive disorder caused by mutations in the Ataxia Telangiectasia Mutated (ATM) gene, encoding a serine/threonine kinase essential for DNA damage repair and cellular stress responses. Clinically, A-T is characterized by progressive cerebellar degeneration, leading to ataxia, impaired coordination, and motor dysfunction. Despite its severity, there are no disease-modifying therapies, highlighting the need to identify optimal intervention windows. In this study, we use a compound ATM/APTX double knockout (dKO) mouse model that recapitulates key features of A-T, including cerebellar dysfunction. We hypothesize that motor impairments arise at specific developmental stages and can be detected using behavioral assays to inform intervention timing. To test this, we performed longitudinal behavioral assessments at age cohorts (P60, P120, and P200), using flat-ladder, rotarod, and ataxia scoring to capture motor deficits. Motor performance was quantified through limb-specific foot slips, coordination, and balance and compared to wild-type controls. Our results demonstrate that dKO mice exhibit progressive motor impairment, with early deficits emerging across timepoints (P60, P120, P200) and detectable through increased foot-fault rates and impaired coordination. These findings identify the earliest onset of motor dysfunction, defining a temporal window for effective intervention.