Author(s): Baylee Christensen, Karli Babcock, Tyle Sorenson, Dalton Scott, Kenyon Mantle, Zach Ferguson
Mentor(s): Kevin Johnston
Institution UTech
Treatment of brain tumors often involves radiation treatment. A side effect of this treatment is radiation-induced cognitive dysfunction (RICD), or “brain fog”, in cancer survivors. Previous studies have linked RICD with reduced BDNF (brain derived neurotrophic factor), a critical factor in long-term memory and cognition. A previous study utilized Riluzole, an ALS medication that induces BDNF expression, as treatment for RICD in irradiated mice brains. This study showed upregulated BDNF expression in excitatory neurons, correlated with decreased risk of RICD in mice. The initial study primarily analyzed excitatory neurons in the hippocampus, but the impact (neuroprotective or otherwise) on inhibitory neurons is unknown. Inihibitory neurons are distributed throughout the brain, and typically modulate neural circuits by inducing a decrease in neural firing. These neurons can target dendrites, axons, or somas, to interfere with excitatory signal propagation. Inhibitory neural activity is associated with regulating motor activity in the cortex and cerebellum, and memory formation in the hippocampus. In this study, we utilize spatial transcriptomics to profile the inhibitory neurons in the brains of irradiated mice, with and without Riluzole. MERFISH spatial transcriptomics enables analysis of whole sagittal sections, enabling transcriptomic analysis of cortical, cerebellar, hippocampal (among others) inhibitory neurons within the same mouse. Using 12 sagittal sections, we profile the transcriptomes of over 100,000 and identify the impacts of Riluzole on inhibitory neurons in the context of radiation. Differential expression analysis identifies significantly altered transcriptomic profiles among inhibitory cell types. In this presentation, we will discuss potential cellular pathway alterations differentially altered between treatment and vehicle conditions.