Date of Graduation

Summer 2025

Degree

Master of Science in Cell and Molecular Biology

Department

Biomedical Sciences

Committee Chair

Scott Zimmerman

Abstract

While the cognitive and neuroprotective benefits of chronic exercise are well-studied, the effects of acute exercise on hippocampal gene expression remain poorly understood, with limited data available on how sex and genotype influence these responses. This study investigated the hippocampal transcriptomic response following one and seven bouts of treadmill exercise in male and female C57 inbred and CFW outbred mice, with a focus on genes related to Alzheimer’s disease. RNA sequencing revealed activation of a core set of 16 immediate early genes (IEGs), including Egr4, Jun, Fos, Arc, and others, across all groups and both sexes. These IEGs were associated with enriched Gene Ontology (GO) terms related to transcription, learning, and memory in both sexes. Females exhibited a broader and more sustained transcriptional response. Notably, females showed strong upregulation of genes related to BDNF signaling, ribosomal activity, and mitochondrial metabolism, suggesting enhanced neuroplasticity and energy regulation following acute exercise. In contrast, males demonstrated a narrower transcriptional profile, with selective upregulation of cholinergic signaling (Chrm4) and GPCR pathways (Gnb3), indicating more targeted neuromodulatory adaptations. Gene Set Enrichment Analysis (GSEA) showed females enriched in biosynthetic and mitochondrial pathways, while males showed enrichment in neurotransmitter signaling networks. Regarding AD-related genes, outbred females (FT1, FT7) showed the most pronounced response, with significant upregulation of Bdnf and Hspa1a (Hsp70), downregulation of Apoe (FT7), and upregulation of Lrp2 (FT1), while inbred females (FN7) also showed increased Bdnf expression. In contrast, male mice (MN and MT groups) displayed minimal changes, with only Hspa1a reaching significance in MT1 and MT7, and no other AD-related genes showing significant differential expression. These findings reveal pronounced sex-specific differences in hippocampal gene expression following acute exercise, with females exhibiting a more comprehensive neuroplastic and metabolic response, while most genes associated with AD pathology remained unchanged. However, a few key genes, including Hsp70, Lrp2, and Apoe, showed significant expression changes in females.

Keywords

acute exercise, hippocampus, transcriptomics, gene expression, memory, Alzheimer’s disease

Subject Categories

Bioinformatics | Cell Biology | Cells | Molecular and Cellular Neuroscience | Molecular Biology | Molecular Genetics | Nervous System | Nervous System Diseases | Systems Neuroscience

Copyright

© Jalal (Ako) Rostampour

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Available for download on Friday, December 31, 2027

Open Access

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