The fungus, Hericium erinaceus, has outstanding chemical properties, displaying health benefits in digestive, hepatic, and nervous tissues. Its ease of accessibility and use makes it one of the most common substances used for treatment in Eastern medicine. More and more recent research is confirming the incredible health benefits of this fungus, especially the impact that is seen on nervous tissue growth and recovery post-treatment. Such neurite outgrowth and myelin sheath regeneration could illustrate the beginning of the cure to lifelong neurodegenerative diseases such as Multiple Sclerosis. In this first-of-its-kind study, we cultured and differentiated fetal rat neural stem cells while treating the samples with varying concentrations of aqueous extract of Hericium erinaceus mycelium. The cells were then harvested and lysed at various time points as the proteins were isolated and purified prior to analysis by LC-ESI mass spectrometry. A proteomic analysis was conducted where statistically significant changes in protein expression were observed between the control groups and the treated trials of both time points. While our initial targets of interest were not found, an up to 4-fold increase in protein expression was seen in a group of Histone H1 variants following treatment with Hericium erinaceus. These Histone H1 variants are known to be linker histones which interact with the core histone bead and play a role in chromatin remodeling. It is clear that Hericium erinaceus plays a role in increasing the protein expression of Histone H1 variants which could lead to downstream effects yet to be revealed. This exploratory research should serve as a helpful launching point for those determined to understand the underlying mechanisms behind this phenomenon and the results it may have on the nervous system.