Dementia with Lewy bodies (DLB) is a neurodegenerative disease characterized by severe decline in cognition and memory due to the accumulation of the α-synuclein protein in the brain. It has been shown that music therapy as well as gamma entrainment using auditory and visual stimuli can improve the cognition and behavioral states of Alzheimer’s disease patients, but it has not yet been determined whether these two strategies can be feasibly combined as an intervention for patients with DLB. The aim of this study is to determine if using music with 40-Hz enhancements (40-Hz music) is 1) effective for improving gamma oscillations in patients with DLB, mild cognitive impairment (MCI), Alzheimer’s disease (AD), and normal cognition and 2) feasible for patients to use chronically. We have used an electroencephalogram (EEG) to measure the brain activity of participants listening to 40-Hz music during a one-hour session, with questionnaires being administered after each session as a measure of enjoyment and long-term feasibility. Thus far, all participants (MCI, AD, DLB, control) have preferred 40-Hz music to other forms of stimulation (i.e., light), and would be willing to use the intervention if there were clear benefits. Following analysis of EEG recordings, in future studies, we will assess memory and disease proteins to determine whether or not a protocol with 40-Hz music is indeed beneficial to one’s cognitive function and neuropathology. This would provide a worthwhile and long-term therapeutic strategy for DLB patients.

Creating mouse oocytes in vitro starts with differentiating pluripotent stem cells into the precursor of oocytes, primordial germ cells. However, when produced in vitro, they are called primordial germ cell-like cells (PGCLC). PGCLCs develop within a 3D-spheroid which are then combined with fetal ovarian somatic cells (FOSCs) to make a reconstituted ovary (rOvary). PGCLCs mature into oocytes over 21 days within the rOvary. This process is inefficient, since on average, 35 oocytes are produced at the end of each rOvary experiment, meaning that <1% of PGCLCs become oocytes. To analyze this problem, single-cell RNA sequencing was performed on 3D-spheroids. The data reveals that some PGCLCs express Dazl, a gene essential for the sexual differentiation of germ cells in mice. Immunofluorescence (IF) of the 3D-spheroids confirms DAZL protein expression in PGCLCs, which were represented by expression of the protein STELLA. IF quantification shows that 10% of PGCLCs are DAZL+STELLA+, while 90% are STELLA+ only. Based on these findings, we hypothesize that DAZL+STELLA+ PGCLCs are more likely to become oocytes and survive the massive germ cell loss observed in the rOvary system. We added a fluorescent reporter under the control of Dazl in the stem cell line we use to produce PGCLCs, allowing for the enrichment of DAZL+ PGCLCs for use as a starting germ cell source in the rOvary. In the future, we plan to create rOvaries with this new stem cell line to test our hypothesis that DAZL+ PGCLCs generate oocytes at a higher rate that DAZL- PGCLCs.

Approximately 1.71 billion people suffer from musculoskeletal conditions affecting athletes and the aging population. In response to injury, muscle stem cells, celled satellite cells (SCs), become activated, expand through proliferation, differentiate, and fuse to promote muscle regeneration. Enhancing these repair mechanisms may unveil novel approaches for certain muscular pathophysiological states. Irisin is cleaved from the exercise-induced membrane protein, FNDC5. Research shows that an increase in circulation level has a beneficial effect on some tissues, and it is sufficient to confer the advantages of exercise on cognitive function. Therefore, the goal of the present study is to determine whether increasing the level of circulating irisin can enhance SCs’ functions. We treated isolated SCs with recombinant irisin to evaluate its effects in vitro. Irisin in low concentrations (20 and 40 ng/mL) increased SCs proliferation and differentiation, calculated based on EdU incorporation and myotubes size and fusion. To confirm the positive effect of irisin on muscle regeneration in vivo, we injected mice with AAV8-irisin to overexpress irisin protein and increase its circulating level. After 3 weeks, we injured the tibialis anterior (TA) muscle using BaCl2. The area of newly generated fibers (expressing eMHC), and cross sectional area (CSA) were significantly lower in muscle from mice overexpressing irisin 4 and 10 days postinjury, respectively. These data suggest that the effect of irisin might depend on the stage of SCs activation. More research is needed to determine why irisin enhances SCs proliferation and differentiation in vitro, but not in vivo.