Oligodendrocyte Maturation Alters the Cell Death Mechanisms That Cause Demyelination.

Myelinating oligodendrocytes die in human disease and early in aging. Despite this, the mechanisms that underly oligodendrocyte death are not resolved and it is also not clear whether these mechanisms change as oligodendrocyte lineage cells are undergoing differentiation and maturation. Here, we used a combination of intravital imaging, single-cell ablation, and cuprizone-mediated demyelination, in both female and male mice, to discover that oligodendrocyte maturation dictates the dynamics and mechanisms of cell death. After single-cell phototoxic damage, oligodendrocyte precursor cells underwent programmed cell death within hours, differentiating oligodendrocytes died over several days, while mature oligodendrocytes took weeks to die. Importantly cells at each maturation stage all eventually died but did so with drastically different temporal dynamics and morphological features. Consistent with this, cuprizone treatment initiated a caspase-3-dependent form of rapid cell death in differentiating oligodendrocytes, while mature oligodendrocytes never activated this executioner caspase. Instead, mature oligodendrocytes exhibited delayed cell death which was marked by DNA damage and disruption in poly-ADP-ribose subcellular localization. Thus, oligodendrocyte maturation plays a key role in determining the mechanism of death a cell undergoes in response to the same insult. This means that oligodendrocyte maturation is important to consider when designing strategies for preventing cell death and preserving myelin while also enhancing the survival of new oligodendrocytes in demyelinating conditions.

Training to Improve Spatial Hearing and Situation Awareness when Wearing Hearing Protection.

INTRODUCTION: Hearing protection devices (HPDs) are standard personal protective equipment in military settings, but many service members may choose to not use HPDs because they impair spatial hearing and situation awareness. In an effort to reduce barriers to compliance by improving situation awareness while wearing HPDs, this study investigated whether brief training could counteract spatial hearing deficits when wearing HPDs. Participant's ability to correctly apply the HPDs across days was also examined. MATERIALS AND METHODS: Young adults were randomly assigned to one of two groups: training or control (n = 25/group). Participants in each group performed a spatial hearing task while wearing HPDs and in an open ear condition without HPDs. Individual targets were battlefield sounds or white noise presented from a speaker array that surrounded the participant in the horizontal plane. After presentation of each target sound, the participant then controlled a white noise "auditory pointer," which they moved to the perceived location of the target. The two primary measures were the percent of trials with very large errors (> 45°), which were usually due to confusing front and back locations, and absolute localization, which is the difference between the pointer location and the true sound location. Both groups were tested on Days 1 (baseline) and 5 (post-test). On Days 2 to 4, the training group wore HPDs while receiving auditory and visual feedback after each trial. RESULTS: Across all participants on Day 1, wearing HPDs increased the frequency of very large errors by about 3× and impaired localization by about 40%, relative to the open ear condition. When comparing performance at baseline (Day 1) and post-training Day 5, the training group with HPDs had significant reductions in very large errors and improved absolute localization (P values < .001). The training group also had significant improvements from Days 1 to 5 in the open ear condition. When the control group wore HPDs, there were also significant improvements from Days 1 to 5 (fewer very large errors and better localization), with smaller effect sizes vs. the training group. Controls did not have significant improvement in the open ear condition, but had similar trends. Most participants consistently applied the HPDs, but a subset of ∼20% frequently failed to achieve the criterion attenuation of 15 dB (over 0.25-4.0 kHz) in both ears. CONCLUSIONS: These findings show that simple, relatively brief practice and training can substantially reduce HPD impairments on spatial hearing and situation awareness. The gains from training and practice can inform the development of relatively simple, brief methods to reduce HPD spatial hearing impairments, potentially leading to increased HPD compliance. Longitudinal data show that a subset of participants would not have received the full benefit of hearing protection because of improper application of the HPDs.