The Batten Disease Palmitoyl Protein Thioesterase 1 Gene Regulates Neural Specification and Axon Connectivity during Drosophila Embryonic Development

Palmitoyl Protein Thioesterase 1 (PPT1) is an essential lysosomal protein in the mammalian nervous system whereby defects result in a fatal pediatric disease called Infantile Neuronal Ceroids Lipofuscinosis (INCL). Flies bearing mutations in the Drosophila ortholog Ppt1 exhibit phenotypes similar to the human disease: accumulation of autofluorescence deposits and shortened adult lifespan. Since INCL patients die as young children, early developmental neural defects due to the loss of PPT1 are postulated but have yet to be elucidated. Here we show that Drosophila Ppt1 is required during embryonic neural development. Ppt1 embryos display numerous neural defects ranging from abnormal cell fate specification in a number of identified precursor lineages in the CNS, missing and disorganized neurons, faulty motoneuronal axon trajectory, and discontinuous, misaligned, and incorrect midline crossings of the longitudinal axon bundles of the ventral nerve cord. Defects in the PNS include a decreased number of sensory neurons, disorganized chordotonal neural clusters, and abnormally shaped neurons with aberrant dendritic projections. These results indicate that Ppt1 is essential for proper neuronal cell fates and organization; and to establish the local environment for proper axon guidance and fasciculation. Ppt1 function is well conserved from humans to flies; thus the INCL pathologies may be due, in part, to the accumulation of various embryonic neural defects similar to that of Drosophila. These findings may be relevant for understanding the developmental origin of neural deficiencies in INCL

Examining technology use and mental health among parents with newborns in the intensive care unit during the COVID-19 pandemic: A cross-sectional study

Objectives: To investigate the relationship between pandemic-related stressors, mental health, and technology use among parents of hospitalized infants during the COVID-19 pandemic. Methods: A cross-sectional study of 47 participants who had an infant in the Neonatal Intensive Care Unit (NICU) during the pandemic was completed. Participants ranked several statements on a Likert scale to assess mental health, technology use, and COVID-19-related stress during their infant's stay in the NICU. Results: Mental health wellness scores were negatively associated with COVID-19-related stress (rs − 0.40, p = .015). The most prevalent stressor was hospital visitation restriction. Higher COVID-19-related stress was associated with greater use of text and video chat [(rs 0.35, p = 0.016) and (rs 0.33, p = .025)]. Enjoyment of technology use and access to technology were positively associated with higher mental health wellness scores [(rs 0.42, p = .003) and (rs 0.38, p = .009)]. Conclusions: Social uses of technology were valuable in a cohort of parents with infants hospitalized during the COVID-19 pandemic. Innovation: Technology is a tool that can help parents cope with the stress of having a hospitalized infant. Digital literacy and technology access should be promoted in the post-pandemic landscape to help parents of infants in the NICU attain more benefit from these resources

Temporal dynamics of a homeostatic pathway controlling neural network activity

Neurons use a variety of mechanisms to homeostatically regulate neural network activity in order to maintain firing in a bounded range. One such process involves the bi-directional modulation of excitatory synaptic drive in response to chronic changes in network activity. Down-scaling of excitatory synapses in response to high activity requires Arc-dependent endocytosis of glutamate receptors. However, the temporal dynamics and signaling pathways regulating Arc during homeostatic plasticity are not well understood. Here we determine the relative contribution of transcriptional and translational control in the regulation of Arc, the signaling pathways responsible for the activity-dependent production of Arc, and the time course of these signaling events as they relate to the homeostatic adjustment of network activity in hippocampal neurons. We find that an ERK1/2-dependent transcriptional pathway active within 1-2 hours of up-regulated network activity induces Arc leading to a restoration of network spiking rates within twelve hours. Under basal and low activity conditions, specialized mechanisms are in place to rapidly degrade Arc mRNA and protein such that they have half-lives of less than one hour. In addition, we find that while mTOR signaling is regulated by network activity on a similar time scale, mTOR-dependent translational control is not a major regulator of Arc production or degradation suggesting that the signaling pathways underlying homeostatic plasticity are distinct from those mediating synapse-specific plasticity