Biology subjects

Johnson, C. E.

Publications and source records attributed to Johnson, C. E..

4 recordsLinked to original sources

bioRxiv2026

Lipidome of Compact Myelin from Cortical Regions of the Aging Murine Brain

Age-related cognitive decline has been associated with neurodegeneration in cortical white matter tracts. The trajectory of white matter degeneration over the lifespan follows a similar pattern in humans, primates and rodents including the loss of myelin integrity and concomitant loss in myelinated axonal segments. Previous studies suggest that biochemical alterations in myelin begin to occur well prior to myelin loss. To better understand these biochemical determinants underlying white matter degeneration, we investigated the lipid composition of myelin isolated from young adult, middle-aged and aged murine brain. Compact myelin was enriched from cortical regions using a refined density centrifugation protocol and profiled the lipidome using LC-MS/MS. Over 2000 lipid species were identified, with the relative expression of 414 species changing over the age-span. The myelin lipidome from young mice was biochemically distinct compared to the aging cohorts. Aging was characterized by an overall decrease in high abundant species of glycerophospholipid and sphingolipids, including phosphocholine, phosphoethanolamine, sphingomyelin and cerebrosides. Pathway analysis by LipidSig 2.0 and lipid ontology analysis by LION/web highlighted alterations to lipid metabolism and membrane biophysical properties related to bilayer stability and organization. These data support the concept that myelin lipid compositional changes are apparent by middle age which underly structural changes in myelin at later ages. The findings provide greater insight into age-related biochemical alterations in the myelin sheath and may aid in strategies to mitigate white matter degeneration over the lifespan.

neuroscience↗

bioRxiv2025

Dim light at night impacts circadian rhythms and Alzheimer's disease-like neuroinflammation and neuropathology in humanized APP SAA knock-in mice

Artificial light at night (light pollution) is widespread but understudied in the context of Alzheimers disease (AD). Sleep and circadian disruption have been linked to amyloid-{beta} (A{beta}) accumulation and neuroinflammation, but whether dim light at night (dLAN) modifies these processes remains unclear. We tested whether chronic dLAN exposure (8 lux during the dark phase, 8 weeks) alters circadian rhythms, amyloid pathology, and neuroinflammation in 12-13 month-old humanized APP knock-in (KI) mice. hAPPSAA KI mice, which develop plaques, were compared with hAPPWT KI controls carrying only a humanized APP sequence. dLAN reduced circadian rhythm amplitude and stability while increasing fragmentation in both genotypes within two weeks. In hAPPSAA KI mice, dLAN modestly increased hippocampal plaque burden and soluble neocortical A{beta}. Astrocyte reactivity was elevated by genotype but not altered by nighttime light exposure. In contrast, microglial markers (CD45, MHCII) were increased with dLAN with CD45+ area elevated in hippocampus, and MHCII+ cell counts greater in the cortex and hippocampus of hAPPSAA KI mice. There were also distinct spatial responses between the microglia markers suggesting that dLAN primes microglia toward an antigen-presenting phenotype (MHCII) in the presence of A{beta}. Yet, the microglia/macrophage priming was not associated with amplified cytokine or chemokine levels at the 8-week dLAN exposure timepoint in the brain. These findings add to growing evidence that nighttime light exposure can disrupt circadian and immune regulation, and suggest that environmental light pollution should be further explored as a modifiable factor contributing to Alzheimers disease progression. Statement of SignificanceLight at night is a common feature of modern life, yet its influence on Alzheimers disease remains poorly understood. We show that dim light at night disrupts circadian rhythms, modestly increases amyloid pathology, and shifts microglia toward an antigen-presenting state in an amyloid-prone model. These findings identify light at night as a modifiable factor that may worsen risk or progression of neurodegenerative disease. A critical gap is whether circadian and immune changes resolve after darkness at night is restored. If they persist, early exposure could leave lasting imprints on brain aging. Addressing this question is essential for guiding strategies to mitigate the impact of light pollution.

neuroscience↗

bioRxiv2025

Remodeling-mediated changes in left ventricular mechanics under settings of chronic pressure overload and exercise

Left ventricular (LV) remodeling, whether occurring as a part of somatic growth or as a chronic response to a sustained stimulus, is a primary factor underlying cardiac mechanical function. Although LV remodeling is a complex process that can be described at several levels (i.e. biochemical, cellular, tissue, organ, system), response variables that govern cardiac mechanics include changes in LV wall and chamber geometry, the mechanical properties of the LV myocardium, and functionally-deterministic LV structural mechanical properties such as LV chamber stiffness. In this study, we leverage two-dimensional speckle-tracking echocardiography (STE) to serially monitor key LV remodeling response variables in porcine models of LV pressure overload (LVPO), chronic exercise (CE), and the superposition of both settings (CE+LVPO), and compare changes to those occurring in age-matched referent control (RC) animals. Our findings show that over a 28-day study period, LVPO and CE both induce hypertrophy in comparison to RC, but passive LV myocardial stiffness increases with the former and decreases with the latter. As a net effect of geometrical and mechanical property changes, these settings induce divergent changes in LV chamber stiffness, namely an elevation with LVPO and reduction with CE. In the CE+LVPO cohort, exercise was found to attenuate the LVPO-induced increase in LV myocardial and LV chamber stiffnesses and insomuch supports its continued integration and refinement as a cardiac rehabilitation therapy. Data obtained across study cohorts were used to identify a phenomenological model of LV chamber stiffness, providing the first explicit relation of LV geometry and myocardial mechanical properties to a key LV structural property. Additional data processing was performed to develop a predictive mathematical model of late changes in LV chamber stiffness based on early remodeling response variables irrespective of stimulus, suggesting that STE can be extended to predict cardiac disease risk/progression in certain patient populations.

bioengineering↗

bioRxiv2023

De novo genome assembly and comparative genomics for a colonial ascidian

Ascidians have the potential to reveal fundamental biological insights related to coloniality, regeneration, immune function, and the evolution of these traits. This study implements a hybrid assembly technique to produce a genome assembly and annotation for the botryllid ascidian, Botrylloides violaceus. A hybrid genome assembly was produced using Illumina, Inc. short and Oxford Nanopore Technologies long-read sequencing technologies. The resulting assembly is comprised of 831 contigs, has a total length of 121 Mbp, N50 of 1 Mbp and a BUSCO score of 96.1%. Genome annotation identified 13K protein-coding genes. Comparative genomic analysis with other tunicates reveals patterns of conservation and divergence within orthologous gene families even among closely related species. Characterization of the Wnt gene family, encoding signaling ligands involved in development and regeneration, reveals conserved patterns of subfamily presence and gene copy number among botryllids. This supports the use of genomic data from non-model organisms in the investigation of biological phenomena.

genomics↗