Biology subjects

Duncan, M. J.

Publications and source records attributed to Duncan, M. J..

3 recordsLinked to original sources

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↗

bioRxiv2022

Three-dimensional humanized gingival tissue model to study oral microbiome

The oral cavity contains different microenvironments, as the non-shedding surface of the teeth and the epithelial mucosa, where oral barriers and microbial communities coexist. The interactions and balances between these two communities are responsible for oral tissue homeostasis or dysbiosis, that ultimately dictate health or disease. Disruption of this equilibrium is the first necessary step towards chronic inflammation and permanent tissue damage in the case of chronic periodontitis. There are currently no experimental models able to mimic the structural, physical, and metabolic conditions present in the oral gingival tissue to support the long-term investigation of host-pathogens unbalances. Herein, we report a 3D anatomical gingival in vitro model based on human primary culture that recapitulates the native tissue organization, and a native oxygen gradient within the gingival pocket to support human microbiome persistence with a physiologically relevant level of microbial diversity as well as native spatial organization. The modulation of inflammatory markers in the presence of oral microbiome suggested the humanized functional response of this model. The model will be used in future studies to investigate host-pathogen unbalances in gingivitis and periodontal disease.

bioengineering↗

bioRxiv2020

Active Time-Restricted Feeding Protects the Blood Pressure Circadian Rhythm in Diabetic Mice

The quantity and quality of food intake have been considered crucial for peoples wellness. Only recently has it become appreciated that the timing of food intake, independent of total calorie consumption, is also critical. The involvement and contribution of the timing of food intake in nondipping blood pressure (BP), the most common disruption of the BP circadian rhythm in diabetes, however, remains uncertain. Here, we demonstrate that the loss of diurnal rhythm in food intake coincided with nondipping BP in type 2 diabetic db/db mice, and imposing a food intake diurnal rhythm by active time-restricted feeding (ATRF) remarkably prevented db/db mice from the development of nondipping BP. Moreover, ATRF, independent of calorie restriction, also effectively restored the already disrupted BP circadian rhythm in db/db mice. Mechanistically, ATRF reduced the sympathetic vascular tone and BP during the light phase via fasting, thus protecting the BP circadian rhythm in db/db mice. Moreover, we identified BMAL1, an obligatory core clock gene, as a potentially key molecule that links ATRF, sympathetic vascular tone, and BP circadian rhythm. Collectively, these data reveal an important but previously unrecognized role of the timing of food intake in the onset, prevention, and treatment of nondipping BP in diabetes.

physiology↗