Biology subjects

Bartman, S.

Publications and source records attributed to Bartman, S..

4 recordsLinked to original sources

bioRxiv2025

Associations Between Frailty and Cognitive Outcomes Across the Lifespan of Mice

Advancements in monitoring biological and brain aging with precise measures of health and longevity have the potential to accelerate research on pharmacological, genetic, and aging-related interventions. Over the past decade, frailty index has been used as an assessment tool for rodents, evaluating more than 30 non-invasive parameters that are strongly associated with chronological age, correlated with mortality, and sensitive to lifespan-altering interventions. However, whether aging phenotypes captured by the frailty index reflect brain aging remains unclear. In this study, we examined the relationship between frailty index and cognitive ability in young (3-4 months), middle-aged (12 months), and old (24 months) male and female C57BL/6J mice using a battery of behavioral and locomotor assays to determine whether frailty index scores can predict performance in tasks evaluating behavioral and cognitive function. Among the behavioral assays tested, frailty index scores had good correlation with the percentage of time spent in the center of the open-field apparatus, the duration spent in the open arms of the elevated plus maze, and the time spent in the target hole of the Barnes maze. These findings indicate that the frailty index not only reflects general physiological aging but may also serve as a reliable predictor of age-related cognitive decline in mice, providing a valuable tool for studies of interventions targeting brain aging.

neuroscience↗

bioRxiv2025

DNA Break Induced Epigenetic Alterations Promote Plaque Formation and Behavioral Deficits in an Alzheimer's Disease Mouse Model

The dramatic increase in human longevity over recent decades has contributed to a rising prevalence of age-related diseases, including neurodegenerative disorders such as Alzheimers disease (AD). While accumulating evidence implicates DNA damage and epigenetic alterations in the pathogenesis of AD, their precise mechanistic role remains unclear. To address this, we developed a novel mouse model, DICE (Dementia from Inducible Changes to the Epigenome), by crossing the APP/PSEN1 (APP/PS1) transgenic AD model with the ICE (Inducible Changes to the Epigenome) model, which allows for the controlled induction of double-strand DNA breaks (DSBs) to stimulate aging-related epigenetic drift. We hypothesized that DNA damage induced epigenetic alterations could influence the onset and progression of AD pathology. After experiencing DNA damage for four weeks, DICE mice, together with control, ICE, and APP/PS1 mice, were allowed to recover for six weeks before undergoing a battery of behavioral assessments including the open-field test, light/dark preference test, elevated plus maze, Y-maze, Barnes maze, social interaction, acoustic startle, and pre-pulse inhibition (PPI). Molecular and histological analyses were then performed to assess A{beta} pathology and neuroinflammatory markers. Our findings reveal that DNA damage-induced epigenetic changes significantly affect cognitive behavior and alters A{beta} plaque morphology and neuroinflammation as early as six months of age. These results provide the first direct evidence that DNA damage can modulate amyloid pathology in a genetically susceptible AD model. Future studies will be aimed at investigating DNA damage- induced epigenetic remodeling across additional models of AD and neurodegeneration to further elucidate its role in brain aging and disease progression.

neuroscience↗

bioRxiv2025

Short-Term Exposure to Polystyrene Microplastics Alters Cognition, Immune, and Metabolic Markers in an APOE Genotype and Sex-Dependent Manner

Alzheimers disease (AD) is one of the most prevalent neurodegenerative disorders and one of the leading causes of death in individuals over the age of 65. Most cases of AD develop sporadically, however, there are several risk factors that have been identified which significantly increases an individuals risk for developing AD. The most prominent of these is Apolipoprotein E4 (APOE4), which can potentially result in an up to 10-fold greater risk of developing AD. The presence of APOE4 alone, however, cannot be solely responsible for AD as the disease may occur even in the absence of APOE4. Therefore, there must be other contributing factors such as exposure to environmental toxins including heavy metals and pesticides, which have independently been shown to contribute to AD. Nano- and microplastics (NMPs) are plastic particles less than 1 m and 5 mm in size, respectively, and have only recently been identified as a major environmental pollutant with serious health concerns. Given the adverse health effects that are increasingly being associated with NMPs exposure, we sought to understand how the combination of APOE4 and NMPs exposure may work synergistically to promote cognitive dysfunction and alter key regulatory pathways to impact overall health. Following an acute (3 week) exposure to pristine spherical fluorescently-labeled 0.1 and 2 {micro}m polystyrene (PS) NMPs, we found significant sex-dependent alterations in locomotor and recognition memory in APOE4 mice, but not in APOE3 controls. We additionally found that exposure to PS-NMPs resulted in sex and genotype specific alterations in astrocytic and microglial markers in the brain, and in CYP1A1, a major metabolizer of environmental polycyclic aromatic hydrocarbons, in the liver. These results suggest PS-NMPs may interact with the APOE4 allele to promote cognitive dysfunction and alter immune and metabolic pathways which may contribute to disease-like states.

neuroscience↗

bioRxiv2025

A novel inducible mtDNA mutator mouse model to study mitochondrial dysfunction with temporal and spatial control

Mitochondrial dysfunction is a hallmark of aging and numerous age-related diseases. A wealth of studies supports the accumulation of mitochondrial DNA (mtDNA) mutations as a contributing factor to mitochondrial dysfunction in aging and disease. One of the best models to study the relationship between mtDNA mutations and mitochondrial dysfunction is the mtDNA mutator mouse, which expresses a proofreading-deficient version of mtDNA polymerase-{gamma} (PolgA). Despite its groundbreaking contributions to mitochondrial biology and aging research, this model is limited by the whole-body accumulation of mtDNA mutations, which prevents the investigation of tissue-specific differences in mitochondrial dysfunction. To overcome this limitation, we developed a novel inducible knock-in mtDNA mutator mouse model that allows spatial and temporal control of mtDNA mutations, enabling the precise study of mitochondrial dysfunction in a tissue- and time-specific manner. Here, we report the generation and validation of this novel model through whole-body induction via Cre recombinase. Our data demonstrate that, upon induction, this model recapitulates the phenotype of the original mtDNA mutator mouse manifesting the same behavioral and biochemical alterations. This work establishes the functionality of our model and highlights its value as a powerful tool for studying the impact of mtDNA mutations with enhanced specificity and control.

genetics↗