Biology subjects

Ulland, T. K.

Publications and source records attributed to Ulland, T. K..

5 recordsLinked to original sources

bioRxiv2025

Cellular deconvolution of the brain with topological magnetic resonance image analysis

Magnetic resonance imaging (MRI) is foundational tool in neuroscience, enabling characterization of neuroanatomical markers of disease, behavior, and cognition. However, the precise cellular processes driving the structural and functional readouts provided by MRI remain opaque. Non-invasively assessing cell type, abundance, and location using MRI has the potential to revolutionize both basic science and clinical practice. To this end, we developed SpaTial Representation and Analysis using Topological Architecture (STRATA), an image-based gradient-boosted machine learning framework, which quantifies cell type proportions of neurons, astrocytes, oligodendrocytes, and microglia from MR images. Here we demonstrate and validate STRATA on diverse disease models, species, and regions of interest that together highlight the generalizability of the STRATA framework.

neuroscience↗

bioRxiv2025

Non-invasive longitudinal imaging reveals aging-associated changes in neuroimmune cells in adult zebrafish

Zebrafish are a powerful model for imaging studies of development and neurobiology. However, most studies have focused on developing zebrafish due to technical and biological challenges of imaging adult stages. These include increased tissue opacity and illumination depth limitations, and difficulty maintaining life support and anesthesia in a 2-4cm long fish. There are currently limited tools for intravital imaging of the adult zebrafish brain. The ability to image the brain in the same individual repeatedly without physical damage would allow zebrafish to be better utilized to study aging and neurodegenerative disease. We designed and applied a 3D-printable device for non-invasive, repeatable multiphoton neural imaging of genetically non-pigmented adult zebrafish from 2 months to 19 months old. Animals successfully recovered after multi-hour imaging sessions and can be imaged repeatedly over periods of weeks to years. We show the utility of this approach through imaging the neuroimmune system, revealing that microglia in aged zebrafish have enhanced cellular dynamics. This technique could be widely used and beneficial for other cell-scale neuroimaging studies in the adult fish. Summary StatementAn open-source, 3D printable device that enables non-invasive neuroimaging in adult zebrafish reveals aging-associated changes in neuroimmune cell behavior.

neuroscience↗

bioRxiv2025

Gut bacterial metabolite imidazole propionate potentiates Alzheimer's disease pathology

The gut microbiome modulates metabolic and neurovascular processes implicated in Alzheimers disease and related dementias (ADRD), but the underlying mechanisms remain unclear. Here, we identify the bacterial metabolite imidazole propionate (ImP) as a modifier of ADRD pathology. In a cohort of 1,196 cognitively unimpaired adults, higher plasma ImP levels were associated with lower preclinical cognitive scores and biomarkers of ADRD, both cross-sectionally and longitudinally. Fecal metagenomic analysis linked putative ImP producers to ADRD phenotypes. Genome-wide integrative analysis revealed a locus on chromosome 12 associated with both plasma ImP levels and AD risk in humans, supporting a host genetic contribution to ImP regulation and a causal role of this metabolite in AD. In mice, chronic ImP administration exacerbated AD-like pathology. Mechanistically, ImP impaired brain endothelial barrier and promoted tau hyperphosphorylation in primary neurons, an effect blocked by glycogen synthase kinase-3{beta} inhibition. Together, our study links ImP to hallmarks of neurodegeneration and suggest that targeting ImP may represent a potential strategy to modify ADRD risk.

pathology↗

bioRxiv2025

Amyloid-beta deposition and reduced drainage at the cribriform plate lymphatics in APP/PS1 mouse model of Alzheimer's Disease

Alzheimers disease (AD) is the most common cause of dementia, leading to substantial personal, economic, and medical costs to patients and society; it is characterized by the build-up of toxic amyloid-beta (A{beta}) and hyperphosphorylated tau. It is crucial to the health of the brain that these proteins are processed or drained effectively, but mounting research has shown that in AD pathology there is dysfunction in the ability of the brain to effectively clear pathological A{beta} and tau. In this report, we detail the involvement of one important brain drainage pathway and potential site of A{beta} clearance, the cribriform plate lymphatics, in 24-month old APP/PS1 mice. We show that cerebrospinal fluid (CSF) efflux is decreased across the cribriform plate area utilizing multiple methods. Moreover, we demonstrate that A{beta} aggregates at the cribriform plate - coating surface of olfactory bulbs (OB), olfactory nerve (ON) bundles, and cribriform plate lymphatic endothelial cells (cpLECs). At 24-months, APP/PS1 mice have increased CD45+ cell infiltration and decreased LYVE-1+ vessel area at the cribriform plate, suggesting local inflammation and lymphatic atrophy. Additionally, cpLECs have higher expression of caspase-3 suggesting the decreased LYVE-1 area is due to cellular toxicity resulting in apoptosis. This study demonstrates that the cribriform plate is an important area for further research elucidating its contribution to AD disease pathogenesis.

neuroscience↗

bioRxiv2022

Trimethylamine N-oxide reduces neurite density and plaque intensity in a murine model of Alzheimer disease

BackgroundAlzheimers disease (AD) is the most common aging-associated neurodegenerative disease; nevertheless, the etiology and progression of the disease is still incompletely understood. We have previously shown that the microbially-derived metabolite trimethylamine N-oxide (TMAO) is elevated in the cerebrospinal fluid (CSF) of individuals with cognitive impairment due to AD and positively correlates with increases in CSF biomarkers for tangle, plaque, and neuronal pathology. ObjectiveWe assessed the direct impact of TMAO on AD progression. MethodsTo do so, transgenic 5XFAD mice were supplemented with TMAO for 12 weeks. ResultsOral TMAO administration resulted in significantly reduced neurite density in several regions of the brain, as assessed through quantitative brain microstructure imaging with neurite orientation dispersion and density imaging (NODDI) magnetic resonance imaging (MRI). Amyloid-{beta} plaque mean intensity was reduced, while plaque count and size remained unaltered. Proteomics analysis of the cortex revealed that TMAO treatment impacted the expression of 31 proteins (1.5-fold cut-off) in 5XFAD mice, including proteins known to influence neuronal health and amyloid-{beta} precursor protein processing. TMAO treatment did not alter astrocyte and microglial response (as determined by histological analysis) nor cortical synaptic protein expression. ConclusionThese data suggest that elevated plasma TMAO impacts AD pathology via reductions in neurite density.

neuroscience↗