Biology subjects

Shipman, A. L.

Publications and source records attributed to Shipman, A. L..

3 recordsLinked to original sources

bioRxiv2026

HERO: A hierarchy-aware analysis pipeline for reducing and refining whole-brain atlas-mapped cellular datasets

Advances in high-throughput mesoscale microscopy and machine learning-based image analysis pipelines have made unbiased whole-brain imaging widely accessible. However, translating the resulting atlas-mapped datasets into biologically meaningful results remains a substantial barrier owing to their sheer magnitude and complex hierarchical organization. Consequently, reporting structure and analysis methods vary widely across studies, undermining rigor and reproducibility. To address this, we developed a user-friendly data reduction workflow, HERO (Hierarchy-aware Expression Region Organization), designed to perform hierarchy-aware selection, refinement, ranking, and visualization of whole-brain cell detection datasets. The workflow is customizable to specific needs, requires minimal coding experience, and outputs transparent, curated results. HERO is designed to function as a seamless plug-in within larger-scale whole-brain cell-detection analysis pipelines, providing efficient, unbiased region selection to streamline subsequent statistical analyses and comparative evaluations. Although HERO is developed with mouse cell-detection datasets, it can, in principle, be applied to any atlas-mapped dataset that contains hierarchical information. In sum, HERO offers a standardized analysis workflow to reduce whole-brain cell-detection datasets, transforming raw regional cell counts into curated results and advancing the effectiveness, interpretability, and accessibility of whole-brain imaging in neuroscience.

neuroscience↗

bioRxiv2025

Brief disruption of the microbiome has age-dependent effects on morphine reward and gene expression in the medial prefrontal cortex of adolescent and adult mice

Adolescence is a critical period for the initiation of problematic drug use, which significantly increases the risk of developing substance use disorders later in life. This heightened vulnerability is partly attributed to the immaturity of the prefrontal cortex, a brain region both essential for decision-making and implicated in drug reward. During adolescence, peripheral systems, such as the gut microbiome, also undergo substantial changes. Emerging evidence suggests that disruptions to the gut microbiome can influence gene expression and drug reward behaviors in rodent models. In this study, we investigated the effects of microbiome disruption on morphine reward and prefrontal cortical gene expression in adolescent and adult mice. Using oral antibiotics to transiently disrupt the microbiome, we found that short-term antibiotic exposure reduced morphine place preference specifically in adolescent mice. In a separate cohort, we observed that antibiotic treatment altered the transcriptomic response to morphine in the medial prefrontal cortex across all age groups. Notably, the transcriptomic changes induced by antibiotics and morphine were age-specific, with distinct gene expression patterns observed in adolescents compared to adults. These findings establish a foundation for future research into the role of the gut microbiome in opioid reward and highlight potential gene pathways underlying age-dependent differences in opioid sensitivity.

neuroscience↗

bioRxiv2022

Dietary polyphenols drive alterations in behavior, transcriptional regulation, and commensal microbiota in models of opioid use.

Opioid Use Disorder (OUD) is a neuropsychiatric condition associated with tremendous medical and social consequences. Despite this burden, current pharmacotherapies for OUD are ineffective or intolerable for many patients. As such, interventions aimed at promoting overall health and resilience against OUD are of immense clinical and societal interest. Recently, treatment with a Bioactive Dietary Polyphenol Preparation (BDPP) was shown to promote behavioral resilience and adaptive neuroplasticity in multiple models of neuropsychiatric disease. Here, we assessed effects of BDPP treatment on behavioral and molecular responses to repeated morphine treatment. We find that BDPP pre-treatment alters responses across the dose range for both locomotor sensitization and conditioned place preference. Most notably, polyphenol treatment consistently reduced formation of preference at low dose (5mg/kg) morphine but enhanced it at high dose (15mg/kg). In parallel, we performed transcriptomic profiling of the nucleus accumbens, which again showed a dose x polyphenol interaction. At high dose morphine, BDPP pre-treatment potentiated gene expression changes induced by morphine particularly for genes related to synaptic function. We also profiled microbiome composition and function, as polyphenols are metabolized by the microbiome and can act as prebiotics. The profile revealed polyphenol treatment markedly altered microbiome composition and function, particularly in the low dose morphine group. Finally, we investigated involvement of the SIRT1 histone deacetylase, and the role of specific polyphenol metabolites in these behavioral phenotypes. Taken together, these results demonstrate that polyphenols have robust dose-dependent effects on behavioral and physiological responses to morphine and lay the foundation for future translational work.

neuroscience↗