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Selander, L.

Publications and source records attributed to Selander, L..

2 recordsLinked to original sources

Aberrant microglial responses shape hypothalamic circuits in anorexia nervosa

Multimodal data indicates that microglia contribute to the pathophysiology of anorexia nervosa (AN). Here, we investigated microglial modulation of hypothalamic circuits, key regulators of energy balance, hypothesising an implication in the prolonged starvation and low body weight of AN. First, we generated microglia as well as hypothalamic and cortical neurons from patient-derived induced pluripotent stem cells (iPSCs) to discover upregulation of synapse-related genes in hypothalamic neurons, reduced microglial uptake of hypothalamic synaptic structures, and a microglial unresponsivness to the satiety hormone glucagon-like peptide-1. In an AN animal model (anx/anx mouse), spatial transcriptomics indicated hypothalamic microglial activation and disrupted microglia-synapse signaling. Despite an increased microglia density in both the arcuate nucleus (ARC) and the dorsomedial hypothalamus region (DMH), microglia displayed a decreased per cell uptake of synaptic material in Arc. Together, these data suggest that microglial responses shape hypothalamic circuits with possible implications for the maintained negative energy balance of AN.

neuroscience↗

High-plex protein profiling on cytospin slides with bronchoalveolar lavage cells from asthma and COPD

Protein profiling of whole cells can accurately define cell subsets specific to disease identity and/or severity. Preserving whole cells on cytospin slides is common practice but is often used only for differential counts. Here we ran two studies and successfully applied a high-plex protein panel using the NanoString GeoMx, quantifying up to 47 proteins (of immune, cell death, and MAPK signalling markers) in bronchoalveolar lavage (BAL) cytospins from the four major cell types: macrophages, neutrophils, type-2 granulocytes and lymphocytes. Despite the small sample size for this feasibility study, several significant differences between disease and controls within several BAL cell types for both the asthma cohort (n=21) and the COPD cohort (n=20) were found. Overall, we believe applying this method can maximise biomarker discover of any precious preserved cytospin clinical samples and that the significant disease specific cell subsets discovered during the method testing are worthy of future investigation.

immunology↗