Biology subjects

Schalling, M.

Publications and source records attributed to Schalling, M..

3 recordsLinked to original sources

bioRxiv2026

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↗

bioRxiv2023

Oligodendrocyte precursor cells engulf synapses in a model of the developing human forebrain

Recent work in animal models suggests the role of oligodendrocyte precursor cells (OPCs) is not limited to oligodendrogenesis. Here, we report that OPCs derived from human induced pluripotent stem cells are capable of engulfing synaptosomes. We then develop a novel multi-lineage forebrain organoid in which OPCs alongside microglia display a spontaneous internalization of synaptic material in their phagolysosomes. Collectively, these findings suggest that OPCs contribute to synapse elimination in the developing human forebrain and provide a versatile platform for evaluating the interplay between microglia and OPCs in remodeling neuronal circuits in health and disease.

neuroscience↗

bioRxiv2018

Contribution of rare copy number variants to bipolar disorder risk is limited to schizoaffective cases

BackgroundGenetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. BD subtypes schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I) and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania and depression. The factors contributing to the combination of symptoms within a given patient are poorly understood.\n\nMethodsRare, large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis], 1436 BD II, 579 SAB) and 8656 controls. Measures of CNV burden were integrated with polygenic risk scores (PRS) for schizophrenia (SCZ) to evaluate the relative contributions of rare and common variants to psychosis risk.\n\nResultsCNV burden did not differ in BD relative to controls when treated as a single diagnostic entity. Burden in SAB was increased compared to controls (p-value = 0.001), BD I (p-value = 0.0003) and BD II (p-value = 0.0007). Burden and SCZ PRS were higher in SAB compared to BD I with psychosis (CNV p-value = 0.0007, PRS p-value = 0.004) and BD I without psychosis (CNV p-value = 0.0004, PRS p-value = 3.9 x 10-5). Within BD I, psychosis was associated with higher SCZ PRS (p-value = 0.005) but not with CNV burden.\n\nConclusionsCNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.

genetics↗