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…
Recent studies using multimodal data have revealed that microglia may play a role in the pathophysiology of anorexia nervosa (AN). The researchers focused on how microglia interact with hypothalamic circuits, which are crucial for regulating energy balance. They hypothesized that these interactions could contribute to the prolonged starvation and low body weight commonly seen in AN patients.
To test their hypothesis, the researchers first generated microglia, hypothalamic, and cortical neurons from patient-derived induced pluripotent stem cells (iPSCs). They discovered that hypothalamic neurons showed upregulation of synapse-related genes. Moreover, they found that microglial uptake of hypothalamic synaptic structures was reduced, and microglia showed reduced responsiveness to the satiety hormone glucagon-like peptide-1.
In an animal model of AN, the anxious/anxious mouse (anx/anx mouse), spatial transcriptomics revealed microglial activation in the hypothalamus and disrupted microglia-synapse signaling. Despite a higher density of microglia in both the arcuate nucleus (ARC) and the dorsomedial hypothalamus region (DMH), these microglia displayed a decreased per cell uptake of synaptic material in the ARC.
Overall, these findings suggest that microglial responses may shape hypothalamic circuits, potentially contributing to the persistent negative energy balance observed in AN.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
