Background: Neutrophil extracellular traps (NETs) are DNA meshes that snare and kill microorganisms, impeding their dissemination.Results: Glucose but not fructose supports NET formation through a metabolic shift toward pentose phosphate pathway (PPP).Conclusion: PPP impairment leads to decreased NET production.Significance: This study provides novel knowledge about the mechanisms of NET induction, opening new avenues of study and intervention.

Hunger, driven by negative energy balance, elicits the search for and consumption of food. While this response is in part mediated by neurons in the hypothalamus, the role of specific cell types in other brain regions is less well defined. Here, we show that neurons in the dorsal raphe nucleus, expressing vesicular transporters for GABA or glutamate (hereafter, DRN and DRN neurons), are reciprocally activated by changes in energy balance and that modulating their activity has opposite effects on feeding-DRN neurons increase, whereas DRN neurons suppress, food intake. Furthermore, modulation of these neurons in obese (ob/ob) mice suppresses food intake and body weight and normalizes locomotor activity. Finally, using molecular profiling, we identify druggable targets in these neurons and show that local infusion of agonists for specific receptors on these neurons has potent effects on feeding. These data establish the DRN as an important node controlling energy balance. PAPERCLIP.

Highlights d Hippocampal Dopamine 2 Receptor (hD2R) neurons are activated by food cues d hD2R neurons connect with the entorhinal cortex (LEC) and the septal area (SA) d The LEC-hD2R-SA circuit decreases food intake in mice d hD2R cells activation influences food-place, but not objectplace, associations

Considerable clinical and epidemiological evidence links Alzheimer's disease (AD) and depression. However, the molecular mechanisms underlying this connection are largely unknown. We reported recently that soluble A␤ oligomers (A␤Os), toxins that accumulate in AD brains and are thought to instigate synapse damage and memory loss, induce depressive-like behavior in mice. Here, we report that the mechanism underlying this action involves A␤O-induced microglial activation, aberrant TNF-␣ signaling, and decreased brain serotonin levels. Inactivation or ablation of microglia blocked the increase in brain TNF-␣ and abolished depressive-like behavior induced by A␤Os. Significantly, we identified serotonin as a negative regulator of microglial activation. Finally, A␤Os failed to induce depressive-like behavior in Toll-like receptor 4-deficient mice and in mice harboring a nonfunctional TLR4 variant in myeloid cells. Results establish that A␤Os trigger depressive-like behavior via a double impact on brain serotonin levels and microglial activation, unveiling a cross talk between brain innate immunity and serotonergic signaling as a key player in mood alterations in AD.