Biology session

Psychosocial and physical stressors posed by the modern lifestyle induce centrally mediated complex adaptive changes referred to as systemic stress response. In addition to the neuroendocrine and immune changes, chronic stress results in significant rearrangements in the metabolism.

Microglia - the resident macrophages of the brain - play an important role in generating neuroinflammatory processes, and contribute to the formation, operation and adaptation of neuronal circuitry in health and disease. Fractalkine is a key regulator of microglial activity and is highly involved in neuron-microglia communication upon binding to G-protein coupled receptor CX3CR1 on microglial cells.

The aim of our experiment was to characterize chronic variable stress (CVS) -induced metabolic changes, and associated microglial morphofunctional alterations in metabolic-related brain regions. In the experiment we used wild type C57Bl6 mice and transgenic mice with impaired fractalkine signaling (CX3CR1 -/-, C57Bl6 background). Adult male mice were exposed to chronic variable stress for four weeks. Body weight of the animals and the main metabolic parameters were analyzed by indirect calorimetry. Iba-1 immunohistochemistry followed by morphometrical analysis was used to visualize morphological changes of microglia in the brain.

The CVS procedure significantly increased the weight of the adrenal glands and plasma corticosterone indicating increased hypothalamo-pituitary-adrenocortical activation. In addition, we detected significant changes in body composition, home cage locomotor activity and metabolic parameters after CVS. Chronic stress resulted in increased respiratory exchange ratio (RER) in wild type but not in CX3CR1-/- animals. Furthermore, chronic stress resulted in microglia activation in the arcuate nucleus, which is one of the main energy sensor in the brain, but this activation was not seen in CX3CR1 -/- mice.

In conclusion, we provided evidence for chronic stress induced metabolic changes in mice and that were parallel with activation of microglia in the hypothalamic arcuate nucleus, which have a key regulatory role in food intake and energy metabolism. Because these stress-induced changes were not fully seen in CX3CR1-/- mice, we hypothesized the role of fractalkine signaling in mediating chronic stress induced activation of hypothalamic microglia and related metabolic changes.