AI Insight
This study reveals that glucocorticoid receptor (GR) expression in the mouse suprachiasmatic nucleus (SCN), the brain's central circadian clock, undergoes a developmental shift from being present in all cells during early life to being primarily restricted to astrocytes in adulthood. The researchers found that prenatal exposure to excess glucocorticoids impairs the offspring's ability to adapt to shifted light-dark cycles and reduces GR expression in SCN astrocytes. Adult SCN astrocytes actively sense and respond to glucocorticoids through rapid calcium signaling that spreads between neighboring cells, demonstrating that the adult SCN maintains glucocorticoid sensitivity through its astrocyte population rather than being resistant as previously thought.
Why it matters
These findings could help explain how the body's circadian clock responds to stress hormones and reestablishes synchrony after disruptions like jet lag or shift work. Understanding that prenatal glucocorticoid exposure affects circadian adaptation in offspring may have implications for maternal stress management during pregnancy and the use of glucocorticoid medications.
Understand the Science
by Kristian Händler, Varun K. A. Sreenivasan, Violetta Pilorz, Celia Martinez-Perez, Iratxe Elorduy, Tomas J. Casas, Marianne Lehmann, Jon Olano Bringas, Laura Escobar Castañondo, Nora Bengoa-Vergniory, Federico N. Soria, Henrik Oster, Malte Spielmann, Mariana Astiz
The circadian system synchronizes physiology, improving the adaptation to daily environmental changes. In mammals, the central pacemaker, in the suprachiasmatic nuclei (SCN) of the hypothalamus, coordinates “wake” functions by inducing the circadian release of glucocorticoids (GCs). GCs entrain the clocks of a wide variety of tissues through GC receptor (GR) activation, however, the influence of GCs on the SCN is unclear and seems to depend on the maturity of the circuit. During the perinatal period, the mouse SCN express GR and respond directly to GCs while the adult SCN express low GR and have been traditionally considered resistant to GCs. To understand the change of sensitivity to GCs we followed the developmental trajectory of the mouse SCN, and found that while GR is expressed in all SCN cells early in life, it remains expressed mainly in astrocytes in the adult. Using a model of prenatal exposure to GCs, we found that offspring from treated mothers, adapt slower to shifted light–dark cycle and shows reduced expression of GR in SCN astrocytes. The adult SCN astrocytes can indeed sense and respond to GCs with rapid astrocytic Ca2+ events that propagate across neighboring cells, an effect that is prevented by the specific inhibition of astrocyte–astrocyte communication. Our findings provide a conceptual advance on how the mouse clock develops and on the influence that GCs have on the SCN. This might be relevant to understand how circadian synchrony is restored in conditions of temporal misalignment, such as jet lag.