Sleep and immune function: glial contributions and consequences of aging

- Microglia modulate NREMS and slow wave activity via production of immunomodulators.
- Astrocytic gliotransmission mediates NREMS and sleep pressure.
- ATP (via P2X7R) and adenosine (via A1R) may be effectors of glial sleep regulation.
- Aging is associated with poor sleep quality and chronic, low-grade inflammation.
- Primed microglia and activated astrocytes contribute to changes of the aging CNS.

The reciprocal interactions between sleep and immune function are well-studied. Insufficient sleep induces innate immune responses as evidenced by increased expression of pro-inflammatory mediators in the brain and periphery. Conversely, immune challenges upregulate immunomodulator expression, which alters central nervous system-mediated processes and behaviors, including sleep. Recent studies indicate that glial cells, namely microglia and astrocytes, are active contributors to sleep and immune system interactions. Evidence suggests glial regulation of these interactions is mediated, in part, by adenosine and adenosine 5′-triphosphate actions at purinergic type 1 and type 2 receptors. Furthermore, microglia and astrocytes may modulate declines in sleep-wake behavior and immunity observed in aging.