Sleep and immunomodulatory responses to systemic lipopolysaccharide in mice selectively expressing interleukin‐1 receptor 1 on neurons or astrocytes

Sleep‐wake behavior is altered in response to immune challenge. Although the precise mechanisms that govern sickness‐induced changes in sleep are not fully understood, interleukin‐1β (IL‐1) is one mediator of these responses. To better understand mechanisms underlying sleep and inflammatory responses to immune challenge, we used two transgenic mouse strains that express IL‐1 receptor 1 (IL1R1) only in the central nervous system and selectively on neurons or astrocytes. Electroencephalographic recordings from transgenic and wild‐type mice reveal that systemic challenge with lipopolysaccharide (LPS) fragments sleep, suppresses rapid eye movement sleep (REMS), increases non‐REMS (NREMS), diminishes NREM delta power, and induces fever in all genotypes. However, the magnitude of REMS suppression is greater in mice expressing IL1R1 on astrocytes compared with mice in which IL1R1 is selectively expressed on neurons. Furthermore, there is a delayed increase in NREM delta power when IL1R1 is expressed on astrocytes. LPS‐induced sleep fragmentation is reduced in mice expressing IL1R1 on neurons. Although LPS increases IL‐1 and IL‐6 in brain of all genotypes, this response is attenuated when IL1R1 is expressed selectively on neurons or on astrocytes. Collectively, these data suggest that in these transgenic mice under the conditions of this study it is neuronal IL1R1 that plays a greater role in LPS‐induced suppression of REMS and NREM delta power, whereas astroglial IL1R1 is more important for sleep fragmentation after this immune challenge. Thus, aspects of central responses to LPS are modulated by IL1R1 in a cell type‐specific manner. GLIA 2016;64:780–791     

The astrocyte odyssey

Neurons have long held the spotlight as the central players of the nervous system, but we must remember that we have equal numbers of astrocytes and neurons in the brain. Are these cells only filling up the space and passively nurturing the neurons, or do they also contribute to information transfer and processing? After several years of intense research since the pioneer discovery of astrocytic calcium waves and glutamate release onto neurons in vitro, the neuronal-glial studies have answered many questions thanks to technological advances. However, the definitive in vivo role of astrocytes remains to be addressed. In addition, it is becoming clear that diverse populations of astrocytes coexist with different molecular identities and specialized functions adjusted to their microenvironment, but do they all belong to the umbrella family of astrocytes? One population of astrocytes takes on a new function by displaying both support cell and stem cell characteristics in the neurogenic niches. Here, we define characteristics that classify a cell as an astrocyte under physiological conditions. We will also discuss the well-established and emerging functions of astrocytes with an emphasis on their roles on neuronal activity and as neural stem cells in adult neurogenic zones.     

Contribution of P2Y(1) receptors to ADP signalling in mouse spinal cord cultures

Mixed neuronal and glial cell spinal cord cultures from neonates express ADP sensitive P2Y(1,12&13) receptors. ADP (10microM) evoked increases in intracellular calcium that were essentially abolished by the P2Y(1) receptor antagonist MRS2179 (10microM), responses were also absent in preparations from P2Y(1) receptor deficient mice however UTP (100microM) evoked calcium rises were unaffected. ADP also evoked a robust increase in extracellular signal-regulated protein kinase (ERK) phosphorylation that was of similar magnitude in the cultures from wild type and P2Y(1) receptor deficient mice. These results suggest that ADP acts through P2Y(1) receptors to mediate an increase in intracellular calcium but not to stimulate ERK phosphorylation in the spinal cord.