Neural Plasticity

Review Article

The Role of Mammalian Glial Cells in Circadian Rhythm Regulation

Table 1

Circadian functions regulated by the glial cells.


CG/CCG/molecule	Circadian functions	References

Astrocytes
Clock	Regulation of the glutamatergic system (Glast mRNA and protein levels)	[32]
Clock	Modulates ATP release	[55]
Npas2	Regulation of the glutamatergic system (Glast mRNA and protein levels)	[32]
Per1	Regulation of nociceptive processes	[51]
Per1	Modulates ATP release	[55]
Per2	Regulation of the glutamatergic system (GLAST protein levels)	[31, 32]
	Regulation of nociceptive processes	[51]
	Modulates ATP release	[55]
	Regulates to cyclin D1	[66]
Bmal1	Modulates the period of the SCN and behavior	[36]
Bmal1	Regulation of nociceptive processes	[51]
Cry1	Regulation of nociceptive processes	[51]
Gfap	Participates in metabolic exchanges and plasticity	[38, 40–42]
NF-κB	SCN astrocytes mediate the immune signals to the circadian system via NF-κB signaling	[43]
RORα	Participates in the regulation of the inflammatory response (inhibits NF-κB pathway and regulates IL-6 expression)	[44–46]
REV-ERBα/REV-ERB β	Participates in the regulation of the inflammatory response (both isoforms inhibit TNF-induced upregulation of Ccl-2 and Mmp-9; and REV-ERBα inhibits Il-6 upregulation)	[47–50]
GS	Regulation of the glutamatergic system (glutamate-glutamine metabolic cycle)	[51]
GS	Regulation of various spinal sensory functions	[51]
COX-1	Regulation of various spinal sensory functions	[51]
IP₃	Modulates ATP release (IP₃-dependent calcium signaling)	[55]
ATP	Regulation of the energy metabolism and glial activity	[55]
Ca²⁺	Modulation of circadian behavior	[19]
Ca²⁺	Regulates the release of gliotransmitters	[35]
Glu	Regulates BMAL1 expression (Glu time- and dose-dependent)	[22]
Glu	Provides the inhibitory astrocytic-neuronal coupling signal during nighttime in the SCN via NMDAR2C	[35]

Microglia
ATP	Upregulates the Per1 mRNA expression via P2X7 purinergic receptor subtype	[58]
CatS	Regulates the synaptic strength, including neuronal transmission and spine density via the proteolytic modification of the perineuronal environment	[20, 21, 59]
Bmal1	Implicated in the inflammatory response (modulates Il-6 upregulation)	[62]

Oligodendrocytes
Cyclin D1	Regulation of the OPC proliferation	[18]

ATP: adenosine triphosphate; Bmal1: brain and muscle ARNT-like protein 1; Ca²⁺: calcium; CatS: cathepsin S; CGs: clock genes; CCGs: clock-controlled genes; Ccl-2: monocyte chemoattractant protein-1; Clock: circadian locomotor output cycles kaput; COX-1: cyclooxygenase-1; Cry1: cryptochrome 1; Gfap: glial fibrillary acidic protein; GLAST: glutamate aspartate transporter; Glu: glutamate; GS: glutamine synthetase; Il-6: interleukin-6; IP₃: inositol triphosphate; Mmp-9: matrix metalloprotease-9; NF-κB: nuclear factor-kappaB; NMDAR2C: N-methyl-D-aspartate receptor 2C subunit; Npas2: neuronal PAS domain protein 2; P2X7: purinoreceptor; OPCs: oligodendrocyte precursor cells; Per: period; REV-ERB: reverse Erb; RORα: retinoid-related orphan receptor-alpha; SCN: suprachiasmatic nucleus; TNF: tumor necrosis factor.