Limits...
Clock Genes in Glia Cells

View Article: PubMed Central - PubMed

ABSTRACT

Circadian rhythms are periodic patterns in biological processes that allow the organisms to anticipate changes in the environment. These rhythms are driven by the suprachiasmatic nucleus (SCN), the master circadian clock in vertebrates. At a molecular level, circadian rhythms are regulated by the so-called clock genes, which oscillate in a periodic manner. The protein products of clock genes are transcription factors that control their own and other genes’ transcription, collectively known as “clock-controlled genes.” Several brain regions other than the SCN express circadian rhythms of clock genes, including the amygdala, the olfactory bulb, the retina, and the cerebellum. Glia cells in these structures are expected to participate in rhythmicity. However, only certain types of glia cells may be called “glial clocks,” since they express PER-based circadian oscillators, which depend of the SCN for their synchronization. This contribution summarizes the current information about clock genes in glia cells, their plausible role as oscillators and their medical implications.

No MeSH data available.


Related in: MedlinePlus

Model of a glutamatergic synapse and the molecular circadian clockwork. In the presynaptic neuron, glutamine (Gln) is converted to glutamate (Glu) by Glutaminase and packaged into synaptic vesicles by the vesicular glutamate transporter (VGluT). After its release into the extracellular space, Glu binds to ionotropic glutamate receptors (NMDAR and AMPAR) and metabotropic glutamate receptors (mGluRs) in the membranes of postsynaptic neuron and glia cells. Later, Glu is cleared from the synaptic space through excitatory amino acid transporters (EAATs) on neighboring glia cells (GLAST); this Glu uptake leads to Na+ influx, which activates the Na+/Ca2+ exchanger, increasing intracellular Ca2+ levels. Within the glia cell, Glu is converted to Gln by Glutamine synthetase and the Gln is subsequently released by system N sodium-coupled neutral amino acid transporters (SNAT3/5) and taken up by neurons through system A transporters (SNAT1/2) to complete the Glu-Gln cycle. Interestingly, Glu plays an important role in circadian rhythms since they express molecular oscillators. Glu activates NMDAR-induced Ca2+ influx, which together with other second messengers triggers the activation of diverse signal transduction cascades, including calmodulin kinase II (CaMKII) activity and cAMP-dependent protein kinase (PKA). Although the cross talk between these diverse cascades is not currently well known, it is plausible that a common mechanism involved in this pathway is the phosphorylation of the cAMP response element binding protein (CREB). In turn, pCREB activates Per1 and Per2 transcription (these genes are also activated by CLOCK/BMAL1 binding to E-box). Circadian transcription factors also regulate the expression of numerous proteins, molecules, and second messengers, including GLAST, GFAP, ATP, and Ca2+. Solid lines represent mechanisms that have been described experimentally, and dashed lines indicate possible additional links of this pathway. AMPAR, α-amino-3-hydroxy-5-methyl-4-isoaxazolepropionate receptor; ATP, adenosine triphosphate; BMAL1, brain and muscle ARNT-like protein 1; CaM, calmodulin; cAMP, cyclic adenosine monophosphate; CCGs, clock-controlled genes; CLOCK, circadian locomotor output cycles kaput; Cry, cryptochrome; GFAP, glial fibrillary acidic protein; GLAST, glutamate aspartate transporter; NMDAR, N-methyl-D-aspartate receptor; Per, period.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2 - License 3
getmorefigures.php?uid=PMC5037500&req=5

fig2-1759091416670766: Model of a glutamatergic synapse and the molecular circadian clockwork. In the presynaptic neuron, glutamine (Gln) is converted to glutamate (Glu) by Glutaminase and packaged into synaptic vesicles by the vesicular glutamate transporter (VGluT). After its release into the extracellular space, Glu binds to ionotropic glutamate receptors (NMDAR and AMPAR) and metabotropic glutamate receptors (mGluRs) in the membranes of postsynaptic neuron and glia cells. Later, Glu is cleared from the synaptic space through excitatory amino acid transporters (EAATs) on neighboring glia cells (GLAST); this Glu uptake leads to Na+ influx, which activates the Na+/Ca2+ exchanger, increasing intracellular Ca2+ levels. Within the glia cell, Glu is converted to Gln by Glutamine synthetase and the Gln is subsequently released by system N sodium-coupled neutral amino acid transporters (SNAT3/5) and taken up by neurons through system A transporters (SNAT1/2) to complete the Glu-Gln cycle. Interestingly, Glu plays an important role in circadian rhythms since they express molecular oscillators. Glu activates NMDAR-induced Ca2+ influx, which together with other second messengers triggers the activation of diverse signal transduction cascades, including calmodulin kinase II (CaMKII) activity and cAMP-dependent protein kinase (PKA). Although the cross talk between these diverse cascades is not currently well known, it is plausible that a common mechanism involved in this pathway is the phosphorylation of the cAMP response element binding protein (CREB). In turn, pCREB activates Per1 and Per2 transcription (these genes are also activated by CLOCK/BMAL1 binding to E-box). Circadian transcription factors also regulate the expression of numerous proteins, molecules, and second messengers, including GLAST, GFAP, ATP, and Ca2+. Solid lines represent mechanisms that have been described experimentally, and dashed lines indicate possible additional links of this pathway. AMPAR, α-amino-3-hydroxy-5-methyl-4-isoaxazolepropionate receptor; ATP, adenosine triphosphate; BMAL1, brain and muscle ARNT-like protein 1; CaM, calmodulin; cAMP, cyclic adenosine monophosphate; CCGs, clock-controlled genes; CLOCK, circadian locomotor output cycles kaput; Cry, cryptochrome; GFAP, glial fibrillary acidic protein; GLAST, glutamate aspartate transporter; NMDAR, N-methyl-D-aspartate receptor; Per, period.

Mentions: The presence of clock genes in glia cells has great importance for maintaining the homeostasis of the various functions performed by these cells (Figure 2). Due to the nature of glia cells, most of the changes reported by alterations in the expression of clock genes lead to problems related to imbalance of the glutamatergic system, leading to severe pathophysiological scenarios. Future work should focus on the role of glia in different aspects of circadian behavior and medical implications that could strengthen for our understanding the role of glia cells in brain physiology.Figure 2.


Clock Genes in Glia Cells
Model of a glutamatergic synapse and the molecular circadian clockwork. In the presynaptic neuron, glutamine (Gln) is converted to glutamate (Glu) by Glutaminase and packaged into synaptic vesicles by the vesicular glutamate transporter (VGluT). After its release into the extracellular space, Glu binds to ionotropic glutamate receptors (NMDAR and AMPAR) and metabotropic glutamate receptors (mGluRs) in the membranes of postsynaptic neuron and glia cells. Later, Glu is cleared from the synaptic space through excitatory amino acid transporters (EAATs) on neighboring glia cells (GLAST); this Glu uptake leads to Na+ influx, which activates the Na+/Ca2+ exchanger, increasing intracellular Ca2+ levels. Within the glia cell, Glu is converted to Gln by Glutamine synthetase and the Gln is subsequently released by system N sodium-coupled neutral amino acid transporters (SNAT3/5) and taken up by neurons through system A transporters (SNAT1/2) to complete the Glu-Gln cycle. Interestingly, Glu plays an important role in circadian rhythms since they express molecular oscillators. Glu activates NMDAR-induced Ca2+ influx, which together with other second messengers triggers the activation of diverse signal transduction cascades, including calmodulin kinase II (CaMKII) activity and cAMP-dependent protein kinase (PKA). Although the cross talk between these diverse cascades is not currently well known, it is plausible that a common mechanism involved in this pathway is the phosphorylation of the cAMP response element binding protein (CREB). In turn, pCREB activates Per1 and Per2 transcription (these genes are also activated by CLOCK/BMAL1 binding to E-box). Circadian transcription factors also regulate the expression of numerous proteins, molecules, and second messengers, including GLAST, GFAP, ATP, and Ca2+. Solid lines represent mechanisms that have been described experimentally, and dashed lines indicate possible additional links of this pathway. AMPAR, α-amino-3-hydroxy-5-methyl-4-isoaxazolepropionate receptor; ATP, adenosine triphosphate; BMAL1, brain and muscle ARNT-like protein 1; CaM, calmodulin; cAMP, cyclic adenosine monophosphate; CCGs, clock-controlled genes; CLOCK, circadian locomotor output cycles kaput; Cry, cryptochrome; GFAP, glial fibrillary acidic protein; GLAST, glutamate aspartate transporter; NMDAR, N-methyl-D-aspartate receptor; Per, period.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2 - License 3
Show All Figures
getmorefigures.php?uid=PMC5037500&req=5

fig2-1759091416670766: Model of a glutamatergic synapse and the molecular circadian clockwork. In the presynaptic neuron, glutamine (Gln) is converted to glutamate (Glu) by Glutaminase and packaged into synaptic vesicles by the vesicular glutamate transporter (VGluT). After its release into the extracellular space, Glu binds to ionotropic glutamate receptors (NMDAR and AMPAR) and metabotropic glutamate receptors (mGluRs) in the membranes of postsynaptic neuron and glia cells. Later, Glu is cleared from the synaptic space through excitatory amino acid transporters (EAATs) on neighboring glia cells (GLAST); this Glu uptake leads to Na+ influx, which activates the Na+/Ca2+ exchanger, increasing intracellular Ca2+ levels. Within the glia cell, Glu is converted to Gln by Glutamine synthetase and the Gln is subsequently released by system N sodium-coupled neutral amino acid transporters (SNAT3/5) and taken up by neurons through system A transporters (SNAT1/2) to complete the Glu-Gln cycle. Interestingly, Glu plays an important role in circadian rhythms since they express molecular oscillators. Glu activates NMDAR-induced Ca2+ influx, which together with other second messengers triggers the activation of diverse signal transduction cascades, including calmodulin kinase II (CaMKII) activity and cAMP-dependent protein kinase (PKA). Although the cross talk between these diverse cascades is not currently well known, it is plausible that a common mechanism involved in this pathway is the phosphorylation of the cAMP response element binding protein (CREB). In turn, pCREB activates Per1 and Per2 transcription (these genes are also activated by CLOCK/BMAL1 binding to E-box). Circadian transcription factors also regulate the expression of numerous proteins, molecules, and second messengers, including GLAST, GFAP, ATP, and Ca2+. Solid lines represent mechanisms that have been described experimentally, and dashed lines indicate possible additional links of this pathway. AMPAR, α-amino-3-hydroxy-5-methyl-4-isoaxazolepropionate receptor; ATP, adenosine triphosphate; BMAL1, brain and muscle ARNT-like protein 1; CaM, calmodulin; cAMP, cyclic adenosine monophosphate; CCGs, clock-controlled genes; CLOCK, circadian locomotor output cycles kaput; Cry, cryptochrome; GFAP, glial fibrillary acidic protein; GLAST, glutamate aspartate transporter; NMDAR, N-methyl-D-aspartate receptor; Per, period.
Mentions: The presence of clock genes in glia cells has great importance for maintaining the homeostasis of the various functions performed by these cells (Figure 2). Due to the nature of glia cells, most of the changes reported by alterations in the expression of clock genes lead to problems related to imbalance of the glutamatergic system, leading to severe pathophysiological scenarios. Future work should focus on the role of glia in different aspects of circadian behavior and medical implications that could strengthen for our understanding the role of glia cells in brain physiology.Figure 2.

View Article: PubMed Central - PubMed

ABSTRACT

Circadian rhythms are periodic patterns in biological processes that allow the organisms to anticipate changes in the environment. These rhythms are driven by the suprachiasmatic nucleus (SCN), the master circadian clock in vertebrates. At a molecular level, circadian rhythms are regulated by the so-called clock genes, which oscillate in a periodic manner. The protein products of clock genes are transcription factors that control their own and other genes’ transcription, collectively known as “clock-controlled genes.” Several brain regions other than the SCN express circadian rhythms of clock genes, including the amygdala, the olfactory bulb, the retina, and the cerebellum. Glia cells in these structures are expected to participate in rhythmicity. However, only certain types of glia cells may be called “glial clocks,” since they express PER-based circadian oscillators, which depend of the SCN for their synchronization. This contribution summarizes the current information about clock genes in glia cells, their plausible role as oscillators and their medical implications.

No MeSH data available.


Related in: MedlinePlus