Circadian Rhythm Generation and Entrainment in Astrocytes

Overview

Journal J Neurosci

Specialty Neurology

Date 2005 Jan 14

PMID 15647483

Citations 134

Authors

Laura M Prolo

Joseph S Takahashi

Erik D Herzog

Affiliations

Soon will be listed here.

Abstract

In mammals, the master circadian pacemaker is considered the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN consists of a heterogeneous population of neurons and relatively understudied glia. We investigated whether glia, like neurons, rhythmically express circadian genes. We generated pure cultures of cortical astrocytes from Period2::luciferase (Per2::luc) knock-in mice and Period1::luciferase (Per1::luc) transgenic rats and recorded bioluminescence as a real-time reporter of gene activity. We found that rat Per1::luc and mouse Per2::luc astroglia express circadian rhythms with a genetically determined period. These rhythms damped out after several days but were reinitiated by a variety of treatments, including a full volume exchange of the medium. If cultures were treated before damping out, the phase of Per1::luc rhythmicity was shifted, depending on the time of the pulse relative to the peak of Per1 expression. Glial rhythms entrained to daily 1.5 degrees C temperature cycles and were significantly sustained when cocultured with explants of the adult SCN but not with cortical explants. Thus, multiple signals, including a diffusible factor(s) from the SCN, are sufficient to either entrain or restart circadian oscillations in cortical glia.

Citing Articles

Mutual coupling of neurons in the circadian master clock: What we can learn from fruit flies.

Helfrich-Forster C, Reinhard N Neurobiol Sleep Circadian Rhythms. 2025; 18:100112.

PMID: 39906412 PMC: 11791320. DOI: 10.1016/j.nbscr.2025.100112.

Glia: the cellular glue that binds circadian rhythms and sleep.

Cavalhas-Almeida C, Carvalhas-Almeida C, Sehgal A Sleep. 2025; 48(3).

PMID: 39812780 PMC: 11893543. DOI: 10.1093/sleep/zsae314.

Daily glucocorticoids promote glioblastoma growth and circadian synchrony to the host.

Gonzalez-Aponte M, Damato A, Simon T, Aripova N, Darby F, Jeon M Cancer Cell. 2024; 43(1):144-160.e7.

PMID: 39672168 PMC: 11732716. DOI: 10.1016/j.ccell.2024.11.012.

Circadian regulation of endoplasmic reticulum calcium response in cultured mouse astrocytes.

Ryu J, Shim K, Roh H, Park M, Lee J, Kim E Elife. 2024; 13.

PMID: 39601391 PMC: 11602189. DOI: 10.7554/eLife.96357.

Epigenetic events influencing the biological clock: Panacea for neurodegeneration.

Latha Laxmi I, Tamizhselvi R Heliyon. 2024; 10(19):e38836.

PMID: 39430507 PMC: 11489350. DOI: 10.1016/j.heliyon.2024.e38836.

References

Shinohara K, Honma S, Katsuno Y, Honma K . Circadian release of excitatory amino acids in the suprachiasmatic nucleus culture is Ca(2+)-independent. Neurosci Res. 2000; 36(3):245-50. DOI: 10.1016/s0168-0102(99)00131-5. View

Ruby N, Burns D, Heller H . Circadian rhythms in the suprachiasmatic nucleus are temperature-compensated and phase-shifted by heat pulses in vitro. J Neurosci. 1999; 19(19):8630-6. PMC: 6783024. View

Balsalobre A, Marcacci L, Schibler U . Multiple signaling pathways elicit circadian gene expression in cultured Rat-1 fibroblasts. Curr Biol. 2000; 10(20):1291-4. DOI: 10.1016/s0960-9822(00)00758-2. View

Stokkan K, Yamazaki S, Tei H, Sakaki Y, Menaker M . Entrainment of the circadian clock in the liver by feeding. Science. 2001; 291(5503):490-3. DOI: 10.1126/science.291.5503.490. View

Yagita K, Tamanini F, van der Horst G, Okamura H . Molecular mechanisms of the biological clock in cultured fibroblasts. Science. 2001; 292(5515):278-81. DOI: 10.1126/science.1059542. View

Buijs R, Kalsbeek A . Hypothalamic integration of central and peripheral clocks. Nat Rev Neurosci. 2001; 2(7):521-6. DOI: 10.1038/35081582. View

Baltrons M, Garcia A . The nitric oxide/cyclic GMP system in astroglial cells. Prog Brain Res. 2001; 132:325-37. DOI: 10.1016/s0079-6123(01)32086-1. View

Allen G, RAPPE J, Earnest D, Cassone V . Oscillating on borrowed time: diffusible signals from immortalized suprachiasmatic nucleus cells regulate circadian rhythmicity in cultured fibroblasts. J Neurosci. 2001; 21(20):7937-43. PMC: 6763840. View

Abrahamson E, Moore R . Suprachiasmatic nucleus in the mouse: retinal innervation, intrinsic organization and efferent projections. Brain Res. 2001; 916(1-2):172-91. DOI: 10.1016/s0006-8993(01)02890-6. View

10.

Abe M, Herzog E, Yamazaki S, Straume M, Tei H, Sakaki Y . Circadian rhythms in isolated brain regions. J Neurosci. 2002; 22(1):350-6. PMC: 6757616. View

11.

Nakamura W, Honma S, Shirakawa T, Honma K . Clock mutation lengthens the circadian period without damping rhythms in individual SCN neurons. Nat Neurosci. 2002; 5(5):399-400. DOI: 10.1038/nn843. View

12.

Albus H, Bonnefont X, Chaves I, Yasui A, Doczy J, van der Horst G . Cryptochrome-deficient mice lack circadian electrical activity in the suprachiasmatic nuclei. Curr Biol. 2002; 12(13):1130-3. DOI: 10.1016/s0960-9822(02)00923-5. View

13.

Pando M, Morse D, Cermakian N, Sassone-Corsi P . Phenotypic rescue of a peripheral clock genetic defect via SCN hierarchical dominance. Cell. 2002; 110(1):107-17. DOI: 10.1016/s0092-8674(02)00803-6. View

14.

Herzog E, Huckfeldt R . Circadian entrainment to temperature, but not light, in the isolated suprachiasmatic nucleus. J Neurophysiol. 2003; 90(2):763-70. DOI: 10.1152/jn.00129.2003. View

15.

Yamaguchi S, Isejima H, Matsuo T, Okura R, Yagita K, Kobayashi M . Synchronization of cellular clocks in the suprachiasmatic nucleus. Science. 2003; 302(5649):1408-12. DOI: 10.1126/science.1089287. View

16.

Izumo M, Johnson C, Yamazaki S . Circadian gene expression in mammalian fibroblasts revealed by real-time luminescence reporting: temperature compensation and damping. Proc Natl Acad Sci U S A. 2003; 100(26):16089-94. PMC: 307697. DOI: 10.1073/pnas.2536313100. View

17.

Granados-Fuentes D, Prolo L, Abraham U, Herzog E . The suprachiasmatic nucleus entrains, but does not sustain, circadian rhythmicity in the olfactory bulb. J Neurosci. 2004; 24(3):615-9. PMC: 6729269. DOI: 10.1523/JNEUROSCI.4002-03.2004. View

18.

Granados-Fuentes D, Saxena M, Prolo L, Aton S, Herzog E . Olfactory bulb neurons express functional, entrainable circadian rhythms. Eur J Neurosci. 2004; 19(4):898-906. PMC: 3474850. DOI: 10.1111/j.0953-816x.2004.03117.x. View

19.

Tousson E, Meissl H . Suprachiasmatic nuclei grafts restore the circadian rhythm in the paraventricular nucleus of the hypothalamus. J Neurosci. 2004; 24(12):2983-8. PMC: 6729855. DOI: 10.1523/JNEUROSCI.5044-03.2004. View

20.

Yoo S, Yamazaki S, Lowrey P, Shimomura K, Ko C, Buhr E . PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues. Proc Natl Acad Sci U S A. 2004; 101(15):5339-46. PMC: 397382. DOI: 10.1073/pnas.0308709101. View