Timing - Understanding Central and Peripheral Clocks

Stepien, JM; Coates, A; Banks, S.

doi:10.21307/esw-2020-002

Figures & Tables

The non-visual pathway of light from the environment to the suprachiasmatic nucleus (SCN) and how it regulates the timing of the transcriptional/translational feedback loop (19). Once the light signal reaches the cells of the SCN, it is the induction of Per1 and Per2 gene expression that synchronises SCN timing with the environment.

The differences in the timing of peak Per1 expression in central and peripheral clocks as measured in mice over the 24 hour period drawn from data in Yamanaka et al. (56). This demonstrates that under normal circumstances the timing of Per1 expression in each tissue is not precisely synchronised. Zeitgeber time (ZT) 0 is the time of exposure to the timegiver (in this case time of lights on). SCN=suprachiasmatic nucleus.

Evidence for the effect of identified entrainers on central and peripheral clock timing in humans and animal models_

Tissue where the clock is found	Model	Entrainer
Tissue where the clock is found	Model	Light	Activity	Temperature	Food
SCN	Animal	Yes	No	No	No (timing)Yes (caloric restriction 66%)
SCN	Human	Yes	Yes (partial)	-	No (timing)Yes (caffeine)
Liver	Animal	Yes - rat and mouse	Yes - mouse	Yes/no - mouse	Yes (timing) - rat and mouseYes (caffeine) - mouse
Pineal Gland	Animal	Yes - rat	-	-	-
Adrenal Gland	Animal	Yes - rat and mouse	-	-	-
Adrenal Gland	Human	Assumed (salivary cortisol)	-	-	-
Heart	Animal	Yes - rat	-	-	Yes (timing) - rat and mouse
Skeletal Muscle	Animal	Yes - rat and mouse	Yes - mouse	-	-
Skeletal Muscle	Human	-	Possible	-	-
Lung	Animal	Yes - mouse	Yes - mouse	-	Yes (timing) - ratYes (caffeine) - mouse
Hair Follicle	Human	Yes	-	-	-
Kidney	Animal	-	-	No - mouse	No (timing) - mouseYes (caffeine) - mouse
Submandibular Gland	Animal	-	-	No - mouse	-
Pancreas	Animal	-	-	-	Unsure (timing) - mouse

Human tissues where primary and secondary loop clock gene expression has been measured and the clock genes that were examined_

System	Tissue/Cell	Clock Gene Measured			Reference
Integumentary	hair follicle	Bmal1Per1	Per2Per3	Rev-ERBαRev-ERBβ	(58, 61, 62)
	oral mucosa	Bmal1Cry1	Per1Per2	Rev-ERBα	(57, 63-65)
	skin	Bmal1	Per1		(57)
	skin fibroblasts	Bmal1Cry1	Cry2Per1	Per2Per3	(66-69)
	skin keratinocytes	Bmal1Cry1Cry2	Per 1Per2Per3	Rev-ERBαRORα	(69)
	skin melanocytes	Bmal1Cry1Cry2	Per 1Per2Per3	Rev-ERBα	(69)
	epidermal stem cells	Bmal1Cry1Cry2	Per1Per2Per3	Rev-ERBαRev-ERBβ	(59)
Circulatory	whole blood	ClockBmal1Cry1Cry2	Per1Per2Per3	Rev-ERBαRev-ERBβRORα	(70-74)
	monocytes	ClockBmal1Cry1	Cry2Per1Per2	Per3Rev-ERBα	(75)
	mononuclear blood cells	ClockBmal1Cry1	Cry2Per1Per2α	Per3Rev-ERBα	(76-85)
	leukocytes	ClockBmal1Cry1	Cry2Per1Per2	Per3Rev-ERBαRORα	(58, 85-91)
	lymphocytes	ClockBmal1Cry1	Cry2Per1Per2	Per3Rev-ERBα	(92)
	mast cells	ClockBmal1	Cry1Per1	Per2	(93)
	eosinophils	ClockBmal1	Cry1Per1	Per2	(93)
	CD4+ T-cells	ClockBmal1Cry1	Cry2Per2Per3	Rev-ERBαRORα	(94)
	polymorphonuclear cells	Cry1Cry2	Per1Per2	Per 3	(83, 85)
	papillary muscle cells	Bmal1Cry1	Per1Per2		(95)
Endocrine	pancreatic islet cells	ClockCry1	Per3Rev-ERBα	Rev-ERBβ	(96)
	visceral adipose tissue	ClockBmal1	Cry1	Per2	(97, 98)
	subcutaneous adipose tissue	ClockBmal1	Cry1	Per2	(97, 98)
Bone	CD4+ (haematopoietic) bone marrow cells	ClockBmal1	Cry1Cry2	Per2Rev-ERBα	(99)
Bone	whole bone marrow cell samples	ClockBmal1	Cry1Cry2	Per2Rev-ERBα	(99)

Timing - Understanding Central and Peripheral Clocks

Figures & Tables

Figure 1.

Figure 2.

Evidence for the effect of identified entrainers on central and peripheral clock timing in humans and animal models_

Human tissues where primary and secondary loop clock gene expression has been measured and the clock genes that were examined_

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