Clock Outputs and physiological rhythms Flashcards
How do circadian clocks drive 24h rhythms in physiology and behavior?
Control at the molecular and physciolocial level (two part response)
What is the difference between clock controlled genes and clock genes?
Both are controlled by CLOCK-BMAL1
But if the gene encodes for clock proteins it is a clock gene
And if it codes for any other protein it’s a clock-controlled gene
Explain why the discovery of tonic vasopressin expression in the Supraoptic nucleus is important
It explains that even though a gene is rhythmic in one organ, that doesn’t mean it is rhythmic everywhere
(Clock and Bmal1 doesn’t necessarily affect all AVP genes)
What did a large scale analysis of all clock controlled genes show (compare liver vs SCN)
Most Clock controlled genes are different between the SCN and Liver
True/False? Less than a tenth of all genes are clock-controlled
False, it’s about 16%
What is the rate limiting step for production of melatonin? Is it rhythmic? Why?
AANAT
Rhythmic, Lots at night because AANAT synthesis is dependent on rhythmic pulses of Noradrenaline
Describe the neuroendocrine pathways to the adrenal glands
SCN sends CRH to the pituitary gland, which releases ACTH, which travels in the blood to the adrenal gland, causing it to release corticosterone/cortisol
The SCN also connects to adrenal (para)sympathetic nerves which directly innervate the adrenal gland
True/False? In the liver, most rhythmic transcripts need a local clock to be rhythmic
True (a few do not need the local clock though)
How does the adrenal clock alter the secretion of ACTH in the absence of SCN impulses? What is this phenomenon called?
The tissue loses its ‘readiness’ and can’t secrete as much ACTH
This is an example of gating
What happens when a wt mouse has its adrenals swapped with a clockless mouse?
ACTH secretion
mt host and wt adrenals: no more night/day differentiation in DD, light restores wt phenotype
How is metabolism affected in clockless mice?
clockless mice gained more weight, and did not sequester glucose as quickly (Secreted less insulin)
How can you knock out a clock in a specific cell type?
Cre-lox system
Insert LoxP before and after the gene you want removed
Cross with a mouse with Cre (which can be expressed only in certain tissues)
Recombinant mouse will have gene excised
What was surprising about the metabolism of hepatocyte-specific BMAL1-KO mice?
Faster glucose recovery during tolerance test
What is the effect on pancreatic islet-specific BMAL1-KO mice?
Clockless mice have lots of glucose in the blood (similar to diabetic phenotype)
