Impaired function of the suprachiasmatic nucleus rescues the loss of body temperature homeostasis caused by time-restricted feeding

The suprachiasmatic nucleus(SCN)is the master circadian pacemaker that drives body temperature rhythm.Time-restricted feeding(TRF)has potential as a preventative or therapeutic approach against many diseases.The potential side effects of TRF remain unknown.Here we show that daily 4-h TRF treatment in mice can severely impair body temperature homeostasis and can result in lethality.Nearly half of the mice died at 21℃,and all mice died at 18℃during 4-h TRF.This effect was modulated by the circadian clock and was associated with severe hypothermia due to loss of body temperature homeostasis.Remarkably,disrupting the circadian clock by SCN lesions or constant light rescued lethality during TRF.Analysis of circadian gene expression in the dorsomedial hypothalamus(DMH)demonstrated that TRF reprograms rhythmic transcriptome in DMH and suppresses expression of genes,such as Ccr5 and Calcrl,which are involved in thermoregulation.Together,our results demonstrated a potent effect of TRF on body temperature homeostasis and the role of SCN function in this process.Our results further suggested that circadian arrhythmicity can have potential beneficial effects under certain stress conditions.

Role of the cation-chloride-cotransporters in the circadian system

The circadian system plays an immense role in controlling physiological processes in our body.The suprachiasmatic nucleus (SCN) supervises this system,regulating and harmonising the circadian rhythms in our body.Most neurons present in the SCN are GABAergic neurons.Although GABA is considered the main inhibitory neurotransmitter of the CNS,recent studies have shown that excitatory responses were recorded in this area.These responses are enabled by an increase in intracellular chloride ions[Cl;];levels.The chloride (Cl;) levels in GABAergic neurons are controlled by two solute carrier 12 (SLC12)cation-chloride-cotransporters (CCCs):Na^(+)/K^(+)/Cl^(-)co-transporter (NKCC1) and K^(+)/Cl^(-)cotransporter (KCC2),that respectively cause an influx and efflux of Cl^(-).Recent works have found altered expression and/or activity of either of these co-transporters in SCN neurons and have been associated with circadian rhythms.In this review,we summarize and discuss the role of CCCs in circadian rhythms,and highlight these recent advances which attest to CCC’s growing potential as strong research and therapeutic targets.

The effect of lens aging and cataract surgery on circadian rhythm

Many organisms have evolved an approximately 24-hour circadian rhythm that allows them to achieve internal physiological homeostasis with external environment.Suprachiasmatic nucleus（SCN） is the central pacemaker of circadian rhythm,and its activity is entrained to the external light-dark cycle.The SCN controls circadian rhythm through regulating the synthesis of melatonin by pineal gland via a multisynaptic pathway.Light,especially shortwavelength blue light,is the most potent environmental time cue in circadian photoentrainment.Recently,the discovery of a novel type of retinal photoreceptors,intrinsically photosensitive retinal ganglion cells,sheds light on the mechanism of circadian photoentrainment and raises concerns about the effect of ocular diseases on circadian system.With age,light transmittance is significantly decreased due to the aging of crystalline lens,thus possibly resulting in progressive loss of circadian photoreception.In the current review,we summarize the circadian physiology,highlight the important role of light in circadian rhythm regulation,discuss about the correlation between age-related cataract and sleep disorders,and compare the effect of blue light-filtering intraocular lenses（lOLs） and ultraviolet only filtering lOLs on circadian rhythm.

Effect of Electro-Acupuncture on Expression of Circadian Clock Gene Per2 and Bmal1 in Sleep Deprivation Rat

Objective: The objective is to observe the treatment effect of electro-acupuncture (EA) on core circadian clock gene Per2 and Bmal1 expression in hypothalamus of sleep-deprivation (SD) rats. Methods: Thirty-two Wistar male rats were randomly divided into 4 groups. Mice in the blank control group did not receive any treatment;the remaining groups were applied with para-chlorophenylalanine (PCPA) 300 mg/kg intraperitoneal injection for 2 days. Diazepam group received intraperitoneal injection of Diazepam (0.9 mg/kg, i.p.) one time a day for 5 days, while M group was treated with saline (0.9 mg/kg, i.p.) at the same time. Rats in EA group were given EA treatment, 20 minutes, once a day for 5 days, and rats in remaining groups were put into fixation-machine for the same time everyday, lasting for 5 days. Rats were sacrificed after anesthesia at the 8th day. Real-time PCR was adopted to detect the expression in clock gene Per2 and Bmal1 of each group. Results: Compared with blank control group, the expression of Per2 was significant decreased in PCPA model group (P 0.05). Conclusion: EA can significant up-regulate the expression of Per2 in SD rats, and down-regulate gene Bmal1 expression, and benefiting the weight of rats. Thus, EA is a potentially promising intervention to treat sleep-deprivation.