Vasopressin receptor V1a regulates circadian rhythms of locomotor activity and expression of clock-controlled genes in the suprachiasmatic nuclei

Li, Jia-Da; Burton, Katherine J.; Zhang, Chengkang; Hu, Shuang-Bao; Zhou, Qun‐Yong

doi:10.1152/ajpregu.90463.2008

Cited by 112 publications

(106 citation statements)

References 42 publications

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“…Although it remains unknown how this polymorphism was associated with these findings, disturbed circadian rhythms of physical activity might be partially involved in the mechanisms, as suggested in V1a knockout mice. 22 Thus, we confirmed in the present study that TT men had higher metabolic risk factors. In addition to the higher BMI in TT men, we found that DBP before training was higher in TT men than in other Allele frequencies in men with lower (gray columns) and higher (striated columns) BMI, DBP, or LDL cholesterol values than the criteria for lifestyle-related diseases in the present study.…”

Section: Bmi and Blood Pressure Before Training And V1a Receptor Polysupporting

confidence: 85%

Vasopressin V1a Receptor Polymorphism and Interval Walking Training Effects in Middle-Aged and Older People

et al. 2010

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Abstract-We assessed whether single nucleotide polymorphism rs1042615 of the vasopressin V1a receptor altered the indices of lifestyle-related diseases in middle-aged and older people (meanϮSD: 64Ϯ7 years), and, if so, whether it also altered the effects of interval walking training (IWT). CC, CT, and TT carriers of rs1042615 (42, 118, and 64 men, respectively; 113, 263, and 154 women, respectively) performed IWT. We included 5 sets of 3-minute fast walking at Ն70% peak aerobic capacity for walking and 3-minute slow walking at 40% peak aerobic capacity per day for Ն4 days per week for 5 months. Before IWT, the body mass index and diastolic blood pressure (DBP) for men were 25.1Ϯ0.3 kg/m 2 (meanϮSE) and 84Ϯ1 mm Hg in TT, higher than the 23.6Ϯ0.4 kg/m 2 and 78Ϯ1 mm Hg in CC, respectively (PϽ0.01), differences that disappeared after IWT despite similar training achievement between groups (PϾ0.6). After IWT, body mass index and DBP decreased in TT (Ϫ0.9Ϯ0.1 kg/m 2 and Ϫ5Ϯ1 mm Hg, respectively), more than in CC (Ϫ0.5Ϯ0.1 kg/m 2 and 1Ϯ1 mm Hg, respectively; PϽ0.05), with a greater decrease in low-density lipoprotein cholesterol in TT than CC carriers (PϽ0.01). The decreases in DBP and low-density lipoprotein cholesterol were still greater in TT carriers even after adjustment for their pretraining values. On the other hand, for women, these parameters before IWT and their changes after IWT were similar among CC, CT, and TT carriers. Thus, polymorphism rs1042615 of the V1a receptor altered body mass index and DBP in middle-aged and older men and the training-induced responses of DBP and low-density lipoprotein cholesterol, whereas women did not show any of these responses. Key Words: exercise training Ⅲ elderly Ⅲ hypertension Ⅲ obesity Ⅲ cholesterol Ⅲ receptors Ⅲ vasopressin Ⅲ polymorphism A ccumulated evidence suggests the importance of obesity prevention to protect against age-and lifestyle-related diseases, such as hypertension. [1][2][3][4] Although exercise training has been highlighted as one of the most effective strategies, 4 -7 few studies have assessed how gene polymorphisms affect interindividual variation in response to exercise training in a large population of middle-aged and older people. 8 This might be because there have been no uniformly and broadly available exercise training regimens calibrated to their individual physical fitness with few limitations on time and place. Without such a regimen, it might have been difficult to distinguish which caused the interindividual variation in the effects of exercise training, genetic or training regimen differences.Recently, we have developed an exercise training regimen fitted to individual physical fitness broadly available in middle-aged and older people by combining interval walking training (IWT) and an information technology network system to track exercise intensity in individuals. 9,10 Because the IWT regimen is so simple and because training achievements can be measured precisely by triaxial accelerometry, 11 they have enabled us to seek polymorphisms...

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Section: Bmi and Blood Pressure Before Training And V1a Receptor Polysupporting

confidence: 85%

Vasopressin V1a Receptor Polymorphism and Interval Walking Training Effects in Middle-Aged and Older People

et al. 2010

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“…Their surgical separation desynchronizes the dorsomedial shell, presumably due to loss of VIPand GRP-ergic signals (29), and a simple model is that core and shell contain reciprocally supportive oscillators coupled by peptidergic signals. Thus, the shell receives a dense innervation by VIP and GRP (30) and expresses VPAC2 (31) and BB2r (26) whereas the V1a receptor is widely distributed across SCN (27). This model complements the conclusion that there is no uniquely specialized or anatomically localized class of cell-autonomous pacemakers (11): rather, AVP, VIP, and other SCN neurons are intrinsic but unstable circadian oscillators that rely on network interactions to stabilize their otherwise noisy cycling.…”

Section: Discussionmentioning

confidence: 78%

“…Similarly, although loss of the AVP V1a receptor may disrupt behavioral rhythms to a variable extent (27), Per gene expression in the SCN is unaffected in AVP V1a-null mice and blockade of AVP-Gq/ 11-coupled signaling with specific antagonists to both the V1a and V1b subtypes did not affect bioluminescence rhythms in WT SCN. Critically, however, V1a, V1b, and BB2r blockade revealed how both peptidergic pathways are necessary in SCN lacking VIP/VPAC2.…”

Section: Discussionmentioning

confidence: 99%

A diversity of paracrine signals sustains molecular circadian cycling in suprachiasmatic nucleus circuits

Maywood

Chesham²,

O’Brien³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

259

311

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The suprachiasmatic nucleus (SCN) is the principal circadian pacemaker of mammals, coordinating daily rhythms of behavior and metabolism. Circadian timekeeping in SCN neurons revolves around transcriptional/posttranslational feedback loops, in which Period (Per) and Cryptochrome (Cry) genes are negatively regulated by their protein products. Recent studies have revealed, however, that these "core loops" also rely upon cytosolic and circuit-level properties for sustained oscillation. To characterize interneuronal signals responsible for robust pacemaking in SCN cells and circuits, we have developed a unique coculture technique using wild-type (WT) "graft" SCN to drive pacemaking (reported by PER2::LUCIFER-ASE bioluminescence) in "host" SCN deficient either in elements of neuropeptidergic signaling or in elements of the core feedback loop. We demonstrate that paracrine signaling is sufficient to restore cellular synchrony and amplitude of pacemaking in SCN circuits lacking vasoactive intestinal peptide (VIP). By using grafts with mutant circadian periods we show that pacemaking in the host SCN is specified by the genotype of the graft, confirming graft-derived factors as determinants of the host rhythm. By combining pharmacological with genetic manipulations, we show that a hierarchy of neuropeptidergic signals underpins this paracrine regulation, with a preeminent role for VIP augmented by contributions from arginine vasopressin (AVP) and gastrin-releasing peptide (GRP). Finally, we show that interneuronal signaling is sufficiently powerful to maintain circadian pacemaking in arrhythmic Cry-null SCN, deficient in essential elements of the transcriptional negative feedback loops. Thus, a hierarchy of paracrine neuropeptidergic signals determines cell-and circuit-level circadian pacemaking in the SCN.T he circadian pacemaker of the suprachiasmatic nucleus (SCN) directs, on a daily basis, the most fundamental processes of physiology and metabolism, sleep and wakefulness (1). The established molecular model of the SCN oscillator involves interlocked transcriptional/posttranslational negative feedback loops, centered on rhythmic expression of the transcriptional inhibitors Period (Per) and Cryptochrome (Cry), driven by the positive activators Clock and Bmal1. The period of the daily oscillation is determined by the transcriptional activity of Clock (1) and by the stability of Per and Cry proteins (2, 3). More recently the model of SCN neurons as autonomous transcriptional/translational feedback oscillators has been reappraised. Rhythmic cytosolic signaling pathways, particularly cAMP and Ca 2+ , not only are driven by the core feedback loops, but also support them in a mutually dependent fashion (4, 5). Furthermore, within SCN circuits, loss of signaling by the neuropeptide vasoactive intestinal peptide (VIP) through its VPAC2 receptor (a positive regulator of cAMP) both desynchronizes and damps cellular transcriptional pacemaking (6, 7). Conversely, intercellular coupling maintains robustness within SCN cells deficie...

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“…Furthermore, rhythms of bioluminescence in Cry1/2-null SCN are induced by paracrine signaling from a WT SCN graft (15). Of these paracrine-signaling molecules, AVP is thought to play a role in SCN synchronization (26), with genetic loss of V1a and V1b receptors loosening coupling within the SCN, facilitating re-entrainment of molecular and behavioral rhythms (13). Additionally, when the molecular clock is abolished in AVP-expressing cells, coupling between SCN neurons is weakened, and the period of behavioral rhythms is lengthened (14).…”

Section: Discussionmentioning

confidence: 99%

Rhythmic expression of cryptochrome induces the circadian clock of arrhythmic suprachiasmatic nuclei through arginine vasopressin signaling

Edwards

Brancaccio

Chesham

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Circadian rhythms in mammals are coordinated by the suprachiasmatic nucleus (SCN). SCN neurons define circadian time using transcriptional/ posttranslational feedback loops (TTFL) in which expression of Cryptochrome (Cry) and Period (Per) genes is inhibited by their protein products. Loss of Cry1 and Cry2 stops the SCN clock, whereas individual deletions accelerate and decelerate it, respectively. At the circuit level, neuronal interactions synchronize cellular TTFLs, creating a spatiotemporal wave of gene expression across the SCN that is lost in Cry1/2-deficient SCN. To interrogate the properties of CRY proteins required for circadian function, we expressed CRY in SCN of Cry-deficient mice using adeno-associated virus (AAV). Expression of CRY1::EGFP or CRY2:: EGFP under a minimal Cry1 promoter was circadian and rapidly induced PER2-dependent bioluminescence rhythms in previously arrhythmic Cry1/2-deficient SCN, with periods appropriate to each isoform. CRY1::EGFP appropriately lengthened the behavioral period in Cry1-deficient mice. Thus, determination of specific circadian periods reflects properties of the respective proteins, independently of their phase of expression. Phase of CRY1::EGFP expression was critical, however, because constitutive or phase-delayed promoters failed to sustain coherent rhythms. At the circuit level, CRY1::EGFP induced the spatiotemporal wave of PER2 expression in Cry1/2-deficient SCN. This was dependent on the neuropeptide arginine vasopressin (AVP) because it was prevented by pharmacological blockade of AVP receptors. Thus, our genetic complementation assay reveals acute, protein-specific induction of cell-autonomous and network-level circadian rhythmicity in SCN never previously exposed to CRY. Specifically, Cry expression must be circadian and appropriately phased to support rhythms, and AVP receptor signaling is required to impose circuit-level circadian function.he suprachiasmatic nucleus (SCN) is a precise biological clock that coordinates circadian (∼24 h) rhythms in mammals. Composed of ∼10,000 neurons, the SCN sits atop the optic chiasm, through which it receives retinal innervation that entrains its cellular clockwork to the light/dark cycle. In turn, the SCN entrains peripheral circadian clocks distributed across the organism through neural pathways incorporating neuropeptidergic and GABA-ergic signaling (1). At the molecular level, circadian timing in SCN neurons revolves around transcriptional/posttranslational feedback loops (TTFL), in which the positive components BMAL1 and CLOCK activate E/E′-box-mediated transcription of the negative components Period (Per1, Per2) and Cryptochrome (Cry1, Cry2). PER/CRY heterodimers then inhibit BMAL1/CLOCK activity and thus prevent their own transcription. Subsequent proteasomal degradation of PER and CRY proteins relieves this inhibition, allowing the molecular cycle to begin again. Genetic studies have established that CRY1 and CRY2 are essential for behavioral and molecular circadian rhythmicity, acting as core components of th...

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Vasopressin receptor V1a regulates circadian rhythms of locomotor activity and expression of clock-controlled genes in the suprachiasmatic nuclei

Cited by 112 publications

References 42 publications

Vasopressin V1a Receptor Polymorphism and Interval Walking Training Effects in Middle-Aged and Older People

Vasopressin V1a Receptor Polymorphism and Interval Walking Training Effects in Middle-Aged and Older People

A diversity of paracrine signals sustains molecular circadian cycling in suprachiasmatic nucleus circuits

Rhythmic expression of cryptochrome induces the circadian clock of arrhythmic suprachiasmatic nuclei through arginine vasopressin signaling

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