bims-ciryme 2025-11-02 papers

Proc Natl Acad Sci U S A. 2025 Nov 04. 122(44): e2506164122

A functional clock in only two dorsal clock neurons is sufficient to restore the basal circadian activity pattern of Drosophila melanogaster.

Nils Reinhard, Enrico Bertolini, Takuya Kuwahara, Manabu Sekiguchi, Dirk Rieger, Weihua Li, Paul H Taghert, Taishi Yoshii, Charlotte Helfrich-Förster.

Circadian clocks form complex networks to orchestrate the behavior and physiology of animals. Elucidating the organization of these clock networks is critical to understanding how circadian clocks achieve robust timing. Clock neurons have been best characterized in the model organism Drosophila melanogaster. At the early stages of development, Drosophila has a clock network consisting of only nine neurons per hemisphere. This set of clock neurons consists of lateral and dorsal neurons and persists in the adult fly, in which the clock network is greatly expanded to a total of ~240 neurons. The function of the early-born lateral clock neurons is well established in the adult fly. They control morning and evening activity and are responsible for circadian rhythmicity under constant conditions. Only recent studies have begun to dissect the function of the dorsal clock neurons. Using clock rescue experiments, we show here that a functional clock in only four of them, the DN1a, is sufficient to restore a bimodal locomotor activity pattern and rhythmic activity under constant conditions in the adult fly. This is achieved by CCHamide-1 signaling most likely to the lateral morning neurons, which are considered the main pacemakers of the clock, and by glutamate signaling to the lateral evening neurons. Interestingly, all the neurons involved are part of the early-born clock network, strongly suggesting that a core clock is already formed during early development. This set of clock neurons appears sufficient in the adult fly to drive the basal circadian activity pattern.

Keywords: Drosophila; circadian rhythm; dorsal neurons; neuropeptides; period

DOI: https://doi.org/10.1073/pnas.2506164122

Cell Rep. 2025 Oct 28. pii: S2211-1247(25)01255-0. [Epub ahead of print]44(11): 116484

Circadian clock control of ribosome composition promotes rhythmic translation and termination fidelity.

Teresa M Lamb, Kathrina D Castillo, Rachel Porter, Cheng Wu, Samuel O Purvine, Griffin Best, Erika Zink, Ebimobowei O Preh, Lunda Shen, Matthew S Sachs, Deborah Bell-Pedersen.

Ribosome composition is dynamic, shifting with cell state and stress, but whether it varies with circadian time is unknown. Here, we uncover circadian clock-driven changes in ribosome composition in Neurospora crassa. Mass spectrometry of ribosomes across circadian time identified six ribosomal proteins and one associated factor under clock control. Rhythms in eL31 abundance were validated in purified ribosomes, and deletion of el31 disrupted translation rhythms in nearly half of rhythmically translated mRNAs. N. crassa eL31 promotes circadian control of translation termination and impacts elongation fidelity while maintaining Mg homeostasis, a key determinant of translational accuracy. These findings reveal that the circadian clock reprograms ribosome composition to orchestrate rhythmic translation and fidelity, temporally expanding the proteome beyond the static genome to align cellular function with time of day.

Keywords: CP: Molecular biology; Zuotin; circadian clock; eL31; magnesium ion homeostasis; ribosome composition; translation; translation fidelity

DOI: https://doi.org/10.1016/j.celrep.2025.116484

Pflugers Arch. 2025 Oct 30.

Circadian adaptations to regular treadmill exercise alter temporal changes in dopamine and serotonin activity in brain areas.

Frederico Sander Mansur Machado, Nayara Abreu Coelho Horta, Quezia Teixeira Rodrigues, Thais Santana Rocha Cardoso, Nayara Soares Sena Aquino, Raphael Escorsim Szawka, Maristela Oliveira Poletini, Cândido Celso Coimbra.

The beneficial effects of regular exercise may be mediated through its regulatory influence on circadian rhythm. Here, we investigated how regular exercise training affects spontaneous locomotor activity (SLA) and body temperature (T-body) rhythms and its influence on temporal changes in brain dopaminergic and serotonergic activity, corticosterone levels, and muscle Per1 and Bmal1 gene expression. The aerobic exercise schedule consisted of five days of training in the light phase (Zeitgeber time = ZT4 to ZT6, with light on at 7:00 h) followed by a two-day recovery period. After 8 weeks, brain, blood, and muscle samples were collected from adult male rats. Dopamine (DA) and serotonin (5-HT) and their respective metabolites, DOPAC and 5-HIAA, were measured in microdissections of the caudate putamen (CP), preoptic area (POA), and the paraventricular nucleus of the hypothalamus (PVN). Exercise increased the SLA at the end of the night, delayed the acrophase, and increased the mesor of the SLA rhythm. No alterations were found in the T-body rhythm and corticosterone blood levels, although hyperthermia was observed after exercise sessions. Exercise increased muscle Per1 expression at ZT0, leading to a non-rhythmic profile in exercised animals. There were no changes in the CP dopaminergic and serotonergic activity, but there was a decrease in POA at ZT6 and an increase in PVN serotonergic activity at ZT0, resulting in a non-rhythmic profile in exercised animals. Thus, regular physical exercise during the light phase with alterations in SLA promotes adjustments in the daily oscillation in monoaminergic activity in areas directly involved in regulating daily T-body and SLA.

Keywords: Circadian; Dopamine; Entrainment; Locomotor activity; Physical activity; Serotonin; Thermoregulation

DOI: https://doi.org/10.1007/s00424-025-03128-x

Sci Transl Med. 2025 Oct 29. 17(822): eadv6787

Intended isocaloric time-restricted eating shifts circadian clocks but does not improve cardiometabolic health in women with overweight.

Beeke Peters, Julia Schwarz, Bettina Schuppelius, Agnieszka Ottawa, Daniela A Koppold, Daniela Weber, Nico Steckhan, Knut Mai, Tilman Grune, Andreas F H Pfeiffer, Andreas Michalsen, Achim Kramer, Olga Pivovarova-Ramich.

Time-restricted eating (TRE) is a promising strategy to improve metabolic outcomes. However, it remains unclear whether TRE has cardiometabolic benefits in an isocaloric setting and whether its effects depend on the eating timing. We conducted a randomized crossover trial in 31 women with overweight or obesity to directly compare the effects of a 2-week early TRE (eTRE; eating from 8:00 to 16:00) and a 2-week late TRE (lTRE; eating from 13:00 to 21:00) on insulin sensitivity, cardiometabolic risk factors, and the internal circadian phase. During the restricted 8-hour eating period, participants were asked to consume their habitual food quality and quantity. Insulin sensitivity did not differ between (-0.07; 95% CI, -0.77 to 0.62; P = 0.60) or within (eTRE: 0.31; 95% CI, -0.14 to 0.76; P = 0.11; lTRE: 0.19; 95% CI, -0.22 to 0.60; P = 0.25) interventions. Twenty-four-hour glucose, lipid, inflammatory, and oxidative stress markers showed no clinically meaningful between- or within-intervention differences. Participants demonstrated high timely adherence (eTRE, 96.5%; lTRE, 97.7%), unchanged dietary composition and physical activity, minor daily calorie deficit (eTRE, -167 kilocalories/day), and weight loss (eTRE, -1.08 kilograms; lTRE, -0.44 kilograms). In lTRE, the circadian phase in blood monocytes (24 minutes; 95% CI, -5 to 54 minutes; P = 0.10) and sleep midpoint (15 minutes; 95% CI, 7 to 23 minutes; P < 0.001) occurred later compared with eTRE. Overall, in an intended isocaloric setting, neither eTRE nor lTRE improves insulin sensitivity or other cardiometabolic traits, despite a shift of internal circadian clocks.

DOI: https://doi.org/10.1126/scitranslmed.adv6787