Bonmatí Carrión, María de los Ángeles

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Bonmatí Carrión, María de los Ángeles

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Anatomía Humana y Psicobiología

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Open Access
Melatonin as a mediator of the gut microbiota–host interaction: implications for health and disease
(MDPI, 2023-12-23) Rol de Lama, María de los Ángeles; Bonmatí Carrión, María de los Ángeles; Fisiología
In recent years, the role played by melatonin on the gut microbiota has gained increasingly greater attention. Additionally, the gut microbiota has been proposed as an alternative source of melatonin, suggesting that this antioxidant indoleamine could act as a sort of messenger between the gut microbiota and the host. This review analyses the available scientific literature about possible mechanisms involved in this mediating role, highlighting its antioxidant effects and influence on this interaction. In addition, we also review the available knowledge on the effects of melatonin on gut microbiota composition, as well as its ability to alleviate dysbiosis related to sleep deprivation or chronodisruptive conditions. The melatonin–gut microbiota relationship has also been discussed in terms of its role in the development of different disorders, from inflammatory or metabolic disorders to psychiatric and neurological conditions, also considering oxidative stress and the reactive oxygen species-scavenging properties of melatonin as the main factors mediating this relationship.
Open Access
The interplay among sleep patterns, social habits, and environmental cues: insights from the Spanish population and implications for aligning daily rhythms
(Frontiers Media, 2024-10-25) Vicente Martínez, Jesús; Madrid, Juan Antonio; Rol de Lama, María de los Ángeles; Bonmatí Carrión, María de los Ángeles; Fisiología
Introduction: The interplay among sleep patterns, social habits and environmental cues is becoming increasingly more important for public health and wellbeing due to its connection to circadian desynchronization. This paper explores said connections in Spain (which has an official and solar time mismatch), introducing the “Three Times Score” ‒which is based on questions widely used in the field‒ as a complementary tool for exploring the interplay of daily rhythms. Methods: The questionnaire covers sleep-related habits, social time, and environmental time. The study includes 9,947 participants (34.89 ± 12.15 y/o, mean ± SD; 5,561 women) from different Spanish regions. Sleep parameters were obtained for work and free days, as well as a modified version of the sleep-corrected midsleep on free days (MBFbc) and a parameter similar to social jet lag, both derived from bed time rather than sleep time. A number of indexes were computed to compare bed and work-related habits, together with natural light/dark cycle, along with the Three Times Score. Mixed-effect regression analysis was used to test whether the biological, social and environmental factors included in the study significantly predicted the sleep-related parameters: bedtime, wake-up time, time in bed and mid-bedtime. Results and discussion: Temporal differences were found between work and free days, with waking-up occurring 2 h earlier on work days (7:10 ± 0:01) than on free days (9:15 ± 0:01). Bed times were 1 h earlier on work days (23:46 ± 0:01) than on free days (00:45 ± 0:01), whereas time in bed was over 1 h shorter on work (7 h 23 min) versus free (8 h 29 min) days. Strong correlations were found between work starting time and waking-up and bedtimes on workdays. Women went to bed earlier and woke up later, spending more time in bed. Differences in sleep habits were observed between work and free days across all age groups. The group of younger adults (18–30) reported going to bed later than older and younger groups, especially on free days. Adolescents and young adults also woke-up later than other age groups, especially on free days. Social jet lag (relative to bed time) and desynchronization indexes also varied with age, with younger adult participants exhibiting higher levels. Seasonal differences were limited, with minor variations between winter and summer. According to the multiple regression analysis, social (day type, work start time, alarm clock usage), biological (age, gender, in most cases related to sex) and environmental (sunset time) factors significantly contribute to predicting sleep/bed related schedules. This study provides insights into sleep habits in the Spanish population, introducing the Three Times Score as a complementary tool for exploring the interactions between sleep/bed-related habits, natural darkness and work-related schedules. Understanding this interplay is crucial for developing tailored interventions to improve sleep and wellbeing.
Open Access
Effect of 60 days of head down tilt bed rest on amplitude and phase of rhythms in physiology and sleep in men
(Nature Research, 2024-03-29) Santhi, Nayantara; Atzori, Giuseppe; Mendis, Jeewaka; Kaduk, Sylwia; Dijk, Derk-Jan; Archer, Simon N.; Bonmatí Carrión, María de los Ángeles; Anatomía Humana y Psicobiología
Twenty-four-hour rhythms in physiology and behaviour are shaped by circadian clocks, environmental rhythms, and feedback of behavioural rhythms onto physiology. In space, 24 h signals such as those associated with the light-dark cycle and changes in posture, are weaker, potentially reducing the robustness of rhythms. Head down tilt (HDT) bed rest is commonly used to simulate effects of microgravity but how HDT affects rhythms in physiology has not been extensively investigated. Here we report effects of −6° HDT during a 90-day protocol on 24 h rhythmicity in 20 men. During HDT, amplitude of light, motor activity, and wrist-temperature rhythms were reduced, evening melatonin was elevated, while cortisol was not affected during HDT, but was higher in the morning during recovery when compared to last session of HDT. During recovery from HDT, time in Slow-Wave Sleep increased. EEG activity in alpha and beta frequencies increased during NREM and REM sleep. These results highlight the profound effects of head-down-tilt-bed-rest on 24 h rhythmicity.
Open Access
Light color importance for circadian entrainment in a diurnal (Octodon degus) and a nocturnal (Rattus norvegicus) rodent
(Nature Research, 2017-08-18) Baño Otalora, Beatriz; Madrid, Juan Antonio; Rol, María Ángeles; Bonmatí Carrión, María de los Ángeles; Anatomía Humana y Psicobiología
The central circadian pacemaker (Suprachiasmatic Nuclei, SCN) maintains the phase relationship with the external world thanks to the light/dark cycle. Light intensity, spectra, and timing are important for SCN synchronisation. Exposure to blue-light at night leads to circadian misalignment that could be avoided by using less circadian-disruptive wavelengths. This study tests the capacity of a diurnal Octodon degus and nocturnal Rattus norvegicus to synchronise to different nocturnal lights. Animals were subjected to combined red-green-blue lights (RGB) during the day and to: darkness; red light (R); combined red-green LED (RG) lights; and combined red-green-violet LED (RGV) lights during the night. Activity rhythms free-ran in rats under a RGB:RG cycle and became arrhythmic under RGB:RGV. Degus remained synchronised, despite the fact that day and night-time lighting systems differed only in spectra, but not in intensity. For degus SCN c-Fos activation by light was stronger with RGB-light than with RGV. This could be relevant for developing lighting that reduces the disruptive effects of nocturnal light in humans, without compromising chromaticity.
Open Access
Evening types as determined by subjective and objective measures are more emotional eaters
(Wiley, 2023-04-26) Garaulet, Marta; Vizmanos, Barbara; Muela, Teresa; Betancourt-Núñez, Alejandra; Vetter, Céline; Dashti, Hassan S.; Saxena, Richa; Scheer, Frank A. J. L.; Bonmatí Carrión, María de los Ángeles; Anatomía Humana y Psicobiología
Objective This study aimed to determine the association between being an evening type (ET; defined subjectively by the Morning-Evening Questionnaire or objectively by the dim-light melatonin onset [DLMO] timing) and reporting emotional eating (EE) behaviors. Methods Cross-sectional analyses were conducted in 3964 participants (four international cohorts: ONTIME and ONTIME-MT [both Spain], SHIFT [the US], and DICACEM [Mexico]), in which chronotype (Morning-Evening Questionnaire), EE behaviors (Emotional Eating Questionnaire), and dietary habits (dietary records or food-frequency questionnaire) were assessed. Among 162 participants (ONTIME-MT subsample), additional measures of DLMO (physiological gold standard of circadian phase) were available. Results In three populations, ETs presented with a higher EE score than morning types (p < 0.02); and they made up a higher proportion of emotional eaters (p < 0.01). ETs presented with higher scores on disinhibition/overeating as well as food craving factors and experienced these behaviors more frequently than morning types (p < 0.05). Furthermore, a meta-analysis showed that being an ET was associated with a higher EE score by 1.52 points of a total of 30 points (95% CI: 0.89–2.14). The timing of DLMO in the early, intermediate, and late objective chronotypes occurred at 21:02 h, 22:12 h, and 23:37 h, with late types showing a higher EE score (p = 0.043). Conclusions Eveningness associated with EE in populations with different cultural, environmental, and genetic backgrounds. Individuals with late DLMO also showed more EE.
Open Access
Evaluación de la fase circadiana mediante monitorización ambulatoria en humanos: correlación con el dim light melatonin onset
(2020-04-14) Rol de Lama, María de los Ángeles; Madrid, Juan Antonio; Bonmatí Carrión, María de los Ángeles; Facultades, Departamentos, Servicios y Escuelas::Departamentos de la UMU::Fisiología
RESUMEN Es fundamental desarrollar un sistema que detecte la fase endógena de forma sencilla, ya que las actuales técnicas implican cuantificación de melatonina o monitorización de temperatura central mediante sondas rectales. En este trabajo se validó un sistema de registro ambulatorio. Las variables monitorizadas, durante 10 días en 13 sujetos, fueron temperatura periférica, mediante un sensor en la muñeca; actividad y posición, utilizando un actímetro en el brazo; y luz, mediante un sensor colgado alrededor del cuello. Se obtuvo el marcador de fase estándar dim light melatonin onset (DLMO) en saliva para evaluar la precisión de las demás variables. Además, rellenaron un diario de sueño que evaluó la probabilidad de sueño y los cuestionarios de matutinidad-vespertinidad (Horne-Östberg), de calidad de sueño (Pittsburgh) y de somnolencia (Epworth) para evaluar la preferencia diurna y su influencia en la calidad del sueño. El aumento vespertino de la temperatura periférica se produjo con anterioridad a la elevación de melatonina; el descenso en la actividad, la posición, la variable compuesta TAP, y el aumento en la probabilidad de sueño, con posterioridad al incremento de melatonina. Las puntuaciones de los cuestionarios de matutinidad-vespertinidad y calidad del sueño mostraron alta correlación con el DLMO, confirmando que DLMO tardíos implican mayor vespertinidad y peor calidad del sueño. Este método permite detectar de manera precisa la fase del sistema circadiano sin modificar los hábitos de vida. Los nuevos marcadores de fase propuestos basados en el ritmo de temperatura periférica (WTOn and WTiO) serían adecuados en ámbitos clínicos en los que es fundamental conocer la fase circadiana del sujeto, como en la cronoterapia del cáncer y en la luminoterapia.
Open Access
Assessing Chronotypes by Ambulatory Circadian Monitoring
(Frontiers Media, 2019-11-20) Martinez-Nicolas, A; Martinez-Madrid, M J; Almaida Pagán, Pedro Francisco; Madrid, Juan A; Rol, M A; Bonmatí Carrión, María de los Ángeles; Fisiología; Chronobiology Lab, Department of Physiology, College of Biology, University of Murcia, Mare Nostrum Campus, IUIE, IMIB-Arrixaca, Murcia, Spain; Ciber Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain
In order to develop objective indexes for chronotype identification by means of direct measurement of circadian rhythms, 159 undergraduate students were recruited as volunteers and instructed to wear ambulatory circadian monitoring (ACM) sensors that continuously gathered information on the individual’s environmental light and temperature exposure, wrist temperature, body position, activity, and the integrated TAP (temperature, activity, and position) variable for 7 consecutive days under regular freeliving conditions. Among all the proposed indexes, the night phase marker (NPM) of the TAP variable was the best suited to discriminate among chronotypes, due to its relationship with the Munich ChronoType Questionnaire (b = 0.531; p < 0.001). The NPM of TAP allowed subjects to be classified as early- (E-type, 20%), neither- (N-type, 60%), and late-types (L-type, 20%), each of which had its own characteristics. In terms of light exposure, while all subjects had short exposure times to bright light (>100 lux), with a daily average of 93.84 5.72 min, the earlier chronotypes were exposed to brighter days and darker nights compared to the later chronotypes. Furthermore, the earlier chronotypes were associated with higher stability and day–night contrast, along with an earlier phase, which could be the cause or consequence of the light exposure habits. Overall, these data support the use of ACM for chronotype identification and for evaluation under free living conditions, using objective markers.
Open Access
Prevention of chronodisruption through circadian friendly lighting obtained by spectral modulation = Prevención de la cronodisrupción mediante iluminación circadiana saludable obtenida por modulación espectral
(2015-10-28) Bonmatí Carrión, María de los Ángeles; Madrid Pérez, Juan Antonio; Rol de Lama, María de los Ángeles; Facultad de Medicina
OBJETIVOS Desarrollar luz nocturnal respetuosa con el sistema circadiano, explorando los efectos no visuales de la luz, validando la metodología para evaluar cronodisrupción. Objetivos específicos: 1. Investigar efecto antiproliferativo de la melatonina en un amplio rango de concentraciones en melanoma y fibroblastos 2. Validar sistema de monitorización circadiana ambulatoria, proponeiendo un nuevo marcador de fase equivalente al DLMO. 3. Determinar la utilidad de la pupilometría para evaluar el efecto de la luz sobre el sistema circadiano y su posible relación con los ritmos de salida de este sistema. 4. Evaluar los efectos cronobiológicos de una luz nocturna, basada en tecnología LED, en la que se reemplaza la parte azul del espectro por longitudes de onda más cortas en un animal diurno (Octodon degus) y uno nocturno (Rattus norvegicus). METODOLOGÍA - Monitorización circadiana ambulatoria y análisis circadiano - Cuantificación de melatonina - Pupilometría - Monitorización actividad de rueda en modelos animales - Inmunohistoquímica CONCLUSIONES 1. La melatonina, a bajas concentraciones tuvo un efecto antiproliferativo sobre una línea celular de melanoma murino, mientras que protegió la viabilidad en el caso de los fibroblastos, no tumorales. Sin embargo, a altas concentraciones, tuvo mayor efecto antiproliferativo en la línea no tumoral. El mecanismo de acción, a altas concentraciones de melatonina, podría estar mediado por el incremento de ROS intracelular. 2. El método alternativo de actimetría (AA) desarrollado puede utilizarse para evaluar también la fase circadiana. La monitorización circadiana ambulatoria que integra este método alternativo de actimetría (que permite evaluar también la postura corporal), junto con el ritmo de temperatura de la muñeca y el patrón de exposición a la luz, constituye un buen método para evaluar el estado del sistema circadiano. 3. Se ha comprobado la utilidad del software desarrollado, PupiLabWare®, para procesar y analizar los datos obtenidos de pupilometría, registrándolo como propiedad intelectual. 4. La respuesta pupilar transitoria y sostenida son más intensas con las longitudes de onda de 460 a 490 nm, y con mayores flujos fotónicos. La sustitución de la luz azul por violeta debería, por tanto, considerarse para el diseño de nuevas fuentes de luz de uso nocturno. 5. La pupilometría constituye una técnica adecuada para predecir el estatus del sistema circadiano y la potencial eficacia de la luminoterapia, ya que la contracción pupilar en respuesta a luces monocromáticas de alrededor de 460 nm es mayor en aquellos sujetos con disrupción circadiana, evaluada a partir de los patrones de temperatura de la piel de la muñeca, actividad motora y exposición de la luz. 6. Una luz nocturna, obtenida reemplazando la parte azul del espectro por violeta (longitud de onda más corta) puede preservar el patrón de actividad diurna en un animal diurno (Octodon degus), pero no el patrón propio de un animal nocturno (Rattus norvegicus), indicando que este tipo de luz nocturna constituye una posible alternativa para su utilización por humanos, minimizando los efectos cronodisruptores de la luz durante la noche. CONCLUSIÓN GENERAL La cronodisrupción se puede medir fácilmente en humanos, con un bajo coste económico y de manera poco invasiva, utilizando un sistema de monitorización circadiana ambulatoria basada en la temperatura de la muñeca, la actividad motora, la postura corporal y la exposición a la luz, mientras que la pupilometría, como tal, constituye una herramienta útil a la hora de evaluar la calidad de la luz como sincronizadora del sistema circadiano. Una luz nocturna en la que se reemplace la parte azul del espectro por longitudes de onda más cortas sería útil para preservar la cromaticidad, evitando los efectos cronodisruptores de la luz azul durante la noche. This thesis aims to develop a circadian friendly nocturnal light, through exploring non-visual effects of light, validating the necessary methodology to assess chronodisruption in humans. In order to pursue this final goal, the following specific objectives were established: 1. To confirm melatonin antiproliferative effect is also present under a wide range of concentrations tumor and non-tumor cell lines, clarifying its possible mechanism of action. 2. To validate a recent ambulatory circadian monitoring (ACM) system finding a DLMO-equivalent new phase marker. 3. To assess the usefulness of pupillometry for evaluating light circadian power and its possible relation with several circadian system outputs. 4. To evaluate the chronobiological effects on the diurnal Octodon degus and nocturnal Rattus norvegicus of a LED-based nocturnal light consisting of replacing the blue part of the spectrum with shorter wavelengths. METHODOLOGY - Ambulatory circadian monitoring and circadian analysis - Melatonin quantification - Pupillometry - Wheel running activity monitorization in animal models - Immunohystochemistry SPECIFIC CONCLUSIONS 1. Melatonin at low concentrations showed selective antiproliferative effects in tumor murine melanoma cell line, while protecting non-tumor murine fibroblast viability. However, at high concentrations, it produces more marked deleterious effects on non-tumor than in tumor cell line. A possible action mechanism points to the increase of intracellular ROS under high melatonin concentrations. 2. The alternative actigraphy method (AA), can also serve to assess also circadian phase since it presents a higher agreement rate and sensitivity for detecting sleep compared to the classical actigraphy method based on wrist acceleration detection and good correlation with the gold standard phase marker, the DLMO. The ambulatory circadian monitoring integrating this alternative actigraphy method which permits evaluate body position, together with wrist temperature, and light exposure, results in a good method to evaluate the circadian system status. 3. The usefulness of the developed software Pupilabware (R) to process and analyse pupillometry data has been proven and inconsequence, it has been registered in the copyright office. 4. Both transient and sustained pupillary light responses are more marked with wavelengths from 460 to 490 nm and with increasing photon fluxes. Total or partial substitution of blue by purple should be considered in the design of new nocturnal light sources. 5. Pupillometry constitutes a suitable technique to predict the circadian system status and the potential efficacy of light therapy since higher pupilar constriction in response to monochromatic blue lights around 460 nm is found when circadian disruption, assessed by wrist skin temperature, motor activity and light exposure patterns, is present. 6. A nocturnal light, obtained by replacing the blue part of the spectrum by violet (shorter wavelength) has proven to preserve the diurnal pattern in a diurnal animal (Octodon degus), while failing to maintain the circadian pattern in the a commonly used nocturnal rodent model (Rattus norvegicus), indicating that this kind of nocturnal light could constitute a circadian friendly light to be used by humans minimizing the chronodisruptive effects of light at night . GENERAL CONCLUSION Chronodisruption can be easy, inexpensive and unobtrusively measured in humans, using an ambulatory monitoring system based on wrist temperature, motor activity (based in tilt changes), body position and light exposure, while pupillometry, by its own, constitutes a useful tool to evaluate the quality of light as a circadian input. A nocturnal light consisting of replacing the blue part of the spectrum with shorter wavelengths would be able to preserve chromaticity while avoiding chronodisruptive effects of blue light during the night.
Open Access
Living at the wrong time: effects of unmatching official time in Portugal and western Spain
(MDPI, 2022-07-28) Casado Ramírez, Elvira; Moreno Casbas, María Teresa; Campos Martínez, Manuel; ModulEN Consortium; Madrid, Juan Antonio; Rol de Lama, María de los Ángeles; Bonmatí Carrión, María de los Ángeles; Fisiología
Human circadian rhythmicity is subjected to the internal circadian clock, the sun and social clocks (official time, social/work schedules). The discrepancy among these clocks, as occurs when official time does not match its geographical time zone, may produce circadian disruption. Western Spain (GMT+1/+2) and Portugal (GMT0/+1) share similar longitudes (sun time) but have different official times. This provides a unique opportunity to evaluate the effects of official time on circadian rhythmicity and sleep in elderly and retired populations (with no remunerated duties presumed, although other social commitments may be present) at both locations. Although both populations slept enough for their age (7–8 h), circadian robustness (e.g., interdaily stability, relative amplitude) was greater in Portugal, especially during weekdays, while greater desynchronization (both body temperature vs. motor activity and body temperature vs. light exposure) tended to occur in the Spaniards. Once corrected by GMT0, meals took place later in Spain than in Portugal, especially as the day progresses, and a possible interplay between bed/meal timings and internal desynchronization was found. Our results point to the possible deleterious effect on circadian system robustness when official time is misaligned with its geographical time zone.
Open Access
Extensive dynamic changes in the human transcriptome and its circadian organization during prolonged bed rest
(Cell Press, 2024-03-15) Archer, Simon N.; Möller-Levet, Carla; Laing, Emma E.; Derk-Jan, Dijk; Bonmatí Carrión, María de los Ángeles; Anatomía Humana y Psicobiología
Physiological and molecular processes including the transcriptome change across the 24-h day, driven by molecular circadian clocks and behavioral and systemic factors. It is not known how the temporal organization of the human transcriptome responds to a long-lasting challenge. This may, however, provide insights into adaptation, disease, and recovery. We investigated the human 24-h time series transcriptome in 20 individuals during a 90-day constant bed rest protocol. We show that the protocol affected 91% of the transcriptome with 76% of the transcriptome still affected after 10 days of recovery. Dimensionality-reduction approaches revealed that many affected transcripts were associated with mRNA translation and immune function. The number, amplitude, and phase of rhythmic transcripts, including clock genes, varied significantly across the challenge. These findings of long-lasting changes in the temporal organization of the transcriptome have implications for understanding the mechanisms underlying health consequences of conditions such as microgravity and bed rest.