Effects of Nocturnal Light on (Clock) Gene Expression in Peripheral Organs: A Role for the Autonomic Innervation of the Liver

BACKGROUND:The biological clock, located in the hypothalamic suprachiasmatic nucleus (SCN), controls the daily rhythms in physiology and behavior. Early studies demonstrated that light exposure not only affects the phase of the SCN but also the functional activity of peripheral organs. More recently it was shown that the same light stimulus induces immediate changes in clock gene expression in the pineal and adrenal, suggesting a role of peripheral clocks in the organ-specific output. In the present study, we further investigated the immediate effect of nocturnal light exposure on clock genes and metabolism-related genes in different organs of the rat. In addition, we investigated the role of the autonomic nervous system as a possible output pathway of the SCN to modify the activity of the liver after light exposure. METHODOLOGY AND PRINCIPAL FINDINGS:First, we demonstrated that light, applied at different circadian times, affects clock gene expression in a different manner, depending on the time of day and the organ. However, the changes in clock gene expression did not correlate in a consistent manner with those of the output genes (i.e., genes involved in the functional output of an organ). Then, by selectively removing the autonomic innervation to the liver, we demonstrated that light affects liver gene expression not only via the hormonal pathway but also via the autonomic input. CONCLUSION:Nocturnal light immediately affects peripheral clock gene expression but without a clear correlation with organ-specific output genes, raising the question whether the peripheral clock plays a "decisive" role in the immediate (functional) response of an organ to nocturnal light exposure. Interestingly, the autonomic innervation of the liver is essential to transmit the light information from the SCN, indicating that the autonomic nervous system is an important gateway for the SCN to cause an immediate resetting of peripheral physiology after phase-shift inducing light exposures

Les noyaux suprachiasmatiques organisent la physiologie journalière,Rôle du système nerveux autonome et des gènes horloges périphériques

Le maintien de la concentration en glucose à l'intérieur de limites strictes en dépit des contraintes extérieures est important pour le bon fonctionnement de l'organisme. L'efficacité du maintien de l'homéostasie repose également sur la capacité de l'organisme à anticiper les variations extérieures. Les noyaux suprachiasmatiques NSC (ou l'horloge biologique), localisées dans l'hypothalamus, joue un role essentiel dans ces phénomènes d'anticipation. Dans notre travail, nous nous sommes principalement attaché à répondre à la question de savoir comment l'horloge circadienne contrôlait/régulait l'homéostasie du glucose, avec un intérêt particulier sur le rôle du système nerveux autonome. Notre hypothèse était que le message journalier délivré par l'horloge est intégrée par les oscillateurs, localisés dans les organes périphériques (foie), afin de synchroniser la fonctionnalité de chaque organe avec le cycle jour/nuit (homéostasie du glucose).Pas de résum

Les noyaux suprachiasmatiques organisent la physiologie journalière,Rôle du système nerveux autonome et des gènes horloges périphériques

Le maintien de la concentration en glucose à l'intérieur de limites strictes en dépit des contraintes extérieures est important pour le bon fonctionnement de l'organisme. L'efficacité du maintien de l'homéostasie repose également sur la capacité de l'orgaPas de résum

Les noyaux suprachiasmatiques organisent la physiologie journalière (Rôle du système nerveux autonome et des gènes horloges périphériques)

Le maintien de la concentration en glucose à l'intérieur de limites strictes en dépit des contraintes extérieures est important pour le bon fonctionnement de l organisme. L efficacité du maintien de l homéostasie repose également sur la capacité de l organisme à anticiper les variations extérieures. Les noyaux suprachiasmatiques NSC (ou l horloge biologique), localisées dans l hypothalamus, joue un role essentiel dans ces phénomènes d anticipation. Dans notre travail, nous nous sommes principalement attaché à répondre à la question de savoir comment l horloge circadienne contrôlait/régulait l homéostasie du glucose, avec un intérêt particulier sur le rôle du système nerveux autonome. Notre hypothèse était que le message journalier délivré par l horloge est intégrée par les oscillateurs, localisés dans les organes périphériques (foie), afin de synchroniser la fonctionnalité de chaque organe avec le cycle jour/nuit (homéostasie du glucose).STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceNetherlandsFRN

Cholinergic signalling in gut immunity

The gut immune system shares many signalling molecules and receptors with the autonomic nervous system. A good example is the vagal neurotransmitter acetylcholine (ACh), for which many immune cell types express cholinergic receptors (AChR). In the last decade the vagal nerve has emerged as an integral part of an immune regulation network via its release of ACh; a system coined "the cholinergic anti-inflammatory reflex". The perspective of cholinergic immune regulation in the gut mucosa has been widened by the recent discovery of populations of ACh producing immune cells in the spleen and other organs. As such, ACh, classically referred to as neurotransmitter, may serve a much broader function as bi-directional signalling molecule between neurons and non-neuronal cell types of the immune system. (C) 2012 Elsevier Inc. All rights reserve

Peripheral oscillators: the driving force for food-anticipatory activity

Food-anticipatory activity (FAA) and especially the food-entrained oscillator (FEO) have driven many scientists to seek their mechanisms and locations. Starting our research on FAA we, possibly like many other scientists, were convinced that clock genes held the key to the location and the underlying mechanisms for FAA. In this review, which is aimed especially at discussing the contribution of the peripheral oscillators, we have put together the accumulating evidence that the clock gene machinery as we know it today is not sufficient to explain food entrainment. We discuss the contribution of three types of oscillating processes: (i) within the suprachiasmatic nucleus (SCN), neurons capable of maintaining a 24-h oscillation in electrical activity driven by a set of clock genes; (ii) oscillations in metabolic genes and clock genes in other parts of the brain and in peripheral organs driven by the SCN or by food, which damp out after a few cycles; (iii) an FEO which, we propose, is a system built up of different oscillatory processes and consisting of an as-yet-unidentified network of central and peripheral structures. In view of the evidence that clock genes and metabolic oscillations are not essential for the persistence of FAA we propose that food entrainment is initiated by a repeated metabolic state of scarcity that drives an oscillating network of brain nuclei in interaction with peripheral oscillators. This complex may constitute the proposed FEO and is distributed in our peripheral organs as well as within the central nervous syste

Differential Involvement of the Suprachiasmatic Nucleus in Lipopolysaccharide-Induced Plasma Glucose and Corticosterone Responses

The hypothalamic suprachiasmatic nucleus (SCN) is an essential component of the circadian timing system, and an important determinant of neuroendocrine and metabolic regulation. Recent data indicate a modulatory role for the immune system on the circadian timing system. The authors investigated how the circadian timing system affects the hypothalamo-pituitary-adrenal (HPA) axis and glucose regulatory responses evoked by an immune challenge induced by lipopolysaccharide (LPS). LPS-induced increases in corticosterone were minimal during the trough of the daily corticosterone rhythm; in contrast, LPS effects on glucose, glucagon, and insulin did not vary across time-of-day. Complete ablation of the SCN resulted in increased corticosterone responses but did not affect LPS-induced hyperglycemia. The paraventricular nucleus (PVN) of the hypothalamus is an important neuroendocrine and autonomic output pathway for hypothalamic information, as well as one of the main target areas of the SCN. Silencing the neuronal activity in the PVN did not affect the LPS-induced corticosterone surge and only slightly delayed the LPS-induced plasma glucose and glucagon responses. Finally, surgical interruption of the neuronal connection between hypothalamus and liver did not affect the corticosterone response but slightly delayed the LPS-induced glucose response. Together, these data support the previously proposed circadian modulation of LPS-induced neuroendocrine responses, but they are at variance with the suggested major role for the hypothalamic pacemaker on the autonomic output of the hypothalamus, as reflected by the effects of LPS on glucose homeostasis. The latter effects are more likely due to direct interactions of LPS with peripheral tissues, such as the liver. (Author correspondence: [email protected]

Absence of diurnal variation in visceromotor response to colorectal distention in normal Long Evans rats

BACKGROUND: Enhanced colorectal sensitivity (i.e. visceral hypersensitivity) is thought to be a pathophysiological mechanism in irritable bowel syndrome (IBS). In healthy men a circadian variation in rectal perception to colonic distention was described. Disturbed day and night rhythms, which occur in shift work and trans meridian flights, are associated with the prevalence of IBS. This raises the question whether disruptions of circadian control are responsible for the observed pathology in IBS. Prior to investigating altered rhythmicity in relation to visceral hypersensitivity in a rat model for IBS, it is relevant to establish whether normal rats display circadian variation similar to healthy men. METHODOLOGY AND FINDINGS: In rodents colorectal distension leads to reproducible contractions of abdominal musculature. We used quantification of this so called visceromotor response (VMR) by electromyography (EMG) to assess visceral sensitivity in rats. We assessed the VMR in normal male Long Evans rats at different time points of the light/dark cycle. Although a control experiment with male maternal separated rats confirmed that intentionally inflicted (i.e. stress induced) changes in VMR can be detected, normal male Long Evans rats showed no variation in VMR along the light/dark cycle in response to colorectal distension. CONCLUSIONS: In the absence of a daily rhythm of colorectal sensitivity in normal control rats it is not possible to investigate possible aberrancies in our rat model for IBS

The role of feeding rhythm, adrenal hormones and neuronal inputs in synchronizing daily clock gene rhythms in the liver

The master clock in the hypothalamic suprachiasmatic nucleus (SCN) is assumed to distribute rhythmic information to the periphery via neural, humoral and/or behavioral connections. Until now, feeding, corticosterone and neural inputs are considered important signals for synchronizing daily rhythms in the liver. In this study, we investigated the necessity of neural inputs as well as of the feeding and adrenal hormone rhythms for maintaining daily hepatic clock gene rhythms. Clock genes kept their daily rhythm when only one of these three signals was disrupted, or when we disrupted hepatic neuronal inputs together with the adrenal hormone rhythm or with the daily feeding rhythm. However, all clock genes studied lost their daily expression rhythm after simultaneous disruption of the feeding and adrenal hormone rhythm. These data indicate that either a daily rhythm of feeding or adrenal hormones should be present to synchronize clock gene rhythms in the liver with the SCN