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The present study explored the effects of malnutrition and nutritional rehabilitation on the response to glucose in hypothalamic nuclei involved in metabolic homeostasis. Male Wistar rats were malnourished during gestation–lactation (MGL) or at weaning to 55 days (MPW). Two groups of rats were rehabilitated with a balanced diet until 90 days (MGL-R and MPW-R, respectively). After a glucose tolerance test (GTT), brains were processed for Fos immunoreactivity (Fos-IR). Both malnourished groups displayed hyperglycemia after GTT. MGL exhibited an increased number of Fos-IR neurons in the ventromedial hypothalamic nucleus (VMH), while MPW showed increased Fos-IR in the arcuate nucleus (ARC) and VMH and a decrease in the paraventricular nucleus (PVN), as compared with their controls. Nutritional rehabilitation normalized values of glucose after GTT in both groups, while low number of Fos-IR neurons remained in the ARC, PVN and VMH of MPW-R rats, indicating a deleterious, long-lasting effect after post-weaning malnutrition. [ABSTRACT FROM AUTHOR]

Food is considered a potent Zeitgeber for peripheral oscillators but not for the suprachiasmatic nucleus (SCN), which is entrained principally by the light–dark cycle. However, when food attains relevant properties in quantity and quality, it can be a potent Zeitgeber even for the SCN. Here we evaluated the entrainment influence of a daily palatable meal, without regular food deprivation, on the circadian rhythm of locomotor activity and the c-Fos and PER-1 protein expression in the SCN. Rats fed ad libitum, in constant darkness, received a palatable meal for 6 weeks starting in the middle of the subjective day. Locomotor activity showed entrainment when the offset of activity coincided with the palatable meal-time. In the SCN, the peak expression of c-Fos was observed at palatable meal-time and PER-1 showed a peak during the onset of subjective night, as predicted according to the behavioural entrained pattern. In addition, c-Fos and PER-1 expression in the paraventricular thalamic nucleus (PVT) showed increased expression at palatable meal-time, while the intergeniculate leaflet did not, suggesting that the PVT may be involved as an input pathway of palatable food-entrainment to the SCN. These results demonstrate that daily access to a palatable meal can entrain the SCN; several stimuli can be implicated in this process, including motivation and arousal. [ABSTRACT FROM AUTHOR]

Abstract: Restricted feeding schedules (RFS) entrain behavioral and physiological rhythms even in suprachiasmatic nucleus ablated animals, suggesting the existence of a food-entrained oscillator. The nucleus accumbens is an important structure for the expression of motivational behaviors and because its anatomical subterritories, Shell (Acc-Sh) and Core (Acc-Co) establish connections with different functional systems, they may participate in a differential way in food-entrainment. A first experiment, explored the role of Acc-Sh and Acc-Co in food-entrainment using the immunohistochemical detection of the protein c-Fos as a transcriptional activation marker. Experiment 2 tested the differential effect of Acc-Sh and Acc-Co, NMDA excitotoxic lesions. Lesioned rats were entrained to RFS and locomotor activity and free fatty acids (FFA) concentrations were evaluated. Results data show that in the Acc-Sh there is an increase of c-Fos immunoreactivity in food-entrained rats principally during feeding, whereas c-Fos expression in the Acc-Co region was increased during feeding and also anticipating mealtime. FFA were entrained in both lesioned groups, but the basal level was lower in Core-lesion rats. All rats exhibited food anticipatory activity (FAA). However, FAA was increased in Shell-lesioned animals and was almost abolished in the Core-lesion rats. These data indicate that the accumbens nucleus is involved with behavioral and metabolic food-entrainment, and that there is a differential role between both subregions. [Copyright &y& Elsevier]

Food entrainment of clock genes in peripheral tissues and anticipatory response in the liver of rats maintained under a restricted feeding schedule have suggested that the liver may be a relevant element for a food entrained oscillator (FEO). Recent data suggest that mechanisms underlying food-entrainment for metabolic and behavioral or locomotor food anticipatory activity may depend on different regulatory systems. In a previous study we reported that a dysfunctional liver does not prevent animals from exhibiting behavioral anticipatory activity associated with restricted feeding schedules (RFS). The present study aimed to determine whether in CCl4 cirrhotic rats metabolic parameters are entrained to RFS. Chronic CCl4 treated cirrhotic rats and oil treated controls were entrained to RFS. After 2 weeks, rats were sacrificed 2 and 0?h before and 2 and 4?h after mealtime. Serum glucose and free fatty acids were determined as well as liver glycogen. Both groups exhibited a similar entrained pattern in the three parameters. Thus we conclude that anatomical and functional alterations produced by chronic administration of CCl4 do not interfere with entrainment of metabolic parameters to RFS and point out the relevance of other mechanisms independent of the liver to drive peripheral food entrained rhythms. [ABSTRACT FROM AUTHOR]

The present study aimed to identify the hypothalamic nuclei involved with food entrainment by using c-Fos-like immunoreactivity (c-Fos-IR) as a marker of functional activation. We studied rats entrained 3 wk to restricted feeding schedules (RF), their ad libitum (AL) controls, and the persistence of c-Fos-IR temporal patterns in entrained-fasted rats. In addition, we included 22-h fasting and 22-h fasting-refeeding groups as controls of fasting and refeeding acute effects. Diurnal patterns of c-Fos-IR were observed in the tuberomammilar nucleus (TM) and suprachiasmatic nucleus (SCN) in AL rats. In all nuclei, except the SCN and ventromedial nucleus (VMH), restricted feeding schedules imposed a temporal pattern of increased c-Fos-IR around mealtime. An increase in c-Fos-IR before and after meal time was observed in dorsomedial nucleus (DMH), lateral nucleus (LH), perifornical area (PeF), and TM, and a marked increase was observed in the paraventricular nucleus (PVN) after feeding. Food-entrained c-Fos-IR patterns persisted after 3 days in fasting in DMH, LH, and PeF. Present data suggest that FEO might not rely on a single nucleus and rather may be a distributed system constituted of interacting nuclei in which the PVN is mainly involved with the response to signals elicited by food ingestion and, therefore, with the entraining pathway. We can suggest that the PeF and TM may be involved with the arousal state during food anticipation and the DMH and LH with the time-keeping mechanism of FEO or its output. [ABSTRACT FROM AUTHOR]

The Continuous bright light conditions to which premature infants are subjected while hospitalized in Neonatal Intensive Care Units (NICU) can have deleterious effects in terms of growth and development. This study evaluates the benefits of a light/darkness cycle (LDC) in weight and early hospital discharge from the NICU. Subjects were recruited from three participating institutions in Mexico. Eligible patients (n = 294) were premature infants who were hospitalized in the low-risk and high-risk neonatal units classified as stable. The subjects randomized to the experimental group (n = 150) were allocated to LDC conditions are as follows: light from 07:00 to 19:00 and darkness (25 lx) from 19:00 to 07:00. The control group (n = 144) was kept under normal room light conditions (CBL) 24 h a day. Main outcome was weight gain and the effect of reducing the intensity of nocturnal light in development of premature infants. Infants to the LDC gained weight earlier, compared with those randomized to CBL, and had a significant reduction in length of hospital stay. These results highlight those premature infants subjected to a LDC exhibit improvements in physiological development, favoring earlier weight gain and consequently a decrease in hospital stays. ClinicalTrials.gov; 02/09/2020 ID: NCT05230706. [ABSTRACT FROM AUTHOR]

Highlights: [•] Constant light alters temporal patterns of c-Fos in the suprachiasmatic nucleus. [•] Chronic constant light disturbs the overt expression of activity and hormonal circadian rhythms. [•] Rats exposed chronically to constant light develop depressive like symptoms characterized by low sucrose ingestion. [•] Extended light at night can alter the activity of the biological clock and lead to depression. [ABSTRACT FROM AUTHOR]

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 system. [ABSTRACT FROM AUTHOR]

Restricted feeding schedules (RFS) are a potent Zeitgeber that uncouples daily metabolic and clock gene oscillations in peripheral tissues from the suprachiasmatic nucleus (SCN), which remains entrained to the light–dark cycle. Under RFS, animals develop food anticipatory activity (FAA), characterized by arousal and increased locomotion. Food availability in nature is not precise, which suggests that animals need to adjust their food-associated activity on a daily basis. This study explored the capacity of rats to adjust to variable and unpredictable feeding schedules. Rats were exposed either to RFS with fixed daily meal (RF) or to a variable meal time (VAR) during the light phase. RF and VAR rats exhibited daily metabolic oscillations driven by the last meal event; however, VAR rats were not able to show a robust adjustment in the anticipating corticosterone peak. VAR rats were unable to exhibit FAA but exhibited a daily activation pattern in phase with the previous meal. In both groups the dorsomedial nucleus of the hypothalamus and arcuate nucleus, involved in energy balance, exhibited increased c-Fos expression 24 h after the last meal, while only RF rats exhibited low c-Fos expression in the SCN. Data show that metabolic and behavioural food-entrained rhythms can be reset on a daily basis; the two conditions elicit a similar hypothalamic response, while only the SCN is inhibited in rats exhibiting anticipatory activity. The variable feeding strategy uncovered a rapid (24-h basis) resetting mechanism for metabolism and general behaviour. [ABSTRACT FROM AUTHOR]

Food anticipatory activity (FAA) is the expression of a food entrained oscillator, which manifests under restricted feeding schedules (RFS). Food restriction to 2?h daily represents a metabolic challenge and requires behavioral and physiological adaptations in order to allow animals to ingest sufficient food for a 24?h cycle in a short 2?h interval. In order to characterize the behavioral and physiological adaptations during restricted feeding, rats were maintained for 3 weeks under a fixed RFS, an unpredictable RFS and ad libitum (AL) feeding conditions. Feeding behavior was recorded for 2?h during meal access for RFS groups and during the first 2?h of the dark period in AL controls. Body and stomach weight were also measured for the three feeding groups. There was a significant difference between restricted groups and AL controls in the latency and duration of feeding during the 2?h of food access. Restricted rats which could predict mealtime showed the shortest latency. In both RFS groups the stomach attained a large distension in contrast to AL controls, and total time spent in food ingestion was 3?–?4 fold higher than the AL. However, and despite these behavioral and physiological adaptations, restricted rats did not achieve a body weight gain at the end of the experiment, unlike the AL group. Present data indicate that during RFS rats develop behavioral and physiological adaptations to ingest increased amounts of food in a short interval. [ABSTRACT FROM AUTHOR]

Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal and rapidly progressive form of dementia caused by the spread of a prion protein within the brain. Its real incidence is unknown since its definitive diagnosis requires histopathological analysis of brain specimens. However, novel tests that detect prion proteins in cerebrospinal fluid samples, such as the real-time quaking-induced conversion (RT-QuIC) technique, now allow the pre-mortem diagnosis of sCJD. Here, we report the first case of sCJD confirmed by RT-QuIC in Latin America, providing evidence of its diagnostic performance and clinical correlation. [ABSTRACT FROM AUTHOR]

Abstract: Food is a potent time signal for the circadian system and has shown to entrain and override temporal signals transmitted by the biological clock, the suprachiasmatic nucleus, which adjusts mainly to the daily light/dark (LD) alternation. Organisms mostly ingest food in their active period and this permits a correct coordination between the LD and the food elicited time signals with the circadian system. Under conditions when feeding opportunities are shifted to the usual resting/sleep phase, the potent entraining force of food, shifts circadian fluctuations in several tissues, organs, and brain structures toward meal time, resulting a desynchrony within the body and between the organism and the external LD cycle. The daily scheduled access to a palatable snack exerts similar changes specifically to brain areas involved in motivation and reward responses. This review describes the phenomenology of food entrainment and entrainment by a palatable snack. It suggests how scheduled feeding can lead to food addiction and how shifted feeding schedules toward the sleep phase can result in altered ingestive behavior, obesity and disturbed metabolic responses. [Copyright &y& Elsevier]

Food anticipatory behavior (FAA) is induced,by limiting access to food for a few hours daily. Animals anticipate this scheduled meal event even without the suprachiasmatic nucleus (SCN), the biological clock. Consequently, a food-entrained oscillator has been proposed to be responsible for meal time estimation. Recent studies suggested the dorsomedial hypothalamus (DMH) as the site for this food-entrained oscillator, which has led to considerable controversy in the literature. Herein we demonstrate by means of c-Fos immunohistochemistry that the neuronal activity of the suprachiasmatic nucleus (SCN), which signals the rest phase in nocturnal animals, is reduced when animals anticipate the scheduled food and, simultaneously, neuronal activity within the DMH increases. Using retrograde tracing and confocal analysis, we show that inhibition of SCN neuronal activity is the consequence of activation of GABA-containing neurons in the DMH that project to the SCN. Next, we show that DMH lesions result in a loss or diminution of FAA. simultaneous with increased activity in the SCN. A subsequent lesion of the SCN restored FAA. We conclude that in intact animals, FAA may only occur when the DMH inhibits the activity of the SCN, thus permitting locomotor activity. As a result, FAA originates from a neuronal network comprising an interaction between the DMH and SCN. Moreover, this study shows that the DMH-SCN interaction may serve as an intrahypothalamic system to gate activity instead of rest overriding circadian predetermined temporal patterns. [ABSTRACT FROM AUTHOR]