Light at night and melatonin have opposite effects on breast cancer tumors in mice assessed by growth rates and global DNA methylation.

Light-at-night (LAN) is a worldwide problem co-distributed with breast cancer prevalence. We hypothesized that exposure to LAN is coincided with a decreased melatonin (MLT) secretion level, followed by epigenetic modifications and resulted in higher breast cancer tumors growth-rate. Accordingly, we studied the effect of LAN exposure and exogenous MLT on breast cancer tumors growth-rate. 4T1 cells were inoculated into BALB/c short day-acclimated mice, resulting in tumors growth. Growth rates were followed under various light exposures and global DNA methylations were measured. Results demonstrated the positive effect of LAN on tumors growth-rate, reversed by MLT through global DNA methylation.

Reproductive and metabolic responses of desert adapted common spiny male mice (Acomys cahirinus) to vasopressin treatment.

Sufficient amounts of water and food are important cues for reproduction in an unpredictable environment. We previously demonstrated that increased osmolarity levels, or exogenous vasopressin (VP) treatment halt reproduction of desert adapted golden spiny mice Acomys russatus. In this research we studied gonad regulation by VP and food restriction (FR) in desert adapted common spiny mouse (A. cahirinus) males, kept under two different photoperiod regimes-short (SD-8L:16D) and long (LD-16L:8D) days. Mice were treated with VP, FR, and VP+FR for three weeks. Response was assessed from changes in relative testis mass, serum testosterone levels and mRNA receptor gene expression of VP, aldosterone and leptin in treated groups, compared with their controls. SD-acclimation increased testosterone levels, VP treatment decreased expression of aldosterone mRNA receptor in the testes of SD-acclimated males. FR under SD-conditions resulted in testosterone decrease and elevation of VP- receptor gene expression in testes. Aldosterone receptor mRNA expression was also detected in WAT. These results support the idea that water and food availability in the habitat may be used as signals for activating the reproductive system through direct effects of VP, aldosterone and leptin on the testes or through WAT by indirect effects.

Photoperiodicity and increasing salinity as environmental cues for reproduction in desert adapted rodents.

Understanding the ways environmental signals, regulate reproduction and reproductive behavior of desert adapted rodents is a major gap in our knowledge. In this study, we assessed the roles of photoperiod and diet salinity, as signals for reproduction. We challenged desert adapted common spiny mice, Acomys cahirinus, males and females with osmotic stress, by gradually increasing salinity in their water source - from 0.9% to 5% NaCl under short and long days (SD and LD, respectively). Photoperiodicity affected testosterone levels, as under LD-acclimation, levels were significantly (p<0.05) higher than under SD-acclimation. Salinity treatment (ST) significantly reduced SD-acclimated male body mass (W(b)) and testis mass (p<0.005; normalized to W(b)). ST-LD-females significantly (p<0.005) decreased progesterone levels and the numbers of estrous cycles. A reduction in white adipose tissue (WAT) to an undetectable level was noted in ST-mice of both sexes under both photoperiod regimes. Receptors for vasopressin (VP) and aldosterone were revealed on testes of all male groups and on WAT in control groups. Our results suggest that photoperiod serves as an initial signal while water availability, expressed by increased salinity in the water source, is an ultimate cue for regulation of reproduction, in both sexes of desert-adapted A. cahirinus. We assume that environmental changes also affect behavior, as water seeking behavior by selecting food items, or locomotor activity may change in extreme environment, and thus indirectly affect reproduction and reproductive behavior. The existence of VP and aldosterone receptors in the gonads and WAT suggests the involvement of osmoregulatory hormones in reproductive control of desert adapted rodents.

Effects of light and melatonin treatment on body temperature and melatonin secretion daily rhythms in a diurnal rodent, the fat sand rat.

Many mammals display predictable daily rhythmicity in both neuroendocrine function and behavior. The basic rest-activity cycles are usually consistent for a given species and vary from night-active (nocturnal), those mostly active at dawn and dusk (i.e., crepuscular), and to day-active (diurnal) species. A number of daily rhythms are oppositely phased with respect to the light/dark (LD) cycle in diurnal compared with nocturnal mammals, whereas others are equally phased with respect to the LD cycle, regardless of diurnality/nocturnality. Pineal produced melatonin (MLT) perfectly matches this phase-locked feature in that its production and secretion always occurs during the night in both diurnal and nocturnal mammals. As most rodents studied to date in the field of chronobiology are nocturnal, the aim in this study was to evaluate the effect of light manipulations and different photoperiods on a diurnal rodent, the fat sand rat, Psammomys obesus. The authors studied its daily rhythms of body temperature (T(b)) and 6-sulphatoxymelatonin (6-SMT) under various photoperiodic regimes and light manipulations (acute and chronic exposures) while maintaining a constant ambient temperature of 30 degrees C +/- 1 degrees C. The following protocols were used: (A) Control (CON) conditions 12L:12D; (A1) exposure to one light interference (LI) of CON-acclimated individuals for 30 min, 5 h after lights-off; (A2) short photoperiod (SP) acclimation (8L:16D) for 3 wks; (A3) 3 wks of SP acclimation with chronic LI of 15 min, three times a night at 4-h intervals; (A4) chronic exposure to constant dim blue light (470 nm, 30 lux) for 24 h for 3 wks (LL). (B) The response to exogenous MLT administration, provided in drinking water, was measured under the following protocols: (B1) After chronic exposure to SP with LI, MLT was provided once, starting 1 h before the end of photophase; (B2) after a continuous exposure to dim blue light, MLT was provided at 15:00 h for 2 h for 2 wks; (B3) to CON animals, MLT was given intraperitoneally (i.p.) at 14:00 h. The results demonstrate that under CON acclimation, Psammomys obesus has robust T(b) and 6-SMT daily rhythms in which the acrophase (peak time) of T(b) is during the photophase, whereas that of 6-SMT is during scotophase. LI resulted in an elevation of T(b) and a reduction of 6-SMT levels. A significant difference in the response was noted between acute and chronic exposure to LI, particularly in 6-SMT levels, which were lower than CON after LI and higher after chronic LI, implying an acclimation process. Constant exposure to blue light abolished T(b) and 6-SMT rhythms in all the animals. MLT administration resumed the T(b) daily rhythm in these animals, and had a recovery effect on the chronic LI-exposed animals, resulting in a T(b) decrease. Altogether, the authors show in this study the different modifications of T(b) rhythms and MLT levels in response to environmental light manipulations. These series of experiments may serve as a basis for establishing P. obesus as an animal model for further studies in chronobiology.

Physiological adaptations of small mammals to desert ecosystems.

Adaptations of animals to the xeric environment have been studied in various taxonomic groups and across several deserts. Despite the impressive data that have been accumulated, the focus in most of these studies is mainly on the significance of one variable at a time. Here, we attempt to integrate between responses of several physiological systems, challenged by increasing diet and water salinity and extreme temperatures, acquired in different studies of thermo and osmo-regulatory adaptations, of small rodents, to the xeric environment. Studies have shown differential thermoregulatory responses to increased dietary salinity, which were attributed to habitat and habits of the relevant species. In the thermoregulatory studies, a potential adaptive significance of low metabolic rate was demonstrated. From an evolutionary point of view, the most important adaptation is in the timing of reproduction, as it enables the transfer of genetic properties to the next generation in an unpredictable ecosystem, where reproduction might not occur every year. Results in this aspect show that increased dietary salinity, through an increase in vasopressin plasma levels, plays an important role as a regulator of the reproductive system. We assume that the amount of food existing in the habitat and the amount of reserves in the animal in the form of white adipose tissue are important for reproduction. Photoperiod affects all studied physiological responses, emphasizing the importance of pre-acclimation to seasonal characteristics. We summarize the existing data and suggest neuro-endocrine pathways, which have a central role in these adaptations by affecting thermoregulation, osmoregulation and reproduction to create the optimal response to xeric conditions. These hypotheses can be used as the basis for future studies.

Acclimatory-phase specificity of gene expression during the course of heat acclimation and superimposed hypohydration in the rat hypothalamus.

The induction of the heat-acclimated phenotype involves reprogramming the expression of genes encoding both constitutive and inducible proteins. In this investigation, we studied the global genomic response in the hypothalamus during heat acclimation, with and without combined hypohydration stress. Rats were acclimated for 2 days (STHA) or for 30 days (LTHA) at 34 degrees C. Hypohydration (10% decrease in body weight) was attained by water deprivation. 32P-labeled RNA samples from the hypothalamus were hybridized onto cDNA Atlas array (Clontech no. 1.2) membranes. Clustering and functional analyses of the expression profile of a battery of genes representing various central regulatory functions of body homeostasis demonstrated a biphasic acclimation profile with a transient upregulation of genes encoding ion channels, transporters, and transmitter signaling upon STHA. After LTHA, most genes returned to their preacclimation expression levels. In both STHA and LTHA, genes encoding hormones and neuropeptides, linked with metabolic rate and food intake, were downregulated. This genomic profile, demonstrating an enhanced transcription of genes linked with neuronal excitability during STHA and enhanced metabolic efficiency upon LTHA, is consistent with our previously established integrative acclimation model. The response to hypohydration was characterized by an upregulation of a large number of genes primarily associated with the regulation of ion channels, cell volume, and neuronal excitability. During STHA, the response was transiently desensitized, recovering upon LTHA. We conclude that hypohydration overrides the heat acclimatory status. It is notable that STHA and hypohydration gene profiles are analogous with the physiological profile described in the response to various types of brain injury.