Dim Light at Night Promotes Circadian Disruption in Female Rats, at the Metabolic, Reproductive, and Behavioral Level.

Inhabitants of urban areas are constantly exposed to light at night, which is an important environmental factor leading to circadian disruption. Streetlights filtering light through the windows and night dim light lamps are common sources of dim light at night (DLAN). The female population is susceptible to circadian disruption. The present study is aimed to determine the impact of DLAN on female Wistar rats circadian rhythms, metabolism, reproductive physiology, and behavior. After 5 weeks of DLAN exposure daily, oscillations in activity and body temperature of female rats are abolished. DLAN also decreases nocturnal food ingestion, which results in a diminishment in total food consumption. These alterations in the temporal organization of the body are associated with a significant decrease in melatonin plasmatic levels, reproductive disruptions, decreased exploration times, and marked anhedonia. This study highlights the importance of avoiding exposure to light at night, even at low intensities, to maintain the circadian organization of physiology, and denotes the great necessity of increasing the studies in females since the sexual dimorphism within the effects of desynchronizing protocols has been poorly studied.

Circadian modulation of microglial physiological processes and immune responses.

Microglia is considered the central nervous system (CNS) resident macrophages that establish an innate immune response against pathogens and toxins. However, the recent studies have shown that microglial gene and protein expression follows a circadian pattern; several immune activation markers and clock genes are expressed rhythmically without the need for an immune stimulus. Furthermore, microglia responds to an immune challenge with different magnitudes depending on the time of the day. This review examines the circadian control of microglia function and the possible physiological implications. For example, we discuss that synaptic prune is performed in the cortex at a certain moment of the day. We also consider the implications of daily microglial function for maintaining biological rhythms like general activity, body temperature, and food intake. We conclude that the developmental stage, brain region, and pathological state are not the only factors to consider for the evaluation of microglial functions; instead, emerging evidence indicates that circadian time as an essential aspect for a better understanding of the role of microglia in CNS physiology.

Time-restricted feeding prevents depressive-like and anxiety-like behaviors in male rats exposed to an experimental model of shift-work.

Individuals who regularly shift their sleep timing, like night and/or shift-workers suffer from circadian desynchrony and are at risk of developing cardiometabolic diseases and cancer. Also, shift-work is are suggested to be a risk factor for the development of mood disorders such as the burn out syndrome, anxiety, and depression. Experimental and clinical studies provide evidence that food intake restricted to the normal activity phase is a potent synchronizer for the circadian system and can prevent the detrimental health effects associated with circadian disruption. Here, we explored whether adult male Wistar rats exposed to an experimental model of shift-work (W-AL) developed depressive and/or anxiety-like behaviors and whether this was associated with neuroinflammation in brain areas involved with mood regulation. We also tested whether time-restricted feeding (TRF) to the active phase could ameliorate circadian disruption and therefore would prevent depressive and anxiety-like behaviors as well as neuroinflammation. In male Wistar rats, W-AL induced depressive-like behavior characterized by hypoactivity and anhedonia and induced increased anxiety-like behavior in the open field test. This was associated with increased number of glial fibrillary acidic protein and IBA-1-positive cells in the prefrontal cortex and basolateral amygdala. Moreover W-AL caused morphological changes in the microglia in the CA3 area of the hippocampus indicating microglial activation. Importantly, TRF prevented behavioral changes and decreased neuroinflammation markers in the brain. Present results add up evidence about the importance that TRF in synchrony with the light-dark cycle can prevent neuroinflammation leading to healthy mood states in spite of circadian disruptive conditions.

Chocolate for breakfast prevents circadian desynchrony in experimental models of jet-lag and shift-work.

Night-workers, transcontinental travelers and individuals that regularly shift their sleep timing, suffer from circadian desynchrony and are at risk to develop metabolic disease, cancer, and mood disorders, among others. Experimental and clinical studies provide evidence that food intake restricted to the normal activity phase is a potent synchronizer for the circadian system and can prevent the detrimental metabolic effects associated with circadian disruption. As an alternative, we hypothesized that a timed piece of chocolate scheduled to the onset of the activity phase may be sufficient stimulus to synchronize circadian rhythms under conditions of shift-work or jet-lag. In Wistar rats, a daily piece of chocolate coupled to the onset of the active phase (breakfast) accelerated re-entrainment in a jet-lag model by setting the activity of the suprachiasmatic nucleus (SCN) to the new cycle. Furthermore, in a rat model of shift-work, a piece of chocolate for breakfast prevented circadian desynchrony, by increasing the amplitude of the day-night c-Fos activation in the SCN. Contrasting, chocolate for dinner prevented re-entrainment in the jet-lag condition and favored circadian desynchrony in the shift-work models. Moreover, chocolate for breakfast resulted in low body weight gain while chocolate for dinner boosted up body weight. Present data evidence the relevance of the timing of a highly caloric and palatable meal for circadian synchrony and metabolic function.

Oral Silica Nanoparticles Lack of Neurotoxic Effects in a Parkinson's Disease Model: A Possible Nanocarrier?

Silica nanoparticles (SiO2-NP) are an option as drug carriers due to their biodegradability, biocompatibility, and capacity to bind themselves to other compounds. However, until now, the effect of these particles on the brain when neurodegeneration occurs is unknown. Hence, this work focused on the in vivo evaluation of the neurotoxic effects of SiO2-NP when oxidative and inflammation are present during the development of Parkinson's disease. To determine whether SiO2-NP may act as a non-neurotoxic carrier we evaluated if the intragastric administration (ig) of SiO2-NP of 150 nm (25, 50 and 100 mg/kg administered for five consecutive days) increased neuronal damage induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. SiO2-NP administration did not further decrease cell viability assessed by MTT reduction, nor increased lipid peroxidation measured by TBARS or TNF α levels in the striatum and the substantia nigra in the MPTP model. Furthermore, we observed no additional reduction in striatal dopamine levels. The present results suggest that SiO2-NP of 150 nm are suitable nanocarrier for Parkinson's disease drugs without generating any additional damage.

Circadian disruption promotes tumor growth by anabolic host metabolism; experimental evidence in a rat model.

BACKGROUND: Light at night creates a conflicting signal to the biological clock and disrupts circadian physiology. In rodents, light at night increases the risk to develop mood disorders, overweight, disrupted energy metabolism, immune dysfunction and cancer. We hypothesized that constant light (LL) in rats may facilitate tumor growth via disrupted metabolism and increased inflammatory response in the host, inducing a propitious microenvironment for tumor cells. METHODS: Male Wistar rats were exposed to LL or a regular light-dark cycle (LD) for 5 weeks. Body weight gain, food consumption, triglycerides and glucose blood levels were evaluated; a glucose tolerance test was also performed. Inflammation and sickness behavior were evaluated after the administration of intravenous lipopolysaccharide. Tumors were induced by subcutaneous inoculation of glioma cells (C6). In tumor-bearing rats, the metabolic state and immune cells infiltration to the tumor was investigated by using immunohistochemistry and flow cytometry. The mRNA expression of genes involved metabolic, growth, angiogenes and inflammatory pathways was measured in the tumor microenvironment by qPCR. Tumor growth was also evaluated in animals fed with a high sugar diet. RESULTS: We found that LL induced overweight, high plasma triglycerides and glucose levels as well as reduced glucose clearance. In response to an LPS challenge, LL rats responded with higher pro-inflammatory cytokines and exacerbated sickness behavior. Tumor cell inoculation resulted in increased tumor volume in LL as compared with LD rats, associated with high blood glucose levels and decreased triglycerides levels in the host. More macrophages were recruited in the LL tumor and the microenvironment was characterized by upregulation of genes involved in lipogenesis (Acaca, Fasn, and Pparγ), glucose uptake (Glut-1), and tumor growth (Vegfα, Myc, Ir) suggesting that LL tumors rely on these processes in order to support their enhanced growth. Genes related with the inflammatory state in the tumor microenvironment were not different between LL and LD conditions. In rats fed a high caloric diet tumor growth was similar to LL conditions. CONCLUSIONS: Data indicates that circadian disruption by LL provides a favorable condition for tumor growth by promoting an anabolic metabolism in the host.