Reflections on Several Landmark Advances in Circadian Biology.

Circadian Biology intersects with diverse scientific domains, intricately woven into the fabric of organismal physiology and behavior. The rhythmic orchestration of life by the circadian clock serves as a focal point for researchers across disciplines. This retrospective examination delves into several of the scientific milestones that have fundamentally shaped our contemporary understanding of circadian rhythms. From deciphering the complexities of clock genes at a cellular level to exploring the nuances of coupled oscillators in whole organism responses to stimuli. The field has undergone significant evolution lately guided by genetics approaches. Our exploration here considers key moments in the circadian-research landscape, elucidating the trajectory of this discipline with a keen eye on scientific advancements and paradigm shifts.

Timely Questions Emerging in Chronobiology: The Circadian Clock Keeps on Ticking.

Chronobiology investigations have revealed much about cellular and physiological clockworks but we are far from having a complete mechanistic understanding of the physiological and ecological implications. Here we present some unresolved questions in circadian biology research as posed by the editorial staff and guest contributors to the Journal of Circadian Rhythms. This collection of ideas is not meant to be comprehensive but does reveal the breadth of our observations on emerging trends in chronobiology and circadian biology. It is amazing what could be achieved with various expected innovations in technologies, techniques, and mathematical tools that are being developed. We fully expect strengthening mechanistic work will be linked to health care and environmental understandings of circadian function. Now that most clock genes are known, linking these to physiological, metabolic, and developmental traits requires investigations from the single molecule to the terrestrial ecological scales. Real answers are expected for these questions over the next decade. Where are the circadian clocks at a cellular level? How are clocks coupled cellularly to generate organism level outcomes? How do communities of circadian organisms rhythmically interact with each other? In what way does the natural genetic variation in populations sculpt community behaviors? How will methods development for circadian research be used in disparate academic and commercial endeavors? These and other questions make it a very exciting time to be working as a chronobiologist.

Suckling induces a daily rhythm in the preoptic area and lateral septum but not in the bed nucleus of the stria terminalis in lactating rabbit does.

Maternal behavior in the rabbit is restricted to a brief nursing period every day. Previously, we demonstrated that this event induces daily rhythms of Period1 (PER1) protein, the product of the clock gene Per1, in oxytocinergic and dopaminergic populations in the hypothalamus of lactating rabbit does. This is significant for the periodic production and ejection of milk, but the activation of other areas of the brain has not been explored. Here, we hypothesised that daily suckling would induce a rhythm in the preoptic area, lateral septum, and bed nucleus of the stria terminalis, which are important areas for the expression of maternal behavior in mammals, including the rabbit. To this end, we analysed PER1 expression in those areas through a complete 24-h cycle at lactation day 7. Does were scheduled to nurse during either the day at 10:00 h [zeitgeber time (ZT)03] or the night at 02:00 h (ZT19). Non-pregnant, non-lactating females were used as controls. In contrast to control females, lactating does showed a clear, significant rhythm of PER1 that shifted in parallel with the timing of nursing in the preoptic area and lateral septum. We determined that the maximal expression of PER1 at 8 h after scheduled nursing decreased significantly at 24 and 48 h after the absence of suckling. This effect was more pronounced in the lateral septum than in the preoptic area. We conclude that daily suckling is a powerful stimulus inducing rhythmic activity in brain structures in the rabbit that appear to form part of a maternal entrainable circuit.

Glutamate-Dependent BMAL1 Regulation in Cultured Bergmann Glia Cells.

Glutamate, the major excitatory amino acid, activates a wide variety of signal transduction cascades. This neurotransmitter is involved in photic entrainment of circadian rhythms, which regulate physiological and behavioral functions. The circadian clock in vertebrates is based on a transcription-translation feedback loop in which Brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like protein 1 (BMAL1) acts as transcriptional activator of others clock genes. This protein is expressed in nearly all suprachiasmatic nucleus neurons, as well as in the granular layer of the cerebellum. In this context, we decided to investigate the role of glutamate in the molecular mechanisms involved in the processes of transcription/translation of BMAL1 protein. To this end, primary cultures of chick cerebellar Bergmann glial cells were stimulated with glutamatergic ligands and we found that BMAL1 levels increased in a dose- and time dependent manner. Additionally, we studied the phosphorylation of serine residues in BMAL1 under glutamate stimulation and we were able to detect an increase in the phosphorylation of this protein. The increased expression of BMAL1 is most probably the result of a stabilization of the protein after it has been phosphorylated by the cyclic AMP-dependent protein kinase and/or the Ca(2+)/diacylglycerol dependent protein kinase. The present results strongly suggest that glutamate participates in regulating BMAL1 in glial cells and that these cells might prove to be important in the control of circadian rhythms in the cerebellum.

Inverse correlation among organochlorine pesticide levels to total lipid serum contents: a preliminary study in Veracruz, México.

Organochlorine pesticides, due to their hydrophobic nature and persistence, accumulate in tissues rich in lipids, which had been used as a biomarker for environmental pollution. In humans, organochlorine pesticides are continuously circulating and equilibrating among body compartments. The objective of the study was to evaluate the concentrations of organochlorine pesticides in blood serum and compare their levels to the total lipid contents in Veracruz, México inhabitants. Our hypothesis is that concentrations of organochlorine pesticides will increase just as lipid concentrations. Levels of organochlorine pesticides were divided in ascending tertils according to their total lipid content. The linear trend model applied surprisingly reveals that the average level of all organochlorine pesticides decreases as the lipid concentration increases. From one tertil to the next ß-HCH, it shows a decrease of -3.19 mg kg(-1) on lipid basis, pp.'DDE levels decrease by -3.70 mg kg(-1) on lipid basis and pp.'DDT levels decrease -1.13 mg kg(-1) on lipid basis. We conclude that the levels and the orderly sequence of organochlorine pesticide distributions in the blood serum maintain an inverse relationship to total lipid blood serum concentrations.

Maternal Overweight and Obesity and Their Effect on the Growth of the Newborn During the First Six Months of Life.

INTRODUCTION:  Maternal overweight and obesity during pregnancy have been shown to have multiple negative effects on the mother's health, which can even affect the infant's growth by increasing weight gain and altering various indicators, such as weight for age, length for age and weight for length. While breast milk on the other hand reduces these risks, and it's the best and most complete food for the newborn. It's a dynamic fluid capable of being modified to meet the needs of each stage of the newborn, but despite this capacity and the fact that maternal body mass index can have an impact on its components, through complex biological mechanisms, it manages to reduce the negative effects accumulated during pregnancy and even promotes a healthy state in the baby. In a country like Mexico, where overweight and obesity affect a large part of the population, it is important to study their causes and which could be the effect of this increased maternal overweight during pregnancy and lactation on newborns. OBJECTIVE: Identify the alterations associated with increased maternal body mass index during pregnancy and breastfeeding on mothers' health and their possible effect on the growth of the newborn during the first six months of life. MATERIAL AND METHODS: This was a prospective cohort study. Forty-two healthy binomials (mother and child), without problems during delivery and without serious illnesses during the breastfeeding period, were included. Maternal body mass index at the beginning of pregnancy allowed us to create two comparison groups between mothers: one with adequate weight, another with overweight or obesity. Follow-up was carried out once a month during the first six months of life, evaluating the somatometric development of mothers and children. All mothers completed the six-month period of exclusive breastfeeding. RESULTS:  There were differences between both groups of women. The one that included overweight and obese women compared to the group of women with adequate weight had a higher number of pregnancies, abortions, plasma glucose levels in the third trimester of pregnancy, and a lower number of prenatal control visits and plasma platelet levels (all with p<0.05). Regarding the baby's growth, there was a difference between the weight for length classification at 60-, 120-, 150- and 180-day follow-ups. The group to which the mother was assigned with respect to her body mass index at the beginning of pregnancy (adequate weight group and overweight/obese group) was the only factor associated with the risk of the baby being overweight according to weight for length indicator at the 180-day follow-up, with an OR = 5.2 (95%CI 1.02-26.59). CONCLUSIONS: Maternal overweight and obesity during pregnancy have a negative effect on the mother's health and baby's weight gain in its weight-for-length classification during the first six months of life. Although breastfeeding has been shown to have a positive effect on the growth of the baby, exposure to a higher maternal body mass index during pregnancy triggers important metabolic alterations that promote the development of diseases. It is important to establish weight control guidelines in women who wish to become pregnant to reduce the negative effects on the mother and offspring.

Changes in the Immunology of Breast Milk From Obese or Overweight Women: a Brief Review.

A systematic search was carried out through search platforms and specialized databases, such as Academic Google, PubMed, and Scopus, using thesauri: breast feeding, obesity, immunology, and human milk in English and Spanish, and those articles published from January 2000 to December 2021, in both languages. Only those reports that included quantitative data on immunological components in the milk of normal-weight and overweight women were considered. The PRISMA 2020 guides were used, and a total of 306 articles were reviewed, of which a total of 33 were included, according to the basic inclusion criteria. It was observed that in obese mothers, there is an increase in certain immune cells, such as B lymphocytes, cytotoxic T lymphocytes, and NK cells, and cytokines, such as IL-6 and IFN-γ; other alterations included the bacterial population and proteins with antibacterial action. Also, a decrease in growth factors such as TGF-ß and IFG-1 was documented in overweight women. Immunoglobulin concentrations did not show substantial changes. This brief review shows that maternal overweight is associated with changes in the biochemical and immunological parameters of milk.

GLAST/EAAT1-induced glutamine release via SNAT3 in Bergmann glial cells: evidence of a functional and physical coupling.

Glutamate, the major excitatory transmitter in the vertebrate brain, is removed from the synaptic cleft by a family of sodium-dependent glutamate transporters profusely expressed in glial cells. Once internalized, it is metabolized by glutamine synthetase to glutamine and released to the synaptic space through sodium-dependent neutral amino acid carriers of the N System (SNAT3/slc38a3/SN1, SNAT5/slc38a5/SN2). Glutamine is then taken up by neurons completing the so-called glutamate/glutamine shuttle. Despite of the fact that this coupling was described decades ago, it is only recently that the biochemical framework of this shuttle has begun to be elucidated. Using the established model of cultured cerebellar Bergmann glia cells, we sought to characterize the functional and physical coupling of glutamate uptake and glutamine release. A time-dependent Na⁺-dependent glutamate/aspartate transporter/EAAT1-induced System N-mediated glutamine release could be demonstrated. Furthermore, D-aspartate, a specific glutamate transporter ligand, was capable of enhancing the co-immunoprecipitation of Na⁺-dependent glutamate/aspartate transporter and Na⁺-dependent neutral amino acid transporter 3, whereas glutamine tended to reduce this association. Our results suggest that glial cells surrounding glutamatergic synapses may act as sensors of neuron-derived glutamate through their contribution to the neurotransmitter turnover.

Seroprevalence of Trypanosoma cruzi and Leishmania mexicana in free-ranging howler monkeys in southeastern Mexico.

Natural infection of wild mammals by protozoa parasites is quite common in nature. For Neotropical Primates different infections of parasites that are etiological agent of disease in human have been identified. In particular, infections by Trypanosoma cruzi and Leishmania sp., have been reported for some New World primate species, but there are no reports of infection with these parasites in any primate species in Mexico. A serological study was conducted on two howler monkey species (Alouatta pigra and A. palliata) from the Mexican states of Campeche and Tabasco. A total of 55 serum samples (20 samples from A. pigra, 20 samples from A. palliata, and 15 samples from semifree ranging A. palliata of Los Tuxtlas, Veracruz as negative controls) were analyzed for the detection of immunoglobulin G antibodies against T. cruzi and Leishmania mexicana through enzyme linked immunosorbent assay test, indirect immunofluorescence assay and Western blot. The overall prevalence of antibodies in howler monkeys was 17.5% for T. cruzi and 30% for L. mexicana. Our results also indicate that A. pigra is more susceptible to develop leishmaniasis than A. palliata. Finally, the finding of positive serology in these primates should be given serious consideration for public health, given the potential role of these primate species as wild reservoirs for these diseases and the increasing contact of monkeys with human populations due to habitat loss and fragmentation.

Obesity-mediated Lipoinflammation Modulates Food Reward Responses.

Accumulation of white adipose tissue (WAT) during obesity is associated with the development of chronic low-grade inflammation, a biological process known as lipoinflammation. Systemic and central lipoinflammation accumulates pro-inflammatory cytokines including IL-6, IL-1ß and TNF-α in plasma and also in brain, disrupting neurometabolism and cognitive behavior. Obesity-mediated lipoinflammation has been reported in brain regions of the mesocorticolimbic reward circuit leading to alterations in the perception and consumption of ultra-processed foods. While still under investigation, lipoinflammation targets two major outcomes of the mesocorticolimbic circuit during food reward: perception and motivation ("Wanting") and the pleasurable feeling of feeding ("Liking"). This review will provide experimental and clinical evidence supporting the contribution of obesity- or overnutrition-related lipoinflammation affecting the mesocorticolimbic reward circuit and enhancing food reward responses. We will also address neuroanatomical targets of inflammatory profiles that modulate food reward responses during obesity and describe potential cellular and molecular mechanisms of overnutrition linked to addiction-like behavior favored by brain lipoinflammation.