Second-Hand Risk Health Tragedies and Human Right Violations due to Ethanol Consumption. Biochemical basis for metabolic and behavioral Tragedies due to Ethanol Consumption

Everywhere a nonsmoker who is an alcohol consumer, complains of secondhand smoke, without being aware of second-hand risk health tragedies and human rights violations provoked by alcohol consumption. Here we analyze the concept, mainly unexplored, of dramatic adverse health effects and of human rights violations against third parties generated for alcohol consumption by others; and also, the harm due to the chemical transient prefrontal lobotomy generated by alcohol consumption. Alcohol consumption has been a part of the everyday human diet for centuries, especially because of the fact that alcoholic beverages are a safe means of hydration wherever clear water has not been available [1]. Old patients could, simultaneously be part of the alcohol consumers and/or secondhand victims. Before deciding to analyze the geriatric problems, we propose the allegorical model, based on Scott, Ellison, and Sinclair, as it was published in Nature Aging, in July 2021. We divide the theoretical analysis with four fundamental alternatives [2]: The extension of life (Struldbrug case). In Jonathan Swift's 1726 novel “Gulliver's Travels”, the struldbrugs were humans born apparently normal. The Struldbruggs, however immortal however they age normally, live in continuously deteriorating health. This takes us to the philosophical alternative of: “living or lasting” [2]. To lower morbidity (Dorian Gray case). Narratively, in “The Picture of Dorian Gray” a philosophical novel by Oscar Wilde, Dorian Gray owns a portrait of himself and while the picture ages, Dorian Gray does not change, maintaining his health and appearance until death [2]. Slowing aging (Peter Pan case), In this extreme case, where aging is not just slowed but canceled, the mortality and the health become independent of the age, and thus the individual is ‘forever young’. This constitutes the ‘Peter Pan’ case, after the play and novel about a boy who never grows old. This closely corresponds to the Hypocaloric diet claiming that it slows aging [2]. To reverse aging physical damage is repaired instead of slowed. This is a close analogy to the “Theseus Boat” as well as the regeneration of salamanders and lizards and transplants from donors. Desiderative, this is the future of organoids and the engineering of the pluripotent cell [2].

Artificial Intelligence Identified Resilient and Vulnerable Female Rats After Traumatic Stress and Ethanol Exposure: Investigation of Neuropeptide Y Pathway Regulation

Post-traumatic stress disorder (PTSD) is initiated by traumatic-stress exposure and manifests into a collection of symptoms including increased anxiety, sleep disturbances, enhanced response to triggers, and increased sympathetic nervous system arousal. PTSD is highly co-occurring with alcohol use disorder. Only some individuals experiencing traumatic stress develop PTSD and a subset of individuals with PTSD develop co-occurring alcohol use disorder. To investigate the basis of these individual responses to traumatic stress, single prolonged stress (SPS) a rodent model of traumatic stress was applied to young adult female rats. Individual responses to SPS were characterized by measuring anxiety-like behaviors with open field and elevated plus maze tests. Rats were then allowed to drink ethanol under an intermittent two bottle choice procedure for 8 weeks, and ethanol consumption was measured. An artificial intelligence algorithm was built to predict resilient and vulnerable individuals based on data from anxiety testing and ethanol consumption. This model was implemented in a second cohort of rats that underwent SPS without ethanol drinking to identify resilient and vulnerable individuals for further study. Analysis of neuropeptide Y (NPY) levels and expression of its receptors Y1R and Y2R mRNA in the central nucleus of the amygdala (CeA), basolateral amygdala (BLA), and bed nucleus stria terminalis (BNST) were performed. Results demonstrate that resilient rats had higher expression of Y2R mRNA in the CeA compared with vulnerable and control rats and had higher levels of NPY protein in the BNST compared to controls. The results of the study show that an artificial intelligence algorithm can identify individual differences in response to traumatic stress which can be used to predict subsequent ethanol drinking, and the NPY pathway is differentially altered following traumatic stress exposure in resilient and vulnerable populations. Understanding neurochemical alterations following traumatic-stress exposure is critical in developing prevention strategies for the vulnerable phenotype and will help further development of novel therapeutic approaches for individuals suffering from PTSD and at risk for alcohol use disorder.

Ethanol consumption during gestation promotes placental alterations in IGF-1 deficient mice

Background: During pregnancy, the placenta is an extremely important organ as it secretes its own hormones, e.g. insulin-like growth factor 1 (IGF-1), to ensure proper intrauterine fetal growth and development. Ethanol, an addictive and widely used drug, has numerous adverse effects during pregnancy, including fetal growth restriction (FGR). To date, the molecular mechanisms by which ethanol triggers its toxic effects during pregnancy, particularly in the placenta, are not entirely known. For this reason, a murine model of partial IGF-1 deficiency was used to determine ethanol alterations in placental morphology and AAH expression. Methods: Heterozygous (HZ, Igf1+/-) female mice were given 10% ethanol during 14 days as an acclimation period and throughout pregnancy. HZ female mice given water were used as controls. At gestational day 19, pregnant dams were sacrificed, placentas were collected and genotyped for subsequent studies. Results: IGF-1 deficiency and ethanol consumption during pregnancy altered placental morphology, and decreased placental efficiency and aspartyl/asparaginyl β-hydroxylase (AAH) expression in placentas from all genotypes. No differences were found in Igf1, Igf2, Igf1r and Igf2r mRNA expression in placentas from all groups. Conclusions: IGF-1 deficiency and ethanol consumption throughout gestation altered placental development, suggesting the crucial role of IGF-1 in the establishment of an adequate intrauterine environment that allows fetal growth. However, more studies are needed to study the precise mechanism to stablish the relation between both insults.

Maternal Separation Stress Affects Voluntary Ethanol Intake in a Sex Dependent Manner

Maternal separation (MS) stress is a predictive animal model for evaluating the effects of early stress exposure on alcohol use disorders (AUD). The extended amygdala (AMY) is a complex circuit involved in both stress- and ethanol-related responses. We hypothesized that MS stress may increase ethanol consumption in adulthood, as well as augment neuronal activity in extended AMY, in a sex-dependent manner. We aimed to investigate the influence of MS stress on the ethanol consumption of male and female mice, and the involvement of extended amygdala sub-nuclei in this process. The C57BL/6J pups were subjected to 180min of MS, from postnatal day (PND) 1 to 14. The control group was left undisturbed. On PND 45, mice (n=28) in cages were exposed to a bottle containing 20% ethanol (w/v) for 4h during the dark period of the light-dark cycle, for 3weeks. Afterward, mice underwent ethanol self-administration training in operant chambers under fixed ratio (FR) schedule. Then, subjects were tested under 2h sessions of a progressive-ratio (PR) schedule of reinforcement (the last ratio achieved was considered the breaking point), and at the end, a 4h session of FR schedule (binge-intake). An immunohistochemistry assay for Fos protein was performed in Nucleus Accumbens (NAcc), Bed Nucleus of Stria Terminalis (BNST), and AMY. Our results showed that in the third week of training, the female MS group consumed more ethanol than the respective control group. The MS group presented increased breakpoint parameters. Female control group and male MS group were more resistant to bitter quinine taste. Increased Fos-immunoreactive neurons (Fos-IR) were observed in the central nucleus of AMY, but not in NAcc nor BNST in male maternal-separated mice. Maternal separation stress may influence ethanol intake in adulthood, and it is dependent on the sex and reinforcement protocol.

On the Use of Heterogeneous Stock Mice to Map Transcriptomes Associated With Excessive Ethanol Consumption

We and many others have noted the advantages of using heterogeneous (HS) animals to map genes and gene networks associated with both behavioral and non-behavioral phenotypes. Importantly, genetically complex Mus musculus crosses provide substantially increased resolution to examine old and new relationships between gene expression and behavior. Here we report on data obtained from two HS populations: the HS/NPT derived from eight inbred laboratory mouse strains and the HS-CC derived from the eight collaborative cross inbred mouse strains that includes three wild-derived strains. Our work has focused on the genes and gene networks associated with risk for excessive ethanol consumption, individual variation in ethanol consumption and the consequences, including escalation, of long-term ethanol consumption. Background data on the development of HS mice is provided, including advantages for the detection of expression quantitative trait loci. Examples are also provided of using HS animals to probe the genes associated with ethanol preference and binge ethanol consumption.

Determination of cortisol in hair using UHPLC–MS/MS: application to patients admitted for ethanol dependence treatment

Aim: Cortisol hair levels can be used to evaluate chronic stress status. In this context, an improved UHPLC–MS/MS assay for the determination of cortisol in hair was developed and validated. Materials & methods: Hair was extracted with methanol for 4 h at 25°C. Chromatographic run time was 5.5 min. The assay was linear in the range of 1–250 pg mg-1. Precision was 3.6–12.2% and accuracy 97.1–103.8%. The method was applied in hair from 19 volunteers admitted at a rehabilitation clinic, with ethanol consumption classified using ethyl glucuronide hair levels. Conclusion: Abstinent/chronic moderate ethanol consumers had significantly lower cortisol hair levels than chronic excessive consumers. This is the first study evaluating cortisol hair levels in ethanol abuse patients using an objective marker for ethanol consumption.