Behavioral changes and transcriptional regulation of mesolimbic dopaminergic genes in a mouse model of binge eating disorder by diet intermittent access.

Binge Eating Disorder (BED) is among the most prevalent eating disorders worldwide. It is characterized by recurrent episodes of excessive consumption of palatable foods in short periods, accompanied by a sense of loss of control and distress around the episode, which tends to worsen over time. The mesolimbic dopaminergic system influences on reinforcement and reward-seeking behaviors is implicated in the disorder's pathogenesis.

Differential expression of alpha-synuclein in the hippocampus of SHR and SLA16 isogenic rat strains.

Two inbred strains, Lewis (LEW) and Spontaneously Hypertensive Rats (SHR), are well-known for their contrasting behavior related to anxiety/emotionality. Studies with these two strains led to the discovery of the Quantitative Trait Loci (QTL) on chromosome 4 (Anxrr16). To better understand the influences of this genomic region, the congenic rat strain SLA16 (SHR.

Ethanol Preference Leads to Alterations in Telomere Length, Mitochondria Copy Number, and Antioxidant Enzyme Activity in Zebrafish Brains.

Background: The motivations for and effects of ethanol consumption vary considerably among individuals, and as such, a significant proportion of the population is prone to substance abuse and its negative consequences in the physical, social, and psychological spheres. In a biological context, the characterization of these phenotypes provides clues for understanding the neurological complexity associated with ethanol abuse behavior. Therefore, the objective of this research was to characterize four ethanol preference phenotypes described in zebrafish: Light, Heavy, Inflexible, and Negative Reinforcement.

Animal model for high consumption and preference of ethanol and its interplay with high sugar and butter diet, behavior, and neuroimmune system.

Introduction: Mechanisms that dictate the preference for ethanol and its addiction are not only restricted to the central nervous system (CNS). An increasing body of evidence has suggested that abusive ethanol consumption directly affects the immune system, which in turn interacts with the CNS, triggering neuronal responses and changes, resulting in dependence on the drug. It is known that neuroinflammation and greater immune system reactivity are observed in behavioral disorders and that these can regulate gene transcription.

Acute ethanol exposure leads to long-term effects on memory, behavior, and transcriptional regulation in the zebrafish brain.

Alcohol consumption is associated with alterations in memory and learning processes in humans and animals. In this context, research models such as the zebrafish (Danio rerio) arise as key organisms in behavioral and molecular studies that attempt to clarify alterations in the Central Nervous System (CNS), like those related to alcohol use. Accordingly, we used the zebrafish as a model to evaluate the effects of ethanol on the learning and memory process, as well as its relationship with behavior and transcriptional regulation of lrfn2, lrrk2, grin1a, and bdnf genes in the brain.

Putative Causal Variant on for the Epileptic Phenotype in the Model Wistar Audiogenic Rat.

Wistar Audiogenic Rat is an epilepsy model whose animals are predisposed to develop seizures induced by acoustic stimulation. This model was developed by selective reproduction and presents a consistent genetic profile due to the several generations of inbreeding. In this study, we performed an analysis of WAR RNA-Seq data, aiming identified at genetic variants that may be involved in the epileptic phenotype.

Gene Variants Associated With a Higher Risk for Alcohol Dependence in Multiethnic Populations.

Genetics influence the vulnerability to alcohol use disorders, and among the implicated genes, three previous studies have provided evidences for the involvement of in alcohol dependence (AD). expression is broadly dysregulated in postmortem brain from AD humans, as well as in the brain of mice with alcohol dependent-like behaviors and in a zebrafish model of alcohol preference. The aim of the present study was to evaluate the association of variants in the gene with AD in multiethnic populations from South and North America.

Diet-induced obesity leads to alterations in behavior and gut microbiota composition in mice.

The high prevalence of obesity and associated metabolic disorders are one of the major public health problems worldwide. Among the main causal factors of obesity, excessive consumption of food rich in sugar and fat stands out due to its high energy density. The regulation of food intake relies on hypothalamic control by the action of several neuropeptides.

Behavioral plasticity and gene regulation in the brain during an intermittent ethanol exposure in adult zebrafish population.

Ethanol consumption is correlated with different neurobiological and behavioral impairments. Acute and chronic exposure to this drug is associated with alterations in the regulation of the mesolimbic dopaminergic system as well as with transcriptional modulation of other receptors in the central nervous system and can unleash seeking behavior or behavioral adaptations and phenotypes such as loss of control, dependence and tolerance. In the present work, we characterized the chronological effects of acute and chronic intermittent exposure to ethanol (1% v/v) in an adult zebrafish population (Danio rerio).

Inhibition of Lrrk2 reduces ethanol preference in a model of acute exposure in zebrafish.

Due to its multifactorial and yet to be fully understood origin, ethanol addiction is a field that still requires studies for the elucidation of novel genes and pathways that potentially influence the establishment and maintenance of addiction-like phenotypes. In this context, the present study aimed to evaluate the role of the LRRK2 pathway in the modulation of ethanol preference behavior in Zebrafish (Danio rerio). Using the behavioral Conditioned Place Preference (CPP) paradigm, we accessed the preference of animals for ethanol.

Interaction between high-fat diet and ethanol intake leads to changes on the fecal microbiome.

It is known that high-fat diet and alcohol intake can modulate the gut microbiota and consequently affect physiological processes such as fat storage and conditional behavior. However, the effects of the interaction between high-fat diet, its withdrawal and ethanol intake in gut microbiota remain unclear. To address this question, we used an animal model in which C57BL/6 mice were fed on standard (AIN93G) or high-sugar and -butter (HSB) diet for 8 weeks.

Effect of alcohol use disorder on cellular aging.

Rationale: Human telomeres consist of tandem repeats at chromosome ends which protect chromosomal DNA from degradation. Telomere shortening occurs as part of natural aging; however, life stressors, smoking, drug use, BMI, and psychiatric disorders could disrupt cell aging and affect telomere length (TL). In this context, studies have evaluated the effects of alcohol consumption on TL; however, results have been inconsistent, which may reflect diverse drinking cut-offs and categorizations.

High-fat diet withdrawal modifies alcohol preference and transcription of dopaminergic and GABAergic receptors.

The bidirectional and positive relation between the ingestion of fat and alcohol has become the subject of extensive discussion. However, this relation is more studied in animal models of binge eating with intermittent access of high-fat diet or in a model of short period of this diet consumption. Here, we developed a model to elucidate how chronic high-fat diet and its withdrawal influence alcohol intake (two-bottle choice) and anxiety behavior (marble burying test).

Transcriptome of the Wistar audiogenic rat (WAR) strain following audiogenic seizures.

The Wistar Audiogenic Rat (WAR) is a model whose rats are predisposed to develop seizures following acoustic stimulation. We aimed to establish the transcriptional profile of the WAR model, searching for genes that help in understanding the molecular mechanisms involved in the predisposition and seizures expression of this strain. RNA-Seq of the corpora quadrigemina of WAR and Wistar rats subjected to acoustic stimulation revealed 64 genes differentially regulated in WAR.

Maternal separation affects expression of stress response genes and increases vulnerability to ethanol consumption.

Introduction: Maternal separation is an early life stress event associated with behavioral alterations and ethanol consumption. We aimed to expand the current understanding on the molecular mechanisms mediating the impact of postnatal stress on ethanol consumption.

Methods: In the first experiment (T1), some of the pups were separated from their mothers for 6 hr daily (Maternal Separation group - MS), whereas the other pups remained in the cage with their respective mothers (Control group - C).

Loss of control over the ethanol consumption: differential transcriptional regulation in prefrontal cortex.

Alcohol use disorder (AUD) is a complex multifactorial disease with heritability of ∼50% and corresponds to the state in which the body triggers a reinforcement or reward compulsive behavior due to ethanol consumption, even when faced with negative consequences. Although several studies have shown the impact of high ethanol intake on the prefrontal cortex (PFC) gene expression, few have addressed the relationship between the patterns of gene expression underlying the compulsive behaviour associated with relapsing. In this study, we used a chronic three-bottle free-choice mouse model to investigate the PFC transcriptome in three different groups of mice drinkers: 'Light drinkers' (preference for water throughout the experiment); 'Heavy drinkers' (preference for ethanol with a non-compulsive intake), and 'Inflexible drinkers' (preference for ethanol with a compulsive drinking component).

Possible involvement of ACSS2 gene in alcoholism.

Alcoholism is a psychiatric disorder that composes one of the principal causes of health disabilities in the world population. Furthermore, the available pharmacotherapy is limited. Therefore, this research was carried out to better understand the basis of the underlying neurobiological processes of this disorder and to discover potential therapeutic targets.

Evaluating the effects of refined carbohydrate and fat diets with acute ethanol consumption using a mouse model of alcoholic liver injury.

Alcoholism is a multifactorial and complex disorder responsible for 5.9% of deaths worldwide. Excessive consumption of ethanol (Et-OH) induces alcoholic liver disease (ALD), a condition comprising a spectrum of clinical signs and morphological changes, ranging from fatty liver (steatosis) to more severe forms of chronic liver injury.

Inflexible ethanol intake: A putative link with the Lrrk2 pathway.

Alcoholism is a complex multifactorial disorder with a strong genetic influence. Although several studies have shown the impact of high ethanol intake on the striatal gene expression, few have addressed the relationship between the patterns of gene expression underlying the compulsive behaviour associated with the two major concerns in addiction: the excessive drug consumption and relapsing. In this study, we used a chronic three-bottle free-choice murine model to address striatal transcript regulation among animals with different ethanol intakes and preferences: Light Drinkers (preference for water throughout the experiment), Heavy Drinkers (preference for ethanol with a non-compulsive intake) and Inflexible Drinkers (preference for ethanol and simultaneous loss of control over the drug intake).

High sugar and butter (HSB) diet induces obesity and metabolic syndrome with decrease in regulatory T cells in adipose tissue of mice.

Objective: The purpose of the study was to develop a novel diet based on standard AIN93G diet that would be able to induce experimental obesity and impair immune regulation with high concentrations of both carbohydrate and lipids.

Methods: To compare the effects of this high sugar and butter (HSB) diet with other modified diets, male C57BL/6 mice were fed either mouse chow, or AIN93G diet, or high sugar (HS) diet, or high-fat (HF) diet, or high sugar and butter (HSB) diet for 11 weeks ad libitum. HSB diet induced higher weight gain.

Polymorphisms of CYP2C9, VKORC1, MDR1, APOE and UGT1A1 genes and the therapeutic warfarin dose in Brazilian patients with thrombosis: a prospective cohort study.

Background: There are several pharmacogenetic algorithms to determine the warfarin doses required in patients treated for thromboembolism, but they only explain 60% of dose variation, suggesting that other genes may influence the dose required.

Objectives: This study aimed to evaluate the impact of clinical factors and CYP2C9*2, CYP2C9*3, VKORC1-1639G>A, MDR1 3435C>T, APOE* ε4, and UGT1A1(TA)n polymorphisms on the warfarin dose required, especially in those individuals requiring a high warfarin dose.

Methods: We studied 116 Brazilian patients who received warfarin therapy for thromboembolism.

Comparison of vitrification and slow cooling for umbilical tissues.

The tissue cryopreservation maintains the cellular metabolism in a quiescence state and makes the conservation possible for an indefinite period of time. The choice of an appropriate cryopreservation protocol is essential for maintenance of cryopreserved tissue banks. This study evaluated 10 samples of umbilical cord, from which small fragments of tissue (Wharton's jelly and cord lining membrane) were subjected to two protocols of cryopreservation: slow cooling and vitrification.

GABA(B) receptor agonist only reduces ethanol drinking in light-drinking mice.

Baclofen, a GABA(B) agonist, reduces ethanol intake in animals and humans, but the contrary or no effect was also reported. Our previous study demonstrated that mice characterized as "loss of control over ethanol intake" had different Gabbr1 and Gabbr2 transcription levels, which express, respectively, the GABA(B1) and GABA(B2) subunits in brain areas related to addictive behavior. In the present study, we tested baclofen on ethanol intake in mice exposed to the free-choice paradigm.

A transcriptional study in mice with different ethanol-drinking profiles: possible involvement of the GABA(B) receptor.

Previous studies have suggested that γ-aminobutyric acid-B (GABA(B)) receptor agonists effectively reduce ethanol intake. The quantification using real-time polymerase chain reaction of Gabbr1 and Gabbr2 mRNA from the prefrontal cortex, hypothalamus, hippocampus, and striatum in mice exposed to an animal model of the addiction developed in our laboratory was performed to evaluate the involvement of the GABA(B) receptor in ethanol consumption. We used outbred, Swiss mice exposed to a three-bottle free-choice model (water, 5% v/v ethanol, and 10% v/v ethanol) that consisted of four phases: acquisition (AC), withdrawal (W), reexposure (RE), and quinine-adulteration (AD).