A High-Sugar Diet Consumption, Metabolism and Health Impacts with a Focus on the Development of Substance Use Disorder: A Narrative Review.

Carbohydrates are important macronutrients in human and rodent diet patterns that play a key role in crucial metabolic pathways and provide the necessary energy for proper body functioning. Sugar homeostasis and intake require complex hormonal and nervous control to proper body energy balance. Added sugar in processed food results in metabolic, cardiovascular, and nervous disorders.

Trait sensitivity to negative feedback determines the intensity of compulsive alcohol seeking and taking in male rats.

Background: Alcohol use disorder is one of the most common psychiatric disorders, and it is a leading cause of mortality worldwide. It has been demonstrated previously that people with alcohol use disorder are less sensitive to the negative outcomes of their actions and less able to use negative feedback to guide and adjust their ongoing behaviour. However, far less is known about the aberrant processing of negative feedback before the onset of alcohol use disorder.

KSK-74: Dual Histamine H and Sigma-2 Receptor Ligand with Anti-Obesity Potential.

Many studies involving compounds that enhance histamine release, such as histamine H receptor (HR) antagonists, have shown efficacy in inhibiting weight gain, but none have passed clinical trials. As part of the search for H receptor ligands that have additional properties, the aim of this study is to evaluate the activity in the reduction in weight gain in a rat model of excessive eating, as well as the impact on selected metabolic parameters, and the number and size of adipocytes of two new HR antagonists, KSK-60 and KSK-74, which also exert a significant affinity at the sigma-2 receptor. Compounds KSK-60 and KSK-74 are homologues and the elongation of the distal part of the molecule resulted in an approximate two-fold reduction in affinity at HR, but simultaneously an almost two-fold increase in affinity at the sigma-2 receptor.

Cognitive Processes and Personality Traits Underlying Four Phenotypes of Susceptibility to (Mis)Information.

Misinformation on social media poses a serious threat to democracy, sociopolitical stability, and mental health. Thus, it is crucial to investigate the nature of cognitive mechanisms and personality traits that contribute to the assessment of news items' veracity, failures in the discernment of their truthfulness, and behavioral engagement with the news, especially if one wants to devise any intervention to stop the spread of misinformation in social media. The current research aimed to develop and test a 4-fold taxonomy classifying people into four distinct phenotypes of susceptibility to (mis)information.

Transmission Distortion of MCT1 rs1049434 among Polish Elite Athletes.

Background: To date, nearly 300 genetic markers were linked to endurance and power/strength traits. The current study aimed to compare genotype distributions and allele frequencies of the common polymorphisms: rs1049434, rs12594956, rs1052373 and rs1799945 in Polish elite athletes versus nonathletes.

Methods: The study involved 101 male elite Polish athletes and 41 healthy individuals from the Polish population as a control group.

Impact of the Polymorphisms on the Effectiveness of the Training Program.

Dopamine receptor D2 gene () polymorphisms have been associated with cognitive abilities, obesity, addictions, and physical-activity-related behaviors, which may underlie differences in the effectiveness of training programs. What is not yet clear is the impact of polymorphisms on the effectiveness of exercise programs. Thus, the aim of this study was to investigate the association between the polymorphic sites (rs1076560, rs12364283, rs1799732, rs1800497, and rs1800498) and the body's response to regular physical activity.

Trade-offs between male fertility reduction and selected growth factors or the klotho response in a lipopolysaccharide-dependent mouse model.

The increasing number of depression cases leads to a greater need for new antidepressant treatment development. It is postulated that antidepressants may harm male fertility, but the cellular mechanism is still poorly understood. The role of growth factors and klotho protein in maintaining normal male reproductive function is well documented.

The Effect of Glutathione Deficit During Early Postnatal Brain Development on the Prepulse Inhibition and Monoamine Levels in Brain Structures of Adult Sprague-Dawley Rats.

Recent studies suggest that impaired glutathione synthesis and distorted dopaminergic transmission are important factors in the pathophysiology of schizophrenia. In the present study, on the postnatal days p5-p16, male pups were treated with the inhibitor of glutathione synthesis, L-buthionine-(S,R)- sulfoximine (BSO, 3.8 or 7.

New N-aryl-N'-aryl-/(thio)ureido-/sulfamoylamino-derivatives of alkyl/alkylcarbamoyl piperazines: Effect of structural modifications on selectivity over 5-HT receptor.

The 5-HT receptors are an important biological target in the treatment of CNS diseases. Recently, their importance in the context of non-CNS disease entities has also been postulated. In the light of these reports, we designed a new group of urea derivatives of N-aryl-N'-aryl-/(thio)ureido-/sulfamoylamino-derivatives of alkyl/alkylcarbamoyl piperazines as 5-HTR ligands, focusing on increasing receptor selectivity.

Understanding the Links among Maternal Diet, Myelination, and Depression: Preclinical and Clinical Overview.

Depression is one of the most common mental disorders in the general population, and multiple mechanisms are involved in the etiology of this disease, including myelination. According to the Developmental Origins of Health and Disease (DOHaD) hypothesis, maternal diet affects the lifetime of the individual during adulthood and may contribute to the development of neuropsychiatric disorders. Additionally, the intensive processes of myelination contribute to the development of the central nervous system in the perinatal period, while any alterations during this crucial process providing the physiological functioning of neurons may lead to neuropsychiatric disorders in the next generation.

Repeated co-treatment with mirtazapine and aripiprazole reversed the schizophrenia-like behaviors and increased the brain-derived neurotrophic factor mRNA expression in the adult Sprague-Dawley rats exposed to glutathione deficit during early postnatal brain development.

Recent studies suggest that impaired glutathione synthesis and dopaminergic transmission are important factors in the pathophysiology of schizophrenia. Moreover, some studies have suggested that antidepressants are able to increase the activity of atypical antipsychotics which may efficiently improve the treatment of negative and some cognitive symptoms of schizophrenia. In the present study, we investigated the influence of repeated co-treated with mirtazapine and aripiprazole on the schizophrenia-like behavior and brain-derived neurotrophic factor (BDNF) mRNA expression in adult rats exposed to glutathione deficit during early postnatal development.

The Pathophysiology and Treatment of Essential Tremor: The Role of Adenosine and Dopamine Receptors in Animal Models.

Essential tremor (ET) is one of the most common neurological disorders that often affects people in the prime of their lives, leading to a significant reduction in their quality of life, gradually making them unable to independently perform the simplest activities. Here we show that current ET pharmacotherapy often does not sufficiently alleviate disease symptoms and is completely ineffective in more than 30% of patients. At present, deep brain stimulation of the motor thalamus is the most effective ET treatment.

Influence of Incorporation of Different d-Electron Metal Cations into Biologically Active System on Its Biological and Physicochemical Properties.

Three new compounds, namely [HL][CuCl], [HL][ZnCl], and [HL][CdCl] () were synthesized and their physicochemical and biological properties were thoroughly investigated. All three compounds form isostructural, crystalline systems, which have been studied using Single-Crystal X-ray diffraction analysis (SC-XRD) and Fourier-transform infrared spectroscopy (FTIR). The thermal stability was investigated using thermogravimetric analysis (TGA) and melting points for all compounds have been determined.

Histamine H Receptor Ligands-KSK-59 and KSK-73-Reduce Body Weight Gain in a Rat Model of Excessive Eating.

Noting the worldwide rapid increase in the prevalence of overweight and obesity new effective drugs are now being sought to combat these diseases. Histamine H receptor antagonists may represent an effective therapy as they have been shown to modulate histamine synthesis and release and affect a number of other neurotransmitters (norepinephrine, acetylcholine, γ-aminobutyric acid, serotonin, substance P) thus influencing the food intake. Based on the preliminary studies determining affinity, intrinsic activity, and selected pharmacokinetic parameters, two histamine H receptor ligands were selected.

Neuromolecular Underpinnings of Negative Cognitive Bias in Depression.

This selective review aims to summarize the recent advances in understanding the neuromolecular underpinnings of biased cognition in depressive disorder. We begin by considering the cognitive correlates of depressed mood and the key brain systems implicated in its development. We then review the core findings across two domains of biased cognitive function in depression: pessimistic judgment bias and abnormal response to negative feedback.

Nuclear Receptors in Myocardial and Cerebral Ischemia-Mechanisms of Action and Therapeutic Strategies.

Nearly 18 million people died from cardiovascular diseases in 2019, of these 85% were due to heart attack and stroke. The available therapies although efficacious, have narrow therapeutic window and long list of contraindications. Therefore, there is still an urgent need to find novel molecular targets that could protect the brain and heart against ischemia without evoking major side effects.

Two Rare Variants in and Genes-Do They Contribute to Semantic Dementia Clinical Phenotype?

We have performed whole-genome sequencing to identify the genetic variants potentially contributing to the early-onset semantic dementia phenotype in a patient with family history of dementia and episodic memory deficit accompanied with profound semantic loss. Only very rare variants of unknown significance (VUS) have been identified: a nonsense variant c.366C>A/p.

Preclinical Evidence for the Interplay between Oxidative Stress and RIP1-Dependent Cell Death in Neurodegeneration: State of the Art and Possible Therapeutic Implications.

Neurodegenerative diseases are the most frequent chronic, age-associated neurological pathologies having a major impact on the patient's quality of life. Despite a heavy medical, social and economic burden they pose, no causative treatment is available for these diseases. Among the important pathogenic factors contributing to neuronal loss during neurodegeneration is elevated oxidative stress resulting from a disturbed balance between endogenous prooxidant and antioxidant systems.

The Phenoxyalkyltriazine Antagonists for 5-HT Receptor with Promising Procognitive and Pharmacokinetic Properties In Vivo in Search for a Novel Therapeutic Approach to Dementia Diseases.

Among the serotonin receptors, one of the most recently discovered 5-HT subtype is an important protein target and its ligands may play a key role in the innovative treatment of cognitive disorders. However, none of its selective ligands have reached the pharmaceutical market yet. Recently, a new chemical class of potent 5-HT receptor agents, the 1,3,5-triazine-piperazine derivatives, has been synthesized.

Enhancement of the GluN2B subunit of glutamatergic NMDA receptors in rat brain areas after cocaine abstinence.

Background: Cocaine use disorder is associated with compulsive drug-seeking and drug-taking, whereas relapse may be induced by several factors, including stress, drug-related places, people, and cues. Recent observations strongly support the involvement of the N-methyl-D-aspartate (NMDA) receptors in cocaine use disorders and abstinence, whereas withdrawal in different environments may affect the intensification of relapse.

Methods: The aim of this study was to examine the GluN2B subunit expression and its association with the postsynaptic density protein 95 (PSD95) in several brain structures in rats with a history of cocaine self-administration and housed either in an enriched environment or in an isolated condition.

A Maternal High-Fat Diet during Early Development Provokes Molecular Changes Related to Autism Spectrum Disorder in the Rat Offspring Brain.

Autism spectrum disorder (ASD) is a disruptive neurodevelopmental disorder manifested by abnormal social interactions, communication, emotional circuits, and repetitive behaviors and is more often diagnosed in boys than in girls. It is postulated that ASD is caused by a complex interaction between genetic and environmental factors. Epigenetics provides a mechanistic link between exposure to an unbalanced maternal diet and persistent modifications in gene expression levels that can lead to phenotype changes in the offspring.

Alteration of the Early Development Environment by Maternal Diet and the Occurrence of Autistic-like Phenotypes in Rat Offspring.

Epidemiological and preclinical studies suggest that maternal obesity increases the risk of autism spectrum disorder (ASD) in offspring. Here, we assessed the effects of exposure to modified maternal diets limited to pregnancy and lactation on brain development and behavior in rat offspring of both sexes. Among the studied diets, a maternal high-fat diet (HFD) disturbed the expression of ASD-related genes (, , and ) and proteins (SHANK1 and TAOK2) in the prefrontal cortex of male offspring during adolescence.

Pharmacoprint: A Combination of a Pharmacophore Fingerprint and Artificial Intelligence as a Tool for Computer-Aided Drug Design.

Structural fingerprints and pharmacophore modeling are methodologies that have been used for at least 2 decades in various fields of cheminformatics, from similarity searching to machine learning (ML). Advances in techniques consequently led to combining both these methodologies into a new approach known as the pharmacophore fingerprint. Herein, we propose a high-resolution, pharmacophore fingerprint called Pharmacoprint that encodes the presence, types, and relationships between pharmacophore features of a molecule.