The impact of mGlu2 or mGlu5 receptor activators on the production of L-arginine derivatives and the expression of PMRT5 or DDAH1 enzymes in animal models of cognitive decline.

L-arginine derivatives (ADMA, SDMA, NMMA) are endogenous inhibitors of nitric oxide (NO֗) production, which is essential in critical brain processes including blood-brain barrier (BBB) integrity and long-term potentiation (LTP). ADMA and NMMA are degraded by dimethylarginine dimethylaminohydrolase 1 (DDAH1) and protein arginine methyltransferase 5 (PRMT5) is an emerging epigenetic enzyme that mainly represses transcription of target genes via symmetric dimethylation of arginine residues. There is no data concerning the impact of metabotropic glutamate receptors (mGlu) ligands on this aspect of brain physiology.

NFκB and JNK pathways mediate metabolic adaptation upon ESCRT-I deficiency.

Endosomal Sorting Complexes Required for Transport (ESCRTs) are crucial for delivering membrane receptors or intracellular organelles for lysosomal degradation which provides the cell with lysosome-derived nutrients. Yet, how ESCRT dysfunction affects cell metabolism remained elusive. To address this, we analyzed transcriptomes of cells lacking TSG101 or VPS28 proteins, components of ESCRT-I subcomplex.

Dietary Intervention with Omega-3 Fatty Acids Mitigates Maternal High-Fat Diet-Induced Behavioral and Myelin-Related Alterations in Adult Offspring.

Background: Maternal high-fat diet (HFD) during pregnancy and lactation induces depression- like phenotype and provokes myelin-related changes in rat offspring in the prefrontal cortex (PFCTX), which persist even to adulthood.

Objective: Due to the plasticity of the developing brain, it was decided to analyze whether depressionlike phenotype and myelin-related changes in the early lifetime induced by maternal HFD (60% energy from fat) could be reversed by the omega-3 fatty acid-enriched diet (Ω3D) given from the postweaning period until adulthood (63rd day of life) in offspring.

Methods: We analyzed the effect of post-weaning Ω3D on the depressive-like phenotype (assessed by the forced swimming test) and myelin-related changes (measured using RT-qPCR, ELISA, and immunofluorescence staining) in the PFCTX of adult offspring.

Low-Basicity 5-HT Receptor Ligands from the Group of Cyclic Arylguanidine Derivatives and Their Antiproliferative Activity Evaluation.

The serotonin 5-HT receptor (5-HTR), expressed almost exclusively in the brain, affects the Cdk5 signaling as well as the mTOR pathway. Due to the association of 5-HTR signaling with pathways involved in cancer progression, we decided to check the usefulness of 5-HTR ligands in the treatment of CNS tumors. For this purpose, a new group of low-base 5-HTR ligands was developed, belonging to arylsulfonamide derivatives of cyclic arylguanidines.

Contilisant+Tubastatin A Hybrids: Polyfunctionalized Indole Derivatives as New HDAC Inhibitor-Based Multitarget Small Molecules with and Activity in Neurodegenerative Diseases.

Herein, we describe the design, synthesis, and biological evaluation of 15 + hybrids. These ligands are polyfunctionalized indole derivatives developed by juxtaposing selected pharmacophoric moieties of and to act as multifunctional ligands. Compounds and were identified as potent HDAC6 inhibitors (IC = 0.

μ-Opioid receptor transcriptional variants in the murine forebrain and spinal cord.

Oprm1, the gene encoding the μ-opioid receptor, has multiple reported transcripts, with a variable 3' region and many alternative sequences encoding the C-terminus of the protein. The functional implications of this variability remain mostly unexplored, though a recurring notion is that it could be exploited by developing selective ligands with improved clinical profiles. Here, we comprehensively examined Oprm1 transcriptional variants in the murine central nervous system, using long-read RNAseq as well as spatial and single-cell transcriptomics.

Unveiling the power of optimism: Exploring behavioral and neuromolecular correlates of alcohol seeking and drinking in rats with biased judgement.

Alcohol use disorder (AUD) is a common psychiatric condition with substantial global mortality. Despite extensive research into its pathophysiology, the cognitive predispositions driving alcohol dependence are less understood. This study explores whether biased cognition, specifically traits of optimism and pessimism, predicts susceptibility to alcohol-seeking behaviors using an animal model.

Unlocking the potential of higher-molecular-weight 5-HTR ligands: Synthesis, affinity, and ADMET examination.

An increasing number of drugs introduced to the market and numerous repositories of compounds with confirmed activity have posed the need to revalidate the state-of-the-art rules that determine the ranges of properties the compounds should possess to become future drugs. In this study, we designed a series of two chemotypes of aryl-piperazine hydantoin ligands of 5-HTR, an attractive target in search for innovative CNS drugs, with higher molecular weight (close to or over 500). Consequently, 14 new compounds were synthesised and screened for their receptor activity accompanied by extensive docking studies to evaluate the observed structure-activity/properties relationships.

Anti-diabetes and neuroprotection potential and primary safety studies of Isatis tinctoria L. hydroalcoholic leaf extract.

Purpose: Natural plant raw materials, previously underestimated in therapeutics, are becoming the subject of research for new applications in medicine. In our research, the hydroalcoholic extract of Isatis tinctoria leaf, rich in flavonoid compounds such as vicenin-2 and quercetin, was examined as a potential antidiabetic and neuroprotective agent.

Methods: The effect of the extract and its main flavonoid compounds on protein glycation, alpha-glucosidase activity, and acetylcholinesterase activity was tested.

Iron administered in the neonatal period changed memory, brain monoamine levels, and BDNF mRNA expression in adult Sprague-Dawley rats.

Background: Iron is one of the key microelements in the mammalian body and is the most abundant metal in the brain. Iron, a very important chemical element in the body of mammals, is the most abundant metal in the brain. It participates in many chemical reactions taking place in the central nervous system acting as a cofactor in key enzymatic reactions involved in neurotransmitter synthesis and degradation, dendritic arborization, and myelination.

Uncovering the unique characteristics of different groups of 5-HTR ligands with reference to their interaction with the target protein.

Background: The serotonin 5-HT receptor has attracted much more research attention, due to the therapeutic potential of its ligands being increasingly recognized, and the possibilities that lie ahead of these findings. There is a growing body of evidence indicating that these ligands have procognitive, pro-social, and anti-depressant properties, which offers new avenues for the development of treatments that could address socially important conditions related to the malfunctioning of the central nervous system. The aim of our study was to unravel the molecular determinants for 5-HTR ligands that govern their activity towards the receptor.

Unraveling psilocybin's therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression.

Rationale: Our study aimed to unravel the unknown mechanisms behind the exceptional efficacy of Psilocybin (PSI) in treating treatment-resistant depression (TRD). Focusing on Wistar-Kyoto (WKY) rats with a TRD phenotype and Wistar (WIS) rats as a normative comparison, we investigated behavioral and neuroplasticity-related responses to PSI, striving to shed light on the distinctive features of its antidepressant effects.

Objectives: We set out to assess the behavioral impact of acute and prolonged PSI administration on WKY and WIS rats, employing Novel Object Recognition (NORT), Social Interaction (SI), and Forced Swimming Test (FST).

CC Chemokine Family Members' Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury-A Review of Clinical and Experimental Findings.

Despite significant progress in modern medicine and pharmacology, damage to the nervous system with various etiologies still poses a challenge to doctors and scientists. Injuries lead to neuroimmunological changes in the central nervous system (CNS), which may result in both secondary damage and the development of tactile and thermal hypersensitivity. In our review, based on the analysis of many experimental and clinical studies, we indicate that the mechanisms occurring both at the level of the brain after direct damage and at the level of the spinal cord after peripheral nerve damage have a common immunological basis.

Research Report: A Link between Sertraline Treatment and Susceptibility to (Mis)information.

Recent research revealed that several psycho-cognitive processes, such as insensitivity to positive and negative feedback, cognitive rigidity, pessimistic judgment bias, and anxiety, are involved in susceptibility to fake news. All of these processes have been previously associated with depressive disorder and are sensitive to serotoninergic manipulations. In the current study, a link between chronic treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline and susceptibility to true and fake news was examined.

Further proof on the role of accumbal nNOS in cocaine-seeking behavior in rats.

Background: Cocaine use disorder (CUD) remains a severe health problem with no effective pharmacological therapy. One of the potential pharmacological strategies for CUD pharmacotherapy includes manipulations of the brain glutamatergic (Glu) system which is particularly involved in drug withdrawal and relapse. Previous research indicated a pivotal role of ionotropic N-methyl-D-aspartate (NMDA) receptors or metabotropic receptors' type 5 (mGlu) receptors in controlling the reinstatement of cocaine.

The Impact of LY487379 or CDPPB on eNOS Expression in the Mouse Brain and the Effect of Joint Administration of Compounds with NO Releasers on MK-801- or Scopolamine-Driven Cognitive Dysfunction in Mice.

The role of endothelial nitric oxide synthase (eNOS) in the regulation of a variety of biological processes is well established, and its dysfunction contributes to brain pathologies, including schizophrenia or Alzheimer's disease (AD). Positive allosteric modulators (PAMs) of metabotropic glutamate (mGlu) receptors were shown to be effective procognitive compounds, but little is known about their impact on eNOS expression and stability. Here, we investigated the influence of the acute and chronic administration of LY487379 or CDPPB (mGlu2 and mGlu5 PAMs), on eNOS expression in the mouse brain and the effect of the joint administration of the ligands with nitric oxide (NO) releasers, spermineNONOate or DETANONOate, in different combinations of doses, on MK-801- or scopolamine-induced amnesia in the novel object recognition (NOR) test.

Modulating Stress Susceptibility and Resilience: Insights from miRNA Manipulation and Neural Mechanisms in Mice.

This study explored the impact of microRNAs, specifically mmu-miR-1a-3p and mmu-miR-155-5p, on stress susceptibility and resilience in mice of different strains. Previous research had established that C57BL/6J mice were stress-susceptible, while NET-KO and SWR/J mice displayed stress resilience. These strains also exhibited variations in the serum levels of mmu-miR-1a-3p and mmu-miR-155-5p.