Investigating whether alcohol is transformed to norepinephrine or dopamine in the mouse brain.

Background: A number of rodent studies have investigated the effects of alcohol (ethanol) administration on the catecholaminergic neurotransmitters, norepinephrine (NE) and dopamine (DA). These studies suggest that presentation of alcohol to mice or rats can alter brain levels of NE and DA, in various subregions. Other studies have presented the hypothesis that there may be an unidentified pathway in rodents, and other organisms, that actually transforms ethanol to NE or DA.

Effect of SSR504734, a Selective Glycine Transporter Type 1 Inhibitor, on Seizure Thresholds, Neurotransmitter Levels, and Inflammatory Markers in Mice.

Studies have revealed that inhibition of glycine transporter type 1 (GlyT1) may provide a balanced regulation between excitation and inhibition in some brain structures and, thereby, modulate seizure activity. Data on the role of GlyT1 in epilepsy are, however, very limited. Here, we examined the effect of SSR504734, a highly selective and reversible GlyT1 inhibitor, on three acute seizure tests in mice.

The Novel Imipramine-Magnesium Complex Exerts Antidepressant-like Activity in Mice Subjected to the Forced Swim Test and the Tail Suspension Test.

The objective of this study was to assess the antidepressant efficacy of a novel imipramine-magnesium (IMI-Mg) complex in comparison to the administration of imipramine and magnesium individually. The study utilized adult male albino Swiss mice. Behavioral assessments were conducted using the forced swim test (FST) and the tail suspension test (TST).

Investigating the role of GPR39 in treatment of stress-induced depression and anxiety.

Rationale: Chronic stress is one of the leading causes of depression. Yet, knowledge of the pathomechanism of this process still eludes us. Chronic unpredictable mild stress (CUMS) model of depression enables researchers to look for a root cause of the disease in mice by mimicking a stressful human environment.

Discovery and Profiling of New Multimodal Phenylglycinamide Derivatives as Potent Antiseizure and Antinociceptive Drug Candidates.

We developed a focused series of original phenyl-glycinamide derivatives which showed potent activity across mouse seizure models, namely, maximal electroshock (MES) and 6 Hz (using both 32 and 44 mA current intensities) seizure models. Following intraperitoneal (.) administration, compound , which was identified as a lead molecule, demonstrated potent protection against all seizure models with ED values of 73.

Antidepressant effects of selective adenosine receptor antagonists targeting the A1 and A2A receptors administered jointly with NMDA receptor ligands: behavioral, biochemical and molecular investigations in mice.

Background: The objective of the study was to ascertain the antidepressant potential of the co-administration of NMDA receptor ligands and selective adenosine A1 and A2A receptor antagonists.

Methods: The forced swim test (FST) and spontaneous locomotor activity test were carried out in adult male naïve mice. Before the behavioral testing, animals received DPCPX (a selective adenosine A1 receptor antagonist, 1 mg/kg) or istradefylline (a selective adenosine A2A receptor antagonist, 0.

Luteolin for neurodegenerative diseases: a review.

Neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and multiple sclerosis affect millions of people around the world. In addition to age, which is a key factor contributing to the development of all neurodegenerative diseases, genetic and environmental components are also important risk factors. Current methods of treating neurodegenerative diseases are mostly symptomatic and do not eliminate the cause of the disease.

TRPV1 channel in the pathophysiology of epilepsy and its potential as a molecular target for the development of new antiseizure drug candidates.

Identification of transient receptor potential cation channel, subfamily V member 1 (TRPV1), also known as capsaicin receptor, in 1997 was a milestone achievement in the research on temperature sensation and pain signalling. Very soon after it became evident that TRPV1 is implicated in a wide array of physiological processes in different peripheral tissues, as well as in the central nervous system, and thereby could be involved in the pathophysiology of numerous diseases. Increasing evidence suggests that modulation of TRPV1 may also affect seizure susceptibility and epilepsy.

Novel Alaninamide Derivatives with Drug-like Potential for Development as Antiseizure and Antinociceptive Therapies─In Vitro and In Vivo Characterization.

In the present study, a series of original alaninamide derivatives have been designed applying a combinatorial chemistry approach, synthesized, and characterized in the and assays. The obtained molecules showed potent and broad-spectrum activity in basic seizure models, namely, the maximal electroshock (MES) test, the 6 Hz (32 mA) seizure model, and notably, the 6 Hz (44 mA) model of pharmacoresistant seizures. Most potent compounds and displayed the following pharmacological values: ED = 64.

Role of Adipose Tissue Hormones in Pathogenesis of Cryptoglandular Anal Fistula.

The cryptoglandular perianal fistula is a common benign anorectal disorder that is managed mainly with surgery and in some cases may be an extremely challenging condition. Perianal fistulas are often characterized by significantly decreased patient quality of life. Lack of fully recognized pathogenesis of this disease makes it difficult to treat it properly.

Therapeutic potential of stilbenes in neuropsychiatric and neurological disorders: A comprehensive review of preclinical and clinical evidence.

Neuropsychiatric disorders are anticipated to be a leading health concern in the near future, emphasizing an outstanding need for the development of new effective therapeutics to treat them. Stilbenes, with resveratrol attracting the most attention, are an example of multi-target compounds with promising therapeutic potential for a broad array of neuropsychiatric and neurological conditions. This review is a comprehensive summary of the current state of research on stilbenes in several neuropsychiatric and neurological disorders such as depression, anxiety, schizophrenia, autism spectrum disorders, epilepsy, traumatic brain injury, and neurodegenerative disorders.

The effect of psychoactive bacteria, Bifidobacterium longum Rosell®-175 and Lactobacillus rhamnosus JB-1, on brain proteome profiles in mice.

Rationale: The gut microbiota may play an important role in the development and functioning of the mammalian central nervous system. The assumption of the experiment was to prove that the use of probiotic bacterial strains in the diet of mice modifies the expression of brain proteins involved in metabolic and immunological processes.

Objectives And Results: Albino Swiss mice were administered with Bifidobacterium longum Rosell®-175 or Lactobacillus rhamnosus JB-1 every 24 h for 28 days.

GPR39: An orphan receptor begging for ligands.

Progress in the understanding of the receptor GPR39 is held up by inconsistent pharmacological data. First, the endogenous ligand(s) remain(s) contentious. Data pointing to zinc ions (Zn) and/or eicosanoids as endogenous ligands are a matter of debate.

Effect of dietary supplementation with Lactobacillus helveticus R0052 on seizure thresholds and antiseizure potency of sodium valproate in mice.

Objective: Both animal and human studies, though limited, showed that multi-strain probiotic supplementation may reduce the number of seizures and/or seizure severity. Here, we evaluated the effect of a single strain probiotic supplementation on seizure susceptibility, antiseizure efficacy of sodium valproate, and several behavioral parameters in mice.

Methods: Lactobacillus helveticus R0052 was given orally for 28 days.

TC-G 1008 facilitates epileptogenesis by acting selectively at the GPR39 receptor but non-selectively activates CREB in the hippocampus of pentylenetetrazole-kindled mice.

The pharmacological activation of the GPR39 receptor has been proposed as a novel strategy for treating seizures; however, this hypothesis has not been verified experimentally. TC-G 1008 is a small molecule agonist increasingly used to study GPR39 receptor function but has not been validated using gene knockout. Our aim was to assess whether TC-G 1008 produces anti-seizure/anti-epileptogenic effects in vivo and whether the effects are mediated by GPR39.

In Vivo and In Vitro Characterization of Close Analogs of Compound KA-11, a New Antiseizure Drug Candidate.

Epilepsy is a neurological disorder involving a number of disease syndromes with a complex etiology. A properly matched antiseizure drug (ASD) gives remission in up to 70% of patients. Nevertheless, there is still a group of about 30% of patients suffering from drug-resistant epilepsy.

Anticonvulsant Profile of Selected Medium-Chain Fatty Acids (MCFAs) Co-Administered with Metformin in Mice in Acute and Chronic Treatment.

In contrast to the other components of the medium-chain triglycerides ketogenic diet (MCT KD), i.e., caprylic acid (CA8), a comprehensive evaluation of caproic (CA6) and lauric acids' (CA12) properties in standard chemical and electrical seizure tests in mice has not yet been performed.

Response of murine gut microbiota to a prebiotic based on oligosaccharides derived via hydrolysis of fungal α-(1→3)-d-glucan: Preclinical trial study on mice.

We investigated the modulating effect of α-(1→3)-glucooligosaccharides (GOS), i.e. a product of fungal α-(1→3)-d-glucan hydrolysis, on the gut microbiota composition.

Dietary Zinc Differentially Regulates the Effects of the GPR39 Receptor Agonist, TC-G 1008, in the Maximal Electroshock Seizure Test and Pentylenetetrazole-Kindling Model of Epilepsy.

The G-protein coupled receptor 39 (GPR39) is gaining increasing attention as a target for future drugs, yet there are gaps in the understanding of its pharmacology. Zinc is an endogenous agonist or an allosteric modulator, while TC-G 1008 is a synthetic, small molecule agonist. Zinc is also a positive allosteric modulator for the activity of TC-G 1008 at GPR39.

Is the peroxisome proliferator-activated receptor gamma a putative target for epilepsy treatment? Current evidence and future perspectives.

The peroxisome proliferator-activated receptor gamma (PPARγ), which belongs to the family of nuclear receptors, has been mainly studied as an important factor in metabolic disorders. However, in recent years the potential role of PPARγ in different neurological diseases has been increasingly investigated. Especially, in the search of therapeutic targets for patients with epilepsy the question of the involvement of PPARγ in seizure control has been raised.

Discovery of ()--Benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide [], a Novel Orally Bioavailable EAAT2 Modulator with Drug-like Properties and Potent Antiseizure Activity .

[] showed broad-spectrum antiseizure activity across mouse seizure models: maximal electroshock (MES), 6 Hz (32/44 mA), acute pentylenetetrazol (PTZ), and PTZ-kindling. A remarkable separation between antiseizure activity and CNS-related adverse effects was also observed. studies with primary glia cultures and COS-7 cells expressing the glutamate transporter EAAT2 showed enhancement of glutamate uptake, revealing a stereoselective positive allosteric modulator (PAM) effect, further supported by molecular docking simulations.

Alterations of Serum Magnesium Concentration in Animal Models of Seizures and Epilepsy-The Effects of Treatment with a GPR39 Agonist and Knockout of the Gene.

Several ligands have been proposed for the GPR39 receptor, including the element zinc. The relationship between GPR39 and magnesium homeostasis has not yet been examined, nor has such a relationship in the context of seizures/epilepsy. We used samples from mice that were treated with an agonist of the GPR39 receptor (TC-G 1008) and underwent acute seizures (maximal electroshock (MES)- or 6-hertz-induced seizures) or a chronic, pentylenetetrazole (PTZ)-induced kindling model of epilepsy.

New Phenylglycinamide Derivatives with Hybrid Structure as Candidates for New Broad-Spectrum Anticonvulsants.

In the present study, a focused combinatorial chemistry approach was applied to merge structural fragments of well-known TRPV1 antagonists with a potent anticonvulsant lead compound, , that was previously discovered by our group. Consequently, a series of 22 original compounds has been designed, synthesized, and characterized in the in vivo and in vitro assays. The obtained compounds showed robust in vivo antiseizure activity in the maximal electroshock (MES) test and in the 6 Hz seizure model (using both 32 and 44 mA current intensities).