Anxiety is a severe social problem. It is a disease entity that occurs alone or accompanies other diseases such as depression, phobia, or post-traumatic stress disorder. Our earlier studies demonstrated that blockage of arachidonic acid (AA) pathway via inhibition of cyclooxygenase-2 (COX-2) enzyme can modulate mGluRs-induced anxiety-like behavior.
View Article and Find Full Text PDFMany addictive drugs increase stress hormone levels. They also alter the propensity of organisms to prospectively select actions based on long-term consequences. We hypothesized that cocaine causes inflexible action by increasing circulating stress hormone levels, activating the glucocorticoid receptor (GR).
View Article and Find Full Text PDFMetabotropic glutamate receptors (mGluRs) are part of the G protein-coupled receptors (GPCRs) family. They are coupled to G (group I) or G (groups II and III) proteins, which result in the generation of diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP) or the inhibition of adenylyl cyclase, respectively. mGluRs have been implicated in anxiety, depression, learning, and synaptic plasticity.
View Article and Find Full Text PDFGrowing evidence suggests that activators of nuclear factor erythroid-derived 2-like 2 (Nrf2), such as sulforaphane, may represent promising novel pharmacological targets for conditions related to oxidative stress, including depressive disorder. Therefore, we conducted a study to explore the behavioral and biochemical effects of repeated (14 days) sulforaphane (SFN) treatment in the olfactory bulbectomy (OB) animal model of depression. An open field test (OFT), splash test (ST), and spontaneous locomotor activity test (LA) were used to assess changes in depressive-like behavior and the potential antidepressant-like activity of SFN.
View Article and Find Full Text PDFTo elucidate the effect of cyclooxygenase-2 (COX-2) inhibition on corticosterone release, mice were divided into a group receiving NS398, a selective COX-2 inhibitor at a dose of 3 mg/kg for seven days, and a group receiving NS398 for fourteen days. After this time, the mice were sacrificed, and blood serum was collected. An ELISA protocol was used to analyze serum corticosterone levels.
View Article and Find Full Text PDFN-methyl-D-aspartic acid receptors (NMDARs) are the most studied receptors in mammalian brains. Their role in depression, cognition, schizophrenia, learning and memorization, Alzheimer's disease, and more is well documented. In the search for new drug candidates in depression, intensive studies have been conducted.
View Article and Find Full Text PDFThe lipid endocannabinoid system refers to endogenous cannabinoids (eCBs), the enzymes involved in their synthesis and metabolism, and the G protein-coupled cannabinoid receptors (GPCRs), CB1, and CB2. CB1 receptors (CB1Rs) are distributed in the brain at presynaptic terminals. Their activation induces inhibition of neurotransmitter release, which are gamma-aminobutyric acid (GABA), glutamate (Glu), dopamine, norepinephrine, serotonin, and acetylcholine.
View Article and Find Full Text PDFDepression is a serious neuropsychiatric disease affecting an increasing number of people worldwide. Cognitive deficits (including inattention, poor memory, and decision-making difficulties) are common in the clinical picture of depression. Cognitive impairment has been hypothesized to be one of the most important components of major depressive disorder (MDD; referred to as clinical depression), although typical cognitive symptoms are less frequent in people with depression than in people with schizophrenia or bipolar disorder (BD; sometimes referred to as manic-depressive disorder).
View Article and Find Full Text PDFThe serotonin 1A (5-HT) receptors and serotonin transporter (SERT) are important biological targets in the treatment of diseases of the central nervous system, especially for depression. In this study, new 3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives linked with the 3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole moiety were synthesised and evaluated for their affinity for 5-HT receptor and serotonin reuptake inhibition. Selected compounds were then tested for their affinity for D, 5-HT, 5-HT and 5-HT receptors, and also in in vitro metabolic stability assays in human microsomes.
View Article and Find Full Text PDFThe treatment of depression with pharmaceuticals is associated with many adverse side effects, including male fertility problems. The precise mechanisms by which these agents affect testicular cells remain largely unknown, but they are believed to induce cellular stress, which is sensed by the endoplasmic reticulum (ER) and the Golgi apparatus. These organelles are responsible for maintaining cellular homeostasis and regulating signal pathways that lead to autophagy or apoptosis.
View Article and Find Full Text PDFTrace elements or trace metals are essential components of enzymes, proteins, hormones and play a key role in biochemical processes, cell growth and differentiation, as well as in neurotransmission, affecting human physiology. In nature there are also heavy metals that exhibit toxic effects on the human body, including the brain. The importance of trace elements has been established in neurodegenerative disorders, schizophrenia, depression among others.
View Article and Find Full Text PDFThe strength and quality of the signal propagated by the glutamate synapse (Glu) depend, among other things, on the structure of the postsynaptic part and the quality of adhesion between the interacting components of the synapse. Postsynaptic density protein 95 (PSD95), mammalian target of rapamycin (mTOR), and Down syndrome cell adhesion molecule (DSCAM) are components of the proper functioning of an excitatory synapse. PSD95 is a member of the membrane-associated guanylate kinases protein family, mainly located at the postsynaptic density of the excitatory synapse.
View Article and Find Full Text PDFMental disorders and substance use disorders affect approximately 13% of the world's population [...
View Article and Find Full Text PDFThe brain functions through neuronal circuits and networks that are synaptically connected. This type of connection can exist due to physical forces that interact to stabilize local contacts in the brain. Adhesion is a fundamental physical phenomenon that allows different layers, phases, and tissues to connect.
View Article and Find Full Text PDFArch Biochem Biophys
March 2023
This study aimed to evaluate research findings on the role of polyunsaturated fatty acids (PUFAs) in neuronal signaling. Polyunsaturated fatty acids (PUFAs) are the building blocks of the brain and are responsible for the proper functioning of neurons, synapses, and neuronal communication. The deficiency of a significant component, omega-3 (ω-3) FA, in favor of omega-6 (ω-6) FA can exacerbate the course of mental illness and be one of the triggers of the cascade of neurodegenerative changes.
View Article and Find Full Text PDFSince we previously discovered that simultaneous inhibition of cyclooxygenase-2 (COX-2; a highly inducible enzyme, crucial for the conversion of arachidonic acid to prostaglandin G2, which plays a predominant role in the CNS) by NS398 and metabotropic glutamate receptor 5 (mGluR5) through the use of its antagonist [3-((2-methyl-4-thiazolyl)ethyl)pyridine; MTEP] alters mouse behavior (e.g., affects spatial learning, and induces/intensifies the antidepressant effect), our aim was to discover the mechanism responsible for these changes.
View Article and Find Full Text PDFPSD-95 is a component and a building block of an excitatory synapse. PSD-95 is a specialized protein that is part of a "combination lock" system responsible for plastic events at the synapse, such as receptor expression, which consequently induces changes in the PSD structure and thus affects synaptic plasticity. The possible involvement of PSD-95 in antidepressant side effects related to cognitive function and psychosis will be considered.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFThis study presents research related to the antiviral activity of painted surfaces containing galvanic microcells of zinc and copper. The aim of this study was to investigate the virucidal activity of galvanic microcells of zinc and copper grains fixed with adequate homogeneity and degree of aggregation in water-based acrylic paint layers in reference to a non-treated reference control. This paper provides evidence that a paint coating with a total copper surface area of 4.
View Article and Find Full Text PDFImipramine belongs to a group of tricyclic antidepressants (TCAs). It has been also documented that its antidepressant activity connects with the modulation of cytosolic phospholipase A (cPLA) and arachidonic acid (AA) turnover. Through this mechanism, imipramine can indirectly modify glutamate (Glu) transmission.
View Article and Find Full Text PDFSince we found that inhibition of cyclooxygenase-2 (COX-2) with concomitant application of a metabotropic glutamate receptor subtype 5 (mGluR5) antagonist (MTEP) down-regulates mGluR7 in the hippocampus (HC) and changes behavior of mice, our team decided to investigate the mechanism responsible for the observed changes. The amino acid glutamate (Glu) is a major excitatory neurotransmitter in the brain. Glu uptake is regulated by excitatory amino acid transporters (EAAT).
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