scholarly journals Brain Metabolic Profile after Intranasal vs. Intraperitoneal Clomipramine Treatment in Rats with Ultrasound Model of Depression

2021 ◽  
Vol 22 (17) ◽  
pp. 9598
Author(s):  
Olga Abramova ◽  
Yana Zorkina ◽  
Timur Syunyakov ◽  
Eugene Zubkov ◽  
Valeria Ushakova ◽  
...  
Keyword(s):  
Frontal Cortex ◽  
Molecular Mechanisms ◽  
Intraperitoneal Administration ◽  
Point Of View ◽  
Antidepressant Therapy ◽  
Antidepressant Effect ◽  
Routes Of Administration ◽  
Routes Of Drug Administration ◽  
The Brain ◽  
Clomipramine Treatment

Background: Molecular mechanisms of depression remain unclear. The brain metabolome after antidepressant therapy is poorly understood and had not been performed for different routes of drug administration before the present study. Rats were exposed to chronic ultrasound stress and treated with intranasal and intraperitoneal clomipramine. We then analyzed 28 metabolites in the frontal cortex and hippocampus. Methods: Rats’ behavior was identified in such tests: social interaction, sucrose preference, forced swim, and Morris water maze. Metabolic analysis was performed with liquid chromatography. Results: After ultrasound stress pronounced depressive-like behavior, clomipramine had an equally antidepressant effect after intranasal and intraperitoneal administration on behavior. Ultrasound stress contributed to changes of the metabolomic pathways associated with pathophysiology of depression. Clomipramine affected global metabolome in frontal cortex and hippocampus in a different way that depended on the route of administration. Intranasal route was associated with more significant changes of metabolites composition in the frontal cortex compared to the control and ultrasound groups while the intraperitoneal route corresponded with more profound changes in hippocampal metabolome compared to other groups. Since far metabolic processes in the brain can change in many ways depending on different routes of administration, the antidepressant therapy should also be evaluated from this point of view.

scholarly journals Histomorphometric and immunohistochemical evaluation of the frontal cerebral cortex in diabetic rats after treatment with melatonin

2020 ◽  
Vol 40 (12) ◽  
pp. 1077-1087
Author(s):  
Marina G.P. Baptista ◽  
Cintia G.M. Ferreira ◽  
Yuri M.L. Albuquerque ◽  
Carolline G. D’assunção ◽  
Rebeca C. Alves ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Frontal Cortex ◽  
Intraperitoneal Administration ◽  
Diabetic Rats ◽  
Hypoglycemic Agents ◽  
Albino Rats ◽  
Tnf Α ◽  
Frontal Cerebral Cortex ◽  
The Impact ◽  
The Brain

ABSTRACT: The central nervous system is vulnerable to complications caused by diabetes. These complications lead to increased oxidative stress in the brain, resulting in damage to the cerebral cortex, among other regions. Insulin and hypoglycemic agents are still the most widely used treatments. However, current research with an experimental model of diabetes suggests the use of antioxidants, such as melatonin. Thus, we tested the hypothesis that exogenous melatonin may decrease or prevent the effects of diabetes in the frontal cortex of the rat brain. Fifty albino rats were allocated into five groups: GC = rats without diabetes induction, GD = diabetic rats induced by streptozotocin, GDM = streptozotocin-induced and melatonin-treated diabetic rats, GDI = diabetic rats induced by streptozotocin and treated with insulin, GDMI = diabetic rats induced by streptozotocin and treated with melatonin and insulin simultaneously. Diabetes was induced by intraperitoneal administration of streptozotocin (60mg/kg). Insulin (5U/day) was administered subcutaneously and melatonin (10mg/kg) by drinking water; both treatments last days after. We analyzed animals’ weight, the cytokines IL-6 and TNF-α, apoptosis, glycogen, and did morphometry and histopathology of the frontal cortex were analyzed. The results showed that the cerebral cortex of the diabetic animals presented axonal degeneration, reduced number of neurons in the cortex, reduced glycogen, increased IL-6 and TNF-α expression, high apoptotic index, and reduced animal weight and the brain. Treatment with melatonin associated or not with insulin prevented such effects. Thus, we conclude that melatonin associated with insulin may be an alternative for avoiding the impact of diabetes in the brain’s frontal cortex.

scholarly journals Antidepressant-Like Effect of Bauhinia blakeana Dunn in a Neuroinflammation Model in Mice

2019 ◽  
Vol 29 (2) ◽  
pp. 113-120
Author(s):  
Maribel Herrera-Ruiz ◽  
Mayra A. Santillán-Urquiza ◽  
Ofelia Romero-Cerecero ◽  
Alejandro Zamilpa ◽  
Enrique Jiménez-Ferrer ◽  
...  
Keyword(s):  
Forced Swimming Test ◽  
Intraperitoneal Administration ◽  
Chemical Separation ◽  
Antidepressant Effect ◽  
Hydroalcoholic Extract ◽  
Main Compound ◽  
Tnf Α ◽  
Immobility Time ◽  
Swimming Test ◽  
The Brain

Objective: To evaluate the antidepressant effect of Bauhinia blakeana and a standardized fraction in the forced swimming test (FST) on mice with neuroinflammation induced with lipopolysaccharides (LPS). Materials and Methods: Evaluation of the antidepressant effect of Bauhinia blakeana hydroalcoholic extract (BbHA) and its fractions was carried out in behavioral tests on mice with LPS-induced neuroinflammation. Results: BbHA had a significant antidepressant effect, measured on healthy mice in the FST. Bio-guided chemical separation of the extract produced a methanolic fraction (BbMe), which decreased the immobility time in FST. In this test, the intraperitoneal administration of LPS induced depression in mice, and BbHA and BbMe counteracted this effect, significantly decreasing the induced depression. Quantification of inflammatory mediators (IL-10, IL-4, IL-6, IL-1β, and TNF-α) in the brain demonstrated that BbHA and BbMe effectively decreased the effect of LPS on the brain concentration of all measured cytokines. Conclusions: Bauhinia blakeana produced an antidepressant effect, while BbMe also exerted a modulating effect, on the damage induced by LPS. Rutin, a glycosylated flavonoid, was identified as the main compound in the active fraction, which could mediate in the antidepressant and immunomodulatory effect.

DIRECTIONS OF ASSOCIATIVE IDENTIFICATION OF PERSONAL NAMES

2019 ◽  
Vol 18 (28) ◽  
pp. 118-128
Author(s):  
Olena Karpenko ◽  
Tetiana Stoianova
Keyword(s):  
Proper Names ◽  
Mental Lexicon ◽  
Point Of View ◽  
Sound Symbolism ◽  
Personal Names ◽  
Communicative Process ◽  
Proper Name ◽  
Definition Of ◽  
Scientific Value ◽  
The Brain

The article is devoted to the study of personal names from a cognitive point of view. The study is based on the cognitive concept that speech actually exists not in the speech, not in linguistic writings and dictionaries, but in consciousness, in the mental lexicon, in the language of the brain. The conditions for identifying personal names can encompass not only the context, encyclopedias, and reference books, but also the sound form of the word. In the communicative process, during a free associative experiment, which included a name and a recipient’s mental lexicon. The recipient was assigned a task to quickly give some association to the name. The aggregate of a certain number of reactions of different recipients forms the associative field of a proper name. The associative experiment creates the best conditions for identifying the lexeme. The definition of a monosemantic personal name primarily includes the search of what it denotes, while during the process of identifying a polysemantic personal name recipients tend have different reactions. Scientific value is posed by the effect of the choice of letters for the name, sound symbolism, etc. The following belong to the generalized forms of identification: usage of a hyperonym; synonyms and periphrases or simple descriptions; associations denoting the whole (name stimulus) by reference to its part (associatives); cognitive structures such as “stimulus — association” and “whole (stimulus) — part (associative)”; lack of adjacency; mysterious associations. The topicality of the study is determined by its perspective to identify the directions of associative identification of proper names, which is one of the branches of cognitive onomastics. The purpose of the study is to identify, review, and highlight the directions of associative identification of proper names; the object of the research is the names in their entirety and variety; its subject is the existence of names in the mental lexicon, which determines the need for singling out the directions for the associative identification of the personal names.

Subjectivity as a sentient perspective and the role of interoception

2018 ◽  
Author(s):  
Helena De Preester
Keyword(s):  
Crucial Role ◽  
Point Of View ◽  
Basic Form ◽  
Bodily States ◽  
The Brain ◽  
Phenomenological Point

This chapter argues that the most basic form of subjectivity is different from and more fundamental than having a self, and forwards a hypothesis about the origin of subjectivity in terms of interoception. None of those topics are new, and a consensus concerning the homeostatic-interoceptive origin of subjectivity is rapidly growing in the domains of the neurosciences and psychology. This chapter critically explores that growing consensus, and it argues that the idea that the brain topographically represents bodily states is unfit for thinking about the coming about of subjectivity. In the first part, four inherent characteristics of subjectivity are discussed from a philosophical phenomenological point of view. The second part explores whether a model of subjectivity in which interoception maintains its crucial role is possible without relying on topographical representations of the in-depth body, and giving due to the inherent characteristics of subjectivity.

scholarly journals Cytomegalovirus Infection and Inflammation in Developing Brain

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1078
Author(s):  
Fran Krstanović ◽  
William J. Britt ◽  
Stipan Jonjić ◽  
Ilija Brizić
Keyword(s):  
Cytomegalovirus Infection ◽  
Hcmv Infection ◽  
Severe Disease ◽  
Intraperitoneal Administration ◽  
Inflammatory Factors ◽  
Mcmv Infection ◽  
Newborn Mice ◽  
Organ Systems ◽  
Congenital Hcmv Infection ◽  
The Brain

Human cytomegalovirus (HCMV) is a highly prevalent herpesvirus that can cause severe disease in immunocompromised individuals and immunologically immature fetuses and newborns. Most infected newborns are able to resolve the infection without developing sequelae. However, in severe cases, congenital HCMV infection can result in life-threatening pathologies and permanent damage of organ systems that possess a low regenerative capacity. Despite the severity of the problem, HCMV infection of the central nervous system (CNS) remains inadequately characterized to date. Cytomegaloviruses (CMVs) show strict species specificity, limiting the use of HCMV in experimental animals. Infection following intraperitoneal administration of mouse cytomegalovirus (MCMV) into newborn mice efficiently recapitulates many aspects of congenital HCMV infection in CNS. Upon entering the CNS, CMV targets all resident brain cells, consequently leading to the development of widespread histopathology and inflammation. Effector functions from both resident cells and infiltrating immune cells efficiently resolve acute MCMV infection in the CNS. However, host-mediated inflammatory factors can also mediate the development of immunopathologies during CMV infection of the brain. Here, we provide an overview of the cytomegalovirus infection in the brain, local immune response to infection, and mechanisms leading to CNS sequelae.

scholarly journals Sublethal Exposure Effects of the Neonicotinoid Clothianidin Strongly Modify the Brain Transcriptome and Proteome in the Male Moth Agrotis ipsilon

Insects ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 152
Author(s):  
Camille Meslin ◽  
Françoise Bozzolan ◽  
Virginie Braman ◽  
Solenne Chardonnet ◽  
Cédric Pionneau ◽  
...  
Keyword(s):  
Sex Pheromone ◽  
Molecular Mechanisms ◽  
Insect Pest ◽  
Agrotis Ipsilon ◽  
Positive Effects ◽  
Male Moth ◽  
Hormetic Effect ◽  
Pest Insects ◽  
Neuronal Processes ◽  
The Brain

Insect pest management relies mainly on neurotoxic insecticides, including neonicotinoids such as clothianidin. The residual accumulation of low concentrations of these insecticides can have positive effects on target pest insects by enhancing various life traits. Because pest insects often rely on sex pheromones for reproduction and olfactory synaptic transmission is cholinergic, neonicotinoid residues could indeed modify chemical communication. We recently showed that treatments with low doses of clothianidin could induce hormetic effects on behavioral and neuronal sex pheromone responses in the male moth, Agrotis ipsilon. In this study, we used high-throughput RNAseq and proteomic analyses from brains of A. ipsilon males that were intoxicated with a low dose of clothianidin to investigate the molecular mechanisms leading to the observed hormetic effect. Our results showed that clothianidin induced significant changes in transcript levels and protein quantity in the brain of treated moths: 1229 genes and 49 proteins were differentially expressed upon clothianidin exposure. In particular, our analyses highlighted a regulation in numerous enzymes as a possible detoxification response to the insecticide and also numerous changes in neuronal processes, which could act as a form of acclimatization to the insecticide-contaminated environment, both leading to enhanced neuronal and behavioral responses to sex pheromone.

scholarly journals DNA Methylation Profiles of Tph1A and BDNF in Gut and Brain of L. Rhamnosus-Treated Zebrafish

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 142
Author(s):  
Mariella Cuomo ◽  
Luca Borrelli ◽  
Rosa Della Monica ◽  
Lorena Coretti ◽  
Giulia De Riso ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
The Past ◽  
Targeted Analysis ◽  
Lack Of Information ◽  
High Resolution Power ◽  
Resolution Level ◽  
Health And Disease ◽  
High Doses ◽  
The Brain

The bidirectional microbiota–gut–brain axis has raised increasing interest over the past years in the context of health and disease, but there is a lack of information on molecular mechanisms underlying this connection. We hypothesized that change in microbiota composition may affect brain epigenetics leading to long-lasting effects on specific brain gene regulation. To test this hypothesis, we used Zebrafish (Danio Rerio) as a model system. As previously shown, treatment with high doses of probiotics can modulate behavior in Zebrafish, causing significant changes in the expression of some brain-relevant genes, such as BDNF and Tph1A. Using an ultra-deep targeted analysis, we investigated the methylation state of the BDNF and Tph1A promoter region in the brain and gut of probiotic-treated and untreated Zebrafishes. Thanks to the high resolution power of our analysis, we evaluated cell-to-cell methylation differences. At this resolution level, we found slight DNA methylation changes in probiotic-treated samples, likely related to a subgroup of brain and gut cells, and that specific DNA methylation signatures significantly correlated with specific behavioral scores.

scholarly journals Ketamine Alters Functional Plasticity of Astroglia: An Implication for Antidepressant Effect

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 573
Author(s):  
Matjaž Stenovec
Keyword(s):  
Molecular Mechanisms ◽  
Neuronal Firing ◽  
Fusion Pore ◽  
Antidepressant Effect ◽  
Intracellular Camp ◽  
Lateral Habenula ◽  
Vesicle Recycling ◽  
The Central Nervous System ◽  
Inward Rectifying Potassium Channel ◽  
Antidepressant Action

Ketamine, a non-competitive N–methyl–d–aspartate receptor (NMDAR) antagonist, exerts a rapid, potent and long-lasting antidepressant effect, although the cellular and molecular mechanisms of this action are yet to be clarified. In addition to targeting neuronal NMDARs fundamental for synaptic transmission, ketamine also affects the function of astrocytes, the key homeostatic cells of the central nervous system that contribute to pathophysiology of major depressive disorder. Here, I review studies revealing that (sub)anesthetic doses of ketamine elevate intracellular cAMP concentration ([cAMP]i) in astrocytes, attenuate stimulus-evoked astrocyte calcium signaling, which regulates exocytotic secretion of gliosignaling molecules, and stabilize the vesicle fusion pore in a narrow configuration, possibly hindering cargo discharge or vesicle recycling. Next, I discuss how ketamine affects astrocyte capacity to control extracellular K+ by reducing vesicular delivery of the inward rectifying potassium channel (Kir4.1) to the plasmalemma that reduces the surface density of Kir4.1. Modified astroglial K+ buffering impacts upon neuronal firing pattern as demonstrated in lateral habenula in a rat model of depression. Finally, I highlight the discovery that ketamine rapidly redistributes cholesterol in the astrocyte plasmalemma, which may alter the flux of cholesterol to neurons. This structural modification may further modulate a host of processes that synergistically contribute to ketamine’s rapid antidepressant action.

scholarly journals Molecular mechanisms of metabotropic GABAB receptor function

2021 ◽  
Vol 7 (22) ◽  
pp. eabg3362
Author(s):  
Hamidreza Shaye ◽  
Benjamin Stauch ◽  
Cornelius Gati ◽  
Vadim Cherezov
Keyword(s):  
G Protein ◽  
Molecular Mechanisms ◽  
Gabab Receptor ◽  
Neurological Diseases ◽  
Activation Mechanism ◽  
Allosteric Modulators ◽  
Inhibitory Neurotransmitter ◽  
Therapeutic Drugs ◽  
G Protein Coupled ◽  
The Brain

Metabotropic γ-aminobutyric acid G protein–coupled receptors (GABAB) represent one of the two main types of inhibitory neurotransmitter receptors in the brain. These receptors act both pre- and postsynaptically by modulating the transmission of neuronal signals and are involved in a range of neurological diseases, from alcohol addiction to epilepsy. A series of recent cryo-EM studies revealed critical details of the activation mechanism of GABAB. Structures are now available for the receptor bound to ligands with different modes of action, including antagonists, agonists, and positive allosteric modulators, and captured in different conformational states from the inactive apo to the fully active state bound to a G protein. These discoveries provide comprehensive insights into the activation of the GABAB receptor, which not only broaden our understanding of its structure, pharmacology, and physiological effects but also will ultimately facilitate the discovery of new therapeutic drugs and neuromodulators.

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