The multipotent role of metallothionein in the nervous system

2013 ◽  
Vol 21 (2) ◽  
pp. 113-119
Author(s):  
G. А. Ushakova ◽  
Y. P. Kovalchuk
Keyword(s):  
Nervous System ◽  
Postoperative Pain ◽  
Physiological Activity ◽  
Toxic Metal ◽  
Exploratory Activity ◽  
Cysteine Residues ◽  
Control Group ◽  
The Family ◽  
The Brain

We provide a commentary on current experimental and theoretical advances and frame our consideration in terms of the possible functions of MT I+II in the nervous system. Metallothioneins (MT) are a family of small cysteine rich proteins, which since their discovery in 1957 have been implicated in a range of roles including toxic metal detoxification, protection against oxidative stress, and as a metallochaperone involved in the homeostasis of both zinc and copper. The most well studied member of the family is the mammalian metallothionein, which consists of two domains: a β-domain with 9 cysteine residues and an α-domain with 11 cysteine residues. Despite over half a century of research, the exact functions of MT in the nervous system are still unknown. Our studies have shown that the distribution of MT-I+II in the brain after prolonged intoxication, inhalation of 0.1% CdCl2 for 1 hour twice a week over 19 weeks, is dependent on the part of the brain. The metallothionein level declines more than 4 times in the hippocampus 3 weeks after continuous intoxication of 0.1% CdCl2. The level of MT-I+II in the cerebral cortex decreased by 1.5 times compared with the control group and did not change significantly in the cerebellum and thalamus/hypothalamus. The results of an experimental model of postoperative pain indicated that injection with MT-II prevents the development of postoperative hyperalgesia in response to mild alteration of physiological activity. Activation of locomotory and exploratory activity, and decrease of anxiety in rats under MT-II treatment at 100 µg/rat manifests itself on the 4th day after surgery. Our experimental data indicate the multipotent function of MT I+II in the rat brain both as a metal detoxifier and as an inhibitor of postoperative pain. 

scholarly journals Investigating cytosolic 5′-nucleotidase II family genes as candidates for neuropsychiatric disorders in Drosophila (114/150 chr)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Euginia L. Singgih ◽  
Monique van der Voet ◽  
Marlies Schimmel-Naber ◽  
Emma L. Brinkmann ◽  
Annette Schenck ◽  
...  
Keyword(s):  
Nervous System ◽  
Model Organism ◽  
Neuropsychiatric Disorders ◽  
Genetic Associations ◽  
Altered Expression ◽  
The Family ◽  
Brain Expression ◽  
Hydrolysis Of ◽  
The Brain

AbstractCytosolic 5′-nucleotidases II (cNT5-II) are an evolutionary conserved family of 5′-nucleotidases that catalyze the intracellular hydrolysis of nucleotides. In humans, the family is encoded by five genes, namely NT5C2, NT5DC1, NT5DC2, NT5DC3, and NT5DC4. While very little is known about the role of these genes in the nervous system, several of them have been associated with neuropsychiatric disorders. Here, we tested whether manipulating neuronal expression of cNT5-II orthologues affects neuropsychiatric disorders-related phenotypes in the model organism Drosophila melanogaster. We investigated the brain expression of Drosophila orthologues of cNT5-II family (dNT5A-CG2277, dNT5B-CG32549, and dNT5C-CG1814) using quantitative real-time polymerase chain reaction (qRT-PCR). Using the UAS/Gal4 system, we also manipulated the expression of these genes specifically in neurons. The knockdown was subjected to neuropsychiatric disorder-relevant behavioral assays, namely light-off jump reflex habituation and locomotor activity, and sleep was measured. In addition, neuromuscular junction synaptic morphology was assessed. We found that dNT5A, dNT5B, and dNT5C were all expressed in the brain. dNT5C was particularly enriched in the brain, especially at pharate and adult stages. Pan-neuronal knockdown of dNT5A and dNT5C showed impaired habituation learning. Knockdown of each of the genes also consistently led to mildly reduced activity and/or increased sleep. None of the knockdown models displayed significant alterations in synaptic morphology. In conclusion, in addition to genetic associations with psychiatric disorders in humans, altered expression of cNT5-II genes in the Drosophila nervous system plays a role in disease-relevant behaviors.

scholarly journals The Role of Neuropeptide Y in the Nucleus Accumbens

2021 ◽  
Vol 22 (14) ◽  
pp. 7287
Author(s):  
Masaki Tanaka ◽  
Shunji Yamada ◽  
Yoshihisa Watanabe
Keyword(s):  
Nervous System ◽  
Nucleus Accumbens ◽  
Neuropeptide Y ◽  
Emotional Behavior ◽  
Characteristic Functions ◽  
Receptor Subtypes ◽  
Neuroendocrine Mechanisms ◽  
Fear And Anxiety ◽  
The Brain

Neuropeptide Y (NPY), an abundant peptide in the central nervous system, is expressed in neurons of various regions throughout the brain. The physiological and behavioral effects of NPY are mainly mediated through Y1, Y2, and Y5 receptor subtypes, which are expressed in regions regulating food intake, fear and anxiety, learning and memory, depression, and posttraumatic stress. In particular, the nucleus accumbens (NAc) has one of the highest NPY concentrations in the brain. In this review, we summarize the role of NPY in the NAc. NPY is expressed principally in medium-sized aspiny neurons, and numerous NPY immunoreactive fibers are observed in the NAc. Alterations in NPY expression under certain conditions through intra-NAc injections of NPY or receptor agonists/antagonists revealed NPY to be involved in the characteristic functions of the NAc, such as alcohol intake and drug addiction. In addition, control of mesolimbic dopaminergic release via NPY receptors may take part in these functions. NPY in the NAc also participates in fat intake and emotional behavior. Accumbal NPY neurons and fibers may exert physiological and pathophysiological actions partly through neuroendocrine mechanisms and the autonomic nervous system.

scholarly journals Role of Nitric Oxide in Regulation of Brain Stem Circulation during Hypotension

1997 ◽  
Vol 17 (10) ◽  
pp. 1089-1096 ◽  
Author(s):  
Kazunori Toyoda ◽  
Kenichiro Fujii ◽  
Setsuro Ibayashi ◽  
Tetsuhiko Nagao ◽  
Takanari Kitazono ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Brain Stem ◽  
Topical Application ◽  
Basilar Artery ◽  
Group Versus ◽  
Control Group ◽  
Cranial Window ◽  
Severe Hypotension ◽  
The Brain

We tested the hypothesis that nitric oxide (NO) plays a role in CBF autoregulation in the brain stem during hypotension. In anesthetized rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and its branches were measured through an open cranial window during stepwise hemorrhagic hypotension. During topical application of 10−5 mol/L and 10−4 mol/L Nω-nitro-L-arginine (L-NNA), a nonselective inhibitor of nitric oxide synthase (NOS), CBF started to decrease at higher steps of mean arterial blood pressure in proportion to the concentration of L-NNA in stepwise hypotension (45 to 60 mm Hg in the 10−5 mol/L and 60 to 75 mm Hg in the 10−4 mol/L L-NNA group versus 30 to 45 mm Hg in the control group). Dilator response of the basilar artery to severe hypotension was significantly attenuated by topical application of L-NNA (maximum dilatation at 30 mm Hg: 16 ± 8% in the 10−5 mol/L and 12 ± 5% in the 10−4 mol/L L-NNA group versus 34 ± 4% in the control group), but that of the branches was similar between the control and L-NNA groups. Topical application of 10−5 mol/L 7-nitro indazole, a selective inhibitor of neuronal NOS, did not affect changes in CBF or vessel diameter through the entire pressure range. Thus, endothelial but not neuronal NO seems to take part in the regulation of CBF to the the brain stem during hypotension around the lower limits of CBF autoregulation. The role of NO in mediating dilatation in response to hypotension appears to be greater in large arteries than in small ones.

scholarly journals Activation of central 5-HT2A receptor in brain inhibited the seizure-induced respiratory arrest in the DBA/1 mouse SUDEP model

2020 ◽  
Author(s):  
Yue Shen ◽  
HaiXiang Ma ◽  
XiTing Lian ◽  
LeYuan Gu ◽  
Qian Yu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Drug Resistance ◽  
Nervous System ◽  
Underlying Mechanism ◽  
Respiratory Arrest ◽  
Acoustic Stimulation ◽  
Unexpected Death ◽  
Anti Epileptic Drug ◽  
The Brain

AbstractSudden unexpected death in epilepsy (SUDEP) is the fatal cause leading to the death of epilepsy patients with anti-epileptic drug resistance. However, the underlying mechanism of SUDEP remains to be elusive. Our previous study demonstrated that enhancement of serotonin (5-HT) synthesis by intraperitoneal (IP) injection of 5-hydroxytryptophan in brain significantly reduced the incidence of seizure-induced respiratory arrest (S-IRA) in DBA/1 mice SUDEP models. Given that 5-HT2A receptor (5-HT2AR) acts an important role in mediating respiration system in brain, we hypothesized that 5-HT2AR is of great significance to modulate S-IRA and SUDEP. To test this hypothesis, we examined whether the decreased incidence S-IRA evoked by either acoustic stimulation or PTZ by blocking 5-HT2AR by administration with ketanserin (KET), a selective antagonist of 5HT2AR, in DBA/1 mice SUDEP models to test the role of 5-HT2AR modulating S-IRA. Our results suggested that the decreased incidence of S-IRA by 5-Hydroxytryptophan (5-HTP), a precursor for central nervous system (CNS) serotonin (5-HT) synthesis, was significantly reversed by IP and intracerebroventricularly (ICV) injection of ketanserin in our models. Thus, our data suggested that 5-HT2AR in the brain may be a potential and specific target to prevent SUDEP.

scholarly journals Analysis of electrogenesis’ changes in mental retardation persons by using computer electroencephalography

2021 ◽  
Vol 11 (11) ◽  
pp. 249-265
Author(s):  
B. Lobasyuk ◽  
L. Bartsevich ◽  
A. Zamkovaya
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mental Retardation ◽  
Theta Rhythm ◽  
Cognitive Activity ◽  
Control Group ◽  
Bioelectrical Activity ◽  
The Central Nervous System ◽  
Beta Rhythms ◽  
The Brain

Justification. Mental retardation is a persistent decrease in human cognitive activity against the background of organic damage to the central nervous system. Neurophysiological diagnostics, in particular electroencephalography (EEG), most adequately reflects the morpho-functional state of the central nervous system, which is the basis of the mechanisms of mental activity, and the originality of the bioelectrical activity of the brain can be considered as the main indicator that determines a decrease in the level of intellectual development and, thereby, characterizes this state. This provision actualizes the search for highly informative indicators of the originality of the bioelectrical activity of the brain in children with intellectual disabilities. Purspose. With the use of periodometric analysis investigate EEG’s indicators and interhemispheric asymmetry of rhythms amplitudes in MR patients. Materials and methods. The EEG was recorded in a state of calm wakefulness with closed eyes with Neuron-Spectrum-2 electroencephalograph. Differences in indicators were tracked using the calculation of the coefficient of compliance (CC), EEG functional asymmetry coefficients in amplitude were determined, too. Results. It was revealed that in MR patients the amplitudes of the rhythms were greater than in healthy subjects. The greatest increase was determined in theta rhythm in the anterior temporal and posterior temporal leads in the left hemispheres. Duration indices in the delta, theta and alpha ranges of the EEG in mental retardation compared with the control group were increased, and the indices of the duration of beta rhythms - decreased. When analyzing FMPA in MR persons it turned out that in right-handers the negativeness of FMPA indices increased, and in left-handers there was an increase in the positivity of FMPA indices. Conclusions 1. With mental retardation, the amplitudes of the rhythms were greater than in healthy people. The greatest increase was determined in theta rhythm in the anterior temporal and posterior temporal leads in the left hemispheres. 2. The indices of duration in the delta, theta and alpha ranges of the EEG of MR subjects were increased, and the indices of the duration of beta rhythms – decreased. 3. When analyzing FMPA in MR persons, it turned out that in right-handers the negativeness of FMPA indices increased, and in left-handers there was an increase in the positivity of FMPA indices.

Correction of Psychological Status by Family Focused Technologies

2016 ◽  
pp. 129-131
Author(s):  
Serhii Vdovychenko
Keyword(s):  
Traditional Approach ◽  
Married Couple ◽  
Psychological Status ◽  
Control Group ◽  
Premature Births ◽  
The Family ◽  
Risk Patients ◽  
Individual Preparation

The objective: to show a role of the family focused technologies in correction of psychological status and depression of frequency of pathology of pregnancy at women of high obstetric risk. Patients and methods: for determination of efficiency of prophylaxis of pathology of pregnancy on the basis of use of the family focused technologies complex clinical-psychological and laboratory and tool examination of 300 women with factors of obstetric risk which were divided into two groups was conducted. In the main group – 182 women with motivation on partner labors to which provided training on system of individual preparation of married couple to labors. The control group consisted of 118 women with a traditional approach to pain management that have not been prenatal training. Results. Use of the family focused technologies during pregnancy allows correction of psyhological status and to reduce significantly the frequency of the main complications of pregnancy, especially not incubation and premature births. Conclusion. In our opinion, the technique is simple, available and can widely be used in practical health care at women with high obstetric risk.

Сellular and Molecular Mechanisms of Proinflammatory Monocytes Participation in the Pathogenesis of Mental Disorders. Part 3

Psychiatry ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 125-134
Author(s):  
E. F. Vasilyeva ◽  
O. S. Brusov
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mental Disorders ◽  
Molecular Mechanisms ◽  
Microglial Cells ◽  
Inflammatory Reactions ◽  
Mental Diseases ◽  
The Central Nervous System ◽  
The Brain

Background: at present, the important role of the monocyte-macrophage link of immunity in the pathogenesis of mental diseases has been determined. In the first and second parts of our review, the cellular and molecular mechanisms of activation of monocytes/macrophages, which secreting proinflammatory CD16 receptors, cytokines, chemokines and receptors to them, in the development of systemic immune inflammation in the pathogenesis of somatic diseases and mental disorders, including schizophrenia, bipolar affective disorder (BAD) and depression were analyzed. The association of high levels of proinflammatory activity of monocytes/macrophages in patients with mental disorders with somatic comorbidity, including immune system diseases, is shown. It is known that proinflammatory monocytes of peripheral blood, as a result of violation of the integrity of the hematoencephalic barrier can migrate to the central nervous system and activate the resident brain cells — microglia, causing its activation. Activation of microglia can lead to the development of neuroinammation and neurodegenerative processes in the brain and, as a result, to cognitive disorders. The aim of review: to analyze the results of the main scientific studies concerning the role of cellular and molecular mechanisms of peripheral blood monocytes interaction with microglial cells and platelets in the development of neuroinflammation in the pathogenesis of mental disorders, including Alzheimer’s disease (AD). Material and methods: keywords “mental disorders, AD, proinflammatory monocytes, microglia, neuroinflammation, cytokines, chemokines, cell adhesion molecules, platelets, microvesicles” were used to search for articles of domestic and foreign authors published over the past 30 years in the databases PubMed, eLibrary, Science Direct and EMBASE. Conclusion: this review analyzes the results of studies which show that monocytes/macrophages and microglia have similar gene expression profiles in schizophrenia, BAD, depression, and AD and also perform similar functions: phagocytosis and inflammatory responses. Monocytes recruited to the central nervous system stimulate the increased production of proinflammatory cytokines IL-1, IL-6, tumor necrosis factor alpha (TNF-α), chemokines, for example, MCP-1 (Monocyte chemotactic protein-1) by microglial cells. This promotes the recruitment of microglial cells to the sites of neuronal damage, and also enhances the formation of the brain protein beta-amyloid (Aβ). The results of modern studies are presented, indicating that platelets are involved in systemic inflammatory reactions, where they interact with monocytes to form monocyte-platelet aggregates (MTA), which induce the activation of monocytes with a pro inflammatory phenotype. In the last decade, it has been established that activated platelets and other cells of the immune system, including monocytes, detached microvesicles (MV) from the membrane. It has been shown that MV are involved as messengers in the transport of biologically active lipids, cytokines, complement, and other molecules that can cause exacerbation of systemic inflammatory reactions. The presented review allows us to expand our knowledge about the cellular and molecular aspects of the interaction of monocytes/macrophages with microglial cells and platelets in the development of neuroinflammation and cognitive decline in the pathogenesis of mental diseases and in AD, and also helps in the search for specific biomarkers of the clinical severity of mental disorder in patients and the prospects for their response to treatment.

Plasticity: Cells, Circuits, Brains, and Behavior

2016 ◽  
Author(s):  
Patricia S. Churchland ◽  
Terrence J. Sejnowski
Keyword(s):  
Nervous System ◽  
Synaptic Plasticity ◽  
Classical Conditioning ◽  
Neuronal Plasticity ◽  
Neural Mechanism ◽  
Synaptic Strength ◽  
Physical Mechanisms ◽  
And Behavior ◽  
The Brain

This chapter examines the physical mechanisms in nervous systems in order to elucidate the structural bases and functional principles of synaptic plasticity. Neuroscientific research on plasticity can be divided into four main streams: the neural mechanism for relatively simple kinds of plasticity, such as classical conditioning or habituation; anatomical and physiological studies of temporal lobe structures, including the hippocampus and the amygdala; study of the development of the visual system; and the relation between the animal's genes and the development of its nervous system. The chapter first considers the role of the mammalian hippocampus in learning and memory before discussing Donald Hebb's views on synaptic plasticity. It then explores the mechanisms underlying neuronal plasticity and those that decrease synaptic strength, the relevance of time with respect to plasticity, and the occurrence of plasticity during the development of the nervous system. It also describes modules, modularity, and networks in the brain.

COVID-19 Beyond the Lungs

2022 ◽  
pp. 109-126
Author(s):  
Omar El Hiba ◽  
Hicham Chatoui ◽  
Nadia Zouhairi ◽  
Lahoucine Bahi ◽  
Lhoussaine Ammouta ◽  
...  
Keyword(s):  
Experimental Data ◽  
Nervous System ◽  
Clinical Symptoms ◽  
Case Reports ◽  
The World ◽  
Acute Pneumonia ◽  
The Brain ◽  
Cardinal Feature ◽  
Shed Light

Since December 2019, the world has been shaken by the spread of a highly pathogen virus, causing severe acute respiratory syndrome (SARS-Cov2), which emerged in Wuhan, China. SARS-Cov2 is known to cause acute pneumonia: the cardinal feature of coronavirus disease 2019 (COVID-19). Clinical features of the disease include respiratory distress, loss of spontaneous breathing, and sometimes neurologic signs such as headache and nausea and anosmia, leading to suppose a possible involvement of the nervous system as a potential target of SARS-CoV2. The chapter will shed light on the recent clinical and experimental data sustaining the involvement of the nervous system in the pathophysiology of COVID-19, based on several case reports and experimental data reporting the possible transmission of SARS-CoV2 throughout the peripheral nerves to the brain cardiorespiratory centers. Thus, understanding the role of the nervous system in the course of clinical symptoms of COVID-19 is important in determining the appropriate therapeutic approach to combat the disease.

Neuropsychiatry of neurometabolic, neuroendocrine, and mitochondrial disorders

2020 ◽  
pp. 309-322
Author(s):  
Mark Walterfang ◽  
Ramon Mocellin ◽  
Dennis Velakoulis
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Psychiatric Illness ◽  
Mitochondrial Disorders ◽  
Endocrine Function ◽  
Endocrine Disorders ◽  
Endocrine Tumours ◽  
Neurometabolic Disorders ◽  
The Brain

This chapter examines the role of neurometabolic, neuroendocrine, and mitochondrial disorders in causing neuropsychiatric syndromes. It examines how disorders of cellular metabolic processes, particularly those that affect the brain, can result in major psychiatric syndromes and the over-representation of some neurometabolic disorders in psychiatric illness. It also discusses a range of endocrine disorders, particularly disorders of increased or reduced endocrine function and endocrine tumours, in producing psychiatric syndromes. The chapter also reviews the role of mitochondrial disorders in disrupting central nervous system processes and metabolism, and how some mitochondrial disorders result in psychiatric illness.

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