scholarly journals Impact of Motile Ciliopathies on Human Development and Clinical Consequences in the Newborn

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 125
Author(s):  
Rachael M. Hyland ◽  
Steven L. Brody
Keyword(s):  
Fluid Flow ◽  
Human Development ◽  
Genetic Disorder ◽  
Clinical Consequences ◽  
Brain Ventricle ◽  
Clinical Considerations ◽  
Motile Cilia ◽  
The Brain

Motile cilia are hairlike organelles that project outward from a tissue-restricted subset of cells to direct fluid flow. During human development motile cilia guide determination of the left-right axis in the embryo, and in the fetal and neonatal periods they have essential roles in airway clearance in the respiratory tract and regulating cerebral spinal fluid flow in the brain. Dysregulation of motile cilia is best understood through the lens of the genetic disorder primary ciliary dyskinesia (PCD). PCD encompasses all genetic motile ciliopathies resulting from over 60 known genetic mutations and has a unique but often underrecognized neonatal presentation. Neonatal respiratory distress is now known to occur in the majority of patients with PCD, laterality defects are common, and very rarely brain ventricle enlargement occurs. The developmental function of motile cilia and the effect and pathophysiology of motile ciliopathies are incompletely understood in humans. In this review, we will examine the current understanding of the role of motile cilia in human development and clinical considerations when assessing the newborn for suspected motile ciliopathies.

Neuroinflammation in Huntington’s disease: A starring role for astrocyte and microglia

2021 ◽  
Vol 19 ◽  
Author(s):  
Julieta Saba ◽  
Federico López Couselo ◽  
Julieta Bruno ◽  
Lila Carniglia ◽  
Daniela Durand ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Genetic Disorder ◽  
Cag Repeat ◽  
Inflammatory Factors ◽  
Therapeutic Approaches ◽  
Reactive Microglia ◽  
New Treatments ◽  
The Brain

: Huntington’s disease (HD) is a neurodegenerative genetic disorder caused by a CAG repeat expansion in the huntingtin gene. HD causes motor, cognitive, and behavioral dysfunction. Since no existing treatment affects the course of this disease, new treatments are needed. Inflammation is frequently observed in HD patients before symptom onset. Neuroinflammation, characterized by the presence of reactive microglia and astrocytes and inflammatory factors within the brain, is also detected early. However, in comparison with other neurodegenerative diseases, the role of neuroinflammation in HD is much less known. Work has been dedicated to altered microglial and astrocytic functions in the context of HD, but less attention has been given to glial participation in neuroinflammation. This review describes evidence of inflammation in HD patients and animal models. It also discusses recent knowledge on neuroinflammation in HD, highlighting astrocyte and microglia involvement in the disease and considering anti-inflammatory therapeutic approaches.

Love, the Brain, and Becoming Human

2019 ◽  
pp. 44-71
Author(s):  
Riane Eisler
Keyword(s):  
Human Brain ◽  
Human Development ◽  
Human Evolution ◽  
Evolutionary History ◽  
Negative Effects ◽  
New Perspective ◽  
The Brain ◽  
The Continuum

This chapter introduces a new perspective on the role of love in human evolution and human development. The bonds of love, whether between parent and child, lovers, or close friends, may all have a common biological root, activating neurochemicals that make us feel good. Like other human capacities, such as consciousness, learning, and creativity, love has a long and fascinating evolutionary history. Indeed, the evolution of love appears to be integral to the development of our human brain and hence to much that distinguishes us from other species. Moreover, love plays a vital, though still largely unrecognized, role in human development, with evidence accumulating about the negative effects of love deprivation as well as the benefits of love. But whether or not our needs for meaning and love are met, and whether or not our capacities for creativity and love are expressed, are largely determined by the interaction of biology and culture—specifically, the degree to which a culture or subculture orients to the partnership or domination end of the continuum.

scholarly journals Diagnostic and Treatment Approaches Involving Transthyretin in Amyloidogenic Diseases

2019 ◽  
Vol 20 (12) ◽  
pp. 2982 ◽  
Author(s):  
Gil Yong Park ◽  
Angelo Jamerlan ◽  
Kyu Hwan Shim ◽  
Seong Soo A. An
Keyword(s):  
Cerebrospinal Fluid ◽  
Genetic Mutations ◽  
Hormone Binding ◽  
Wild Type ◽  
Autonomic Motor ◽  
Hormone Binding Protein ◽  
The Brain ◽  
Tetrameric Form

Transthyretin (TTR) is a thyroid hormone-binding protein which transports thyroxine from the bloodstream to the brain. The structural stability of TTR in tetrameric form is crucial for maintaining its original functions in blood or cerebrospinal fluid (CSF). The altered structure of TTR due to genetic mutations or its deposits due to aggregation could cause several deadly diseases such as cardiomyopathy and neuropathy in autonomic, motor, and sensory systems. The early diagnoses for hereditary amyloid TTR with cardiomyopathy (ATTR-CM) and wild-type amyloid TTR (ATTRwt) amyloidosis, which result from amyloid TTR (ATTR) deposition, are difficult to distinguish due to the close similarities of symptoms. Thus, many researchers investigated the role of ATTR as a biomarker, especially its potential for differential diagnosis due to its varying pathogenic involvement in hereditary ATTR-CM and ATTRwt amyloidosis. As a result, the detection of ATTR became valuable in the diagnosis and determination of the best course of treatment for ATTR amyloidoses. Assessing the extent of ATTR deposition and genetic analysis could help in determining disease progression, and thus survival rate could be improved following the determination of the appropriate course of treatment for the patient. Here, the perspectives of ATTR in various diseases were presented.

Familial trichotillomania: role of genetic factors in the determination of subtypes

2013 ◽  
Vol 25 (3) ◽  
pp. 187-190
Author(s):  
Ghaffari Nejad Alireza ◽  
Fariborz Estilaee ◽  
Mohammad M. Sadeghi
Keyword(s):  
Psychiatric Disorders ◽  
Serotonin Receptors ◽  
Genetic Factors ◽  
Genetic Disorder ◽  
Family Members ◽  
Hair Pulling ◽  
Psychiatric Syndrome ◽  
The Family

ObjectivesTrichotillomania (TTM) is a psychiatric syndrome characterised by the inability to control repetitive hair pulling. Psychiatric data reveal that TTM is not usually prevalent among all family members of patients, and so far only one case of familial TTM has been reported.MethodsIn this study, we report a case of familial TTM that afflicted four sisters and discuss the importance of genetic factors in this disorder.ResultsThis report suggests that, similar to many other psychiatric disorders, TTM can be detected in other family members and that genetic factors not only have a significant role in the development of such disorders but also in determination of the disorder subtype. This report also shows that the comorbidities in one member of the family might predict the existence of comorbidities in other members. On the basis of response to medication.Conclusionthe authors suggest that a genetic disorder like polymorphism in serotonin receptors or dopamine can cause such a disorder.

scholarly journals Fear of Death: A Systemic Description

2015 ◽  
Vol 11 (1) ◽  
pp. 13-23 ◽  
Author(s):  
A.A. Bakanova
Keyword(s):  
Content Analysis ◽  
Human Development ◽  
Theoretical Research ◽  
Fear Of Death ◽  
Defence Mechanisms ◽  
Ways Of Coping ◽  
History Of ◽  
Ontological Aspect

The paper presents a systemic description of the fear of death incorporating the following five basic aspects of its study in psychology: anthropologic, gnoseological, axiological, praxeological and ontological. Content analysis of each aspect is built upon theoretical research. Thus, the anthropological aspect is reviewed through the prism of various studies on the differences in experiencing the fear of dying throughout the history of mankind and throughout an individual's life. The gnoseological aspect is revealed through the issues of bio¬logical and social determination of the fear of death realized in explorations of its conscious and subconscious components explored in psychology. The axiological aspect is considered through its orientation (internal and external) and content components reflecting the basic values of an individual that are either destroyed or created by the idea of death. The praxeological aspect represents ways of coping with the fear of death, including various defence mechanisms. The ontological aspect is regarded as the integral one depicting the role of the fear of death in human development and its contributions to the formation of personality.

scholarly journals Genetic approaches to the investigation of serotonergic neuron functions in animals

2019 ◽  
Vol 23 (4) ◽  
pp. 448-455
Author(s):  
U. S. Drozd ◽  
E. V. Shaburova ◽  
N. N. Dygalo
Keyword(s):  
Developmental Stages ◽  
Sensory Information ◽  
Serotonergic System ◽  
Serotonergic Neurons ◽  
Neurotransmitter Systems ◽  
New Therapeutic Approaches ◽  
Serotonin System ◽  
The Brain

The serotonergic system is one of the most important neurotransmitter systems that take part in the regulation of vital CNS functions. The understanding of its mechanisms will help scientists create new therapeutic approaches to the treatment of mental and neurodegenerative diseases and find out how this neurotransmitter system interacts with other parts of the brain and regulates their activity. Since the serotonergic system anatomy and functionality are heterogeneous and complex, the best tools for studying them are based on manipulation of individual types of neurons without affecting neurons of other neurotransmitter systems. The selective cell control is possible due to the genetic determinism of their functions. Proteins that determine the uniqueness of the cell type are expressed under the regulation of cell-specific promoters. By using promoters that are specific for genes of the serotonin system, one can control the expression of a gene of interest in serotonergic neurons. Here we review approaches based on such promoters. The genetic models to be discussed in the article have already shed the light on the role of the serotonergic system in modulating behavior and processing sensory information. In particular, genetic knockouts of serotonin genes sert, pet1, and tph2 promoted the determination of their contribution to the development and functioning of the brain. In addition, the review describes inducible models that allow gene expression to be controlled at various developmental stages. Finally, the application of these genetic approaches in optogenetics and chemogenetics provided a new resource for studying the functions, discharge activity, and signal transduction of serotonergic neurons. Nevertheless, the advantages and limitations of the discussed genetic approaches should be taken into consideration in the course of creating models of pathological conditions and developing pharmacological treatments for their correction.

scholarly journals A novel hypomorphic allele of Spag17 causes primary ciliary dyskinesia phenotypes in mice

2020 ◽  
Vol 13 (10) ◽  
pp. dmm045344
Author(s):  
Zakia Abdelhamed ◽  
Marshall Lukacs ◽  
Sandra Cindric ◽  
Heymut Omran ◽  
Rolf W. Stottmann
Keyword(s):  
Cerebrospinal Fluid ◽  
Fluid Flow ◽  
Primary Ciliary Dyskinesia ◽  
Human Condition ◽  
Central Pair ◽  
Cerebrospinal Fluid Flow ◽  
Hypomorphic Allele ◽  
Motile Cilia ◽  
The Brain ◽  
Ciliary Dyskinesia

ABSTRACTPrimary ciliary dyskinesia (PCD) is a human condition of dysfunctional motile cilia characterized by recurrent lung infection, infertility, organ laterality defects and partially penetrant hydrocephalus. We recovered a mouse mutant from a forward genetic screen that developed many of the hallmark phenotypes of PCD. Whole-exome sequencing identified this primary ciliary dyskinesia only (Pcdo) allele to be a nonsense mutation (c.5236A>T) in the Spag17 coding sequence creating a premature stop codon (K1746*). The Pcdo variant abolished several isoforms of SPAG17 in the Pcdo mutant testis but not in the brain. Our data indicate differential requirements for SPAG17 in different types of motile cilia. SPAG17 is essential for proper development of the sperm flagellum and is required for either development or stability of the C1 microtubule structure within the central pair apparatus of the respiratory motile cilia, but not the brain ependymal cilia. We identified changes in ependymal ciliary beating frequency, but these did not appear to alter lateral ventricle cerebrospinal fluid flow. Aqueductal stenosis resulted in significantly slower and abnormally directed cerebrospinal fluid flow, and we suggest that this is the root cause of the hydrocephalus. The Spag17Pcdo homozygous mutant mice are generally viable to adulthood but have a significantly shortened lifespan, with chronic morbidity. Our data indicate that the c.5236A>T Pcdo variant is a hypomorphic allele of Spag17 that causes phenotypes related to motile, but not primary, cilia. Spag17Pcdo is a useful new model for elucidating the molecular mechanisms underlying central pair PCD pathogenesis in the mouse.This article has an associated First Person interview with the first author of the paper.

Possible role of histamine in brain function: neurochemical, physiological, and pharmacological indications

1984 ◽  
Vol 62 (6) ◽  
pp. 709-714 ◽  
Author(s):  
I. M. Mazurkiewicz-Kwilecki
Keyword(s):  
Psychotropic Drugs ◽  
Brain Function ◽  
Hormonal Regulation ◽  
Inhibitory Effects ◽  
Brain Histamine ◽  
Future Studies ◽  
Cyclic Variations ◽  
The Brain

Recently accumulated neurochemical, physiological, and pharmacological evidence strongly supports a role for histamine as a central neurotransmitter. Neurochemical methods, which became available within the last years, allow determination of small amounts of histamine and its metabolites in the brain and make possible future studies of central histamine regulation. The demonstration of histamine H1 and H2 receptors in the brain of several species suggests a possible role for histamine in brain function. Microelectrophysiological studies on single central neurones suggest both excitatory and depressant effects of histamine which are receptor mediated. In addition, brain histamine has been demonstrated to be subject to cyclic variations, to play a role in hormonal regulation, and to be altered by stressful conditions. Several psychotropic drugs significantly affect brain histamine regulation and elicit inhibitory effects on central histamine receptors. These findings bring new approaches and stimulus to further research on the significance of brain histamine.

L. S. Vygotsky’s cultural-historical theory: globalisation, post-non-classical paradigm and digitalisation

2021 ◽  
Vol 82 (4) ◽  
pp. 52-60
Author(s):  
V. А. Pishchalnikova
Keyword(s):  
Regulatory Mechanism ◽  
Modern Human ◽  
Knowledge Use ◽  
Internal Factors ◽  
Evolution Of Consciousness ◽  
Social Trends ◽  
The Brain ◽  
Historical Theory

L. S. Vygotsky’s cultural-historical theory postulates the underlying unity of psychological and social factors contributing to the formation of man. It explains both internal factors determining the evolution of consciousness and social trends in social development. The paper highlights the role of L. S. Vygotsky’s theory in the interpretation of the changes in the modern human consciousness. These changes are caused by new culture tools of knowledge building currently created in the information space. The author emphasises the following ideas proposed by L. S. Vygotsky: 1) signs are functionally analogous to tools; 2) culture intentionally creates objects to realise its communicative-significative function; 3) sign utilization leads to the formation of fundamentally new associative bonds in the brain. Such bonds create a novel regulatory mechanism of human behaviour; 4) social determination of man is achieved with the help of signs; 5) the formation and functioning of mind depend on the means of thought and individual sociocultural experience; 6) ‘socialised speech’ influences the evolution of inner speech as a specific type of thinking-in-words and the logic of thinking; 7) the historical evolution of human culture plays the key role in the formation and functioning of individual psyches; 8) due to sign usage the nature of human evolution changed from biological to sociohistorical; consequently, mankind’s evolution significantly depends on the signs used by individuals. Modern digital technologies actively generate signs whose nature is contrary to verbal ones. The process of globalisation and the values of the post-non-classical mindset sustain generation of such signs. Globalisation creates a standardised and maximally regimented reality, which contributes to the reinforcement of reduplication as the socially approved way of knowledge use. What is more, globalisation requires revision of the traditional humanistic values and customs. Post-non-classical thinking enhances individuals’ feelings of insecurity and uncertainty, thus nearly making them act within the framework of conventional behavioural and mental models.

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