scholarly journals Quantification of Dendritic Spines Remodeling under Physiological Stimuli and in Pathological Conditions

2021 ◽  
Vol 22 (8) ◽  
pp. 4053
Author(s):  
Ewa Bączyńska ◽  
Katarzyna Karolina Pels ◽  
Subhadip Basu ◽  
Jakub Włodarczyk ◽  
Błażej Ruszczycki
Keyword(s):  
Dendritic Spines ◽  
Quantitative Data ◽  
Statistical Significance ◽  
Brain Diseases ◽  
Synaptic Connections ◽  
Brain Pathology ◽  
Biological Models ◽  
Structural Geometry ◽  
Pathological Conditions ◽  
Experimental Approaches

Numerous brain diseases are associated with abnormalities in morphology and density of dendritic spines, small membranous protrusions whose structural geometry correlates with the strength of synaptic connections. Thus, the quantitative analysis of dendritic spines remodeling in microscopic images is one of the key elements towards understanding mechanisms of structural neuronal plasticity and bases of brain pathology. In the following article, we review experimental approaches designed to assess quantitative features of dendritic spines under physiological stimuli and in pathological conditions. We compare various methodological pipelines of biological models, sample preparation, data analysis, image acquisition, sample size, and statistical analysis. The methodology and results of relevant experiments are systematically summarized in a tabular form. In particular, we focus on quantitative data regarding the number of animals, cells, dendritic spines, types of studied parameters, size of observed changes, and their statistical significance.

scholarly journals Pathological potential of astroglia

2008 ◽  
pp. S101-S110
Author(s):  
A Chvátal ◽  
M Anděrová ◽  
H Neprašová ◽  
I Prajerová ◽  
J Benešová ◽  
...  
Keyword(s):  
Glial Cells ◽  
Brain Parenchyma ◽  
Brain Diseases ◽  
Brain Pathology ◽  
Pathological Conditions ◽  
Recent Developments ◽  
Neurological Defect ◽  
Del Rio ◽  
The Brain ◽  
Brain Homeostasis

The pathological potential of glial cells was recognized already by Rudolf Virchow, Santiago Ramon y Cajal and Pio Del Rio-Ortega. Many functions and roles performed by astroglia in the healthy brain determine their involvement in brain diseases; as indeed any kind of brain insult does affect astrocytes, and their performance in pathological conditions, to a very large extent, determines the survival of the brain parenchyma, the degree of damage and neurological defect. Astrocytes being in general responsible for overall brain homeostasis are involved in virtually every form of brain pathology. Here we provide an overview of recent developments in identifying the role and mechanisms of the pathological potential of astroglia.

scholarly journals Targeting the CCL2-CCR2 axis in depressive disorders

2021 ◽  
Author(s):  
Katarzyna Curzytek ◽  
Monika Leśkiewicz
Keyword(s):  
Nervous System ◽  
Immune System ◽  
Affective Disorders ◽  
Depressive Disorders ◽  
Brain Diseases ◽  
Receptor System ◽  
Proinflammatory Mediators ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
Abnormal Brain

AbstractSince affective disorders are considered to be underlain by the immune system malfunction, an important role in their pathophysiology is assigned to the proinflammatory mediators. Recently, chemokines, the group of chemotactic cytokines, have become a focus for basic and clinical scientists in the context of the development and treatment of brain diseases. Among them, chemokine CCL2 and its main receptor CCR2 have become candidate mediators of abnormal brain-immune system dialogue in depression. Besides the chemotactic activity, the CCL2-CCR2 axis is involved in various neurobiological processes, neurogenesis, neurotransmission, neuroinflammation, neurodegeneration, as well as neuroregeneration. Given the range of immunomodulatory possibilities that the CCL2-CCR2 pair can exert on the nervous system, its proinflammatory properties were initially thought to be a major contributor to the development of depressive disorders. However, further research suggests that the malfunctions of the nervous system are rather associated with impaired homeostatic properties manifested by the CCL2-CCR2 dyad dysfunctions. This review aims to present literature data on the action of the CCL2-CCR2 axis in the central nervous system under physiological and pathological conditions, as well as the contribution of this ligand-receptor system to the processes underlying affective disorders. Additionally, this article draws attention to the importance of the CCL2-CRR2 pathway as a potential pharmacological target with antidepressant potential.

scholarly journals Effects of two different deep digital flexor tenotomy techniques on distal articular angles of equine cadaver forelimbs

2012 ◽  
Vol 42 (11) ◽  
pp. 2005-2010
Author(s):  
Antonio Cezar de Oliveira Dearo ◽  
Vitor Bruno Bianconi Rosa ◽  
Peter Reichmann ◽  
Milton Luis Ribeiro de Oliveira
Keyword(s):  
Quantitative Data ◽  
Statistical Significance ◽  
Surgical Approaches ◽  
Control Groups ◽  
Before And After ◽  
Distal Interphalangeal ◽  
The Difference ◽  
And Control ◽  
Flexor Tenotomy

Deep digital flexor (DDF) tenotomy is a technique employed for years to treat selected disorders of the musculoskeletal system in horses. Although two different surgical approaches (i.e. mid-metacarpal and pastern) have been described for performing the procedure, in vitro quantitative data regarding the modifications induced by either technique on the distal articular angles is lacking. Therefore, the purpose of the study reported here was to investigate the viability of a proposed biomechanical system of induced-traction used to compare the two DDF tenotomy techniques by measuring the distal articular angles of equine cadaver forelimbs. Ten pairs of forelimbs were collected and mounted to a biomechanical system developed to apply traction at the toe level. Dorsal articular angles of the metacarpophalangeal (MP), proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints were determined by geometric lines on radiographs taken before and after performing each technique. Comparisons between each tenotomy group and its own control, for each joint, and between the two tenotomy groups using as variable the difference between the tenotomy and control groups were tested. Despite the lack of statistical significance, the DDF tenotomy technique at the pastern level produced extension, to a lesser and greater extent, of the PIP and DIP joints, respectively when compared to the mid-metacarpal level. No remarkable differences could be observed for the MP joint. The developed traction-induced biomechanical construct seemed to be effective in producing valuable quantitative estimations of the distal articular angles of equine cadaver forelimbs subjected to different DDF tenotomy techniques.

scholarly journals Novel in vitro Experimental Approaches to Study Myelination and Remyelination in the Central Nervous System

2021 ◽  
Vol 15 ◽  
Author(s):  
Davide Marangon ◽  
Nicolò Caporale ◽  
Marta Boccazzi ◽  
Maria P. Abbracchio ◽  
Giuseppe Testa ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Mechanisms ◽  
Disease Modeling ◽  
Brain Physiology ◽  
Pathological Conditions ◽  
Approaches To Study ◽  
The Central Nervous System ◽  
Experimental Approaches

Myelin is the lipidic insulating structure enwrapping axons and allowing fast saltatory nerve conduction. In the central nervous system, myelin sheath is the result of the complex packaging of multilamellar extensions of oligodendrocyte (OL) membranes. Before reaching myelinating capabilities, OLs undergo a very precise program of differentiation and maturation that starts from OL precursor cells (OPCs). In the last 20 years, the biology of OPCs and their behavior under pathological conditions have been studied through several experimental models. When co-cultured with neurons, OPCs undergo terminal maturation and produce myelin tracts around axons, allowing to investigate myelination in response to exogenous stimuli in a very simple in vitro system. On the other hand, in vivo models more closely reproducing some of the features of human pathophysiology enabled to assess the consequences of demyelination and the molecular mechanisms of remyelination, and they are often used to validate the effect of pharmacological agents. However, they are very complex, and not suitable for large scale drug discovery screening. Recent advances in cell reprogramming, biophysics and bioengineering have allowed impressive improvements in the methodological approaches to study brain physiology and myelination. Rat and mouse OPCs can be replaced by human OPCs obtained by induced pluripotent stem cells (iPSCs) derived from healthy or diseased individuals, thus offering unprecedented possibilities for personalized disease modeling and treatment. OPCs and neural cells can be also artificially assembled, using 3D-printed culture chambers and biomaterial scaffolds, which allow modeling cell-to-cell interactions in a highly controlled manner. Interestingly, scaffold stiffness can be adopted to reproduce the mechanosensory properties assumed by tissues in physiological or pathological conditions. Moreover, the recent development of iPSC-derived 3D brain cultures, called organoids, has made it possible to study key aspects of embryonic brain development, such as neuronal differentiation, maturation and network formation in temporal dynamics that are inaccessible to traditional in vitro cultures. Despite the huge potential of organoids, their application to myelination studies is still in its infancy. In this review, we shall summarize the novel most relevant experimental approaches and their implications for the identification of remyelinating agents for human diseases such as multiple sclerosis.

Neuropathology

2012 ◽  
pp. 177-185
Author(s):  
Peter Falkai ◽  
Bernhard Bogerts
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Affective Disorders ◽  
Morphological Changes ◽  
Brain Diseases ◽  
Nigrostriatal System ◽  
Brain Pathology ◽  
Huntington's Chorea

The traditional domains of neuropathology are well-defined organic brain diseases with an obvious pathology, such as tumours, infections, vascular diseases, trauma, or toxic and hypoxemic changes, as well as degenerative brain diseases (e.g. Alzheimer's disease, Parkinson's disease, and Huntington's chorea). Neuropathological investigations of these brain disorders have been rewarding, because patients with any of these conditions can be expected to have gross morphological or more or less specific neurohistological anomalies related to the clinical symptoms of the disorders. Moreover, the type of brain pathology of these well-defined disease entities is quite homogenous. For example, it is highly unlikely that a patient with Parkinson's disease would not exhibit morphological changes and Lewy bodies in the nigrostriatal system, just as much a person with Huntington's chorea would have a normal striatum, or a patient with Pick'sor Alzheimer's disease would have no changes in the cerebralcortex. In contrast, the history of the neuropathology of psychiatric disorders outside primary degenerative diseases is much more controversial, because no such obvious and homogenous types of brain pathology (as seen in neurological disorders) have yet been detected for the major psychiatric illnesses such as schizophrenia, affective disorders, substance-related disorders, or personality disorders. The scope of this chapter is to summarize the neuropathological findings in schizophrenia, affective disorders, and alcoholism. Tables 2.3.5.1, 2.3.5.2, 2.3.5.3, and 2.3.5.4 highlight the significant findings. It goes beyond the scope of this chapter to review thelarge body of literature on the dementias, including specifically Alzheimer's disease. Concerning this matter, the reader is referred to several comprehensive reviews (e.g. Jellinger and Bancher 1998).

scholarly journals Identification, Characterization, and Regulatory Mechanisms of a Novel EGR1 Splicing Isoform

2019 ◽  
Vol 20 (7) ◽  
pp. 1548 ◽  
Author(s):  
Vincenza Aliperti ◽  
Giulia Sgueglia ◽  
Francesco Aniello ◽  
Emilia Vitale ◽  
Laura Fucci ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cell Types ◽  
Regulatory Mechanisms ◽  
Brain Diseases ◽  
Regulation Of Transcription ◽  
Biological Processes ◽  
Activation Domain ◽  
Post Translational Modifications ◽  
Pathological Conditions ◽  
Proliferation And Apoptosis

EGR1 is a transcription factor expressed in many cell types that regulates genes involved in different biological processes including growth, proliferation, and apoptosis. Dysregulation of EGR1 expression has been associated with many pathological conditions such as tumors and brain diseases. Known molecular mechanisms underlying the control of EGR1 function include regulation of transcription, mRNA and protein stability, and post-translational modifications. Here we describe the identification of a splicing isoform for the human EGR1 gene. The newly identified splicing transcript encodes a shorter protein compared to the canonical EGR1. This isoform lacks a region belonging to the N-terminal activation domain and although it is capable of entering the nucleus, it is unable to activate transcription fully relative to the canonical isoform.

scholarly journals Lipotoxicity Downstream of α-Synuclein Imbalance: A Relevant Pathomechanism in Synucleinopathies?

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 40
Author(s):  
Arati Tripathi ◽  
Saranna Fanning ◽  
Ulf Dettmer
Keyword(s):  
Fatty Acids ◽  
Neuronal Loss ◽  
Brain Diseases ◽  
Neuronal Protein ◽  
Lipid Species ◽  
A Cell ◽  
Experimental Approaches ◽  
Toxicity Mechanisms ◽  
Insight Into ◽  
Storage Disorders

Neuronal loss in Parkinson’s disease and related brain diseases has been firmly linked to the abundant neuronal protein α-synuclein (αS). However, we have gained surprisingly little insight into how exactly αS exerts toxicity in these diseases. Hypotheses of proteotoxicity, disturbed vesicle trafficking, mitochondrial dysfunction and other toxicity mechanisms have been proposed, and it seems possible that a combination of different mechanisms may drive pathology. A toxicity mechanism that has caught increased attention in the recent years is αS-related lipotoxicity. Lipotoxicity typically occurs in a cell when fatty acids exceed the metabolic needs, triggering a flux into harmful pathways of non-oxidative metabolism. Genetic and experimental approaches have revealed a significant overlap between lipid storage disorders, most notably Gaucher’s disease, and synucleinopathies. There is accumulating evidence for lipid aberrations causing synuclein misfolding as well as for αS excess and misfolding causing lipid aberration. Does that mean the key problem in synucleinopathies is lipotoxicity, the accumulation of harmful lipid species or alteration in lipid equilibrium? Here, we review the existing literature in an attempt to get closer to an answer.

scholarly journals Reproductive Plans And Utilization of Contraceptives Among Women Living With HIV

2019 ◽  
Vol 8 (2) ◽  
pp. 120-130
Author(s):  
Khadija Kofoworola Adeleye ◽  
Margaret Omowaleola Akinwaare ◽  
Prisca Olabisi Adejumo
Keyword(s):  
Reproductive Health ◽  
Quantitative Data ◽  
Health Care Services ◽  
Universal Access ◽  
Statistical Significance ◽  
Group Discussion ◽  
Sampling Technique ◽  
Systematic Sampling ◽  
Cross Sectional ◽  
Women Living With Hiv

Background: Despite public health policies aimed at providing universal access to reproductive health care services, the reproductive health needs of women living with Human Immunodeficiency Virus (WLHIV) are not adequately met. This study assesses the reproductive plans and utilization of contraceptives among WLHIV. Methods: This was a cross sectional descriptive study, which adopted a mixed method approach. A total of 400 respondents were recruited from two tertiary health institutions in Nigeria using systematic sampling technique. A validated structured self-administered questionnaire developed by the researcher was used to collect quantitative data for the study. The questionnaire consists of close ended questions related to study objectives. Quantitative data collected were coded and analyzed using Statistical Package for Social Sciences (SPSS) windows version 22 and statistical significance was set at p <0.05. The qualitative aspect of the study utilized focus group discussion for data collection. Results: The mean and standard deviation (SD) age of enrolled respondents was 37.42

scholarly journals Gut and Brain: Investigating Physiological and Pathological Interactions Between Microbiota and Brain to Gain New Therapeutic Avenues for Brain Diseases

2021 ◽  
Vol 15 ◽  
Author(s):  
Gabriele Deidda ◽  
Manuele Biazzo
Keyword(s):  
Gut Microbiota ◽  
Therapeutic Strategy ◽  
Brain Diseases ◽  
Microbial Populations ◽  
Normal Brain ◽  
Neuronal Populations ◽  
Brain Physiology ◽  
Pathological Conditions ◽  
The Brain

Brain physiological functions or pathological dysfunctions do surely depend on the activity of both neuronal and non-neuronal populations. Nevertheless, over the last decades, compelling and fast accumulating evidence showed that the brain is not alone. Indeed, the so-called “gut brain,” composed of the microbial populations living in the gut, forms a symbiotic superorganism weighing as the human brain and strongly communicating with the latter via the gut–brain axis. The gut brain does exert a control on brain (dys)functions and it will eventually become a promising valuable therapeutic target for a number of brain pathologies. In the present review, we will first describe the role of gut microbiota in normal brain physiology from neurodevelopment till adulthood, and thereafter we will discuss evidence from the literature showing how gut microbiota alterations are a signature in a number of brain pathologies ranging from neurodevelopmental to neurodegenerative disorders, and how pre/probiotic supplement interventions aimed to correct the altered dysbiosis in pathological conditions may represent a valuable future therapeutic strategy.

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