Since Caenorhabditis elegans was first introduced as a genetic model organism by Sydney Brenner, researchers studying it have made significant contributions in numerous fields including ...investigations of the pathophysiology of neurodegenerative diseases. The simple anatomy, optical transparency, and short life-span of this small nematode together with the development and curation of many openly shared resources (including the entire genome, cell lineage and the neural map of the animal) allow researchers using C. elegans to move their research forward rapidly in an immensely collaborative community. These resources have allowed researchers to use C. elegans to study the cellular processes that may underlie human diseases. Indeed, many disease-associated genes have orthologs in C. elegans, allowing the effects of mutations in these genes to be studied in relevant and reproducible neuronal cell-types at single-cell resolution in vivo. Here we review studies that have attempted to establish genetic models of specific human neurodegenerative diseases (ALS, Alzheimer's Disease, Parkinson's Disease, Huntington's Disease) in C. elegans and what they have contributed to understanding the molecular and genetic underpinnings of each disease. With continuous advances in genome engineering, research conducted using this small organism first established by Brenner, Sulston and their contemporaries will continue to contribute to the understanding of human nervous diseases.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
This review focuses on the neurobiology of integrins, pathophysiological roles of integrins in neuroplasticity and nervous system disorders, and therapeutic implications of integrins as potential ...drug targets and possible delivery pathways. Neuroplasticity is a central phenomenon in many neurological conditions such as seizures, trauma, and traumatic brain injury. During the course of many brain diseases, in addition to intracellular compartment changes, alterations in non-cell compartments such as extracellular matrix (ECM) are recognized as an essential process in forming and reorganizing neural connections. Integrins are heterodimeric transmembrane receptors that mediate cell-ECM and cell-cell adhesion events. Although the mechanisms of neuroplasticity remain unclear, it has been suggested that integrins undergo plasticity including clustering through interactions with ECM proteins, modulating ion channels, intracellular Ca(2+) and protein kinase signaling, and reorganization of cytoskeletal filaments. As cell surface receptors, integrins are central to the pathophysiology of many brain diseases, such as epilepsy, and are potential targets for the development of new drugs for neurological disorders.
Listeriosis is an infectious disease caused by bacteria of the genus Listeria, the neurological form being more common in ruminants. There are many reports of listeriosis in small ruminants in the ...region that includes Brazil, Argentina and Uruguay. However, these diagnoses were mainly based on histological lesions in the central nervous system (CNS) without the isolation and characterization of the involved Listeria strains. The aim of this study was to report sheep and goats listeriosis cases from 2016 to 2021 in northwestern Uruguay. The diagnosis was made according to lesions observed at histopathology, plus Listeria isolation in CNS, identifying it at specie and serotype level. Nine animals (n=9) of three outbreaks and five sporadic cases of listeriosis were studied. Sheep was the species with more cases in relation to goats, and adults were the category most affected. Cases occurred in spring and less frequently in winter. All presented neurological clinical signs and the lesions in the CNS were consistent with suppurative meningoencephalitis and micro-abscesses in the brainstem. In eight of nine CNS samples, Listeria strains were isolated (seven L. monocytogenes and one L. innocua). All the L. monocytogenes isolates carried the inlA gene; serotyping showed that four strains belonged to serotype 1/2b, two isolates belonged to serotype 4b, and one to serotype 1/2a. Considering that listeriosis is a common disease in this region and the fact that isolates are scarcely recovered from small ruminants, it would be important to emphasize the need for Listeria isolation to better characterize the strains that affect animals. Not only to improve knowledge about the epidemiology of disease but also with the objective of developing serotype specific vaccines for animal use.
RESUMO: Listeriose uma doença bacteriana causada pelo gênero Listeria, a forma nervosa é a mais comum em ruminantes. No Brasil, Argentina e Uruguai há vários relatos de listeriose em pequenos ruminantes com diagnóstico baseado na histopatologia do sistema nervoso central (SNC), sem o isolamento e a caracterização do agente. O objetivo deste trabalho foi relatar uma série de casos diagnosticados em ovinos e caprinos no período 2016-2021 no noroeste do Uruguai. O diagnóstico foi feito basado nas lesões observadas na histopatologia, e caracterização das cepas de Listeria recuperadas do SNC quanto à espécie e sorotipo. Nove animais (n=9) do três surtos e cinco casos isolados de listeriose foram estudados. Os ovinos foram a espécie com o maior número de casos em relação aos caprinos, sendo os animais adultos a categoria mais afetada em ambas espécies. A doença ocorreu principalmente na primavera com alguns casos observados no inverno. Todos os casos apresentavam sinais clínicos nervosos e as lesões no SNC caracterizavam-se por meningoencefalite supurativa com presença de microabscessos no tronco encefálico. Em oito de nove amostras do SNC foram isoladas cepas de Listeria (sete L. monocytogenes e uma L. innocua). Todos os isolados de L. monocytogenes continham o gene inlA; a sorotipagem apresentou quatro cepas do serotipo 1/2b, duas cepas serotipo 4b e uma cepa 1/2a. Levando em consideração que nesta região a listeriose é uma doença frequente e que existem poucos isolados recuperados de casos clínicos em pequeño ruminantes, torna-se relevante o isolamento deste agente para caracterização das cepas que afetam os animais. Não só para melhorar o conhecimento sobre a epidemiologia da doença, mas também com o objetivo de desenvolver vacinas sorotipo-especificas para uso animal.
Microexons are small sized (≤51 bp) exons which undergo extensive alternative splicing in neurons, microglia, embryonic stem cells, and cancer cells, giving rise to cell type specific protein ...isoforms. Due to their small sizes, microexons provide a unique challenge for the splicing machinery. They frequently lack exon splicer enhancers/repressors and require specialized neighboring trans‐regulatory and cis‐regulatory elements bound by RNA binding proteins (RBPs) for their inclusion. The functional consequences of including microexons within mRNAs have been extensively documented in the central nervous system (CNS) and aberrations in their inclusion have been observed to lead to abnormal processes. Despite the increasing evidence for microexons impacting cellular physiology within CNS, mechanistic details illustrating their functional importance in diseases of the CNS is still limited. In this review, we discuss the unique characteristics of microexons, and how RBPs participate in regulating their inclusion and exclusion during splicing. We consider recent findings of microexon alternative splicing and their implication for regulating the function of small GTPases in the context of the microglia, and we extrapolate these findings to what is known in neurons. We further discuss the emerging evidence for dysregulation of the Rho GTPase pathway in CNS diseases and the consequences contributed by the mis‐splicing of microexons.
This article is categorized under:
RNA Processing > Splicing Mechanisms
RNA Processing > Splicing Regulation/Alternative Splicing
RNA in Disease and Development > RNA in Disease
Microexons alternative splicing is mediated by the specificRNA binding proteins and splicing regulatory elements that control theRho‐GTPase pathways in CNS cells. The microexon splicing of Rho‐GTPasesassociated transcripts provides versatile means of driving neuronal developmentprocesses and managing the cellular functions, and mis‐splicing of thesemicroexons is implicated in CNS disease progression.
Cell therapies have been explored to treat patients with nervous diseases for over 20 years. Even though most kinds of cell therapies demonstrated neurorestorative effects in non-randomized clinical ...trials; the effects of the majority type cells could not be confirmed by randomized controlled trials. In this review, clinical therapeutic results of neurorestorative cell therapies according to cellular bio-proprieties or cellular functions were introduced. Currently it was demonstrated from analysis of this review that some indications of cell therapies were not appropriate, they might be reasons why their neurorestorative effects could not be proved by multicenter, randomized, double blind, placebo-controlled clinical trials. Theoretically if one kind of cell therapy has neurorestorative effects according to its cellular bio-proprieties, it should have appropriate indications. The cell therapies with special bio-properties is promising if the indication selections are appropriate, such as olfactory ensheathing cells for chronic ischemic stroke, and their neurorestorative effects can be confirmed by higher level clinical trials of evidence-based medicine.
The article describes the history of the Department of Nervous Diseases, Medical Genetics and Neurosurgery of the Daghestan State Medical University on the basis of literature data and archival ...sources introduced into scientific circulation for the first time. The department, created in 1936, has gone through a difficult path in its formation and development. The authors reconstruct the history of the formation of this department of the university, dwelling on the problems faced by its first employees. Special attention is paid to the work of the department during the Great Patriotic War, when its staff was reduced to a minimum. The authors describe the appearance, stages of development and successful functioning of the scientific school for the study of thermoregulation under the guidance of Associate Professor V.A. Liechtenstein. The formation of the teaching of neurosurgery, as well as the work of the department in recent years, is described.
The main milestones of the life and work of L.O. Darkshevich. It is noted that the work of a professor on the study of the pathology of muscles and peripheral nerves is of great interest. As early as ...1903, in a German manual on pathological anatomy of the nervous system, Liverius Osipovich wrote a chapter on the pathological anatomy of muscles. We emphasize that later they wrote several articles on cerebral and arthropathic amiotrophies. Studying the question of the so-called retrograde degeneration of nerves, he pointed to the development of degenerative changes not only in the peripheral, but also in the central segment of the nerve, which is of great interest for clarifying the spread of the process. The article notes that Liveriy Osipovich Darkshevich considered the creation of a manual on nervous diseases as the greatest debt of his life, which was the testament of his late teacher — Professor A.Ya. Kozhevnikov, who had not managed to do this. Well aware of the conditioned reflex principles of the central nervous system, Liverii Osipovich attached special importance to the cerebral cortex as a body of mental activity. He pointed out that normal mental activity is formed under the influence of incessantly arriving stimuli of the external world, which, having reached the cerebral cortex and entering our consciousness, give rise to representations, the appearance of which in turn gives rise to the manifestation of active cortical activity-the emergence of volitional impulses. Liverii Osipovich was an ardent supporter of active disease therapy and was often an innovator in this field.
Following peripheral exposure to transmissible spongiform encephalopathies (TSEs), infectivity usually accumulates in lymphoid tissues before neuroinvasion. The host prion protein (PrPc) is critical ...for TSE agent replication and accumulates as an abnormal, detergent insoluble, relatively proteinase-resistant isoform (PrPSc) in diseased tissues. Early PrPSc accumulation takes place on follicular dendritic cells (FDCs) within germinal centers in lymphoid tissues of patients with variant Creutzfeldt-Jakob disease (vCJD), sheep with natural scrapie or rodents following experimental peripheral infection with scrapie. In mouse scrapie models, the absence of FDCs blocks scrapie replication and PrPSc accumulation in the spleen, and neuroinvasion is significantly impaired. The mechanisms by which the TSE agent initially localizes to lymphoid follicles and interacts with FDCs are unknown. Antigens are trapped and retained on the surface of FDCs through interactions between complement and cellular complement receptors. Here we show that in mice, both temporary depletion of complement component C3 or genetic deficiency of C1q significantly delays the onset of disease following peripheral infection, and reduces the early accumulation of PrPSc in the spleen. Thus, in the early stages of infection, C3 and perhaps C1q contribute to the localization of TSE infectivity in lymphoid tissue and may be therapeutic targets.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Clinical Neuroanatomy offers an extensive review of higher cortical - behavioral functions and their anatomical substrates. The central chapters offer detailed, integrated, and, at times, theoretical ...models of cortical systems and their internal organization. 300 illustrations help identify key structures and pathways.
PDF
