Mutations resulting in transient and localized degeneration in the developing zebrafish brain

1997 ◽  
Vol 75 (5) ◽  
pp. 579-600 ◽  
Author(s):  
Michael Rodriguez ◽  
Wolfgang Driever

In a large-scale mutagenesis screen in the zebrafish, Danio rerio, we have identified a heterogeneous group of 30 recessive, embryonic lethal mutations characterized by degeneration in the developing central nervous system that is either transient or initially localized to one area of the brain. Transient degeneration is defined as abnormal cell death occurring during a restricted period of development. Following degeneration, the affected structures do not appear to regenerate. In each case degeneration is identified after somitogenesis is complete and is not associated with visually identified patterning defects. These 30 mutations, forming 21 complementation groups, have been classified into four phenotypic groups: group 1, transient degeneration (13 mutations); group 2, spreading degeneration, early onset, in which degeneration is initially confined to the optic tectum but subsequently spreads to other areas of the central nervous system (7 mutations); group 3, late-onset degeneration, initially identified after 4 days (6 mutations); and group 4, degeneration with abnormal pigmentation (4 mutations). Although apoptotic cells are seen in the retina and tectum of all mutants, the distribution, temporal progression, and severity of degeneration vary between mutations. Several mutations also show pleiotropic effects, with degeneration involving extraneural structures including the pharyngeal arches and pectoral fins. We discuss some of the pathways important for cell survival in the nervous system and suggest that these mutations will provide entry points for identifying genes that affect the survival of restricted neural populations.

2019 ◽  
Vol 8 (1) ◽  
pp. 18-29
Author(s):  
S. A. Abudeyev ◽  
K. V. Kiselyov ◽  
O. V. Parinov ◽  
Yu. D. Udalov ◽  
M. A. Zabelin ◽  
...  

ABSTRACT Introduction Nosocomial infection of the central nervous system (NI-CNS) is a serious complication in neurocritical patients that leads to deterioration of patient’s condition, worsening of outcomes and increased cost of treatment. The timely diagnosis of NI-CNS is a relevant problem and the search for new reliable markers of NI-CNS is an important issue.MATERIAL AND METHODS The prospective observational study consisted of two parts. The aim of the frst part was to defne normal ranges of cerebral spinal presepsin (CSF PSP). The aim of the second part was investigation of CSF PSP in neurocritical patients. We studied CSF sampling obtained during spinal anesthesia for elective urologic surgery in order to defne the normal CSF PSP. The following data was collected in neurocritical patients: CSF cell count, glucose, lactate, PSP, microbiological tests, polymerase chain reaction (PCR), when it was possible. Blood tests included complete blood count, C-reactive protein (CRP), procalcitonin (PCT), PSP. IBM SPSS Statistics (version 23.0) was used for statistical analysis.RESULTS Fifteen CSF samplings were obtained for investigation of normal CSF PSP ranges, which was 50–100 pg/ml. Nineteen neurocritical patients were included. Sixty-three pairs of CSF and blood samplings were obtained. All pairs were divided into the 4 groups in accordance with presence/absence of NI-CNS or systemic infection. In cases without both NI-CNS and systemic infection (group 4) CSF PSP was 406±203.1 pg/ml. In cases without NI-CNS and with systemic infection (group 2) CSF PSP was 614.9±315 pg/ml. In cases with NI-CNS and without systemic infection (group 3) CSF PSP was 547.8±264.3 pg/ml. In cases with both NI-CNS and systemic infection (group 1) CSF PSP was 731.1±389.7 pg/ml. The ROC analysis showed that in neurocritical patients without systemic infection CSF PSP 537 pg/ml meant NI-CNS with sensitivity 68.8% and specifcity 85.7%.CONCLUSION The normal value of the CSF PSP is 50-100 pg/ml. CSF PSP more than 537 pg/ml in neurocritical patients without systemic infection meant NI-CNS with 688% sensitivity and 857% specifcity. CSF PSP may be used for diagnosing NI-CNS in neurocritical patients as an additional marker only. CSF may be used as an additional diagnostic criterion, but further research is needed.


2019 ◽  
Vol 93 (15) ◽  
Author(s):  
Marie Kubota ◽  
Rei Matsuoka ◽  
Tateki Suzuki ◽  
Koji Yonekura ◽  
Yusuke Yanagi ◽  
...  

ABSTRACT Mumps virus (MuV) is an important aerosol-transmitted human pathogen causing epidemic parotitis, meningitis, encephalitis, and deafness. MuV preferentially uses a trisaccharide containing α2,3-linked sialic acid as a receptor. However, given the MuV tropism toward glandular tissues and the central nervous system, an additional glycan motif(s) may also serve as a receptor. Here, we performed a large-scale glycan array screen with MuV hemagglutinin-neuraminidase (MuV-HN) attachment proteins by using 600 types of glycans from The Consortium for Functional Glycomics Protein-Glycan Interaction Core in an effort to find new glycan receptor motif(s). According to the results of the glycan array, we successfully determined the crystal structures of MuV-HN proteins bound to newly identified glycan motifs, sialyl LewisX (SLeX) and the oligosaccharide portion of the GM2 ganglioside (GM2-glycan). Interestingly, the complex structures showed that SLeX and GM2-glycan share the same configuration with the reported trisaccharide motif, 3′-sialyllactose (3′-SL), at the binding site of MuV-HN, while SLeX and GM2-glycan have several unique interactions compared with those of 3′-SL. Thus, MuV-HN protein can allow an additional spatial modification in GM2-glycan and SLeX at the second and third carbohydrates from the nonreducing terminus of the core trisaccharide structure, respectively. Importantly, MuV entry was efficiently inhibited in the presence of 3′-SL, SLeX, or GM2-glycan derivatives, which indicates that these motifs can serve as MuV receptors. The α2,3-sialylated oligosaccharides, such as SLeX and 3′-sialyllactosamine, are broadly expressed in various tissues, and GM2 exists mainly in neural tissues and the adrenal gland. The distribution of these glycan motifs in human tissues/organs may have bearing on MuV tropism. IMPORTANCE Mumps virus (MuV) infection is characterized by parotid gland swelling and can cause pancreatitis, orchitis, meningitis, and encephalitis. MuV-related hearing loss is also a serious complication because it is usually irreversible. MuV outbreaks have been reported in many countries, even in high-vaccine-coverage areas. MuV has tropism toward glandular tissues and the central nervous system. To understand the unique MuV tropism, revealing the mechanism of receptor recognition by MuV is very important. Here, using a large-scale glycan array and X-ray crystallography, we show that MuV recognizes sialyl LewisX and GM2 ganglioside as receptors, in addition to a previously reported MuV receptor, a trisaccharide containing an α2,3-linked sialic acid. The flexible recognition of these glycan receptors by MuV may explain the unique tropism and pathogenesis of MuV. Structures will also provide a template for the development of effective entry inhibitors targeting the receptor-binding site of MuV.


PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e38310 ◽  
Author(s):  
John F. Staropoli ◽  
Larissa Haliw ◽  
Sunita Biswas ◽  
Lillian Garrett ◽  
Sabine M. Hölter ◽  
...  

2016 ◽  
Vol 22 (6) ◽  
pp. 579-592 ◽  
Author(s):  
Xiaomin Dong ◽  
Yanan You ◽  
Jia Qian Wu

The composition and function of the central nervous system (CNS) is extremely complex. In addition to hundreds of subtypes of neurons, other cell types, including glia (astrocytes, oligodendrocytes, and microglia) and vascular cells (endothelial cells and pericytes) also play important roles in CNS function. Such heterogeneity makes the study of gene transcription in CNS challenging. Transcriptomic studies, namely the analyses of the expression levels and structures of all genes, are essential for interpreting the functional elements and understanding the molecular constituents of the CNS. Microarray has been a predominant method for large-scale gene expression profiling in the past. However, RNA-sequencing (RNA-Seq) technology developed in recent years has many advantages over microarrays, and has enabled building more quantitative, accurate, and comprehensive transcriptomes of the CNS and other systems. The discovery of novel genes, diverse alternative splicing events, and noncoding RNAs has remarkably expanded the complexity of gene expression profiles and will help us to understand intricate neural circuits. Here, we discuss the procedures and advantages of RNA-Seq technology in mammalian CNS transcriptome construction, and review the approaches of sample collection as well as recent progress in building RNA-Seq-based transcriptomes from tissue samples and specific cell types.


Author(s):  
Nilufar Khushvakova ◽  
◽  
Gulrukh Davronova

As a result of the research, it was shown that complex treatment with the preparation of cytoflavin leads to an improvement in cerebral circulation and coronary blood flow, activates metabolic processes in the central nervous system, contributes to a more pronounced regression of neurological symptoms in the main group 2 to 3 times compared to the control group.


2009 ◽  
Vol 15 (2) ◽  
pp. 83-88
Author(s):  
Paulo Breno Noronha Liberalesso ◽  
Izabella Celidônio Bertoldo da Silva ◽  
Karlin Fabianne Klagenberg ◽  
Ari Leon Jurkiewicz ◽  
Bianca Simone Zeigelboim ◽  
...  

INTRODUCTION: The infections of the central nervous system remain as a public health problem in several countries and there is a direct relation between poverty and underdevelopment with high mortality and morbidity rates. Seizures represents a complication related to infections of the central nervous system, are considered a clinical emergency and requiring neurological investigation. OBJECTIVE: In this article, we propose to describe the incidence and risk factors for seizures in central nervous system infections in childhood. METHODS: a retrospective study was performed between October 2007 and October 2008 and all patients who were hospitalized with the diagnosis of infections of the central nervous system were analyzed. Newborns were excluded. The patients were divided into GROUP 1 (without seizures) and GROUP 2 (with seizures). RESULTS: 731 patients were included, 47.75% males, with average age of 15.7 years. GROUP 1 - with fever (652/92.35%), headache (580/82.15%), vomits (550/77.9%), and viral meningitis predominance (652/93.06%). GROUP 2 - with fever (25/100%), vomits (12/48), headache (6/24%), and viral encephalitis predominance (14/56%). Ten (40%) patients from the GROUP 2 presented EEG alterations. The incidence of seizures was 3.42% and a significant statistical difference was noticed related to mean age (p<0.000069), presence of headache (p<0.0000), vomits (p<0.0005), stiff neck (p<0.0105) and drowsiness (p<0.0265). CONCLUSIONS: the occurrence of seizures during the hospitalization is significantly more frequent in cases of viral encephalitis and bacterial meningitis compared to viral meningitis. The risk of seizures increases in early ages. Headache, vomits, stiff neck and drowsiness are more frequent symptoms in children with infection of the central nervous system who presented seizures during the hospitalization.


2010 ◽  
Vol 2010 ◽  
pp. 1-4 ◽  
Author(s):  
Sanjeev Gumber ◽  
Doo-Youn Cho ◽  
Timothy W. Morgan

Cerebellar abiotrophy is a degenerative disorder of the central nervous system and has been reported in humans and animals. This case report documents clinical, histopathological, and immunohistochemical findings of cerebellar abiotrophy in an adult Boxer dog. A 3.5-year-old, female, tan Boxer dog presented with a six-week history of left-sided head tilt. Neurological examination and additional diagnostics during her three subsequent visits over 4.5 months revealed worsening of neurological signs including marked head pressing, severe proprioceptive deficits in all the four limbs, loss of menace response and palpebral reflex in the left eye, and a gradual seizure lasting one hour at her last visit. Based on the immunohistochemical staining for glial fibrillary acidic protein and histopathological examination of cerebellum, cerebellar cortical abiotrophy was diagnosed. This is the first reported case of cerebellar abiotrophy in a Boxer dog to our knowledge.


2020 ◽  
Vol 42 (5) ◽  
pp. 18-24
Author(s):  
Nicholas E. Albrecht ◽  
Courtney A. Burger ◽  
Melanie A. Samuel

Over the centuries, artists, poets, writers and scientists have all attempted to answer a key existential question: what makes us human? Neuroscience has provided us with one exciting possible answer: our brains. To decode the complexities of the brain, many large-scale efforts are aimed at unravelling the cellular, molecular and computational properties of this startlingly complex system. Yet, to date, many important insights towards these problems have come from a surprisingly humble part of the central nervous system – the retina. The retina resides outside the skull within the eye and is responsible for vision. It contains diverse neuron types that detect light and has proven to be a uniquely approachable system for discovering neurobiology principles owing to its inherent organization, wiring and experimental accessibility. In this article, we describe how the retina has been used to make key neuroscience discoveries, and in turn how these principles shed light on how the brain works.


Author(s):  
AG Setko ◽  
OM Zhdanova ◽  
PV Lukyanov

Introduction: In the context of the modern educational process, accompanied by a high intensity of intellectual work, one of the most important tasks of school medicine specialists is to support, maintain and improve cognitive skills of schoolchildren as the main predictors of academic success. Objective: The study aimed to give a physiological and hygienic characteristic of cognitive functions determining academic success of schoolchildren aged 15–17 years under conditions of various schooling intensity. Materials and methods: We conducted a time study to assess schooling intensity of 250 pupils of a multidisciplinary lyceum (Group 1) and 274 pupils of a comprehensive school (Group 2) and evaluated their academic performance. Computer testing was used to study the functional state of the central nervous system, mental performance and cognitive skills of the schoolchildren. Results: We established higher grade point averages in key disciplines among Group 1 students with high schooling intensity (class 3.1) compared to those in Group 2 with optimal intensity of the educational process (class 1). We found that high academic performance in Group 1 was attributed to the optimal functional state of the central nervous system characterized by stabilization of nervous processes and a better ability of the nervous system to form the adaptive functional system of the body in response to various stimuli; to the dominance of the left cerebral hemisphere in 61.2 % of the students, which determined mature skills of verbal, abstract, logical and analytical thinking in 51.9–93.5% of the students; high speed of mental activity and concentration of voluntary attention promoting cognitive activity and maintaining normal mental performance of the schoolchildren. Conclusions: Our findings contribute to a better understanding of the processes of adaptation of schoolchildren to various factors of school environment and learning to be used within the development of school medicine when organizing educational activities of students at schools with an intensive learning regime in order to promote academic performance and achieve high efficiency of the educational process within physiological capabilities of children and adolescents. At the same time, from physiological and hygienic points of view, assessment of cognitive skills in children and teenagers by means of medical and psychological testing in educational establishments implementing profile training of various difficulty levels can become an effective diagnostic tool in predicting academic performance of students and help resolve issues of prevention of maladjustment and stress at school.


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