Ograniczanie wyników

Czasopisma help
Autorzy help
Lata help
Preferencje help
Widoczny [Schowaj] Abstrakt
Liczba wyników

Znaleziono wyników: 21

Liczba wyników na stronie
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 2 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników

Wyniki wyszukiwania

Wyszukiwano:
w słowach kluczowych:  neurotoxin
help Sortuj według:

help Ogranicz wyniki do:
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 2 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
The Gram-negative facultative anaerobe Bacteroides fragilis (B. fragilis) constitutes an appreciable proportion of the human gastrointestinal (GI)‑tract microbiome. As is typical of most Gram-negative bacilli, B. fragilis secretes an unusually complex mixture of neurotoxins including 2 extremely pro-inflammatory species: (i) a B. fragilis‑associated lipopolysaccharide BF‑LPS; and (ii) a B. fragilis-derived proteolytic enterotoxin known as fragilysin (EC 3.4.24.74). BF‑LPS has recently been shown to be associated with the periphery of neuronal nuclei in sporadic Alzheimer’s disease (AD) brain; and the extracellular zinc metalloprotease fragilysin (i) induces endogenous E-cadherin cleavage thereby disrupting cell-cell adhesion and the GI‑tract‑blood barrier (GTBB); and (ii) promotes the generation of the inflammatory transcription factor NF‑kB (p50/p65 complex) in human neuronal‑glial cells in primary culture. In turn, the NF‑kB (p50/p65 complex) strongly induces the transcription of a small family of pro-inflammatory microRNAs (miRNAs) including miRNA‑9, miRNA‑34a, miRNA‑125b, miRNA‑146a, and miRNA‑155. These ultimately bind with the 3’‑untranslated region (3’‑UTR) of several target messenger RNAs (mRNAs) and thereby reduce their expression. Down‑regulated mRNAs include those encoding complement factor-H (CFH), an SH3-proline-rich multi domain-scaffolding protein of the postsynaptic density (SHANK3), and the triggering receptor expressed in myeloid/microglial cells (TREM2), as is observed in sporadic AD brain. Hence, a LPS and an enterotoxic metalloprotease normally confined to the GI tract are capable of driving a disruption in the GI-tract-blood barrier and a NF-kB-miRNA-mediated deficiency in gene expression that contributes to alterations in synaptic-architecture and synaptic-deficits, amyloidogenesis, innate-immune defects, and progressive inflammatory signaling, all of which are characteristic of AD‑type neurodegeneration. This paper will review the most recent research which supports the concept that bacterial components of the GI-tract microbiome such as BF-LPS and fragilysin can transverse normally protective biophysical barriers and contribute to AD‑type changes. For the first‑time, these results indicate that specific GI-tract microbiome-derived neurotoxins have a strong pathogenic potential in disrupting the GI-tract blood barrier and eliciting alterations in NF-kB-miRNA-directed gene expression that drive the AD process.
Human neural stem cells play an important role in in vitro developmental neurotoxicity testing. The purpose of this research was to investigate the sensitivity of neural stem cells derived from human umbilical cord blood (HUCB-NSC) to methylmercury chloride (MeHgCl), and its dependence on the type of interaction on cell membrane/biomolecule interface. MeHgCl is well known neurotoxin with documented adverse influence on human central nervous system (CNS) development. Cells were cultured in 96-well plates covered with different adhesive substrates or on Petri dishes microcontact-printed with biofunctional domains. The following biomaterials were used: poly-L-lysine, the synthetic compound, which allows to create electrostatic interactions with cells, or fibronectin and vitronectin, proteins of extracellular matrix, which create receptor mediated interactions between cells and the adhesive substrate. After the incubation with different concentrations of the neurotoxin, the cell viability, ability to proliferate, and to differentiate into neural precursors of HUCB-NSCs was measured with Alamar Blue assay and immunfluorescence stainings. High concentration of MeHgCl (1 µM) significantly decreased viability of cells and their ability to proliferate. The response of cells to the toxic effect of MeHgCl was different depending on the type of adhesive substrate. Domains covered with fibronectin or vitronectin, decreased significantly HUCB-NSC sensitivity to the neurotoxin when compared to poly-L-lysine. Our results suggest that receptor mediated interactions on cell membrane/biomolecule interface may be protective in neural stem cells’ response to certain neurotoxins. Supported by MSHE grant No 5978/B/P01/38 and NN 302663940
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a neurotoxin, which can damage dopaminergic neurons. It causes symptoms resembling those observed in patients suffering from Parkinson’s disease, and hence this toxin is widely used in studies on animal models of this disorder. Mutagenicity of MPTP was also reported by some authors, but results obtained by others suggested that this compound is not mutagenic. Interestingly, those contrasting results were based on the same assay (the Ames test). Therefore, we aimed to test MPTP mutagenicity by employing a recently developed Vibrio harveyi assay, which was demonstrated previously to be more sensitive than the Ames test, at least for some mutagens. We found that MPTP showed a significant mutagenic activity. Moreover, MPTP mutagenicity was attenuated by methylxanthines, compounds that are known to form complexes with aromatic mutagens.
Botulinum toxin (BTX) belongs to a family of neurotoxins which strongly influence the function of autonomic neurons supplying the urinary bladder. Accordingly, BTX has been used as an effective drug in experimental therapies of a range of neurogenic bladder disorders. However, there is no detailed information dealing with the influence of BTX on the morphological and chemical properties of nerve fibres supplying the urinary bladder wall. Therefore, the present study investigated, using double-labeling immunohistochemistry, the distribution, relative frequency and chemical coding of cholinergic and noradrenergic nerve fibers supplying the wall of the urinary bladder in normal female pigs (n=6) and in the pigs (n=6) after intravesical BTX injections. In the pigs injected with BTX, the number of adrenergic (DβH-positive) nerve fibers distributed in the bladder wall (urothelium, submucosa and muscle coat) was distinctly higher while the number of cholinergic (VAChT-positive) nerve terminals was lower than that found in the control animals. Moreover, the injections of BTX resulted in some changes dealing with the chemical coding of the adrenergic nerve fibers. In contrast to the normal pigs, in BTX injected animals the number of DβH/NPY- or DβH/CGRP-positive axons was higher in the muscle coat, and some fibres distributed in the urothelium and submucosa expressed immunoreactivity to CGRP. The results obtained suggest that the therapeutic effects of BTX on the urinary bladder might be dependent on changes in the distribution and chemical coding of nerve fibers supplying this organ.
Morphologically, physiologically and metabolically, cyanobacteria (blue-green algae) are one of the most diverse groups of prokaryotes. Cyanobacteria bloom abundantly in surface waters as a result of eutrophication and they produce different types of toxins, so they not only hinder recreational use of bodies of water but also cause health problems in humans and animals. Cyanobacterial toxins (cyanotoxins) can be classified in five groups: hepatotoxins, neurotoxins, cytotoxins, dermatotoxins and irritant toxins (lipopolysaccharides).
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 2 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.