During the last decade, the neurotoxicity of the trichothecenes T-2 toxin and deoxynivalenol (DON) has been a major concern, and many important findings have been reported on this topic. Through a summary of relevant research reports in recent years, we discuss the potential neurotoxic mechanisms of T-2 toxin and DON. In neuronal cells, T-2 toxin induces mitochondrial dysfunction and oxidative stress through a series of signalling pathways, including Nrf2/HO-1 and p53. This toxin crosses the blood-brain barrier (BBB) by altering permeability and induces oxidative stress responses, including ROS generation, lipid peroxidation, and protein carbonyl formation. Cellular metabolites (for example, HT-2 toxin) further promote neurotoxic effects. The type B trichothecene DON induces neuronal cell apoptosis via the MAPK and mitochondrial apoptosis pathways. This molecule induces inflammation of the central nervous system, increasing the expression of proinflammatory molecules. DON directly affects brain neurons and glial cells after passing through the BBB and affects the vitality and function of astrocytes and microglia. Exposure to trichothecenes alters brain dopamine levels, decreases ganglion area, and further induces brain damage. In this review, we mainly discuss the neurotoxicity of T-2 toxin and DON. However, our main goal was to reveal the potential mechanism(s) and offer new topics, including the potential of hypoxia-inducible factors, immune evasion, and exosomes, for future research in this context. This review should help elucidate the neurotoxic mechanism of trichothecenes and provides some potential inspiration for the follow-up study of neurotoxicity of mycotoxins.
- MeSH
- apoptóza účinky léků MeSH
- lidé MeSH
- neurony cytologie účinky léků metabolismus MeSH
- neurotoxiny toxicita MeSH
- oxidační stres účinky léků MeSH
- signální transdukce účinky léků MeSH
- T-2 toxin toxicita MeSH
- trichotheceny toxicita MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- dítě MeSH
- fluoridy * škodlivé účinky toxicita MeSH
- glutathion nedostatek MeSH
- hliník škodlivé účinky toxicita MeSH
- lidé MeSH
- neurotoxiny škodlivé účinky toxicita MeSH
- oxidační stres MeSH
- poruchy autistického spektra * epidemiologie patofyziologie prevence a kontrola MeSH
- potravní doplňky MeSH
- registrace MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
OBJECTIVE: To determine electrical changes in the heart in a chronic, nonstatus model of epilepsy. METHODS: Electrocorticography (ECoG) and electrocardiography (ECG) of nine animals (five made epileptic by intrahippocampal injection of tetanus neurotoxin (TeNT) and four controls), are monitored continuously by radiotelemetry for up to 7 weeks. RESULTS: Epileptic animals develop a median of 168 seizures, with postictal tachycardias reaching a mean of 487 beats/min and lasting a mean of 661 seconds. Ictal changes in heart rate include tachycardia and in the case of convulsive seizures, bradyarrhythmias resembling Mobitz type 1 second-degree atrioventricular block; notably the P-R interval increased before block. Postictally, the amplitude of T wave increases. Interictally, QT dependence on RR is modest and conventional QT corrections prove ineffective. Interictal QT intervals, measured at a heart rate of 400 bpm, increased from 65 to 75 ms, an increase dependent on seizure incidence over the preceding 10-14 days. SIGNIFICANCE: Repeated seizures induce a sustained tachycardia and increase in QT interval of the ECG and evoke arrhythmias including periods of atrioventricular block during Racine type 4 and 5 seizures. These changes in cardiac function may predispose to development in fatal arrhythmias and sudden death in humans with epilepsy.
- MeSH
- bradykardie etiologie MeSH
- elektrokardiografie MeSH
- elektrokortikografie MeSH
- krysa rodu rattus MeSH
- náhlá neočekávaná smrt při epilepsii etiologie MeSH
- neurotoxiny toxicita MeSH
- potkani Wistar MeSH
- tachykardie etiologie MeSH
- tetanový toxin toxicita MeSH
- záchvaty chemicky indukované komplikace patofyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Synaptic transmission is a fundamental neurobiological process enabling exchange of signals between neurons as well as neurons and their non-neuronal effectors. The complex molecular machinery of the synaptic vesicle cycle and transmitter release has emerged and developed in the course of the evolutionary race, to ensure adaptive gain and survival of the fittest. In parallel, a generous arsenal of biomolecules and neuroactive peptides have co-evolved, which selectively target the transmitter release machinery, with the aim of subduing natural rivals or neutralizing prey. With advances in neuropharmacology and quantitative biology, neurotoxins targeting presynaptic mechanisms have attracted major interest, revealing considerable potential as carriers of molecular cargo and probes for meddling synaptic transmission mechanisms for research and medical benefit. In this review, we investigate and discuss key facets employed by the most prominent bacterial and animal toxins targeting the presynaptic secretory machinery. We explore the cellular basis and molecular grounds for their tremendous potency and selectivity, with effects on a wide range of neural functions. Finally, we consider the emerging preclinical and clinical data advocating the use of active ingredients of neurotoxins for the advancement of molecular medicine and development of restorative therapies.
- MeSH
- biologické toxiny toxicita MeSH
- lidé MeSH
- nervový přenos účinky léků MeSH
- neurotoxiny toxicita MeSH
- neurotransmiterové látky metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Endocrine Disrupting Chemicals (EDCs) are molecules able to interfere with the vertebrate hormonal system in different ways, a major one being the modification of the activity of nuclear receptors (NRs). Several NRs are expressed in the vertebrate brain during embryonic development and these NRs are suspected to be responsible for the neurodevelopmental defects induced by exposure to EDCs in fishes or amphibians and to participate in several neurodevelopmental disorders observed in humans. Known EDCs exert toxicity not only on vertebrate forms of marine life but also on marine invertebrates. However, because hormonal systems of invertebrates are poorly understood, it is not clear whether the teratogenic effects of known EDCs are because of endocrine disruption. The most conserved actors of endocrine systems are the NRs which are present in all metazoan genomes but their functions in invertebrate organisms are still insufficiently characterized. EDCs like bisphenol A have recently been shown to affect neurodevelopment in marine invertebrate chordates called ascidians. Because such phenotypes can be mediated by NRs expressed in the ascidian embryo, we review all the information available about NRs expression during ascidian embryogenesis and discuss their possible involvement in the neurodevelopmental phenotypes induced by EDCs.
- MeSH
- biologické modely MeSH
- embryo nesavčí účinky léků MeSH
- embryonální vývoj účinky léků MeSH
- endokrinní disruptory toxicita MeSH
- nervový systém * účinky léků embryologie růst a vývoj MeSH
- neurotoxiny toxicita MeSH
- receptory cytoplazmatické a nukleární metabolismus MeSH
- Urochordata * účinky léků embryologie růst a vývoj MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
In the present study, the effect of the medial septal (MS) lesions on exploratory activity in the open field and the spatial and object recognition memory has been investigated. This experiment compares three types of MS lesions: electrolytic lesions that destroy cells and fibers of passage, neurotoxic - ibotenic acid lesions that spare fibers of passage but predominantly affect the septal noncholinergic neurons, and immunotoxin - 192 IgG-saporin infusions that only eliminate cholinergic neurons. The main results are: the MS electrolytic lesioned rats were impaired in habituating to the environment in the repeated spatial environment, but rats with immuno- or neurotoxic lesions of the MS did not differ from control ones; the MS electrolytic and ibotenic acid lesioned rats showed an increase in their exploratory activity to the objects and were impaired in habituating to the objects in the repeated spatial environment; rats with immunolesions of the MS did not differ from control rats; electrolytic lesions of the MS disrupt spatial recognition memory; rats with immuno- or neurotoxic lesions of the MS were normal in detecting spatial novelty; all of the MS-lesioned and control rats clearly reacted to the object novelty by exploring the new object more than familiar ones. Results observed across lesion techniques indicate that: (i) the deficits after nonselective damage of MS are limited to a subset of cognitive processes dependent on the hippocampus, (ii) MS is substantial for spatial, but not for object recognition memory - the object recognition memory can be supported outside the septohippocampal system; (iii) the selective loss of septohippocampal cholinergic or noncholinergic projections does not disrupt the function of the hippocampus to a sufficient extent to impair spatial recognition memory; (iv) there is dissociation between the two major components (cholinergic and noncholinergic) of the septohippocampal pathway in exploratory behavior assessed in the open field - the memory exhibited by decrements in exploration of repeated object presentations is affected by either electrolytic or ibotenic lesions, but not saporin.
- MeSH
- bludiště - učení účinky léků fyziologie MeSH
- hipokampus účinky léků patologie fyziologie MeSH
- imunotoxiny toxicita MeSH
- krysa rodu rattus MeSH
- neurotoxiny toxicita MeSH
- pátrací chování účinky léků fyziologie MeSH
- potkani Wistar MeSH
- rozpoznávání (psychologie) účinky léků fyziologie MeSH
- septální jádra účinky léků patologie fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Cyanobacteria contain various types of bioactive compounds, which could cause adverse effects on organisms. They are released into surface waters during cyanobacterial blooms, but there is little information on their potential relevance for effects in vivo. In this study presence of bioactive compounds was characterized in cyanobacteria Microcystis aeruginosa (Chroococcales), Planktothrix agardhii (Oscillatoriales) and Aphanizomenon gracile (Nostocales) with selected in vitro assays. The in vivo relevance of detected bioactivities was analysed using transgenic zebrafish embryos tg(cyp19a1b-GFP). Teratogenic potency was assessed by analysis of developmental disorders and effects on functions of the neuromuscular system by video tracking of locomotion. Estrogenicity in vitro corresponded to 0.95-54.6 ng estradiol equivalent(g dry weight (dw))(-1). In zebrafish embryos, estrogenic effects could not be detected potentially because they were masked by high toxicity. There was no detectable (anti)androgenic/glucocorticoid activity in any sample. Retinoid-like activity was determined at 1-1.3 μg all-trans-retinoic acid equivalent(g dw)(-1). Corresponding to the retinoid-like activity A. gracile extract also caused teratogenic effects in zebrafish embryos. Furthermore, exposure to biomass extracts at 0.3 gd wL(-1) caused increase of body length in embryos. There were minor effects on locomotion caused by 0.3 gd wL(-1)M. aeruginosa and P. agardhii extracts. The traditionally measured cyanotoxins microcystins did not seem to play significant role in observed effects. This indicates importance of other cyanobacterial compounds at least towards some species or their developmental phases. More attention should be paid to activity of retinoids, estrogens and other bioactive substances in phytoplankton using in vitro and in vivo bioassays.
- MeSH
- Aphanizomenon chemie MeSH
- biotest MeSH
- dánio pruhované embryologie genetika metabolismus MeSH
- embryo nesavčí účinky léků MeSH
- endokrinní disruptory toxicita MeSH
- geneticky modifikovaná zvířata embryologie genetika metabolismus MeSH
- Microcystis chemie MeSH
- neurotoxiny toxicita MeSH
- sinice chemie MeSH
- teratogeny toxicita MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Příčiny vzniku Parkinsonovy nemoci (PN) zůstávají po mnoho let předmětem živých diskuzí a intenzivních mezioborových výzkumů. Přibližně 5–10 % všech případů PN představují monogenní formy, které se projevují především u osob mladšího věku, zatímco většinu případů tvoří sporadická onemocnění multifaktoriálního rázu. Klíčovou molekulární událostí v rozvoji neurodegenerace při PN je porucha konformace malé vezikulární bílkoviny α‑synukleinu, jež iniciuje její fibrilizaci s tvorbou neurotoxických cytoplazmatických agregátů, Lewyho tělísek a Lewyho neuritů. Patologie α‑synukleinu při PN je podmíněna specifickým vzájemným působením faktorů prostředí, zvláštností genomu a systémového metabolizmu, což v souhrnu určuje charakter procesů buněčné detoxikace, fungování mitochondrií, synaptické transmise a endozomálního transportu. V přehledu jsou podrobně posouzeny možné exogenní a endogenní spouštěče patologického procesu při PN. Zvláštní pozornost při analýze rizikových faktorů náleží úloze různých neurotoxinů, prionové hypotéze rozvoje PN a rovněž současným představám o genetice familiárních a sporadických případů PN.
Etiology of Parkinson's disease (PD) for many years has been remaining the matter of active discussions and intensive interdisciplinary studies. About 5–10% of all cases of PD are represented by monogenic forms manifesting predominantly in younger persons, while most cases of the disease are sporadic and have multifactorial nature. The key molecular event in the development of neurodegeneration in PD is the conformational change of a small vesicular protein α‑synuclein initiating its self‑fibrilization with forming neurotoxic cytoplasmic aggregates and Lewy bodies/neurites. Misfolding of α‑synuclein in PD is caused by specific interaction of environmental factors, genomic factors and characteristics of systemic metabolism, which, in combination, determines the processes of cell detoxication, mitochondrial functioning, synaptic transmission and endosomal transport. In this review, possible exogenous and endogenous triggers of pathological process in PD are discussed in detail. Among the risk factors, special consideration is given to the role of different neurotoxins, prion hypothesis of the development of PD, as well as up‑to‑date knowledge about genetics of familial and sporadic cases of PD. Key words: Parkinson's disease – etiology – molecular mechanisms – risk factors – genetics The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.
- MeSH
- alfa-synuklein genetika izolace a purifikace metabolismus MeSH
- biomedicínský výzkum * trendy MeSH
- genetické nemoci vrozené genetika MeSH
- genetické techniky trendy využití MeSH
- kraniocerebrální traumata komplikace MeSH
- lidé MeSH
- molekulární epidemiologie metody trendy MeSH
- molekulární medicína * metody trendy MeSH
- neuroprotektivní látky terapeutické užití MeSH
- neurotoxiny škodlivé účinky toxicita MeSH
- Parkinsonova nemoc * etiologie genetika metabolismus MeSH
- prionové nemoci komplikace MeSH
- rizikové faktory MeSH
- statistika jako téma MeSH
- věkové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
