Vacuolar myelinopathy is a fatal neurological disease that was initially discovered during a mysterious mass mortality of bald eagles in Arkansas in the United States. The cause of this wildlife disease has eluded scientists for decades while its occurrence has continued to spread throughout freshwater reservoirs in the southeastern United States. Recent studies have demonstrated that vacuolar myelinopathy is induced by consumption of the epiphytic cyanobacterial species Aetokthonos hydrillicola growing on aquatic vegetation, primarily the invasive Hydrilla verticillata Here, we describe the identification, biosynthetic gene cluster, and biological activity of aetokthonotoxin, a pentabrominated biindole alkaloid that is produced by the cyanobacterium A. hydrillicola We identify this cyanobacterial neurotoxin as the causal agent of vacuolar myelinopathy and discuss environmental factors-especially bromide availability-that promote toxin production.

• MeSH
• Accipitridae * MeSH
• bakteriální geny MeSH
• bakteriální toxiny biosyntéza   chemie   izolace a purifikace   toxicita   MeSH
• brom analýza   MeSH
• bromidy metabolismus   MeSH
• Caenorhabditis elegans účinky léků   MeSH
• dánio pruhované MeSH
• demyelinizační nemoci chemicky indukované   veterinární   MeSH
• Hydrocharitaceae metabolismus   mikrobiologie   MeSH
• indolové alkaloidy chemie   izolace a purifikace   toxicita   MeSH
• kur domácí MeSH
• LD50 MeSH
• multigenová rodina MeSH
• nemoci ptáků chemicky indukované   MeSH
• neurotoxiny biosyntéza   chemie   izolace a purifikace   toxicita   MeSH
• sinice * genetika   růst a vývoj   metabolismus   MeSH
• tryptofan metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Geografické názvy
• jihovýchod USA MeSH
• Názvy látek
• bakteriální toxiny MeSH
• brom MeSH
• bromidy MeSH
• indolové alkaloidy MeSH
• neurotoxiny MeSH
• tryptofan MeSH

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.

• Klíčová slova
• Blood-brain barrier, Brain damage, Deoxynivalenol, Neurotoxicity, Oxidative stress, T-2 toxin,
• 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
• Názvy látek
• deoxynivalenol MeSH Prohlížeč
• neurotoxiny MeSH
• T-2 toxin MeSH
• trichotheceny 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.

• Klíčová slova
• QT correction, QT prolongation, cardiac dysfunction, 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
• Názvy látek
• neurotoxiny MeSH
• tetanový toxin 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.

• Klíčová slova
• endocrine-disrupting chemicals, marine invertebrate, mode-of-action, neurodevelopment, nuclear receptors,
• 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
• Názvy látek
• endokrinní disruptory MeSH
• neurotoxiny MeSH
• receptory cytoplazmatické a nukleární 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.

• Klíčová slova
• Botulinum neurotoxin, Drug delivery, Exocytosis, Molecular medicine, Nano-carriers, Presynaptic, SNARE proteins, Tetanus toxin, Therapeutic targeting,
• 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
• Názvy látek
• biologické toxiny MeSH
• neurotoxiny MeSH
• neurotransmiterové látky 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
• Názvy látek
• imunotoxiny MeSH
• neurotoxiny 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.

• Klíčová slova
• Blue-green algae, Estrogenicity, Fish, Retinoid-like activity, Teratogenicity,
• 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
• Názvy látek
• endokrinní disruptory MeSH
• neurotoxiny MeSH
• teratogeny MeSH

OBJECTIVES: On the animal model of trimethyltin (TMT) induced behavioral deficits the effect of chronic treatment with spirocyclic dipeptide cyclo/alanyl-l-amino-l-cyclopentane-carbonyl (alaptide, AL) was evaluated in adult male rats. METHODS: Changes in the spontaneous behavioral repertoire were investigated in the open-field test on Day 21 (Session 1) and Day 28 (Session 2) after a single oral TMT administration. RESULTS: In Experiment 1, rats given the highest TMT dose (7.5 mg/kg) exhibited significantly increased total number of behavioral patterns, the floor sniffing being the most frequent pattern. While the medium TMT dose (5 mg/kg) had a similar effect only in Session 1, the lowest TMT dose (2.5 mg/kg) was entirely ineffective. In Experiment 2, an explicit beneficial influence of both AL doses (5 and 10 mg/kg) given for 10 days before and 10 days after TMT (7.5 mg/kg) on the spontaneous behavior repertoire was observed in both Session 1 and Session 2. The total number of patterns and the time spent in individual patterns of AL+TMT treated animals did not differ from the controls and those given AL alone. CONCLUSION: We conclude that sufficiently long AL treatment interfered with deleterious effects of TMT and forestalled changes in the structure and timing of spontaneous behavioral patterns. Thus, AL can be designated as a substance having "neuroprotective" effects.

• MeSH
• chování zvířat účinky léků   fyziologie   MeSH
• cyklické peptidy aplikace a dávkování   farmakologie   MeSH
• krysa rodu Rattus MeSH
• lékové interakce MeSH
• náhodné rozdělení MeSH
• neparametrická statistika MeSH
• neuropeptidy aplikace a dávkování   farmakologie   MeSH
• neuroprotektivní látky aplikace a dávkování   MeSH
• neurotoxiny toxicita   MeSH
• pátrací chování účinky léků   fyziologie   MeSH
• pohybová aktivita účinky léků   fyziologie   MeSH
• potkani Wistar MeSH
• rozvrh dávkování léků MeSH
• trimethylcínové sloučeniny toxicita   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• cyclo(alanine-(1-amino-1-cyclopentane)carbonyl) MeSH Prohlížeč
• cyklické peptidy MeSH
• neuropeptidy MeSH
• neuroprotektivní látky MeSH
• neurotoxiny MeSH
• trimethylcínové sloučeniny MeSH
• trimethyltin MeSH Prohlížeč

Reactivation potency of three newly developed oximes K027, K033 and K048 was tested using standard in vitro and in vivo reactivation tests. K027 and K048 seem to be efficacious reactivators of tabun-inhibited acetylcholinesterase. K033 is sufficient reactivator of cyclosarin-inhibited AChE. However, its potency is poor compared with current "gold standard" oxime HI-6.

• MeSH
• acetylcholinesterasa metabolismus   MeSH
• aktivace enzymů účinky léků   MeSH
• cholinesterasové inhibitory farmakologie   toxicita   MeSH
• neurony účinky léků   enzymologie   MeSH
• neurotoxiny farmakologie   toxicita   MeSH
• oximy farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• cholinesterasové inhibitory MeSH
• neurotoxiny MeSH
• oximy MeSH

Cyanobacteria, formerly called "blue-green algae", are simple, primitive photosynthetic microorganism wide occurrence in fresh, brackish and salt waters. Forty different genera of Cyanobacteria are known and many of them are producers of potent toxins responsible for a wide array of human illnesses, aquatic mammal and bird morbidity and mortality, and extensive fish kills. These cyanotoxins act as neurotoxins or hepatotoxins and are structurally and functionally diverse, and many are derived from unique biosynthetic pathways. All known cyanotoxins and their chemical and toxicological characteristics are presented in this article.

• MeSH
• bakteriální toxiny chemie   farmakologie   toxicita   MeSH
• lidé MeSH
• mikrobiologie vody * MeSH
• mikrocystiny MeSH
• mořské toxiny chemie   farmakologie   toxicita   MeSH
• neurotoxiny * chemie   farmakologie   toxicita   MeSH
• sinice klasifikace   růst a vývoj   metabolismus   MeSH
• toxiny kmene Cyanobacteria MeSH
• znečištění vody MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bakteriální toxiny MeSH
• mikrocystiny MeSH
• mořské toxiny MeSH
• neurotoxiny * MeSH
• toxiny kmene Cyanobacteria MeSH