scholarly journals Organophosphorus diisopropylfluorophosphate (DFP) intoxication in zebrafish larvae causes behavioral defects, neuronal hyperexcitation and neuronal death

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alexandre Brenet ◽  
Julie Somkhit ◽  
Rahma Hassan-Abdi ◽  
Constantin Yanicostas ◽  
Christiane Romain ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Epileptic Seizures ◽  
Causal Link ◽  
Synaptic Activity ◽  
Acetylcholinesterase Inhibition ◽  
Public Health Issue ◽  
Protein Accumulation ◽  
Zebrafish Larvae ◽  
Neuron Damage ◽  
Cholinergic Syndrome

Abstract With millions of intoxications each year and over 200,000 deaths, organophosphorus (OP) compounds are an important public health issue worldwide. OP poisoning induces cholinergic syndrome, with respiratory distress, hypertension, and neuron damage that may lead to epileptic seizures and permanent cognitive deficits. Existing countermeasures are lifesaving but do not prevent long-lasting neuronal comorbidities, emphasizing the urgent need for animal models to better understand OP neurotoxicity and identify novel antidotes. Here, using diisopropylfluorophosphate (DFP), a prototypic and moderately toxic OP, combined with zebrafish larvae, we first showed that DFP poisoning caused major acetylcholinesterase inhibition, resulting in paralysis and CNS neuron hyperactivation, as indicated by increased neuronal calcium transients and overexpression of the immediate early genes fosab, junBa, npas4b, and atf3. In addition to these epileptiform seizure-like events, DFP-exposed larvae showed increased neuronal apoptosis, which were both partially alleviated by diazepam treatment, suggesting a causal link between neuronal hyperexcitation and cell death. Last, DFP poisoning induced an altered balance of glutamatergic/GABAergic synaptic activity with increased NR2B-NMDA receptor accumulation combined with decreased GAD65/67 and gephyrin protein accumulation. The zebrafish DFP model presented here thus provides important novel insights into the pathophysiology of OP intoxication, making it a promising model to identify novel antidotes.

scholarly journals Organophosphorus diisopropylfluorophosphate (DFP) intoxication in zebrafish larvae causes behavioral defects, neuronal hyperexcitation and neuronal death

2019 ◽  
Author(s):  
Alexandre Brenet ◽  
Julie Somkhit ◽  
Rahma Hassan-Abdi ◽  
Constantin Yanicostas ◽  
Christiane Romain ◽  
...  
Keyword(s):  
Neuronal Apoptosis ◽  
Epileptic Seizures ◽  
Causal Link ◽  
Synaptic Activity ◽  
Acetylcholinesterase Inhibition ◽  
Public Health Issue ◽  
Protein Accumulation ◽  
Zebrafish Larvae ◽  
Neuron Damage ◽  
Cholinergic Syndrome

AbstractWith millions of intoxications each year and over 200,000 deaths, organophosphorus (OP) compounds are an important public health issue worldwide. OP poisoning induces cholinergic syndrome, with muscle weakness, hypertension, and neuron damage that may lead to epileptic seizures and permanent psychomotor deficits. Existing countermeasures are lifesaving but do not prevent long-lasting neuronal comorbidities, emphasizing the urgent need for animal models to better understand OP neurotoxicity and identify novel antidotes. Here, using diisopropylfluorophosphate (DFP), a prototypic and moderately toxic OP, combined with zebrafish larvae, we first showed that DFP poisoning caused major acetylcholinesterase inhibition, resulting in paralysis and CNS neuron hyperactivation, as indicated by increased neuronal calcium transients and overexpression of the immediate early genes fosab, junBa, npas4b, and atf3. In addition to these epileptiform seizure-like events, DFP-exposed larvae showed increased neuronal apoptosis, which were both partially alleviated by diazepam treatment, suggesting a causal link between neuronal hyperexcitation and cell death. Last, DFP poisoning induced an altered balance of glutamatergic/GABAergic synaptic activity with increased NR2B-NMDA receptor accumulation combined with decreased GAD65/67 and gephyrin protein accumulation. The zebrafish DFP model presented here thus provides important novel insights into the pathophysiology of OP intoxication, making it a promising model to identify novel antidotes.

Stroke

2017 ◽  
Author(s):  
Didier Leys ◽  
Charlotte Cordonnier ◽  
Valeria Caso
Keyword(s):  
Stroke Unit ◽  
Major Complication ◽  
Epileptic Seizures ◽  
Recombinant Tissue Plasminogen Activator ◽  
Acute Stage ◽  
Public Health Issue ◽  
Stroke Subtype ◽  
Vascular Events ◽  
Increased Risk ◽  
Major Interest

Stroke is a major public health issue. Many are treatable in the acute stage, provided patients are admitted soon enough. The overall incidence of stroke in Western countries is approximately 2400 per year per million inhabitants, and 80% are due to cerebral ischaemia. The prevalence is approximately 12 000 per million inhabitants. Stroke is associated with increased long-term mortality, handicap, cognitive and behavioural impairments, recurrence, and an increased risk of other types of vascular events. It is of major interest to take the heterogeneity of stroke into account, because of differences in the acute management, secondary prevention, and outcomes, according to the subtype and cause of stroke. In all types of stroke, early epileptic seizures, delirium, increased intracranial pressure, and non-specific complications are frequent. In ischaemic strokes, specific complications, such as malignant infarcts, spontaneous haemorrhagic transformation, early recurrence, and a new ischaemic event in another vascular territory, are frequent. In haemorrhagic strokes, the major complication is the subsequent increased volume of bleeding. There is strong evidence that stroke patients should be treated in dedicated stroke units; each time 24 patients are treated in a stroke unit, instead of a conventional ward, one death and one dependence are prevented. This effect does not depend on age, severity, and the stroke subtype. For this reason, stroke unit care is the cornerstone of the treatment of stroke, aiming at the detection and management of life-threatening emergencies, stabilization of most physiological parameters, and prevention of early complications. In ischaemic strokes, besides this general management, specific therapies include intravenous recombinant tissue plasminogen activator, given as soon as possible and before 4.5 hours, mechanical thrombectomy in case of proximal occlusion (middle cerebral artery, intracranial internal carotid artery, basilar artery), on top of thrombolysis in the absence of contraindication or alone otherwise, aspirin 300 mg, immediately or after 24 hours in case of thrombolysis, and, in a few patients, decompressive surgery. In intracerebral haemorrhages, blood pressure lowering and haemostatic therapy, when needed, are the two targets, while surgery does not seem effective to reduce death and disability.

scholarly journals A common molecular mechanism for cognitive deficits and craving in alcoholism

2020 ◽  
Author(s):  
Marcus W. Meinhardt ◽  
Simone Pfarr ◽  
Cathrin Rohleder ◽  
Valentina Vengeliene ◽  
Janet Barroso-Flores ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Executive Control ◽  
Molecular Mechanisms ◽  
Intervention Strategy ◽  
Executive Dysfunction ◽  
Causal Link ◽  
Alcohol Craving ◽  
Pathological Mechanism ◽  
Excessive Alcohol ◽  
Alcohol Dependent

Alcohol-dependent patients commonly show impairments in executive functions that facilitate craving and can lead to relapse. The medial prefrontal cortex, a key brain region for executive control, is prone to alcohol-induced neuroadaptations. However, the molecular mechanisms leading to executive dysfunction in alcoholism are poorly understood. Here using a bi-directional neuromodulation approach we demonstrate a causal link for reduced prefrontal mGluR2 function and both impaired executive control and alcohol craving. By neuron-specific prefrontal knockdown of mGluR2 in rats, we generated a phenotype of reduced cognitive flexibility and excessive alcohol-seeking. Conversely, restoring prefrontal mGluR2 levels in alcohol-dependent rats rescued these pathological behaviors. Also targeting mGluR2 pharmacologically reduced relapse behavior. Finally, we developed a FDG-PET biomarker to identify those individuals that respond to mGluR2-based interventions. In conclusion, we identified a common molecular pathological mechanism for both executive dysfunction and alcohol craving, and provide a personalized mGluR2-mechanism-based intervention strategy for medication development of alcoholism.

Metabolic regulation of synaptic activity

2018 ◽  
Vol 29 (8) ◽  
pp. 825-835 ◽  
Author(s):  
Sergei V. Fedorovich ◽  
Tatyana V. Waseem
Keyword(s):  
Metabolic Disease ◽  
Ketogenic Diet ◽  
Neuronal Death ◽  
Metabolic Regulation ◽  
Glutamate Release ◽  
Epileptic Seizures ◽  
Brain Dysfunction ◽  
Synaptic Activity ◽  
Brain Diseases ◽  
The Brain

AbstractBrain tissue is bioenergetically expensive. In humans, it composes approximately 2% of body weight and accounts for approximately 20% of calorie consumption. The brain consumes energy mostly for ion and neurotransmitter transport, a process that occurs primarily in synapses. Therefore, synapses are expensive for any living creature who has brain. In many brain diseases, synapses are damaged earlier than neurons start dying. Synapses may be considered as vulnerable sites on a neuron. Ischemic stroke, an acute disturbance of blood flow in the brain, is an example of a metabolic disease that affects synapses. The associated excessive glutamate release, called excitotoxicity, is involved in neuronal death in brain ischemia. Another example of a metabolic disease is hypoglycemia, a complication of diabetes mellitus, which leads to neuronal death and brain dysfunction. However, synapse function can be corrected with “bioenergetic medicine”. In this review, a ketogenic diet is discussed as a curative option. In support of a ketogenic diet, whereby carbohydrates are replaced for fats in daily meals, epileptic seizures can be terminated. In this review, we discuss possible metabolic sensors in synapses. These may include molecules that perceive changes in composition of extracellular space, for instance, ketone body and lactate receptors, or molecules reacting to changes in cytosol, for instance, KATPchannels or AMP kinase. Inhibition of endocytosis is believed to be a universal synaptic mechanism of adaptation to metabolic changes.

Pharmacological Evidence for Two Types of Postsynaptic Glycinergic Receptors on the Mauthner Cell of 52-h-Old Zebrafish Larvae

1997 ◽  
Vol 77 (5) ◽  
pp. 2400-2415 ◽  
Author(s):  
P. Legendre
Keyword(s):  
Relative Proportion ◽  
Relative Weight ◽  
Synaptic Activity ◽  
Dependent Manner ◽  
M Cell ◽  
Open Probability ◽  
Concentration Dependent Manner ◽  
Mauthner Cell ◽  
Zebrafish Larvae ◽  
The Mean

Legendre, P. Pharmacological evidence for two types of postsynaptic glycinergic receptors on the Mauthner cell of 52-h-old zebrafish larvae. J. Neurophysiol. 77: 2400–2415, 1997. The presence of homooligomeric and heterooligomeric glycine receptors (GlyRs) on the Mauthner (M) cell in the isolated medulla of 52-h-old zebrafish larvae was investigated by analysis of the effects of picrotoxin on glycine-gated channels and on glycinergic miniature inhibitory postsynaptic currents (mIPSCs). Two functionally different GlyRs have been previously described on the M cell. The effects of picrotoxin on these two GlyRs were first analyzed by measuring the relative change in their total open probability ( NP o) with picrotoxin concentration. Picrotoxin had no significant effect on the glycine channel with a single conductance level of 40–46 pS. In contrast, picrotoxin application decreased the NP o of the GlyR with multiple subconductance levels. On this GlyR, picrotoxin decreased in a concentration-dependent manner the occurrence of the 80- to 86-pS substate (median inhibiting concentration = 0.89 μM) and had no apparent effect on the 40- to 46-pS opening probability. Opening frequency and the mean open times of the 80- to 88-pS main conductance state were reduced in the presence of 10 μM picrotoxin, but their relative weight remained unchanged. These effects of picrotoxin were not voltage dependent. Picrotoxin also modified 40- to 46-pS kinetics. At 100 μM, picrotoxin evoked voltage-independent flickering during channel openings. Short and long mean open times were significantly decreased, whereas the relative proportion of long mean open times was increased. The medium closed time was decreased, whereas medium burst duration was increased. The burst frequency remained unchanged. Spontaneous glycinergic mIPSCs were recorded in the presence of 1 μM tetrodotoxin + 25 μM bicuculline (holding potential = −50 mV). Application of 10 μM picrotoxin did not change the frequency of the synaptic activity, whereas it decreased the amplitude of large mIPSCs. No effect was observed on the time to peak (0.8 ms) or the mean decay time constant (τd = 7.7 ms). Increasing picrotoxin concentration to 100 μM resulted in a decrease of mIPSC frequency (35.6%), amplitude (39.8%), and τd (from 7.7 to 5 ms). These results suggest that these two functionally different GlyRs correspond to α1 homooligomeric-like and α1/β-heterooligomeric-like GlyRs, and that both are synaptically activated. Variation in the proportions of GlyR subtypes from one synapse to another could partly account for the broad amplitude distribution of mIPSCs recorded from the zebrafish M cell.

Phytochemistry and neuroprotective effects of Eclipta alba (L.) Hassk

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Samson Guenné ◽  
Nabèrè Ouattara ◽  
Noufou Ouédraogo ◽  
Alin Ciobica ◽  
Adama Hilou ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Metabolic Disorders ◽  
Epileptic Seizures ◽  
Herbaceous Plant ◽  
Microbial Diseases ◽  
Neuroprotective Effects ◽  
Traditional Medicines ◽  
Eclipta Alba ◽  
Eclipta Prostrata ◽  
Phytochemical Profile

AbstractEclipta alba (L.) Hassk. or Eclipta prostrata (Linn.) or Eclipta erecta (Linn.) is an herbaceous plant well known in Asian as African traditional medicines. These extracts are used in traditional medicine for treatment of microbial diseases and certain metabolic disorders. This review aimed to investigate phytochemical profile and neuroprotective effects of E. alba (L.) Hassk. Several compounds belonging to the families of phenolics, alkaloids, terpenoids and polysaccharides have been isolated, identified or characterized from E. alba extracts. This plant has a diverse neuropharmacological profile. Thus, its extract improves cognitive deficits and also attenuated epileptic seizures. Phytomolecules implicated in these potentials are Eclalbasaponin II and luteolin, respectively. This document updates isolated and identified organic compounds from the extracts of E. alba and reviews their neuropharmacological activities.

Stroke

2016 ◽  
Author(s):  
Didier Leys ◽  
Charlotte Cordonnier ◽  
Valeria Caso
Keyword(s):  
Stroke Unit ◽  
Major Complication ◽  
Epileptic Seizures ◽  
Recombinant Tissue Plasminogen Activator ◽  
Acute Stage ◽  
Public Health Issue ◽  
Stroke Subtype ◽  
Vascular Events ◽  
Increased Risk ◽  
Major Interest

Stroke is a major public health issue. Many are treatable in the acute stage, provided patients are admitted soon enough. The overall incidence of stroke in Western countries is approximately 2400 per year per million inhabitants, and 80% are due to cerebral ischaemia. The prevalence is approximately 12 000 per million inhabitants. Stroke is associated with increased long-term mortality, handicap, cognitive and behavioural impairments, recurrence, and an increased risk of other types of vascular events. It is of major interest to take the heterogeneity of stroke into account, because of differences in the acute management, secondary prevention, and outcomes, according to the subtype and cause of stroke. In all types of stroke, early epileptic seizures, delirium, increased intracranial pressure, and non-specific complications are frequent. In ischaemic strokes, specific complications, such as malignant infarcts, spontaneous haemorrhagic transformation, early recurrence, and a new ischaemic event in another vascular territory, are frequent. In haemorrhagic strokes, the major complication is the subsequent increased volume of bleeding. There is strong evidence that stroke patients should be treated in dedicated stroke units; each time 24 patients are treated in a stroke unit, instead of a conventional ward, one death and one dependence are prevented. This effect does not depend on age, severity, and the stroke subtype. For this reason, stroke unit care is the cornerstone of the treatment of stroke, aiming at the detection and management of life-threatening emergencies, stabilization of most physiological parameters, and prevention of early complications. In ischaemic strokes, besides this general management, specific therapies include intravenous recombinant tissue plasminogen activator, given as soon as possible and before 4.5 hours, otherwise aspirin 300 mg, immediately or after 24 hours in case of thrombolysis, and, in a few patients, decompressive surgery. In intracerebral haemorrhages, blood pressure lowering and haemostatic therapy, when needed, are the two targets, but surgery does not seem effective to reduce death and disability.

Stroke

2015 ◽  
Author(s):  
Didier Leys ◽  
Charlotte Cordonnier ◽  
Valeria Caso
Keyword(s):  
Stroke Unit ◽  
Major Complication ◽  
Epileptic Seizures ◽  
Recombinant Tissue Plasminogen Activator ◽  
Acute Stage ◽  
Public Health Issue ◽  
Stroke Subtype ◽  
Vascular Events ◽  
Increased Risk ◽  
Major Interest

Stroke is a major public health issue. Many are treatable in the acute stage, provided patients are admitted soon enough. The overall incidence of stroke in Western countries is approximately 2400 per year per million inhabitants, and 80% are due to cerebral ischaemia. The prevalence is approximately 12 000 per million inhabitants. Stroke is associated with increased long-term mortality, handicap, cognitive and behavioural impairments, recurrence, and an increased risk of other types of vascular events. It is of major interest to take the heterogeneity of stroke into account, because of differences in the acute management, secondary prevention, and outcomes, according to the subtype and cause of stroke. In all types of stroke, early epileptic seizures, delirium, increased intracranial pressure, and non-specific complications are frequent. In ischaemic strokes, specific complications, such as malignant infarcts, spontaneous haemorrhagic transformation, early recurrence, and a new ischaemic event in another vascular territory, are frequent. In haemorrhagic strokes, the major complication is the subsequent increased volume of bleeding. There is strong evidence that stroke patients should be treated in dedicated stroke units; each time 24 patients are treated in a stroke unit, instead of a conventional ward, one death and one dependence are prevented. This effect does not depend on age, severity, and the stroke subtype. For this reason, stroke unit care is the cornerstone of the treatment of stroke, aiming at the detection and management of life-threatening emergencies, stabilization of most physiological parameters, and prevention of early complications. In ischaemic strokes, besides this general management, specific therapies include intravenous recombinant tissue plasminogen activator, given as soon as possible and before 4.5 hours, otherwise aspirin 300 mg, immediately or after 24 hours in case of thrombolysis, and, in a few patients, decompressive surgery. In intracerebral haemorrhages, blood pressure lowering and haemostatic therapy, when needed, are the two targets, but surgery does not seem effective to reduce death and disability.

scholarly journals Prediction and detection of human epileptic seizures based on SIFT-MS chemometric data

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Amélie Catala ◽  
Cecile Levasseur-Garcia ◽  
Marielle Pagès ◽  
Jean-Luc Schaff ◽  
Ugo Till ◽  
...  
Keyword(s):  
Cross Validation ◽  
Epileptic Seizures ◽  
Public Health Issue ◽  
Flow Tube ◽  
Ion Flow ◽  
Non Invasive ◽  
Different Types ◽  
Selected Ion Flow Tube ◽  
Single Method ◽  
Leave One Out

Abstract Although epilepsy is considered a public health issue, the burden imposed by the unpredictability of seizures is mainly borne by the patients. Predicting seizures based on electroencephalography has had mixed success, and the idiosyncratic character of epilepsy makes a single method of detection or prediction for all patients almost impossible. To address this problem, we demonstrate herein that epileptic seizures can not only be detected by global chemometric analysis of data from selected ion flow tube mass spectrometry but also that a simple mathematical model makes it possible to predict these seizures (by up to 4 h 37 min in advance with 92% and 75% of samples correctly classified in training and leave-one-out-cross-validation, respectively). These findings should stimulate the development of non-invasive applications (e.g., electronic nose) for different types of epilepsy and thereby decrease of the unpredictability of epileptic seizures.

scholarly journals Probable causal link between epilepsy and sleep apnea: case report

2007 ◽  
Vol 65 (1) ◽  
pp. 164-166 ◽  
Author(s):  
Michele Dominici ◽  
Fernando Pompeu Filho ◽  
Marleide da Mota Gomes
Keyword(s):  
Sleep Apnea ◽  
Sleep Apnea Syndrome ◽  
Epileptic Seizures ◽  
Causal Link ◽  
Daytime Somnolence ◽  
Respiratory Events ◽  
Co Morbidity ◽  
Epileptic Patients ◽  
Patients With Epilepsy ◽  
Video Eeg

Patients with epilepsy were reported to have concomitant sleep apnea, but it has been rarely linked to the epilepsy itself. We present a case of a 28-year-old, obese man with secondary medically resistant partial complex epilepsy due to a brain trauma, with progressive snoring, and sleep agitation, apneas, and important daytime somnolence. It was noticed in the polysomnographic study that he had several sleep respiratory events, probably due both to the epileptic seizures and the sleep apnea syndrome as a co-morbidity. Apnea and epilepsy will be discussed. A careful video-EEG-polysomnography study is important in evaluating refractory epileptic patients and/or epileptic patients with snoring.

Sign in / Sign up

Export Citation Format

Share Document