scholarly journals Hyperthermia exacerbates the acute effects of psychoactive substances on neuronal activity measured using microelectrode arrays (MEAs) in rat primary cortical cultures in vitro

2020 ◽  
Vol 397 ◽  
pp. 115015
Author(s):  
Anne Zwartsen ◽  
Laura Hondebrink ◽  
Dylan W. de Lange ◽  
Remco H.S. Westerink
Keyword(s):  
Neuronal Activity ◽  
Microelectrode Arrays ◽  
Acute Effects ◽  
Psychoactive Substances ◽  
Cortical Cultures

Comparison of Acute Effects of Neurotoxic Compounds on Network Activity in Human and Rodent Neural Cultures

2021 ◽  
Author(s):  
L Saavedra ◽  
K Wallace ◽  
Tf Freudenrich ◽  
M Mall ◽  
Wr Mundy ◽  
...  
Keyword(s):  
Neural Network ◽  
Neuronal Activity ◽  
Neuronal Cells ◽  
Environmental Chemicals ◽  
Network Activity ◽  
Inhibitory Neurons ◽  
Multielectrode Arrays ◽  
Cortical Cultures ◽  
Neural Cultures

Abstract Assessment of neuroactive effects of chemicals in cell-based assays remains challenging as complex functional tissue is required for biologically relevant readouts. Recent in vitro models using rodent primary neural cultures grown on multielectrode arrays (MEAs) allow quantitative measurements of neural network activity suitable for neurotoxicity screening. However, robust systems for testing effects on network function in human neural models are still lacking. The increasing number of differentiation protocols for generating neurons from human induced pluripotent stem cells (hiPSCs) holds great potential to overcome the unavailability of human primary tissue and expedite cell-based assays. Yet, the variability in neuronal activity, prolonged ontogeny and rather immature stage of most neuronal cells derived by standard differentiation techniques greatly limit their utility for screening neurotoxic effects on human neural networks. Here, we used excitatory and inhibitory neurons, separately generated by direct reprogramming from hiPSCs, together with primary human astrocytes to establish highly functional cultures with defined cell ratios. Such neuron/glia co-cultures exhibited pronounced neuronal activity and robust formation of synchronized network activity on MEAs, albeit with noticeable delay compared to primary rat cortical cultures. We further investigated acute changes of network activity in human neuron/glia co-cultures and rat primary cortical cultures in response to compounds with known adverse neuroactive effects, including GABAA receptor antagonists and multiple pesticides. Importantly, we observed largely corresponding concentration-dependent effects on multiple neural network activity metrics using both neural culture types. These results demonstrate the utility of directly converted neuronal cells from hiPSCs for functional neurotoxicity screening of environmental chemicals.

Adverse Influence of Cigarette Smoking on the Endothelium

1993 ◽  
Vol 70 (04) ◽  
pp. 707-711 ◽  
Author(s):  
Andrew D Blann ◽  
Charles N McCollum
Keyword(s):  
Endothelial Cells ◽  
Von Willebrand Factor ◽  
Tobacco Smoke ◽  
Lipid Peroxides ◽  
Short Exposure ◽  
Acute Effects ◽  
Adverse Influence ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe effect of smoking on the blood vessel intima was examined by comparing indices of endothelial activity in serum from smokers with that from non-smokers. Serum from smokers contained higher levels of von Willebrand factor (p <0.01), the smoking markers cotinine (p <0.02) and thiocyanate (p <0.01), and was more cytotoxic to endothelial cells in vitro (p <0.02) than serum from non-smokers. The acute effects of smoking two unfiltered medium tar cigarettes was to briefly increase von Willebrand factor (p <0.001) and cytotoxicity of serum to endothelial cells in vitro (p <0.005), but lipid peroxides or thiocyanate were not increased by this short exposure to tobacco smoke. Although there were correlations between von Willebrand factor and smokers consumption of cigarettes (r = 0.28, p <0.02), number of years smoking (r = 0.41, p <0.001) and cotinine (r = 0.45, p <0.01), the tissue culture of endothelial cells with physiological levels of thiocyanate or nicotine suggested that these two smoking markers were not cytotoxic. They are therefore unlikely to be directly responsible for increased von Willebrand factor in the serum of smokers. We suggest that smoking exerts a deleterious influence on the endothelium and that the mechanism is complex.

scholarly journals Extracellular detection of neuronal coupling

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elmer Guzman ◽  
Zhuowei Cheng ◽  
Paul K. Hansma ◽  
Kenneth R. Tovar ◽  
Linda R. Petzold ◽  
...  
Keyword(s):  
Action Potentials ◽  
Microelectrode Arrays ◽  
Short Latency ◽  
Spike Sorting ◽  
Neuronal Connectivity ◽  
Direct Stimulation ◽  
Multiple Electrodes

AbstractWe developed a method to non-invasively detect synaptic relationships among neurons from in vitro networks. Our method uses microelectrode arrays on which neurons are cultured and from which propagation of extracellular action potentials (eAPs) in single axons are recorded at multiple electrodes. Detecting eAP propagation bypasses ambiguity introduced by spike sorting. Our methods identify short latency spiking relationships between neurons with properties expected of synaptically coupled neurons, namely they were recapitulated by direct stimulation and were sensitive to changing the number of active synaptic sites. Our methods enabled us to assemble a functional subset of neuronal connectivity in our cultures.

scholarly journals Human Neuronal Cell Lines as An In Vitro Toxicological Tool for the Evaluation of Novel Psychoactive Substances

2021 ◽  
Vol 22 (13) ◽  
pp. 6785
Author(s):  
Valeria Sogos ◽  
Paola Caria ◽  
Clara Porcedda ◽  
Rafaela Mostallino ◽  
Franca Piras ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell ◽  
In Vitro Study ◽  
Dependent Manner ◽  
Novel Psychoactive Substances ◽  
Psychoactive Substances ◽  
Concentration Dependent Manner ◽  
Mechanisms Of Toxicity ◽  
Neuronal Cell Lines

Novel psychoactive substances (NPS) are synthetic substances belonging to diverse groups, designed to mimic the effects of scheduled drugs, resulting in altered toxicity and potency. Up to now, information available on the pharmacology and toxicology of these new substances is very limited, posing a considerable challenge for prevention and treatment. The present in vitro study investigated the possible mechanisms of toxicity of two emerging NPS (i) 4′-methyl-alpha-pyrrolidinoexanophenone (3,4-MDPHP), a synthetic cathinone, and (ii) 2-chloro-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA), a phenethylamine. In addition, to apply our model to the class of synthetic opioids, we evaluated the toxicity of fentanyl, as a reference compound for this group of frequently abused substances. To this aim, the in vitro toxic effects of these three compounds were evaluated in dopaminergic-differentiated SH-SY5Y cells. Following 24 h of exposure, all compounds induced a loss of viability, and oxidative stress in a concentration-dependent manner. 2-Cl-4,5-MDMA activates apoptotic processes, while 3,4-MDPHP elicits cell death by necrosis. Fentanyl triggers cell death through both mechanisms. Increased expression levels of pro-apoptotic Bax and caspase 3 activity were observed following 2-Cl-4,5-MDMA and fentanyl, but not 3,4-MDPHP exposure, confirming the different modes of cell death.

The neurophysiology of ketamine: an integrative review

2020 ◽  
Vol 31 (5) ◽  
pp. 457-503
Author(s):  
Rebecca McMillan ◽  
Suresh D. Muthukumaraswamy
Keyword(s):  
Spatial Scales ◽  
Integrative Review ◽  
Acute Effects ◽  
Future Work

AbstractThe drug ketamine has been extensively studied due to its use in anaesthesia, as a model of psychosis and, most recently, its antidepressant properties. Understanding the physiology of ketamine is complex due to its rich pharmacology with multiple potential sites at clinically relevant doses. In this review of the neurophysiology of ketamine, we focus on the acute effects of ketamine in the resting brain. We ascend through spatial scales starting with a complete review of the pharmacology of ketamine and then cover its effects on in vitro and in vivo electrophysiology. We then summarise and critically evaluate studies using EEG/MEG and neuroimaging measures (MRI and PET), integrating across scales where possible. While a complicated and, at times, confusing picture of ketamine’s effects are revealed, we stress that much of this might be caused by use of different species, doses, and analytical methodologies and suggest strategies that future work could use to answer these problems.

Synaptic Plasticity In Vitro and In Silico: Insights into an Intracellular Signaling Maze

Physiology ◽  
2006 ◽  
Vol 21 (4) ◽  
pp. 289-296 ◽  
Author(s):  
Sriram M. Ajay ◽  
Upinder S. Bhalla
Keyword(s):  
Experimental Data ◽  
Synaptic Plasticity ◽  
Neuronal Activity ◽  
In Silico ◽  
Intracellular Signaling ◽  
Signaling Networks ◽  
Functional Roles ◽  
Current State ◽  
History Of

Synaptic plasticity provides a record of neuronal activity and is a likely basis for memory. The early apparent simplicity of the process of synaptic plasticity has been lost in a flood of experimental data that now implicates some 200 signaling molecules in cellular memory. It is now clear that these signaling networks perform surprisingly sophisticated cellular decisions that weigh factors such as input patterns, location of stimulus, history of activity, and context. Computer models have followed experiments into this maze of molecular detail, often matching closely with their experimental counterparts, but perhaps losing simplicity in the process. Here, we suggest that the merger of models and experiment have begun to restore the earlier simplicity by outlining a few key functional roles for signaling networks in synaptic plasticity. In this review, we discuss the current state of understanding of synaptic plasticity in terms of models and experiments.

ANG II modifies cardiomyocyte function via extracardiac and intracardiac neurons: in situ and in vitro studies

1997 ◽  
Vol 272 (3) ◽  
pp. R766-R775 ◽  
Author(s):  
M. Horackova ◽  
J. A. Armour
Keyword(s):  
Guinea Pig ◽  
Receptor Antagonist ◽  
Neuronal Activity ◽  
Ang Ii ◽  
Arterial Blood ◽  
Cardiac Ganglia ◽  
In Situ Experiments ◽  
Anesthetized Dogs

To determine whether angiotensin II (ANG II) affects cardiac performance via neurons in intrathoracic cardiac ganglia, studies were performed on anesthetized dogs. To exclude possible vascular regulatory effects of ANG II, experiments were also performed using long-term cultures of adult guinea pig ventricular cardiomyocytes with or without intrathoracic neurons. 1) In in situ experiments in 10 anesthetized dogs, cardiac augmentation occurred when ANG II (10 microl or 0.1 ml; 10-100 microM) was administered into limited loci within acutely decentralized stellate or middle cervical ganglia that were neurally connected to, but not those disconnected from, the heart. In another 18 dogs, ANG II increased intrinsic cardiac neuronal activity when administered adjacent to such neurons or into their local arterial blood supply. Ventricular ionotropic effects elicited by ANG II were eliminated by timolol, whereas increases in intrinsic cardiac neuronal activity were not affected. Effects elicited by ANG II were eliminated by administration of a selective AT1 receptor antagonist (losartan) but not by a selective AT2 receptor antagonist (PD-123319). 2) In in vitro experiments, ANG II (100 nM) induced positive chronotropic effects on cultured adult guinea pig cardiomyocytes innervated with adult extrinsic or intrinsic cardiac neurons, but not those cultured without neurons. The frequency of calcium inward current (Ca(i)) transients (recorded by fura 2 fluorescence) increased in innervated cocultures but not in the noninnervated cardiomyocyte cultures; however, the amplitude of Ca(i) transients was not affected by ANG II in cultures or in freshly isolated adult guinea pig cardiomyocytes. ANG II-induced effects in cocultures were blocked by losartan but not PD-123319 or timolol. Thus 1) ANG II-sensitive neurons exist in intrathoracic extracardiac and intrinsic cardiac ganglia; 2) these neurons possess AT1 receptors; and 3) these neurons appear to act directly and indirectly via adrenergic neurons to enhance cardiomyocyte function.

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