Ammonium chloride influences in vitro-neuronal network activity

Schwarz, Clara-Sophie; Ferrea, Stefano; Quasthoff, Kim; Walter, Janine; Görg, Boris; Häussinger, Dieter; Schnitzler, Alfons; Hartung, Hans‐Peter; Dihné, Marcel

doi:10.1016/j.expneurol.2012.02.019

Cited by 14 publications

(10 citation statements)

References 27 publications

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“…Addition of neuroactive substances, e.g. acting on glutamatergic or GABAergic synapses or modulating voltage-dependant ion channels, change that activity which is described in multiple reports [10,12,14,15]. Thus, pathological-like conditions of this artificial in vitro system can be defined.…”

Section: Discussionmentioning

confidence: 99%

“…Here, we were able to show that the patient’s CSF suppresses global activity in functional neuronal networks while synchrony of population bursts remained unaltered. Recently published results demonstrated that modulation at the NMDA receptor can significantly influence in vitro-neuronal network activity (ivNNA) [10,14]. Importantly, NMDAR modulation was shown to inversely influence burst rates and the degree of synchrony of the network which is expressed by the kappa value [14].…”

Section: Discussionmentioning

confidence: 99%

“…Recently published results demonstrated that modulation at the NMDA receptor can significantly influence in vitro-neuronal network activity (ivNNA) [10,14]. Importantly, NMDAR modulation was shown to inversely influence burst rates and the degree of synchrony of the network which is expressed by the kappa value [14]. Concerning suppression of NMDAR function, the NMDA-receptor antagonist DL-2-Amino-5-phosphono-pentanoic acid (AP-5) can supress the burst rate while preserving the kappa value [10].…”

Section: Discussionmentioning

confidence: 99%

“…MEA experiments were performed between 26 and 64 days in vitro (see below), a time window of preserved synchronous population bursting. Earlier immunocytochemical experiments of identical cell preparations [11] demonstrated that neural population consists of glial fibrillary acid protein-positive astrocytes, vesicular glutamate transporter 2 -positive glutamatergic neurons and γ-aminobutyric acid-positive neurons. Extensive immunocytochemical control experiments for this and other studies confirmed the above mentioned cellular phenotypes which were stable along multiple preparations.…”

Section: Methodsmentioning

confidence: 99%

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In vitro neuronal network activity in NMDA receptor encephalitis

et al. 2013

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BackgroundAnti-NMDA-encephalitis is caused by antibodies against the N-methyl-D-aspartate receptor (NMDAR) and characterized by a severe encephalopathy with psychosis, epileptic seizures and autonomic disturbances. It predominantly occurs in young women and is associated in 59% with an ovarian teratoma.ResultsWe describe effects of cerebrospinal fluid (CSF) from an anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patient on in vitro neuronal network activity (ivNNA). In vitro NNA of dissociated primary rat cortical populations was recorded by the microelectrode array (MEA) system.The 23-year old patient was severely affected but showed an excellent recovery following multimodal immunomodulatory therapy and removal of an ovarian teratoma. Patient CSF (pCSF) taken during the initial weeks after disease onset suppressed global spike- and burst rates of ivNNA in contrast to pCSF sampled after clinical recovery and decrease of NMDAR antibody titers. The synchrony of pCSF-affected ivNNA remained unaltered during the course of the disease.ConclusionPatient CSF directly suppresses global activity of neuronal networks recorded by the MEA system. In contrast, pCSF did not regulate the synchrony of ivNNA suggesting that NMDAR antibodies selectively regulate distinct parameters of ivNNA while sparing their functional connectivity. Thus, assessing ivNNA could represent a new technique to evaluate functional consequences of autoimmune encephalitis-related CSF changes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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In vitro neuronal network activity in NMDA receptor encephalitis

et al. 2013

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“…The studies of ammonia toxicity on neural circuits are very limited and contradictory. It was shown only in recent time [ 43 ], that ammonia induces robust activation of neuronal network grown on microelectrode arrays, causing an increase of neuronal network activity and implicating NMDA receptors. Inhibitors of astrocyte glutamine synthesis or of NMDA receptors prevented network activation and protected these neuronal circuits against dysregulation produced by NH 4 Cl [ 43 ].…”

Section: Introductionmentioning

confidence: 99%

To Break or to Brake Neuronal Network Accelerated by Ammonium Ions?

et al. 2015

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PurposeThe aim of present study was to investigate the effects of ammonium ions on in vitro neuronal network activity and to search alternative methods of acute ammonia neurotoxicity prevention.MethodsRat hippocampal neuronal and astrocytes co-cultures in vitro, fluorescent microscopy and perforated patch clamp were used to monitor the changes in intracellular Ca2+- and membrane potential produced by ammonium ions and various modulators in the cells implicated in neural networks.ResultsLow concentrations of NH4Cl (0.1–4 mM) produce short temporal effects on network activity. Application of 5–8 mM NH4Cl: invariably transforms diverse network firing regimen to identical burst patterns, characterized by substantial neuronal membrane depolarization at plateau phase of potential and high-amplitude Ca2+-oscillations; raises frequency and average for period of oscillations Ca2+-level in all cells implicated in network; results in the appearance of group of «run out» cells with high intracellular Ca2+ and steadily diminished amplitudes of oscillations; increases astrocyte Ca2+-signalling, characterized by the appearance of groups of cells with increased intracellular Ca2+-level and/or chaotic Ca2+-oscillations. Accelerated network activity may be suppressed by the blockade of NMDA or AMPA/kainate-receptors or by overactivation of AMPA/kainite-receptors. Ammonia still activate neuronal firing in the presence of GABA(A) receptors antagonist bicuculline, indicating that «disinhibition phenomenon» is not implicated in the mechanisms of networks acceleration. Network activity may also be slowed down by glycine, agonists of metabotropic inhibitory receptors, betaine, L-carnitine, L-arginine, etc.ConclusionsObtained results demonstrate that ammonium ions accelerate neuronal networks firing, implicating ionotropic glutamate receptors, having preserved the activities of group of inhibitory ionotropic and metabotropic receptors. This may mean, that ammonia neurotoxicity might be prevented by the activation of various inhibitory receptors (i.e. by the reinforcement of negative feedback control), instead of application of various enzyme inhibitors and receptor antagonists (breaking of neural, metabolic and signaling systems).

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