Single-Cell and Neuronal Network Alterations in an In Vitro Model of Fragile X Syndrome

Abstract The Fragile X mental retardation protein (FMRP) is involved in many cellular processes and it regulates synaptic and network development in neurons. Its absence is known to lead to intellectual disability, with a wide range of comorbidities including autism. Over the past decades, FMRP research focused on abnormalities both in glutamatergic and GABAergic signaling, and an altered balance between excitation and inhibition has been hypothesized to underlie the clinical consequences of absence of the protein. Using Fmrp knockout mice, we studied an in vitro model of cortical microcircuitry and observed that the loss of FMRP largely affected the electrophysiological correlates of network development and maturation but caused less alterations in single-cell phenotypes. The loss of FMRP also caused a structural increase in the number of excitatory synaptic terminals. Using a mathematical model, we demonstrated that the combination of an increased excitation and reduced inhibition describes best our experimental observations during the ex vivo formation of the network connections.

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Single-cell and neuronal network alterations in an in vitro model of Fragile X syndrome

10.1101/366997 ◽

2018 ◽

Cited By ~ 1

Author(s):

Anastasiya Moskalyuk ◽

R. Frank Kooy ◽

Michele Giugliano

Keyword(s):

Single Cell ◽

Ex Vivo ◽

Fragile X ◽

Network Development ◽

Cellular Processes ◽

Wide Range ◽

Clinical Consequences ◽

Vitro Model ◽

Cell Phenotypes

AbstractThe Fragile X mental retardation protein (FMRP) is involved in many cellular processes and it regulates synaptic and network development in neurons. Its absence is known to lead to intellectual disability, with a wide range of co-morbidities including autism. Over the past decades, FMRP research focused on abnormalities both in glutamatergic and GABAergic signalling, and an altered balance between excitation and inhibition has been hypothesised to underlie the clinical consequences of absence of the protein. Using FMRP knockout mice, we studied an in vitro model of cortical microcircuitry and observed that the loss of FMRP largely affected the electrophysiological correlates of network development and maturation but caused less alterations in single-cell phenotypes. Using a mathematical model, we demonstrated that the combination of an increased excitation and reduced inhibition describes best predicts our experimental observations during the ex vivo formation of the network connections.

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An in vitro model for the study of human parathyroid gland tissue: Single cell suspensions and monolayer cultures

Research in Experimental Medicine ◽

10.1007/bf01852191 ◽

1982 ◽

Vol 181 (2) ◽

pp. 147-154 ◽

Cited By ~ 4

Author(s):

P. K. Wagner ◽

A. Knuth ◽

U. Krause ◽

H. Gabbert ◽

Th. Schärfe ◽

...

Keyword(s):

Single Cell ◽

Parathyroid Gland ◽

In Vitro Model ◽

Cell Suspensions ◽

Monolayer Cultures ◽

Gland Tissue ◽

Vitro Model

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Development of an in vitro model of calcified cerebral emboli in acute ischemic stroke for mechanical thrombectomy evaluation

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2019-015595 ◽

2020 ◽

Vol 12 (10) ◽

pp. 1002-1007

Author(s):

Sarah Johnson ◽

Ray McCarthy ◽

Brian Fahy ◽

Oana Madalina Mereuta ◽

Seán Fitzgerald ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

In Vitro Model ◽

Mechanical Thrombectomy ◽

Ex Vivo ◽

Guide Catheter ◽

Vitro Model ◽

Calcified Tissues

BackgroundCalcified cerebral emboli (CCEs) are a rare cause of acute ischemic stroke (AIS) and are frequently associated with poor outcomes. The presence of dense calcified material enables reliable identification of CCEs using non-contrast CT. However, recanalization rates with the available mechanical thrombectomy (MT) devices remain low.ObjectiveTo recreate a large vessel occlusion involving a CCE using an in vitro silicone model of the intracranial vessels and to demonstrate the feasability of this model to test different endovascular strategies to recanalize an occlusion of the M1 segment of the middle cerebral artery (MCA).MethodsAn in vitro model was developed to evaluate different endovascular treatment approaches using contemporary devices in the M1 segment of the MCA. The in vitro model consisted of a CCE analog placed in a silicone neurovascular model. Development of an appropriate CCE analog was based on characterization of human calcified tissues that represent likely sources of CCEs. Feasibility of the model was demonstrated in a small number of MT devices using four common procedural techniques.ResultsCCE analogs were developed with similar mechanical behavior to that of ex vivo calcified material. The in vitro model was evaluated with various MT techniques and devices to show feasibility of the model. In this limited evaluation, the most successful retrieval approach was performed with a stent retriever combined with local aspiration through a distal access catheter, and importantly, with flow arrest and dual aspiration using a balloon guide catheter.ConclusionCharacterization of calcified tissues, which are likely sources of CCEs, has shown that CCEs are considerably stiffer than thrombus. This highlights the need for a different in vitro AIS model for CCEs than those used for thromboemboli. Consequentially, an in vitro AIS model representative of a CCE occlusion in the M1 segment of the MCA has been developed.

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Antibiotics modulate the stimulated cytokine response to endotoxin in a human ex vivo, in vitro model

Acta Anaesthesiologica Scandinavica ◽

10.1111/j.1399-6576.2006.01112.x ◽

2006 ◽

Vol 50 (9) ◽

pp. 1103-1110 ◽

Cited By ~ 27

Author(s):

S. Ziegeler ◽

A. Raddatz ◽

G. Hoff ◽

H. Buchinger ◽

I. Bauer ◽

...

Keyword(s):

In Vitro Model ◽

Ex Vivo ◽

Cytokine Response ◽

Vitro Model

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Inhibition of MAO by Fractions and Constituents of Hypericum Extract

Journal of Geriatric Psychiatry and Neurology ◽

10.1177/089198879400701s15 ◽

1994 ◽

Vol 7 (1_suppl) ◽

pp. 57-59 ◽

Cited By ~ 5

Author(s):

S. Bladt ◽

H. Wagner

Keyword(s):

Monoamine Oxidase ◽

In Vitro Model ◽

Ex Vivo ◽

Albino Rats ◽

Total Extract ◽

Antidepressive Effect ◽

Pure Substances ◽

Vitro Model ◽

Hypericum Extract

The inhibition of monoamine oxidase (MAO) by six fractions from hypericum extract and three characteristic constituents (as pure substances) were analyzed in vitro and ex vivo to study the antidepressive mechanism of action. Rat brain homogenates were used as the in vitro model, while the ex vivo analysis was performed after intraperitoneal application of the test substances to albino rats. Massive inhibition of MAO-A could be shown with the total extract and all fractions only at the concentration of 10-3 mol/L. At 10-4 mol/L, one fraction rich in flavonoides showed an inhibition of 39%, and all other fractions demonstrated less than 25% inhibition. Using pure hypericin as well as in ex vivo experiments, no relevant inhibiting effects could be shown. From the results it can be concluded that the clinically proven antidepressive effect of hypericum extract cannot be explained in terms of MAO inhibition.

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