scholarly journals Downregulated GABA and BDNF-TrkB Pathway in Chronic Cyclothiazide Seizure Model

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Shuzhen Kong ◽  
Zhihua Cheng ◽  
Jianhui Liu ◽  
Yun Wang
Keyword(s):  
Animal Model ◽  
Epileptic Seizure ◽  
Hippocampal Neurons ◽  
Drug Testing ◽  
Anticonvulsant Drug ◽  
Recurrent Seizure ◽  
Receptor Inhibition ◽  
Gaba Synthesis ◽  
Freely Moving ◽  
Seizure Model

Cyclothiazide (CTZ) has been reported to simultaneously enhance glutamate receptor excitation and inhibit GABAA receptor inhibition, and in turn it evokes epileptiform activities in hippocampal neurons. It has also been shown to acutely induce epileptic seizure behavior in freely moving rats. However, whether CTZ induced seizure rats could develop to have recurrent seizure still remains unknown. In the current study, we demonstrated that 46% of the CTZ induced seizure rats developed to have recurrent seizure behavior as well as epileptic EEG with a starting latency between 2 weeks and several months. In those chronic seizure rats 6 months after the seizure induction by the CTZ, our immunohistochemistry results showed that both GAD and GAT-1 were significantly decreased across CA1, CA3, and dentate gyrus area of the hippocampus studied. In addition, both BDNF and its receptor TrkB were also decreased in hippocampus of the chronic CTZ seizure rats. Our results indicate that CTZ induced seizure is capable of developing to have recurrent seizure, and the decreased GABA synthesis and transport as well as the impaired BDNF-TrkB signaling pathway may contribute to the development of the recurrent seizure. Thus, CTZ seizure rats may provide a novel animal model for epilepsy study and anticonvulsant drug testing in the future.

scholarly journals A Novel Infection Protocol in Zebrafish Embryo to Assess Pseudomonas aeruginosa Virulence and Validate Efficacy of a Quorum Sensing Inhibitor In Vivo

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 401
Author(s):  
Pauline Nogaret ◽  
Fatima El El Garah ◽  
Anne-Béatrice Blanc-Potard
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Animal Model ◽  
Quorum Sensing ◽  
Drug Testing ◽  
Drug Efficacy ◽  
Embryo Viability ◽  
Immersion Method ◽  
Opportunistic Human Pathogen

The opportunistic human pathogen Pseudomonas aeruginosa is responsible for a variety of acute infections and is a major cause of mortality in chronically infected cystic fibrosis patients. Due to increased resistance to antibiotics, new therapeutic strategies against P. aeruginosa are urgently needed. In this context, we aimed to develop a simple vertebrate animal model to rapidly assess in vivo drug efficacy against P. aeruginosa. Zebrafish are increasingly considered for modeling human infections caused by bacterial pathogens, which are commonly microinjected in embryos. In the present study, we established a novel protocol for zebrafish infection by P. aeruginosa based on bath immersion in 96-well plates of tail-injured embryos. The immersion method, followed by a 48-hour survey of embryo viability, was first validated to assess the virulence of P. aeruginosa wild-type PAO1 and a known attenuated mutant. We then validated its relevance for antipseudomonal drug testing by first using a clinically used antibiotic, ciprofloxacin. Secondly, we used a novel quorum sensing (QS) inhibitory molecule, N-(2-pyrimidyl)butanamide (C11), the activity of which had been validated in vitro but not previously tested in any animal model. A significant protective effect of C11 was observed on infected embryos, supporting the ability of C11 to attenuate in vivo P. aeruginosa pathogenicity. In conclusion, we present here a new and reliable method to compare the virulence of P. aeruginosa strains in vivo and to rapidly assess the efficacy of clinically relevant drugs against P. aeruginosa, including new antivirulence compounds.

scholarly journals Efficient neural decoding of self-location with a deep recurrent network

2018 ◽  
Author(s):  
Ardi Tampuu ◽  
Tambet Matiisen ◽  
H. Freyja Ólafsdóttir ◽  
Caswell Barry ◽  
Raul Vicente
Keyword(s):  
Hippocampal Neurons ◽  
Cell Activity ◽  
Recurrent Network ◽  
Brain Network ◽  
Place Cells ◽  
Neuronal Firing ◽  
Temporal Context ◽  
Central Component ◽  
Neural Decoding ◽  
Freely Moving

AbstractPlace cells in the mammalian hippocampus signal self-location with sparse spatially stable firing fields. Based on observation of place cell activity it is possible to accurately decode an animal’s location. The precision of this decoding sets a lower bound for the amount of information that the hippocampal population conveys about the location of the animal. In this work we use a novel recurrent neural network (RNN) decoder to infer the location of freely moving rats from single unit hippocampal recordings. RNNs are biologically plausible models of neural circuits that learn to incorporate relevant temporal context without the need to make complicated assumptions about the use of prior information to predict the current state. When decoding animal position from spike counts in 1D and 2D-environments, we show that the RNN consistently outperforms a standard Bayesian model with flat priors. In addition, we also conducted a set of sensitivity analysis on the RNN decoder to determine which neurons and sections of firing fields were the most influential. We found that the application of RNNs to neural data allowed flexible integration of temporal context, yielding improved accuracy relative to a commonly used Bayesian approach and opens new avenues for exploration of the neural code.Author summaryBeing able to accurately self-localize is critical for most motile organisms. In mammals, place cells in the hippocampus appear to be a central component of the brain network responsible for this ability. In this work we recorded the activity of a population of hippocampal neurons from freely moving rodents and carried out neural decoding to determine the animals’ locations. We found that a machine learning approach using recurrent neural networks (RNNs) allowed us to predict the rodents’ true positions more accurately than a standard Bayesian method with flat priors. The RNNs are able to take into account past neural activity without making assumptions about the statistics of neuronal firing. Further, by analyzing the representations learned by the network we were able to determine which neurons, and which aspects of their activity, contributed most strongly to the accurate decoding.

Telemetric animal model to evaluate visceral pain in the freely moving rat

Pain ◽  
2003 ◽  
Vol 105 (1) ◽  
pp. 115-123 ◽  
Author(s):  
A M.J.M. Nijsen ◽  
H N.G. Ongenae ◽  
B Coulie ◽  
L A. Meulemans
Keyword(s):  
Animal Model ◽  
Visceral Pain ◽  
Freely Moving

Effect of neuronal precursor cells derived from medial ganglionic eminence in an acute epileptic seizure model

Epilepsia ◽  
2010 ◽  
Vol 51 ◽  
pp. 71-75 ◽  
Author(s):  
Maria E. Calcagnotto ◽  
Lorena P. Ruiz ◽  
Miriam M. Blanco ◽  
Jair G. Santos-Junior ◽  
Maria F. Valente ◽  
...  
Keyword(s):  
Epileptic Seizure ◽  
Precursor Cells ◽  
Medial Ganglionic Eminence ◽  
Ganglionic Eminence ◽  
Neuronal Precursor ◽  
Neuronal Precursor Cells ◽  
Seizure Model

scholarly journals Persistent trajectory-modulated hippocampal neurons support memory-guided navigation

2019 ◽  
Author(s):  
Nathaniel R. Kinsky ◽  
William Mau ◽  
David W. Sullivan ◽  
Samuel J. Levy ◽  
Evan A. Ruesch ◽  
...  
Keyword(s):  
Calcium Imaging ◽  
Hippocampal Neurons ◽  
Spatial Information ◽  
Single Photon ◽  
Place Cells ◽  
Dependent Activity ◽  
Freely Moving ◽  
Stable Trajectory ◽  
Alternation Task

ABSTRACTTrajectory-dependent splitter neurons in the hippocampus encode information about a rodent’s prior trajectory during performance of a continuous alternation task. As such, they provide valuable information for supporting memory-guided behavior. Here, we employed single-photon calcium imaging in freely moving mice to investigate the emergence and fate of trajectory-dependent activity through learning and mastery of a continuous spatial alternation task. We found that the quality of trajectory-dependent information in hippocampal neurons correlated with task performance. We thus hypothesized that, due to their utility, splitter neurons would exhibit heightened stability. We found that splitter neurons were more likely to remain active and retained more consistent spatial information across multiple days than did place cells. Furthermore, we found that both splitter neurons and place cells emerged rapidly and maintained stable trajectory-dependent/spatial activity thereafter. Our results suggest that neurons with useful functional coding properties exhibit heightened stability to support memory guided behavior.

scholarly journals Trends in animal model preference for preclinical drug testing for type-2 diabetes and future directions

2020 ◽  
Author(s):  
Nuno Henrique Franco ◽  
Sónia Batista Miranda ◽  
Nora Kovacs ◽  
Attila Nagy ◽  
Folahanmi Tomiwa Akinsolu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Animal Model ◽  
Animal Models ◽  
Predictive Validity ◽  
Drug Testing ◽  
Drug Efficacy ◽  
Antidiabetic Drug ◽  
Animal Models Of Disease ◽  
Drug Classes

AbstractThe importance of selecting accurate animal models of disease has become increasingly salient in recent years. This is particularly important for preclinical tests carried out to predict drug efficacy and safety for humans. We mapped past and current trends in animal model selection for type-2 Diabetes Mellitus (T2DM) antidiabetic drug research, and evaluate results in light of their implications for translational research.From data gathered from published studies on 41 orally administered antidiabetic drug classes from the ‘MEDLINE Evaluator’ web service, we found animal model choice trends within – and across – drug classes to be substantially similar, with outbred rat strains being more prevalently used, since the 1990s. The observed consistency in choice of animal models in T2DM is advantageous for replicability and comparability of experiments, but prevalence of outbred strains raises a few concerns.In face of current criticism of the translational value of animal tests, predictive validity must be assessed on a case-by-case basis. We address some of the issues pertaining the most popular animal models in antidiabetic drug development and testing, including the lack of information on their predictive validity, and propose a ‘back translation’ approach to estimate it retrospectively.

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