scholarly journals NAAG peptidase inhibitors block cognitive deficit induced by MK-801 and motor activation induced by d-amphetamine in animal models of schizophrenia

2012 ◽  
Vol 2 (7) ◽  
pp. e145-e145 ◽  
Author(s):  
R T Olszewski ◽  
K J Janczura ◽  
S R Ball ◽  
J C Madore ◽  
K M Lavin ◽  
...  
Keyword(s):  
Animal Models ◽  
Cognitive Deficit ◽  
Mk 801 ◽  
Peptidase Inhibitors ◽  
Motor Activation ◽  
Naag Peptidase

scholarly journals NAAG Peptidase Inhibitors Act via mGluR3: Animal Models of Memory, Alzheimer’s, and Ethanol Intoxication

2017 ◽  
Vol 42 (9) ◽  
pp. 2646-2657 ◽  
Author(s):  
Rafal T. Olszewski ◽  
Karolina J. Janczura ◽  
Tomasz Bzdega ◽  
Elise K. Der ◽  
Faustino Venzor ◽  
...  
Keyword(s):  
Animal Models ◽  
Ethanol Intoxication ◽  
Peptidase Inhibitors ◽  
Naag Peptidase

scholarly journals S218. TAURINE DOES NOT PREVENT SOCIAL DEFICITS INDUCED BY MK-801 IN ADULT ZEBRAFISH

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S121-S122
Author(s):  
Franciele Kich Giongo ◽  
Radharani Benvenutti ◽  
Matheus Gallas-Lopes ◽  
Adrieli Sachett ◽  
Angelo Piato ◽  
...  
Keyword(s):  
Social Interaction ◽  
Animal Models ◽  
Negative Symptoms ◽  
Acute Exposure ◽  
First Episode ◽  
Social Deficits ◽  
Zebrafish Model ◽  
Mk 801 ◽  
Total Distance ◽  
The Social

Abstract Background Cognitive and negative symptoms are the core reason for the functional deficits experienced by patients with schizophrenia. Drugs that can modulate these symptoms are especially needed since no progress has been achieved in the last few decades with currently available antipsychotics. Taurine is an amino acid not used for protein synthesis but widely distributed in mammalian tissues. In the central nervous system, it has been shown to act as an inhibitory neuromodulator and possess neuroprotective, antioxidant and immunomodulatory properties. Decreased plasma and brain levels of taurine have been reported in patients as well as in animal models of schizophrenia. Furthermore, taurine improved symptoms and was well tolerated in a clinical trial of patients with first-episode psychosis. We investigated whether taurine counteracts social deficits in a zebrafish model of social interaction following acute exposure to MK-801 (dizocilpine), an NDMA antagonist commonly used in schizophrenia animal models. Methods Ninety-six 3-month-old wild-type zebrafish (Danio rerio, 50:50 male:female ratio) were used. For the social interaction test, animals were individually placed in a beaker with 200 mL of tank water (control) or taurine solution (42, 150 and 400 mg/L) for 20 minutes, and then exposed to water or MK-801 (5 µM) for another 20 minutes (n = 12 animals per group). Immediately after the treatments, zebrafish were transferred to the social interaction apparatus, a tank virtually divided in 3 vertical zones and sided by an empty tank and a tank containing 10 zebrafish. Behavior was recorded for 7 minutes and the last 5 were analyzed by automated tracking with the software ANY-Maze. The time spent in the stimulus zone was measured as a proxy for social interaction; total distance traveled was also computed. Data were analyzed by two-way ANOVA. Results MK-801 increased the total distance traveled (F1,88 = 4.935, p = 0.0289) and reduced the time spent in the tank zone next to the conspecifics (F1,88 = 23.14, p < 0.0001). No main effects of taurine or interaction effects were observed on locomotor or social interaction parameters. Discussion Although taurine has been shown to increase social interaction in rats and modulate shoaling behavior in ethanol-exposed zebrafish, it had not been tested against social deficits induced by NMDA antagonists. We observed that taurine did not counteract the hyperlocomotion and social deficit induced by acute exposure to MK-801 in zebrafish. As schizophrenia etiology has been linked to cortical and hippocampal disruption in GABAergic signaling, taurine may be effective as a preventive treatment in early neurodevelopmental stages. Further testing using animal models that more closely resemble the course of schizophrenia are thus needed to investigate the potential of this molecule.

scholarly journals NAAG peptidase inhibitors and deletion of NAAG peptidase gene enhance memory in novel object recognition test

2013 ◽  
Vol 701 (1-3) ◽  
pp. 27-32 ◽  
Author(s):  
Karolina J. Janczura ◽  
Rafal T. Olszewski ◽  
Tomasz Bzdega ◽  
Dean J. Bacich ◽  
Warren D. Heston ◽  
...  
Keyword(s):  
Object Recognition ◽  
Recognition Test ◽  
Novel Object Recognition ◽  
Object Recognition Test ◽  
Novel Object ◽  
Peptidase Inhibitors ◽  
Novel Object Recognition Test ◽  
Naag Peptidase

scholarly journals Memantine ameliorates cognitive deficit in AD mice via enhancement of entorhinal–CA1 projection

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Peng Li ◽  
Jin Xu ◽  
Huanhuan Gu ◽  
Hua Peng ◽  
You Yin ◽  
...  
Keyword(s):  
Animal Models ◽  
Dendritic Spine ◽  
Cognitive Functions ◽  
Water Maze ◽  
Cognitive Deficit ◽  
Underlying Mechanism ◽  
Aspartate Receptor ◽  
Synaptic Neurotransmission ◽  
Underlying Mechanisms ◽  
Cognitive Defects

Abstract Background Memantine, a low- to moderate-affinity uncompetitive N-methyl-D-aspartate receptor antagonist, has been shown to improve cognitive functions in animal models of Alzheimer’s disease (AD). Here we treated APP/PS1 AD mice with a therapeutic dose of memantine (20 mg/kg/day) and examined its underlying mechanisms in ameliorating cognitive defects. Methods Using behavioral, electrophysiological, optogenetic and morphology approaches to explore how memantine delay the pathogenesis of AD. Results Memantine significantly improved the acquisition in Morris water maze (MWM) in APP/PS1 mice without affecting the speed of swimming. Furthermore, memantine enhanced EC to CA1 synaptic neurotransmission and promoted dendritic spine regeneration of EC neurons that projected to CA1. Conclusions Our study reveals the underlying mechanism of memantine in the treatment of AD mice.

scholarly journals Effect of dizocilpine (MK-801) on the working memory of rats on a three-panel runway apparatus

2018 ◽  
Vol 7 (12) ◽  
pp. 2373
Author(s):  
Naveen Kumar ◽  
Navin Budania ◽  
Arka Mondal ◽  
Sana Tafseer ◽  
Siddarth Ahuja ◽  
...  
Keyword(s):  
Working Memory ◽  
Animal Model ◽  
Nmda Receptor ◽  
Animal Models ◽  
Receptor Antagonist ◽  
Cognitive Deficits ◽  
Latency Period ◽  
Nmda Receptor Antagonist ◽  
Memory Errors ◽  
Mk 801

Background: Understanding the processes underlying cognitive functions is a prerequisite to develop strategies for the treatment of cognitive deficits. There is a great need for valid animal models for investigating the cognitive enhancing effects of potential therapeutics. Many studies have investigated animal models of cognitive deficits by using animals treated with compounds that compromise cognitive abilities. Glutamate, an excitatory neurotransmitter and abundantly distributed in the central nervous system is involved in memory processes through N-methyl-d-aspartate (NMDA) receptors. The behavioural consequences of blocking the NMDA receptor provide the rationale for cognitive impairment as an animal model for the cognitive deficits associated with dementia. Authors investigated the effect of dizocilpine (MK-801), an NMDA-receptor antagonist (non-competitive) on the working memory in rats using the three-panel runway apparatus.Methods: Total 24 trained male albino rats were randomly divided into 4 groups of 6 animals each. Varying doses of MK-801 were administered to the animals. Working memory errors and latency periods were evaluated on the three panel Runway apparatus.Results: Treatment with MK-801 at the dose of 0.03mg/ kg did not result in any significant change in working memory errors or latency period in comparison to saline control. MK-801 treatment at dose of 0.1mg/kg and 0.3mg/kg resulted in a significant increase in the number of working memory errors and latency period as compared to control.Conclusions: Authors conclude that MK-801 treatment in the dose of 0.1mg/ kg and 0.3mg/kg resulted in working memory deficits on the three-panel runway apparatus. Rats with cognitive deficits induced by the prototypical N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 may provide a relevant animal model of dementia based on the mechanistic approach of blocking NMDA/glutamatergic signalling.

Are Animal Models of Cognitive Deficit Relevant for Man? Translational Problems in Schizophrenia

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
P. Boyer
Keyword(s):  
Working Memory ◽  
Animal Models ◽  
Cognitive Deficit ◽  
Memory Deficit ◽  
Normal Brain ◽  
Neural Basis ◽  
Brain Organization ◽  
Glutamatergic Signaling ◽  
Prefrontal Functions ◽  
Contextual Binding

Since long working memory deficit has been considered as one of the major cognitive dysfunction encountered in schizophrenia. Working memory is critical for human reasoning, judgment and decision and depends upon the integrity of prefrontal and cingulate circuitry. As a consequence coupling pharmacological (amphetamine sensitization, subchronic phencyclidine administration, neurodevelopmental insult) and behavioral approaches of prefrontal functions in animals seems to be a cue totally appropriate for elucidating the mechanisms of this dysfunction in man (Castner,2004).In rodent models aberrant dopaminergic and glutamatergic signaling in medial prefrontal cortex has undoubtedly an impact on memory and learning, But the analogy between these deficits and a true working memory deficit in man is not obvious. Due to the higher degree of homology between human and non-human primates behavioral tests in apes seem to be more relevant but once again they can not be considered as reflecting strictly the consequences of working memory dysfunction in schizophrenia. Another approach is to extend the insights gained from the study of normal brain organization in animal models to better understand the neural basis on which working memory functions are based (Tanaka, 2006). Dissecting the cellular and circuit basis of prefrontal and cingulate cortices can give an idea how direct and indirect intercellular mechanisms are modulating working memory Nevertheless the behavioral part of this type of study remains non conclusive. It seems in fact that working memory itself is probably not a good candidate and that contextual-binding tasks (which explore encoding and retrieval) are more appropriate (Boyer,2007).

scholarly journals Effects of Dizocilpine, Midazolam and Their Co-Application on the Trimethyltin (TMT)-Induced Rat Model of Cognitive Deficit

2021 ◽  
Vol 11 (3) ◽  
pp. 400
Author(s):  
Marketa Chvojkova ◽  
Hana Kubova ◽  
Karel Vales
Keyword(s):  
Nmda Receptor ◽  
Gabaa Receptor ◽  
Cognitive Deficit ◽  
Dorsal Hippocampus ◽  
Treatment Options ◽  
Combined Treatment ◽  
Nmda Receptor Antagonist ◽  
Similar Degree ◽  
Gamma Aminobutyric Acid ◽  
Mk 801

Research of treatment options addressing the cognitive deficit associated with neurodegenerative disorders is of particular importance. Application of trimethyltin (TMT) to rats represents a promising model replicating multiple relevant features of such disorders. N-methyl-D-aspartate (NMDA) receptor antagonists and gamma-aminobutyric acid type A (GABAA) receptor potentiators have been reported to alleviate the TMT-induced cognitive deficit. These compounds may provide synergistic interactions in other models. The aim of this study was to investigate, whether co-application of NMDA receptor antagonist dizocilpine (MK-801) and GABAA receptor potentiator midazolam would be associated with an improved effect on the TMT-induced model of cognitive deficit. Wistar rats injected with TMT were repeatedly (12 days) treated with MK-801, midazolam, or both. Subsequently, cognitive performance was assessed. Finally, after a 17-day drug-free period, hippocampal neurodegeneration (neuronal density in CA2/3 subfield in the dorsal hippocampus, dentate gyrus morphometry) were analyzed. All three protective treatments induced similar degree of therapeutic effect in Morris water maze. The results of histological analyses were suggestive of minor protective effect of the combined treatment (MK-801 and midazolam), while these compounds alone were largely ineffective at this time point. Therefore, in terms of mitigation of cognitive deficit, the combined treatment was not associated with improved effect.

Sign in / Sign up

Export Citation Format

Share Document