Translational utility of rodent hippocampal auditory gating in schizophrenia research: a review and evaluation.
Ontology highlight
ABSTRACT:
SUBMITTER: Smucny J
PROVIDER: S-EPMC4490287 | biostudies-other | 2015 Jun
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Rodents, in particular Mus musculus, have a long and invaluable history as models for human diseases in biomedical research, although their translational value has been challenged in a number of cases. We provide some examples in which rodents have been suboptimal as models for human biology and discuss confounders which influence experiments and may explain some of the misleading results. Infections of rodents with protozoan parasites are no exception in requiring close consideration upon model choice. We focus on the significant differences between inbred, outbred and wild animals, and the importance of factors such as microbiota, which are gaining attention as crucial variables in infection experiments. Frequently, mouse or rat models are chosen for convenience, e.g., availability in the institution rather than on an unbiased evaluation of whether they provide the answer to a given question. Apart from a general discussion on translational success or failure, we provide examples where infections with single-celled parasites in a chosen lab rodent gave contradictory or misleading results, and when possible discuss the reason for this. We present emerging alternatives to traditional rodent models, such as humanized mice and organoid primary cell cultures. So-called recombinant inbred strains such as the Collaborative Cross collection are also a potential solution for certain challenges. In addition, we emphasize the advantages of using wild rodents for certain immunological, ecological, and/or behavioral questions. The experimental challenges (e.g., availability of species-specific reagents) that come with the use of such non-model systems are also discussed. Our intention is to foster critical judgment of both traditional and newly available translational rodent models for research on parasitic protozoa that can complement the existing mouse and rat models.
| S-EPMC5461347 | biostudies-literature
Project description:The interrelationship between the ability to inhibit incoming redundant input (gating out) and the ability of the brain to respond when the stimulus changes (gating in), has not been extensively examined. We administered a battery of auditory evoked potential tests to a group of chronic, medicated schizophrenia patients (N=12) and a group of healthy subjects (N=12) in order to examine relationships between "gating out" measures (suppression with repetition of the P50, N100, and P200 evoked responses), and the mismatch negativity (MMN) and the P300 event related potentials as measures of "gating in". Gating ratios for N100 and P200 in a visual attention paired-click task differed significantly between groups. Mismatch negativity and P300 potential amplitudes were also significantly reduced in the patient group. When including all subjects (N=24) a negative correlation was found between the P50 gating and the amplitude of the MMN. In healthy subjects this correlation was significantly stronger compared to schizophrenia patients. While no significant correlation was noted between the amplitudes of the P300 and any gating measures when all 24 subjects were included, a significant negative correlation was seen between the P200 gating and the P300 amplitudes in schizophrenia patients; an opposite trend was noted in healthy subjects. Finally, a positive correlation was seen between the P300 and MMN (to abstract deviance) amplitudes in healthy subjects, but the opposite was found in patients. These results suggest that further study of these interrelationships could inform the understanding of information processing abnormalities in schizophrenia.
| S-EPMC2910174 | biostudies-literature
Project description:The Laboratory of Translational Auditory Research (LTAR/NYUSM) is part of the Department of Otolaryngology at the New York University School of Medicine and has close ties to the New York University Cochlear Implant Center. LTAR investigators have expertise in multiple related disciplines including speech and hearing science, audiology, engineering, and physiology. The lines of research in the laboratory deal mostly with speech perception by hearing impaired listeners, and particularly those who use cochlear implants (CIs) or hearing aids (HAs). Although the laboratory's research interests are diverse, there are common threads that permeate and tie all of its work. In particular, a strong interest in translational research underlies even the most basic studies carried out in the laboratory. Another important element is the development of engineering and computational tools, which range from mathematical models of speech perception to software and hardware that bypass clinical speech processors and stimulate cochlear implants directly, to novel ways of analyzing clinical outcomes data. If the appropriate tool to conduct an important experiment does not exist, we may work to develop it, either in house or in collaboration with academic or industrial partners. Another notable characteristic of the laboratory is its interdisciplinary nature where, for example, an audiologist and an engineer might work closely to develop an approach that would not have been feasible if each had worked singly on the project. Similarly, investigators with expertise in hearing aids and cochlear implants might join forces to study how human listeners integrate information provided by a CI and a HA. The following pages provide a flavor of the diversity and the commonalities of our research interests.
| S-EPMC3677062 | biostudies-literature
Project description:Background: Hippocampal dysconnectivity has been detected in schizophrenia patients with auditory verbal hallucinations (AVHs). Neuroanatomical evidence has indicated distinct sub-regions in the hippocampus, but which sub-regions within the hippocampus may emerge dysfunction in the brain network, and the relationship between connection strength and the severity of this debilitating disorder have yet to be revealed. Masked independent component analysis (mICA), i.e., ICA restricted to a defined region of interest, can provide insight into observing local functional connectivity in a particular brain region. We aim to map out the sub-regions in the hippocampus with dysconnectivity linked to AVHs in schizophrenia. Methods: In this functional magnetic resonance imaging study of schizophrenia patients with (n = 57) and without (n = 83) AVHs, and 71 healthy controls, we first examined hippocampal connectivity using mICA, and then the correlation between connection metric and clinical severity was generated. Results: As compared with patients without AVHs, mICA showed a group of hyper-connections for the left middle part, as well as another group of hypo-connections for the bilateral antero-lateral and right antero-medial parts in patients with AVHs. Connectivity was linked to the clinical symptoms scores in the sample of patients with AVHs. Conclusion: These findings demonstrate that the left middle part is more densely connected, but the bilateral antero-lateral and right antero-medial parts are more sparsely connected in schizophrenia patients with AVHs. The findings in the present study show proof of precious location in the hippocampus mediating the neural mechanism behind AVHs in schizophrenia.
| S-EPMC6509236 | biostudies-literature
Project description:Despite of multiple systematic studies of schizophrenia pathogenesis, reconstruction of the mechanism established on proteomics, metabolomics, and genome-wide significant loci is still a challenging task. We suggested that advanced data for quantitative proteomics, metabolomics, and genome-wide association study (GWAS) may enhance the current evidence and fundamental knowledge about molecular pathogenesis of schizophrenia. Liquide chromatography and ultra-high-resolution mass-spectrometry were utilized for proteomic and metabolomic assay, and high throughput genotyping for the GWAS study. Proteomic and metabolomic results were quantitatively evaluated and overlayed on the GWAS data. After statistical analysis using R-package, the resulting features were associated in a multilayer mode with adjusted biological processes in a reconstructed unified map of molecular events. We have identified 20 DFE proteins that were validated on an independent cohort of patients that are significant for schizophrenia, including ALS, A1AG1, PEDF, VTDB, CERU, APOB, APOH, FASN, GPX3, etc. Almost half of them are new for schizophrenia. The metabolomic survey revealed 18 compounds most of which were the part transformation of tyrosine and steroids with the incline to androgens (androsterone sulfate, thyroliberin, thyroxine, dihydrotestosterone, androstenedione, cholesterol sulfate, metanephrine, dopaquinone, etc.) which were extracted as group-specific determinants that permits to isolate patients with schizophrenia. The GWAS assay revealed 52 loci were integrated into proteome-metabolome data as significantly implicated in schizophrenia. We integrated three layers of omics science (proteomics, metabolomics and GWAS) and quantitative analysis utilized systematic approach to reconstruct the proposed map of molecular events associated with the considered psychopathology. The resulting interplay between different layers emphasized strict implication of lipids metabolism, oxidative stress, imbalance in steroidogenesis and associated impartments of thyroid hormones and sex hormones interconnection. The proposed interplay map can give opportunity in the understanding how the regulation of distinct metabolic axis is achieved and what happens in proteome arrangements to produce a schizophrenia-specific pattern of pathology condition.
2023-02-08 | PXD035863 | Pride
Project description:Subcortical dopamine system dysregulation has been suggested to underlie the positive symptoms of schizophrenia. Recent preclinical investigations and human imaging studies have proposed that the augmented dopamine system function observed in schizophrenia patients may be secondary to aberrant hippocampal activity. Thus, we posit that the hippocampus represents a novel therapeutic target for the treatment of schizophrenia. Here we provide evidence of the effectiveness of a unique approach aimed at decreasing hippocampal function in a rodent model of schizophrenia. Specifically, in a rodent model of schizophrenia, we demonstrate that ventral hippocampal (vHipp) deep brain stimulation (DBS) can normalize aberrant dopamine neuron activity and behaviours associated with positive symptoms. In addition, we provide evidence that this approach may also be effective in restoring deficits in cognitive function, often left unaltered by conventional antipsychotic medications. Therefore, we have provided initial preclinical evidence demonstrating the feasibility of hippocampal DBS as a potential novel approach for the treatment of schizophrenia.
| S-EPMC3685478 | biostudies-literature
Project description:Several polymorphisms of the transcription factor 4 (TCF4) have been shown to increase the risk for schizophrenia, particularly TCF4 rs9960767. This polymorphism is associated with impaired sensorimotor gating measured by prepulse inhibition--an established endophenotype of schizophrenia. We therefore investigated whether TCF4 polymorphisms also affect another proposed endophenotype of schizophrenia, namely sensory gating assessed by P50 suppression of the auditory evoked potential. Although sensorimotor gating and sensory gating are not identical, recent data suggest that they share genetic fundamentals. In a multicenter study at six academic institutions throughout Germany, we applied an auditory P50 suppression paradigm to 1,821 subjects (1,023 never-smokers, 798 smokers) randomly selected from the general population. Samples were genotyped for 21 TCF4 polymorphisms. Given that smoking is highly prevalent in schizophrenia and affects sensory gating, we also assessed smoking behavior, cotinine plasma concentrations, exhaled carbon monoxide, and the Fagerström Test (FTND). P50 suppression was significantly decreased in carriers of schizophrenia risk alleles of the TCF4 polymorphisms rs9960767, rs10401120rs, rs17597926, and 17512836 (P < 0.0002-0.00005). These gene effects were modulated by smoking behavior as indicated by significant interactions of TCF4 genotype and smoking status; heavy smokers (FTND score ? 4) showed stronger gene effects on P50 suppression than light smokers and never-smokers. Our finding suggests that sensory gating is modulated by an interaction of TCF4 genotype with smoking, and both factors may play a role in early information processing deficits also in schizophrenia. Consequently, considering smoking behavior may facilitate the search for genetic risk factors for schizophrenia.
| S-EPMC3341057 | biostudies-literature
Project description:Translational medicine has become a priority, but there is still a big difference between the arrival of new treatments and investment. Basic science should not be neglected because the translation from basic research is not sustained in the absence of basic research. The purpose of this literature review was to analyze the translational medicine in the liver transplant field: liver ischemia-reperfusion injury (IRI), immunosuppression, clinical and surgical complications, small-for-size syndrome (SFSS), rejection, and ongoing innovations (liver machine, liver preservation, artificial livers, and regenerative medicine). We performed a systematic literature review that were updated in October 2016. The searches were performed in the Cochrane Central Register of Controlled Trials and Review, PubMed/Medline, Embase, and LILACS databases. All the selected studies on the management of translational medical research in liver transplantation (LT) were analyzed. Initially the search found 773 articles. Methodological viewing and analysis of the articles, followed by the application of scientific models, including translational medicine in the liver transplant field. In conclusions, this review demonstrates the application of scientific research with translation medical benefits regarding the LT. The literature has a great tendency, improvements and investments in the study of translational medicine in LT. Innovative studies and technologies from basic science help to clarify clinical doubts. Moreover, evidence increases the importance of scientific research in quality of clinical practice care.
| S-EPMC6286921 | biostudies-literature
Project description:A large variety of rodent behavioral tests are currently being used to evaluate traits such as sensory-motor function, social interactions, anxiety-like and depressive-like behavior, substance dependence and various forms of cognitive function. Most behavioral tests have an inherent complexity, and their use requires consideration of several aspects such as the source of motivation in the test, the interaction between experimenter and animal, sources of variability, the sensory modality required by the animal to solve the task as well as costs and required work effort. Of particular importance is a test's validity because of its influence on the chance of successful translation of preclinical results to clinical settings. High validity may, however, have to be balanced against practical constraints and there are no behavioral tests with optimal characteristics. The design and development of new behavioral tests is therefore an ongoing effort and there are now well over one hundred tests described in the contemporary literature. Some of them are well established following extensive use, while others are novel and still unproven. The task of choosing a behavioral test for a particular project may therefore be daunting and the aim of the present review is to provide a structured way to evaluate rodent behavioral tests aimed at drug discovery research.
| S-EPMC4106406 | biostudies-literature
Project description:Genome-wide association studies have identified thousands of consistently replicated associations between genetic markers and complex disease risk, including cancers. Alone, these markers have limited utility in risk prediction; however, when several of these markers are used in combination, the predictive performance appears to be similar to that of many currently available clinical predictors. Despite this, there are divergent views regarding the clinical validity and utility of these genetic markers in risk prediction. There are valid concerns, thus providing a direction for new lines of research. Herein, we outline the debate and use the example of prostate cancer to highlight emerging evidence from studies that aim to address potential concerns. We also describe a translational framework that could be used to guide the development of a new generation of comprehensive research studies aimed at capitalizing on these exciting new discoveries.
| S-EPMC3753782 | biostudies-other