scholarly journals The Utility of Animal Models for Studying the Metabo-Psychiatric Origins of Anorexia Nervosa

2021 ◽  
Vol 12 ◽  
Author(s):  
Jie Zhang ◽  
Stephanie C. Dulawa

Anorexia nervosa (AN) is a severe eating disorder that primarily affects young women and girls, and is characterized by abnormal restrictive feeding and a dangerously low body-mass index. AN has one of the highest mortality rates of any psychiatric disorder, and no approved pharmacological treatments exist. Current psychological and behavioral treatments are largely ineffective, and relapse is common. Relatively little basic research has examined biological mechanisms that underlie AN compared to other major neuropsychiatric disorders. A recent large-scale genome-wide association study (GWAS) revealed that the genetic architecture of AN has strong metabolic as well as psychiatric origins, suggesting that AN should be reconceptualized as a metabo-psychiatric disorder. Therefore, identifying the metabo-psychiatric mechanisms that contribute to AN may be essential for developing effective treatments. This review focuses on animal models for studying the metabo-psychiatric mechanisms that may contribute to AN, with a focus on the activity-based anorexia (ABA) paradigm. We also highlight recent work using modern circuit-dissecting neuroscience techniques to uncover metabolic mechanisms that regulate ABA, and encourage further work to ultimately identify novel treatment strategies for AN.

Metabolites ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 72 ◽  
Author(s):  
Elke Humer ◽  
Thomas Probst ◽  
Christoph Pieh

Biomarkers are a recent research target within biological factors of psychiatric disorders. There is growing evidence for deriving biomarkers within psychiatric disorders in serum or urine samples in humans, however, few studies have investigated this differentiation in brain or cerebral fluid samples in psychiatric disorders. As brain samples from humans are only available at autopsy, animal models are commonly applied to determine the pathogenesis of psychiatric diseases and to test treatment strategies. The aim of this review is to summarize studies on biomarkers in animal models for psychiatric disorders. For depression, anxiety and addiction disorders studies, biomarkers in animal brains are available. Furthermore, several studies have investigated psychiatric medication, e.g., antipsychotics, antidepressants, or mood stabilizers, in animals. The most notable changes in biomarkers in depressed animal models were related to the glutamate-γ-aminobutyric acid-glutamine-cycle. In anxiety models, alterations in amino acid and energy metabolism (i.e., mitochondrial regulation) were observed. Addicted animals showed several biomarkers according to the induced drugs. In summary, animal models provide some direct insights into the cellular metabolites that are produced during psychiatric processes. In addition, the influence on biomarkers due to short- or long-term medication is a noticeable finding. Further studies should combine representative animal models and human studies on cerebral fluid to improve insight into mental disorders and advance the development of novel treatment strategies.


2021 ◽  
Author(s):  
Nicolette Driscoll ◽  
Brian Erickson ◽  
Brendan B. Murphy ◽  
Andrew G. Richardson ◽  
Gregory Robbins ◽  
...  

Soft bioelectronic interfaces for mapping and modulating excitable networks at high resolution and at large scale can enable paradigm-shifting diagnostics, monitoring, and treatment strategies. Yet, current technologies largely rely on materials and fabrication schemes that are expensive, do not scale, and critically limit the maximum attainable resolution and coverage. Solution processing is a cost-effective manufacturing alternative, but biocompatible conductive inks matching the performance of conventional metals are lacking. Here, we introduce MXtrodes, a novel class of soft, high-resolution, large-scale bioelectronic interfaces enabled by Ti3C2 MXene and scalable solution processing. We show that the electrochemical properties of MXtrodes exceed those of conventional materials, and do not require conductive gels when used in epidermal electronics. Furthermore, we validate MXtrodes in a number of applications ranging from mapping large scale neuromuscular networks in humans to delivering cortical microstimulation in small animal models. Finally, we demonstrate that MXtrodes are compatible with standard clinical neuroimaging modalities.


2020 ◽  
Vol 23 (2) ◽  
pp. 135-136
Author(s):  
Cynthia Bulik ◽  
Martin Kennedy ◽  
Tracey Wade

AbstractIdentification of genetic variants associated with eating disorders is underway. The Anorexia Nervosa Genetics Initiative, an initiative of the Klarman Family Foundation, has contributed to advancing the field, yielding a large-scale genome-wide association study published in Nature Genetics. Eight genetic variants significantly associated with anorexia nervosa were identified, along with patterns of genetic correlations that suggest both psychiatric and metabolic origins of this serious and life-threatening illness. This article details the role of Professor Nick Martin in contributing to this important collaboration.


2017 ◽  
Vol 114 (36) ◽  
pp. E7554-E7563 ◽  
Author(s):  
Stephen E. Kurtz ◽  
Christopher A. Eide ◽  
Andy Kaempf ◽  
Vishesh Khanna ◽  
Samantha L. Savage ◽  
...  

Translating the genetic and epigenetic heterogeneity underlying human cancers into therapeutic strategies is an ongoing challenge. Large-scale sequencing efforts have uncovered a spectrum of mutations in many hematologic malignancies, including acute myeloid leukemia (AML), suggesting that combinations of agents will be required to treat these diseases effectively. Combinatorial approaches will also be critical for combating the emergence of genetically heterogeneous subclones, rescue signals in the microenvironment, and tumor-intrinsic feedback pathways that all contribute to disease relapse. To identify novel and effective drug combinations, we performed ex vivo sensitivity profiling of 122 primary patient samples from a variety of hematologic malignancies against a panel of 48 drug combinations. The combinations were designed as drug pairs that target nonoverlapping biological pathways and comprise drugs from different classes, preferably with Food and Drug Administration approval. A combination ratio (CR) was derived for each drug pair, and CRs were evaluated with respect to diagnostic categories as well as against genetic, cytogenetic, and cellular phenotypes of specimens from the two largest disease categories: AML and chronic lymphocytic leukemia (CLL). Nearly all tested combinations involving a BCL2 inhibitor showed additional benefit in patients with myeloid malignancies, whereas select combinations involving PI3K, CSF1R, or bromodomain inhibitors showed preferential benefit in lymphoid malignancies. Expanded analyses of patients with AML and CLL revealed specific patterns of ex vivo drug combination efficacy that were associated with select genetic, cytogenetic, and phenotypic disease subsets, warranting further evaluation. These findings highlight the heuristic value of an integrated functional genomic approach to the identification of novel treatment strategies for hematologic malignancies.


2020 ◽  
Author(s):  
Teena D Moody ◽  
Francesca Morfini ◽  
Gigi Cheng ◽  
Courtney L Sheen ◽  
Wesley Kerr ◽  
...  

AbstractAnorexia nervosa (AN) and body dysmorphic disorder (BDD) are characterized by distorted perception of appearance, yet no studies have directly compared the neurobiology associated with body perception. We compared brain activation and connectivity in relevant networks when viewing images of others’ bodies and tested their relationships with clinical symptoms and subjective appearance evaluations. We acquired fMRI data from 64 unmedicated females (20 weight-restored AN, 23 BDD, 21 controls) during a matching task using photos of others’ bodies that were unaltered or spatial-frequency filtered. With general linear model and independent components analyses we compared brain activation and connectivity in visual, striatal, and parietal networks and performed univariate and partial least squares multivariate analyses to investigate relationships with clinical symptoms and appearance evaluations. BDD but not AN demonstrated hypoactivity in dorsal visual and parietal networks compared to controls. Yet, AN and BDD showed partially overlapping patterns of hyperconnectivity in the dorsal visual network and hypoconnectivity in parietal network compared with controls. Further, there were significant activity and connectivity differences between AN and BDD in both networks. In both groups, activity and/or connectivity were associated with symptom severity and appearance ratings of others’ bodies. AN and BDD demonstrate both distinct and partially overlapping aberrant neural phenotypes involved in body processing and visually encoding global features. Nevertheless, in each disorder, aberrant activity and connectivity show relationships to clinically relevant symptoms and subjective perception. Results have implications for understanding distinct and shared pathophysiology underlying perceptual distortions for appearance and may inform future novel treatment strategies.


2021 ◽  
Vol 13 ◽  
Author(s):  
Klaus W. Lange

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by globally impaired cognition. AD research in animals has shown a substantial deficit in translational relevance. The most extensively used transgenic mouse models overexpress human genes associated with rare familial early-onset AD, which results in the formation of amyloid plaques. However, the most common form of AD (late-onset sporadic AD) is a multifactorial disorder involving different cytotoxic factors, including neurofibrillary pathology. Transgenic mice studies have been valuable in elucidating pathogenetic mechanisms that may be relevant to human AD. However, their utility in the development of novel treatment strategies and as preclinical testbeds of new drugs has been unsatisfactory. Animal models have so far failed to demonstrate predictive value in regard to novel therapies of AD, including the use of bioactive food components. While many therapeutic approaches assessed in animals have shown promising results, attempts to translate these findings to people with AD have been disappointing. Food scientists should be aware that the available animal models appear to be unable to predict clinical success in humans. Therefore, food bioactive research should focus on human-centric preventive approaches to AD in clinically meaningful settings rather than on highly questionable preclinical research in animals.


Author(s):  
Odile Viltart ◽  
Philibert Duriez ◽  
Virginie Tolle

Abstract The exact mechanisms linking metabolic and neuroendocrine adaptations to undernutrition and the pathophysiology of anorexia nervosa (AN) are not fully understood. AN is a psychiatric disorder of complex etiology characterized by extreme starvation while the disease is progressing into a chronic state. Metabolic and endocrine alterations associated to this disorder are part of a powerful response to maintain whole body energy homeostasis. But these modifications may also contribute to associated neuropsychiatric symptoms (reward abnormalities, anxiety, depression) and thus participate to sustain the disease. The current review presents data with both a clinical and basic research point of view on the role of nutritional and energy sensors with neuroendocrine actions in the pathophysiology of the disease, as they modulate metabolic responses, reproductive functions, stress responses as well as physical activity. While clinical data present a full description of changes occurring in AN, animal models that integrate either spontaneous genetic mutations or experimentally-induced food restriction with hyperactivity and/or social stress recapitulate the main metabolic and endocrine alterations of AN and provide mechanistic information between undernutrition state and symptoms of the disease. Further progress on the central and peripheral mechanism involved in the pathophysiology of eating disorders partly relies on the development and/or refinement of existing animal models to include recently identified genetic traits and better mimic the complex and multifactorial dimensions of the disease.


2019 ◽  
Vol 141 (7) ◽  
Author(s):  
Olufunmilayo O. Adebayo ◽  
Derek T. Holyoak ◽  
Marjolein C. H. van der Meulen

Osteoarthritis (OA) is a degenerative joint disease that affects millions of people worldwide, yet its disease mechanism is not clearly understood. Animal models have been established to study disease progression by initiating OA through modified joint mechanics or altered biological activity within the joint. However, animal models often do not have the capability to directly relate the mechanical environment to joint damage. This review focuses on a novel in vivo approach based on controlled, cyclic tibial compression to induce OA in the mouse knee. First, we discuss the development of the load-induced OA model, its different loading configurations, and other techniques used by research laboratories around the world. Next, we review the lessons learned regarding the mechanobiological mechanisms of load-induced OA and relate these findings to the current understanding of the disease. Then, we discuss the role of specific genetic and cellular pathways involved in load-induced OA progression and the contribution of altered tissue properties to the joint response to mechanical loading. Finally, we propose using this approach to test the therapeutic efficacy of novel treatment strategies for OA. Ultimately, elucidating the mechanobiological mechanisms of load-induced OA will aid in developing targeted treatments for this disabling disease.


CNS Spectrums ◽  
2001 ◽  
Vol 6 (7) ◽  
pp. 590-594 ◽  
Author(s):  
Florian Holsboer

AbstractResearch has provided considerable evidence for the hypothesis that corticotropin-releasing hormone (CRH), the key central coordinator of stress-hormone homeostasis, also plays a role in the development and course of depression and anxiety disorders. Studies using animal models of anxiety, as well as mouse mutants, in which the gene coding for the CRH type 1 receptor (CRHR1) was genetically deleted supported the notion that enhanced CRH/CRHR1 signaling underlies depression and anxiety disorders. Therefore, a number of small nonpeptide molecules that antagonize CRHR1 have been developed. In animal models, these molecules had anxiolytic and other stress-alleviating effects. An initial clinical study showed that CRHR1 antagonism has beneficial effects on depression and anxiety symptoms at doses unharmful to neuroendocrine stress responsivity.


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