What’s Wrong with Their Mice?

Author(s):  
Nikolas Rose ◽  
Joelle M. Abi-Rached

This chapter discusses the use of animals to explore issues relating to human cognition, emotion, volition, and their pathologies. Researchers who use animal models in their work point to similarities in the genomes of the two species, in the structure of mouse and human brain, in patterns of brain activation, in neural mechanisms at the cellular and molecular level, in responses to drugs and so forth, perhaps with reference to evolution and the principle of conservation across species when it comes to the most basic aspects of living organisms, including their brains. The chapter then examines four interconnected themes: the question of the artificiality of the laboratory situation within which animal experiments are conducted; the idea of a model in behavioral and psychiatric research; the specificity of the human and the elision of history and human sociality; and the problem of translation.

Author(s):  
Maja Jakovcevski ◽  
Slobodanka Mitrović ◽  
Igor Jakovcevski

Abstract Due to its numerous distinctive functions and unique pathology, the human brain, or rather forebrain has been difficult to study in common animal models. Although many basic molecular and cellular events are conserved across species, human brain connectivity, pertinent especially to the cerebral cortex circuitry, is unique and demands extensive research. Despite a great advancement in functional imaging methods accomplished over the last two decades, many basic features of healthy and diseased human forebrain remain elusive. Here we address difficulties in anatomical studies of developing and adult human brain and indicate the new directions and challenges to be addressed in the future. We pay special attention to possibilities of translating animal brain research to human cases. We consider that, although animal experiments play a vital role in understanding fundamental molecular and cellular mechanisms behind brain function, understanding of higher brain functions (language, intelligence, memory) has to be based on understanding uniqueness of human circuitries. Furthermore, brain is the site of many human-specific diseases, such as multiple sclerosis, schizophrenia, and Alzheimer’s disease, for which only partial animal models exist. To study human brain, thus, remains irreplaceable in the quest for new therapeutic tools, as well as in understanding the essence of our being.


2021 ◽  
Vol 16 ◽  
pp. 263310552110187
Author(s):  
Christopher D Link

Numerous studies have identified microbial sequences or epitopes in pathological and non-pathological human brain samples. It has not been resolved if these observations are artifactual, or truly represent population of the brain by microbes. Given the tempting speculation that resident microbes could play a role in the many neuropsychiatric and neurodegenerative diseases that currently lack clear etiologies, there is a strong motivation to determine the “ground truth” of microbial existence in living brains. Here I argue that the evidence for the presence of microbes in diseased brains is quite strong, but a compelling demonstration of resident microbes in the healthy human brain remains to be done. Dedicated animal models studies may be required to determine if there is indeed a “brain microbiome.”


Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4221
Author(s):  
Aage Kristian Olsen Alstrup ◽  
Svend Borup Jensen ◽  
Ole Lerberg Nielsen ◽  
Lars Jødal ◽  
Pia Afzelius

The development of new and better radioactive tracers capable of detecting and characterizing osteomyelitis is an ongoing process, mainly because available tracers lack selectivity towards osteomyelitis. An integrated part of developing new tracers is the performance of in vivo tests using appropriate animal models. The available animal models for osteomyelitis are also far from ideal. Therefore, developing improved animal osteomyelitis models is as important as developing new radioactive tracers. We recently published a review on radioactive tracers. In this review, we only present and discuss osteomyelitis models. Three ethical aspects (3R) are essential when exposing experimental animals to infections. Thus, we should perform experiments in vitro rather than in vivo (Replacement), use as few animals as possible (Reduction), and impose as little pain on the animal as possible (Refinement). The gain for humans should by far exceed the disadvantages for the individual experimental animal. To this end, the translational value of animal experiments is crucial. We therefore need a robust and well-characterized animal model to evaluate new osteomyelitis tracers to be sure that unpredicted variation in the animal model does not lead to a misinterpretation of the tracer behavior. In this review, we focus on how the development of radioactive tracers relies heavily on the selection of a reliable animal model, and we base the discussions on our own experience with a porcine model.


2021 ◽  
Vol 9 (2) ◽  
pp. 206
Author(s):  
Martyna Cieślik ◽  
Natalia Bagińska ◽  
Andrzej Górski ◽  
Ewa Jończyk-Matysiak

The authors emphasize how extremely important it is to highlight the role played by animal models in an attempt to determine possible phage interactions with the organism into which it was introduced as well as to determine the safety and effectiveness of phage therapy in vivo taking into account the individual conditions of a given organism and its physiology. Animal models in which phages are used make it possible, among other things, to evaluate the effective therapeutic dose and to choose the possible route of phage administration depending on the type of infection developed. These results cannot be applied in detail to the human body, but the knowledge gained from animal experiments is invaluable and very helpful. We would like to highlight how useful animal models may be for the possible effectiveness evaluation of phage therapy in the case of infections caused by gram-negative bacteria from the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species) group of pathogens. In this review, we focus specifically on the data from the last few years.


Materials ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3513
Author(s):  
Nikola Stokovic ◽  
Natalia Ivanjko ◽  
Drazen Maticic ◽  
Frank P. Luyten ◽  
Slobodan Vukicevic

Bone morphogenetic proteins (BMPs) possess a unique ability to induce new bone formation. Numerous preclinical studies have been conducted to develop novel, BMP-based osteoinductive devices for the management of segmental bone defects and posterolateral spinal fusion (PLF). In these studies, BMPs were combined with a broad range of carriers (natural and synthetic polymers, inorganic materials, and their combinations) and tested in various models in mice, rats, rabbits, dogs, sheep, and non-human primates. In this review, we summarized bone regeneration strategies and animal models used for the initial, intermediate, and advanced evaluation of promising therapeutical solutions for new bone formation and repair. Moreover, in this review, we discuss basic aspects to be considered when planning animal experiments, including anatomical characteristics of the species used, appropriate BMP dosing, duration of the observation period, and sample size.


1988 ◽  
Vol 15 (4) ◽  
pp. 313-318
Author(s):  
Anthony Stevens

During the last twenty years, the most enthusiastic advocates of the use of animal models in the study of human psychiatric dysfunction have been Harlow and Suomi. In an influential paper, Induced Depression in Monkeys (1974), they argued that more extensive use of non-human primates “would have great potential utility since many manipulations and measurements presently prohibited in human study by ethical and practical considerations could be readily performed on non-human primate subjects in well-controlled experimental environments.” Harlow & Suomi concluded this paper with the following statement: “The results obtained to date on induced depression in monkeys show that proper and profound depressions can be produced relatively easily by a variety of techniques. These induced depressions either bear a close resemblance to human depression or have such similarity as to suggest that closely correlated human and animal depressive patterns may be achieved with refined techniques. The results to date also provide adequate data for the conduct of meaningful researches on the effects of pharmacological agents which either enhance, inhibit or preclude the experimental production of depression. Further, the existence of firm and fast monkey depression syndromes offers vast opportunities for testing a wide range of therapeutic techniques, either behavioural or biochemical.”


2021 ◽  
pp. 113652
Author(s):  
Maryam Ghafarimoghadam ◽  
Roya Mashayekh ◽  
Mina Gholami ◽  
Pardis Fereydani ◽  
John Shelley-Tremblay ◽  
...  

2021 ◽  
Vol 42 (3) ◽  
pp. 130
Author(s):  
Sudip Dhakal

The difficulties in performing experimental studies related to diseases of the human brain have fostered a range of disease models from highly expensive and complex animal models to simple, robust, unicellular yeast models. Yeast models have been used in numerous studies to understand Alzheimer’s disease (AD) pathogenesis and to search for drugs targeting AD. Thanks to the conservation of fundamental eukaryotic processes including ageing and the availability of appropriate technological platforms, budding yeast are a simple model eukaryote to assist with understanding human cell biology, offering a platform to study human diseases. This article aims to provide insights from yeast models on the contributions of amyloid beta, a causative agent in AD, and recent research findings on AD chemoprevention.


2020 ◽  
Author(s):  
Oliver L. Eichmüller ◽  
Nina S. Corsini ◽  
Ábel Vértesy ◽  
Theresa Scholl ◽  
Victoria-Elisabeth Gruber ◽  
...  

SummaryAlthough the intricate and prolonged development of the human brain critically distinguishes it from other mammals1, our current understanding of neurodevelopmental diseases is largely based on work using animal models. Recent studies revealed that neural progenitors in the human brain are profoundly different from those found in rodent animal models2–5. Moreover, post-mortem studies revealed extensive migration of interneurons into the late-gestational and post-natal human prefrontal cortex that does not occur in rodents6. Here, we use cerebral organoids to show that overproduction of mid-gestational human interneurons causes Tuberous Sclerosis Complex (TSC), a severe neuro-developmental disorder associated with mutations in TSC1 and TSC2. We identify a previously uncharacterized population of caudal late interneuron progenitors, the CLIP-cells. In organoids derived from patients carrying heterozygous TSC2 mutations, dysregulation of mTOR signaling leads to CLIP-cell over-proliferation and formation of cortical tubers and subependymal tumors. Surprisingly, second-hit events resulting from copy-neutral loss-of-heterozygosity (cnLOH) are not causative for but occur during the progression of tumor lesions. Instead, EGFR signaling is required for tumor proliferation, opening up a promising approach to treat TSC lesions. Our study demonstrates that the analysis of developmental disorders in organoid models can lead to fundamental insights into human brain development and neuropsychiatric disorders.


2017 ◽  
Vol 19 (3) ◽  
pp. 247-258 ◽  

In recent years, animal models in psychiatric research have been criticized for their limited translational value to the clinical situation. Failures in clinical trials have thus often been attributed to the lack of predictive power of preclinical animal models. Here, I argue that animal models of voluntary drug intake—under nonoperant and operant conditions—and addiction models based on the Diagnostic and Statistical Manual of Mental Disorders are crucial and informative tools for the identification of pathological mechanisms, target identification, and drug development. These models provide excellent face validity, and it is assumed that the neurochemical and neuroanatomical substrates involved in drug-intake behavior are similar in laboratory rodents and humans. Consequently, animal models of drug consumption and addiction provide predictive validity. This predictive power is best illustrated in alcohol research, in which three approved medications—acamprosate, naltrexone, and nalmefene—were developed by means of animal models and then successfully translated into the clinical situation.


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