scholarly journals When Genetic and Environmental Factors Meet in Modelling Autism

2021 ◽  
Author(s):  
◽  
Michaela Pettie
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Environmental Factors ◽  
Prenatal Exposure ◽  
Chronic Administration ◽  
Communication Delays ◽  
Pregnant Rats ◽  
Non Invasive ◽  
Administration Method ◽  
Interaction Approach

<p>Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, characterised by deficits in verbal and non-verbal communication, social interaction and repetitive behaviours (APA, 2013). The aetiology of ASD is mostly unknown, with continued research identifying a multitude of genetic and non-genetic factors. However, it is the interaction between environmental factors and the genetic background of an individual which leads to the development of ASD. There is an urgent need for improved animal models of ASD to further our understanding of the aetiology and particularly its pathophysiology, as this will aid in the development of much needed pharmaceutical treatments to alleviate the impact of adverse symptoms for individuals with ASD. Current animal models of ASD examine the genetic (e.g. serotonin transporter knock out rats) or the environmental (e.g. prenatal exposure to Valproate) contributions to the disorder, and very rarely a combination of the two.  This thesis aimed to improve the Valproate (VPA) induced ASD animal model with a genetic × environmental interaction approach, as well as optimising chronic administration of the VPA to pregnant rats. To this aim, a non-invasive method of delivering VPA was used, which allowed genetically normal rats to voluntarily consume VPA throughout pregnancy. The prenatal exposure to VPA led to ASD-like behaviours in the offspring (communication delays, increased social behaviour, and social aversion). Next, rats with a genetic deficit in SERT (SERT+/-) exposed to VPA throughout gestation, with an optimised administration method using gelatine pellets, which allowed for voluntary non-invasive consumption, and a more accurate administration of increased VPA doses. Overall, the chronic prenatal exposure to VPA in SERT+/- rats led to a mild ASD-like phenotype, with rats exhibiting communication delays, abnormal play behaviour, disrupted social preference, and to some extent increased anxiety-like behaviour. The brains of the adult offspring were examined for neuronal changes in the GABA interneurons in brain regions associated with social behaviour (amygdala and hippocampus). However, no significant effects of prenatal VPA exposure, genotype, or sex were found. Thus, the variations GABAergic system is unlikely to underlie the earlier identified behavioural alterations. Ultimately, this thesis has furthered the VPA induced ASD animal model with a genetic × environmental interaction approach, as well as optimising the chronic administration method for pregnant rats.</p>

scholarly journals When Genetic and Environmental Factors Meet in Modelling Autism

2021 ◽  
Author(s):  
◽  
Michaela Pettie
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Environmental Factors ◽  
Prenatal Exposure ◽  
Chronic Administration ◽  
Communication Delays ◽  
Pregnant Rats ◽  
Non Invasive ◽  
Administration Method ◽  
Interaction Approach

<p>Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, characterised by deficits in verbal and non-verbal communication, social interaction and repetitive behaviours (APA, 2013). The aetiology of ASD is mostly unknown, with continued research identifying a multitude of genetic and non-genetic factors. However, it is the interaction between environmental factors and the genetic background of an individual which leads to the development of ASD. There is an urgent need for improved animal models of ASD to further our understanding of the aetiology and particularly its pathophysiology, as this will aid in the development of much needed pharmaceutical treatments to alleviate the impact of adverse symptoms for individuals with ASD. Current animal models of ASD examine the genetic (e.g. serotonin transporter knock out rats) or the environmental (e.g. prenatal exposure to Valproate) contributions to the disorder, and very rarely a combination of the two.  This thesis aimed to improve the Valproate (VPA) induced ASD animal model with a genetic × environmental interaction approach, as well as optimising chronic administration of the VPA to pregnant rats. To this aim, a non-invasive method of delivering VPA was used, which allowed genetically normal rats to voluntarily consume VPA throughout pregnancy. The prenatal exposure to VPA led to ASD-like behaviours in the offspring (communication delays, increased social behaviour, and social aversion). Next, rats with a genetic deficit in SERT (SERT+/-) exposed to VPA throughout gestation, with an optimised administration method using gelatine pellets, which allowed for voluntary non-invasive consumption, and a more accurate administration of increased VPA doses. Overall, the chronic prenatal exposure to VPA in SERT+/- rats led to a mild ASD-like phenotype, with rats exhibiting communication delays, abnormal play behaviour, disrupted social preference, and to some extent increased anxiety-like behaviour. The brains of the adult offspring were examined for neuronal changes in the GABA interneurons in brain regions associated with social behaviour (amygdala and hippocampus). However, no significant effects of prenatal VPA exposure, genotype, or sex were found. Thus, the variations GABAergic system is unlikely to underlie the earlier identified behavioural alterations. Ultimately, this thesis has furthered the VPA induced ASD animal model with a genetic × environmental interaction approach, as well as optimising the chronic administration method for pregnant rats.</p>

An Animal Model for Psychopharmacological Research with Relevance to Psychiatry

1973 ◽  
Vol 18 (2) ◽  
pp. 139-146
Author(s):  
John E. Peachey ◽  
Harvey C. Stancer
Keyword(s):  
Animal Model ◽  
Social Interaction ◽  
Animal Models ◽  
Environmental Factors ◽  
Animal Species ◽  
Drug Effect ◽  
Squirrel Monkeys ◽  
Yield Information ◽  
Behavioural Characteristics ◽  
Clinical Methods

The concept is presented that animal models for psychopharmacological research should take into account clinical methods if they are to yield information which is relevant to psychiatry. Animal species with appropriate behavioural characteristics should be selected, drugs should be administered chronically and groups of animals should be used if social interaction is to be observed. Some of the relevant pharmacological, behavioural and environmental factors are presented and illustrated with examples taken from a study on groups of squirrel monkeys who had received parachlorophenylalanine or alpha-methylparatyrosine to lower specific brain amines. It is noted that social interaction may affect the expression of the drug effect.

scholarly journals Effects of Chronic Administration of P-Cymene in an Animal Model of LPS-Induced Autism

2021 ◽  
Vol 8 (03) ◽  
pp. e104-e113
Author(s):  
Rick Wilhiam de Camargo ◽  
Marina Goulart da Silva ◽  
Guilherme Cabreira Daros ◽  
Fabiana Durante de Medeiros ◽  
Naiana da Rosa ◽  
...  
Keyword(s):  
Animal Model ◽  
Prenatal Exposure ◽  
Chronic Administration ◽  
Brain Structures ◽  
Autism Spectrum ◽  
Biochemical Tests ◽  
Behavioral Abnormalities ◽  
Stereotyped Movement ◽  
Behavioral Memory ◽  
Validation Tests

Abstract p-Cymene is a monoterpene found in over 100 plant species. It shows a range of biological activity, including anti-inflammatory and antimicrobial effects. It is possibly a new therapeutic alternative for autism spectrum disorder characterized by deficits in interaction and behavioral abnormalities. These symptoms can occur in response to maternal immune activation through prenatal exposure to lipopolysaccharide. Thus, this study aimed to evaluate the behavioral, memory, and biochemical effects of chronic administration of p-cymene in an animal model of autism by prenatal maternal exposure to lipopolysaccharide. Twenty-four pregnant Wistar rats were used, who received 100 μg/kg of lipopolysaccharide or saline intraperitoneally (i.p.) on the 9.5 gestational day. After birth, the male offspring remained with the mothers until weaning and underwent model validation tests on postnatal day 30. From postnatal day 31 on, chronic administration, via i.p., of saline (1 mL/kg), risperidone (0.2 mg/kg), or p-cymene (100 mg/kg) for 22 days was performed. The animals were submitted to behavioral (postnatal day 52) and memory tests (postnatal days 52–53) and subsequently sacrificed (postnatal day 54) when their brain structures were removed for quantification of proinflammatory cytokines (TNF-α, interleukin 1β, and interleukin 6). Prenatal exposure to lipopolysaccharide significantly increased episodes of stereotyped movement (p=0.0001) and decreased parameters of social interaction in offspring, including sniffing, following, mounting, and allowing mounting (p=0.0043, p<0.0001, p=0.0009, and p=0.0200, respectively). Chronic p-cymene treatment was not significant for behavioral, memory, and biochemical tests. However, due to their pharmacokinetic characteristics, p-cymene nanomaterials’ formulation may be an exciting alternative to be tested for further results.

Reductionist thinking and animal models in neuropsychiatric research

2019 ◽  
Vol 42 ◽  
Author(s):  
Nicole M. Baran
Keyword(s):  
Animal Models ◽  
Mental Disorders ◽  
Environmental Factors ◽  
Neuropsychiatric Disorders ◽  
Model Organisms ◽  
Developmental Genetic ◽  
Term Study ◽  
Genetic And Environmental Factors ◽  
Mechanisms Of Plasticity

AbstractReductionist thinking in neuroscience is manifest in the widespread use of animal models of neuropsychiatric disorders. Broader investigations of diverse behaviors in non-model organisms and longer-term study of the mechanisms of plasticity will yield fundamental insights into the neurobiological, developmental, genetic, and environmental factors contributing to the “massively multifactorial system networks” which go awry in mental disorders.

Inflammational Animal Models for Schizophrenia

2015 ◽  
Vol 223 (3) ◽  
pp. 157-164 ◽  
Author(s):  
Georg Juckel
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Immune Activation ◽  
Microglial Activation ◽  
Treatment Options ◽  
Early Adulthood ◽  
Brain Regions ◽  
Synaptic Connections ◽  
Preventive Interventions ◽  
Immunological System

Abstract. Inflammational-immunological processes within the pathophysiology of schizophrenia seem to play an important role. Early signals of neurobiological changes in the embryonal phase of brain in later patients with schizophrenia might lead to activation of the immunological system, for example, of cytokines and microglial cells. Microglia then induces – via the neurotoxic activities of these cells as an overreaction – a rarification of synaptic connections in frontal and temporal brain regions, that is, reduction of the neuropil. Promising inflammational animal models for schizophrenia with high validity can be used today to mimic behavioral as well as neurobiological findings in patients, for example, the well-known neurochemical alterations of dopaminergic, glutamatergic, serotonergic, and other neurotransmitter systems. Also the microglial activation can be modeled well within one of this models, that is, the inflammational PolyI:C animal model of schizophrenia, showing a time peak in late adolescence/early adulthood. The exact mechanism, by which activated microglia cells then triggers further neurodegeneration, must now be investigated in broader detail. Thus, these animal models can be used to understand the pathophysiology of schizophrenia better especially concerning the interaction of immune activation, inflammation, and neurodegeneration. This could also lead to the development of anti-inflammational treatment options and of preventive interventions.

scholarly journals Differences in Cardiac Effects of Venoms from Tentacles and the Bell of Live Carukia barnesi: Using Non-Invasive Pulse Wave Doppler

Toxins ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 19
Author(s):  
Mark Little ◽  
Peter Pereira ◽  
Jamie Seymour
Keyword(s):  
Animal Models ◽  
Murine Model ◽  
Real World ◽  
Cardiac Dysfunction ◽  
Pulse Wave ◽  
Cardiac Effects ◽  
Post Exposure ◽  
Non Invasive ◽  
Cardiac Decompensation

Carukia barnesi was the first in an expanding list of cubozoan jellyfish whose sting was identified as causing Irukandji syndrome. Nematocysts present on both the bell and tentacles are known to produce localised stings, though their individual roles in Irukandji syndrome have remained speculative. This research examines differences through venom profiling and pulse wave Doppler in a murine model. The latter demonstrates marked measurable differences in cardiac parameters. The venom from tentacles (CBVt) resulted in cardiac decompensation and death in all mice at a mean of 40 min (95% CL: ± 11 min), whereas the venom from the bell (CBVb) did not produce any cardiac dysfunction nor death in mice at 60 min post-exposure. This difference is pronounced, and we propose that bell exposure is unlikely to be causative in severe Irukandji syndrome. To date, all previously published cubozoan venom research utilised parenterally administered venom in their animal models, with many acknowledging their questionable applicability to real-world envenomation. Our model used live cubozoans on anaesthetised mice to simulate normal envenomation mechanics and actual expressed venoms. Consequently, we provide validity to the parenteral methodology used by previous cubozoan venom research.

scholarly journals Preclinical Testing of Radiopharmaceuticals for the Detection and Characterization of Osteomyelitis: Experiences from a Porcine Model

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4221
Author(s):  
Aage Kristian Olsen Alstrup ◽  
Svend Borup Jensen ◽  
Ole Lerberg Nielsen ◽  
Lars Jødal ◽  
Pia Afzelius
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Porcine Model ◽  
Animal Experiments ◽  
Radioactive Tracers ◽  
The Individual ◽  
Selection Of

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.

Recent advances in animal model experimentation in autism research

2013 ◽  
Vol 26 (5) ◽  
pp. 264-271 ◽  
Author(s):  
Mousumi Tania ◽  
Md. Asaduzzaman Khan ◽  
Kun Xia
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Human Condition ◽  
Behavioral Alterations ◽  
Important Place ◽  
Adult Mice ◽  
Recent Advances ◽  
Model Study ◽  
Disease Biology ◽  
Animal Model Study

ObjectiveAutism, a lifelong neuro-developmental disorder is a uniquely human condition. Animal models are not the perfect tools for the full understanding of human development and behavior, but they can be an important place to start. This review focused on the recent updates of animal model research in autism.MethodsWe have reviewed the publications over the last three decades, which are related to animal model study in autism.ResultsAnimal models are important because they allow researchers to study the underlying neurobiology in a way that is not possible in humans. Improving the availability of better animal models will help the field to increase the development of medicines that can relieve disabling symptoms. Results from the therapeutic approaches are encouraging remarkably, since some behavioral alterations could be reversed even when treatment was performed on adult mice. Finding an animal model system with similar behavioral tendencies as humans is thus vital for understanding the brain mechanisms, supporting social motivation and attention, and the manner in which these mechanisms break down in autism. The ongoing studies should therefore increase the understanding of the biological alterations associated with autism as well as the development of knowledge-based treatments therapy for those struggling with autism.ConclusionIn this review, we have presented recent advances in research based on animal models of autism, raising hope for understanding the disease biology for potential therapeutic intervention to improve the quality of life of autism individuals.

scholarly journals Animal Models for Influenza Research: Strengths and Weaknesses

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1011
Author(s):  
Thi-Quyen Nguyen ◽  
Rare Rollon ◽  
Young-Ki Choi
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Research Question ◽  
Viral Pathogenesis ◽  
Influenza Viruses ◽  
High Morbidity ◽  
Host Immune Responses ◽  
Transmission Mechanisms ◽  
Significant Public Health ◽  
Seasonal Epidemics

Influenza remains one of the most significant public health threats due to its ability to cause high morbidity and mortality worldwide. Although understanding of influenza viruses has greatly increased in recent years, shortcomings remain. Additionally, the continuous mutation of influenza viruses through genetic reassortment and selection of variants that escape host immune responses can render current influenza vaccines ineffective at controlling seasonal epidemics and potential pandemics. Thus, there is a knowledge gap in the understanding of influenza viruses and a corresponding need to develop novel universal vaccines and therapeutic treatments. Investigation of viral pathogenesis, transmission mechanisms, and efficacy of influenza vaccine candidates requires animal models that can recapitulate the disease. Furthermore, the choice of animal model for each research question is crucial in order for researchers to acquire a better knowledge of influenza viruses. Herein, we reviewed the advantages and limitations of each animal model—including mice, ferrets, guinea pigs, swine, felines, canines, and non-human primates—for elucidating influenza viral pathogenesis and transmission and for evaluating therapeutic agents and vaccine efficacy.

scholarly journals Animal Models in Pharmacology: A Brief History Awarding the Nobel Prizes for Physiology or Medicine

Pharmacology ◽  
2021 ◽  
pp. 1-13
Author(s):  
Catarina V. Jota Baptista ◽  
Ana I. Faustino-Rocha ◽  
Paula A. Oliveira
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
20Th Century ◽  
Scientific Knowledge ◽  
Mode Of Action ◽  
Experimental Protocol ◽  
Domestic Species ◽  
Scientific Area ◽  
Different Types ◽  
Scientific Fields

<b><i>Background:</i></b> The Nobel Prize of Physiology or Medicine (NPPM) has recognized the work of 222 scientists from different nationalities, from 1901 until 2020. From the total, 186 award researchers used animal models in their projects, and 21 were attributed to scientists and projects directly related to Pharmacology. In the most recent years, genetics is a dominant scientific area, while at the beginning of the 20th century, most of the studies were more related to anatomy, cytology, and physiology. <b><i>Summary:</i></b> Mammalian models were used in 144 NPPM projects, being rodents the most used group of species. Moreover, 92 researchers included domestic species in their work. The criteria used to choose the species, the number of animals used and the experimental protocol is always debatable and dependent on the scientific area of the study; however, the 3R’s principle can be applied to most scientific fields. Independently of the species, the animal model can be classified in different types and criteria, depending on their ecology, genetics, and mode of action. <b><i>Key-Messages:</i></b> The use of animal models in NPPM awarded projects, namely in Pharmacology, illustrates their importance, need and benefit to improve scientific knowledge and create solutions. In the future, with the contribute of technology, it might be possible to refine the use of animal models in pharmacology studies.

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