Growth data on Jersey crossbred calves, maintained at ICAR-National Dairy Research Institute, Eastern Regional Station, Kalyani, Nadia, West Bengal, India, were collected and analysed to assess the influence of maternal effects on growth traits of calves. Traits considered for this study were birth weight (BW) and weights at 3 months (W3M), 6 months (W6M), 9 months (W9M) and 12 months (W12M) of age. Least-squares analyses were employed to obtain the effects of non-genetic factors on the traits of interest. Determination of influence of maternal effects on growth traits was estimated by fitting three univariate animal models (including or excluding maternal effects) using Bayesian approach. The most appropriate model for each trait was selected based on Deviance Information Criterion. Direct heritability (h2) estimates for BW, W3M, W6M, W9M and W12M were 0.31 ± 0.08, 0.26 ± 0.10, 0.48 ± 0.10, 0.44 ± 0.11 and 0.39 ± 0.14, respectively, under the best model. Permanent environmental maternal effects (c2) varied from 0.04 to 0.12 for all traits. Existence of maternal effects for all ages reflects the importance of maternal components for these traits. Moderate to high heritability estimates for growth traits indicate the possibility of modest genetic progress for these traits through selection under prevalent management system.

This study investigates the genetic and phenotypic aspects of early growth performance in the Murciano-Granadina goat breed, using data collected between 2016 and 2022 from a private dairy farm in Ghale-Ganj city, located in the southern area of Kerman province, Iran. Pedigree and data information were collected on several early body weight traits, including birth weight (BW), weaning weight (WW), average daily gain (ADG), Kleiber ratio (KR) and growth efficiency from birth to weaning (GE). Nine univariate animal models included direct additive genetic effects and different combinations of maternal effects were compared by using Akaike information criterion (AIC). Among the tested models, the best genetic analysis model for BW, included direct additive, maternal additive, maternal permanent and maternal temporary environmental effects. The best model for ADG, KR and GE included direct additive, maternal permanent and litter effects. For WW, the best model was determined to be one that included direct additive and maternal additive genetic effects. The estimated direct heritabilities were low values of 0.04, 0.07, 0.08, 0.05 and 0.07 for BW, ADG, KR, GE and WW, respectively. The estimates of genetic correlations among the studied traits were positive and low to high in magnitude which ranged from 0.11 for BW-KR to 0.91 for BW-GE. The phenotypic correlations ranged from 0.03 for KR-WW to 0.87 for ADG-KR. The positive correlations observed among the studied growth traits of the Murciano-Granadina goat breed indicate no negative genetic or phenotypic changes associated with selection for these traits.

To study the influence of maternal stress on neonatal locomotor development, rat pups of mothers housed singly and in groups were treated orally with corticosterone from 2 to 15 days of age. Control animals received almond oil vehicle only. The rat pups were subjected to swim-tests from 8 to 20 days of age to evaluate locomotor development. Swim-test performance demonstrated a retardation of locomotor development in pups treated with corticosterone (P <0.05). Retardation was most marked in the pups from group-housed mothers and between 13 and 15 days of age. Comparing pups not treated with hormones, the pups born to group-housed mothers showed significantly (P <0.05) better performance on swim-testing. The weight gain of pups from group-housed mothers was significantly (P < 0.05) higher than that of pups from individually caged mothers. Corticosteroid treatment had no effect on weight gain.

Globally, an aging population is increasing, and aging is a natural physiological process and a major risk factor for all age-related diseases. It seriously threatens personal health and imposes a great economic burden. Therefore, there is a growing scientific interest in strategies for well-aging with prevention and treatment of age-related diseases. The seed, root, stem or leaves of Cassia tora Linn. are useful for anti-bacteria, anti-hyperlipidemia and anti-obesity due to its pharmacological activities such as anti-inflammation and anti-oxidant both in vitro and in vivo. Nevertheless, no clinical trials have been attempted so far, therefore here we would like to understand the current preclinical activities for aging-related disease models including cataract, metabolic dysfunction and neurodegeneration, then discuss their preparation for clinical trials and perspectives.

Adaptive responding to severe stress or trauma requires an optimized reconfiguration in the activity of large-scale neural networks. In vulnerable individuals, this response can go awry, inducing long-term consequences on mental health, such as posttraumatic stress disorder (PTSD). Improved understanding of the neurobiological mechanisms underlying this maladaptive neural response to trauma might benefit early intervention (i.e., secondary prevention) options in stress-related psychopathology. Yet, because of obvious ethical limitations these acute responses to trauma are inaccessible in humans. Therefore, we here used a mouse model for PTSD to investigate adaptive vs. maladaptive neural responding to trauma, the latter leading to long-term behavioral consequences mimicking symptoms observed in PTSD patients. By using transgenic mice, we were able to fluorescently label all activated neurons during trauma exposure, and relate these activation patterns to later PTSD-like symptomatology. We observed increased neuronal activity in sensory-processing and memory-related areas of mice vulnerable to the long-term consequences of trauma exposure, compared to resilient mice. Moreover, vulnerable mice displayed increased functional connectivity between the default mode network and lateral cortical network (a proxy for the central executive network in humans) during trauma processing relative to resilient mice. As such, these findings provide first insight in how a maladaptive neural response to trauma can result in later symptoms of psychopathology.

This article uses four historical case studies to address epistemological issues related to the animal model of human diseases and its use in medical research on human diseases. The knowledge derived from animal models is widely assumed to be highly valid and predictive of reactions by human organisms. In this contribution, I use three significant historical cases of failure (ca. 1890, 1960, 2006), and a closer look at the emergence of the concept around 1860/70, to elucidate core assumptions related to the specific practices of animal-human knowledge transfer, and to analyze the explanations provided by historical actors after each of the failures. Based on these examples, I argue that the epistemological status of the animal model changed from that of a helpful methodological tool for addressing specific questions, but with precarious validity, to an obligatory method for the production of strong knowledge on human diseases. As a result, there now exists a culture of biomedical research in human disease that, for more than a century, has taken the value of this methodological tool as self-evident, and more or less beyond question.

The parasite Fasciola hepatica is an important zoonotic parasite. The development of an animal model of F. hepatica's life cycle is critical for studying the biological characteristics of the parasite in snails and mammals. Eggs of F. hepatica of bovine origin were cultured, and metacercariae were obtained after infection of Galba pervia snails. The life cycle system of F. hepatica was initiated in 2 different animals by orally infecting rabbits, SD rats and Kunming mice with the metacercariae. The animals' survival after infection, parasite migration in the animals and pathological damage to the liver were observed. We discovered that rabbits died due to acute suppurative hepatitis 60–69 days after infection, and eggs were found in the feces on day 63 of infection. The liver of SD rats showed punctate lesions on day 3 of infection, and further changes occurred as the infection progressed. However, liver repair was observed at week 9. SD rats survived for more than a year after infection and continued the F. hepatica life cycle. The liver lesions in Kunming mice after infection were similar but more severe than those in SD rats. Death was observed on the 31st post-infection day. We discovered that while rabbits, SD rats and Kunming mice can all be used as animal models of F. hepatica, SD rats are more suitable experimental animals in terms of tolerance and pathological response.

The mdx mouse is an experimental model of Duchenne muscular dystrophy, a genetic disorder characterized by progressive muscular degeneration which affects the oral cavity musculature, and promotes difficulty in swallowing. This study aimed to describe morphological, structural, and ultrastructural changes in the tongue mucosa and musculature of mdx mice. Forty six-month-old mice were divided into two groups: Control C57bl/10 (n = 20) and mdx C57bl/10mdx (n = 20). The tongue was dissected and analyzed with light microscopy, scanning electron microscopy, and transmission electron microscopy techniques. Our results showed conical and triangular filiform, fungiform, foliate, and vallate papillae, and their connective tissue cores. The epithelium layers identified were corneum, granulosum, spinosum, and basale. The mdx group had a thicker epithelium. Lamina propria was composed of reddish and greenish collagen. In mdx, collagen was present in the musculature of the tongue's body and in the muscular tissue between mucous and serous glands of the caudal region. Musculature was also characterized by a shorter length of sarcoplasmic invaginations, myocytolysis in mitochondrial groupings, and inflammatory focus. In conclusion, the tongue of 6-month-old mdx mice had morphology, structure, and ultrastructure revealed, showing higher wear of filiform papillae indirect reflex from the muscular degeneration process.

The objective of the current study was to estimate the genetic parameters for ewe productivity traits of Harnali sheep by examining non-genetic effects. The data records of 440 animals born to 85 sires and 259 dams were collected with respect to various traits such as litter size at birth (LSB), litter weight at birth (LWB), litter size at weaning (LSW), litter weight at weaning (LWW) and age at first lambing (AFL) for the period of 2001 to 2020. Genetic parameters were estimated by fitting a series of animal models using an average information restricted maximum likelihood (REML) algorithm in WOMBAT software. Least-squares analysis revealed significant (P < 0.05) influences of period of lambing, age and weight of ewe at lambing on the studied traits. These results indicated that heavier ewes had significantly higher (P < 0.05) values of litter weight traits than their counterparts. On the basis of likelihood ratio test, the estimates of direct heritability under best model for AFL, LSB, LWB, LSW and LWW were 0.06, 0.18, 0.09, 0.07 and 0.16, respectively. Maternal permanent environment effect made a significant contribution to the LSB trait (0.20). The genetic correlation between litter size and LWW was negative, while the remaining correlations were positive. The present results suggest that selection based on ewe productivity traits will result in low genetic progress and therefore the management role is more important for better gains.

Niacin deficiency causes pellagra, the symptoms of which include dermatitis, diarrhoea and dementia. Investigating the mechanism underlying these phenotypes has been challenging due to the lack of an appropriate animal model. Here, we report a mouse model of pellagra-related nausea induced by feeding mice a low-niacin diet and administering isoniazid (INH), which is thought to induce pellagra. Mice fed a normal or low-niacin diet received INH (0·3 or 1·0 mg/mg per animal, twice daily, 5 d), and nausea was evaluated based on pica behaviour, which considered the rodent equivalent of the emetic reflex. Furthermore, the effect of therapeutic niacin administration on nausea was evaluated in this model. Urinary and hepatic metabolite levels were analysed by LC coupled with MS. INH-induced pica was observed in mice fed a low-niacin diet but not in those fed a normal diet. Levels of urinary metabolites, such as 1-methyl-2-pyridone-5-carboxamide, kynurenic acid and xanthurenic acid, were significantly reduced in the mice treated with INH compared with those that did not receive INH. Furthermore, niacin supplementation prevented pica and restored the levels of some metabolites in this mouse model. Our findings suggest that INH-related nausea is pellagra-like. We also believe that our newly established method for quantifying pica is a useful tool for investigating the mechanisms of pellagra-related nausea.

Trichuriasis known as whipworm infection caused by Trichuris trichiura, is a highly prevalent soil-transmitted helminthiasis in low- and middle-income countries located in tropical and subtropical areas and affecting approximately 360 million people. Children typically harbour the largest burden of T. trichiura and they are usually co-infected with other soil-transmitted helminth (STH), including Ascaris lumbricoides and hookworm. The consequences of trichuriasis, such as malnutrition and physical and cognitive growth restriction, lead to a massive health burden in endemic regions. Despite the implementation of mass drug administration of anthelminthic treatment to school-age children, T. trichiura infection remains challenging to control due to the low efficacy of current drugs as well as high rates of post-treatment re-infection. Thus, the development of a vaccine that would induce protective immunity and reduce infection rate or community faecal egg output is essential. Hurdles for human whipworm vaccine development include the lack of suitable vaccine antigen targets and animal models for human T. trichiura infection. Instead, rodent whipworm T. muris infected mouse models serve as a major surrogate for testing immunogenicity and efficacy of vaccine candidates. In this review, we summarize recent advances in animal models for T. trichiura antigen discovery and testing of vaccine candidates, while providing an overall view of the current status of T. trichiura vaccine development.

Neuropsychiatric disorders are major causes of the global burden of diseases, frequently co-occurring with multiple co-morbidities, especially obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease and its various risk factors in the metabolic syndrome. While the determining factors of neuropsychiatric disorders are complex, recent studies have shown that there is a strong link between diet, metabolic state and neuropsychiatric disorders, including anxiety and depression. There is no doubt that rodent models are of great value for preclinical research. Therefore, this article focuses on a rodent model of chronic consumption of high-fat diet (HFD), and/or the addition of a certain amount of cholesterol or sugar, meanwhile, summarising the pattern of diet that induces anxiety/depressive-like behaviour and the underlying mechanism. We highlight how dietary and metabolic risk influence neuropsychiatric behaviour in animals. Changes in dietary patterns, especially HFD, can induce anxiety- or depression-like behaviours, which may vary by diet exposure period, sex, age, species and genetic background of the animals used. Furthermore, dietary patterns significantly aggravate anxiety/depression-like behaviour in animal models of neuropsychiatric disorders. The mechanisms by which diet induces anxiety/depressive-like behaviour may involve neuroinflammation, neurotransmitters/neuromodulators, neurotrophins and the gut–brain axis. Future research should be focused on elucidating the mechanism and identifying the contribution of diet and diet-induced metabolic risk to neuropsychiatric disorders, which can form the basis for future clinical dietary intervention strategies for neuropsychiatric disorders.

It has been shown these last years that optogenetic tool, that uses a combination of optics and genetics technics to control neuronal activity with light on behaving animals, allows to establish causal relationship between brain activity and normal or pathological behaviors [3]. In combination with animal model of neuropsychiatric disorder, optogenetic could help to identify deficient circuitry in numerous pathologies by exploring functional connectivity, with a specificity never reached before, while observing behavioral and/or physiological correlates. To illustrate the promising potential of these tools for the understanding of psychiatric diseases, we will present our recent study where we used optogenetic to block abnormal repetitive behavior in a mutant mouse model of obsessive-compulsive disorder [1]. Using a delay-conditioning task we showed that these mutant mouse model had a deficit in response inhibition that lead to repetitive behaviour. With optogenetic, we could stimulate a specific circuitry in the brain that connect the orbitofrontal cortex with the basal ganglia; a circuitry that has been shown to be dysfunctional in compulsive behaviors. We observed that these optogenetic stimulations, through their effect on inhibitory neurons of the basal ganglia, could restore the behavioral response inhibition and alleviate the compulsive behavior. These findings raise promising potential for the design of targeted deep brain stimulation therapy for disorders involving excessive repetitive behavior and/or for the optimization of already existing stimulation protocol [2].

According to human observations of a syndrome of physical activity dependence and its consequences, we tried to examine if running activity in a free activity paradigm, where rats had a free access to activity wheel, may present a valuable animal model for physical activity dependence and most generally to behavioral dependence. The pertinence of reactivity to novelty, a well-known pharmacological dependence predictor was also tested. Given the close linkage observed in human between physical activity and drugs use and abuse, the influence of free activity in activity wheels on reactivity to amphetamine injection and reactivity to novelty were also assessed. It appeared that (1) free access to wheel may be used as a valuable model for physical activity addiction, (2) two populations differing in activity amount also differed in dependence to wheel-running. (3) Reactivity to novelty did not appeared as a predictive factor for physical activity dependence (4) activity modified novelty reactivity and (5) subjects who exhibited a high appetence to wheel-running, presented a strong reactivity to amphetamine. These results propose a model of dependency on physical activity without any pharmacological intervention, and demonstrate the existence of individual differences in the development of this addiction. In addition, these data highlight the development of a likely vulnerability to pharmacological addiction after intense and sustained physical activity, as also described in man. This model could therefore prove pertinent for studying behavioral dependencies and the underlying neurobiological mechanisms. These results may influence the way psychiatrists view behavioral dependencies and phenomena such as doping in sport or addiction to sport itself.

Animal models are often used for preclinical research on the neurobiology of psychiatric disorders. Whereas many are employed to screen new therapeutic agents, few of them are used to study the genetic bases of psychiatric diseases, probably because of the complex genetic determinism underlying quantitative behavioral traits such as mood, personality or intelligence. The present article presents a short review introducing an analysis model using mi the marker strains model. Using this model it is possible both to display genetic determinism data and to locate some of the chromosomal fragments involved in the regulation of anxiogenic processes. At present it cannot accurately determine the position of one or more genes, but it does provide a valuable means of ‘scanning’ the genome for an approximation. Through genetic analysis, using the model, an attempt will be made to identify autosomal fragments which may be involved in two behavioural traits: anxiety and chemical-induced seizures. In this paper, after reviewing theoretical aspects of looking for genes involved in behaviour, we will successively introduce studies in genetic topics in psychiatric human studies as well as appropriated behavioural animal studies. Then we will present a genetic model in mice which allows us to locate chromosomal fragments associated with a behavioural trait: multiple marker strains.

Essential tremor (ET) is a neurological movement disorder characterised by bilateral limb kinetic/postural tremor, with or without tremor in other body parts including head, voice and lower limbs. Since no causative genes for ET have been identified, it is likely that the disorder occurs as a result of complex genetic factors interacting with various cellular and environmental factors that can result in abnormal function of circuitry involving the cerebello–thalamo–cortical pathway. Genetic analyses have uncovered at least 14 loci and 11 genes that are related to ET, as well as various risk or protective genetic factors. Limitations in ET genetic analyses include inconsistent disease definition, small sample size, varied ethnic backgrounds and many other factors that may contribute to paucity of relevant genetic data in ET. Genetic analyses, coupled with functional and animal studies, have led to better insights into possible pathogenic mechanisms underlying ET. These genetic studies may guide the future development of genetic testing and counselling, and specific, pathogenesis-targeted, therapeutic strategies.

Background: Post-stroke depression (PSD) is the most frequent psychiatric complication following ischemic stroke. It affects up to 60% of all patients and is associated with increased morbidity and mortality following ischemic stroke. The pathophysiology of PSD remains elusive and appears to be multifactorial, rather than “purely” biological or psychosocial in origin. Thus, valid animal models of PSD would contribute to the study of the etiology (and treatment) of this disorder. Methods: The present study depicts a rat model for PSD, using middle cerebral artery occlusion (MCAO). The two-way shuttle avoidance task, Porsolt forced-swim test, and sucrose preference test were employed to assess any depression-like behavior. Localized brain expressions of brain-derived neurotrophic factor (BDNF) protein levels were evaluated to examine the possible involvement of the brain neuronal plasticity in the observed behavioral syndrome. The raw data were subjected to unsupervised fuzzy clustering (UFC) algorithms to assess the sensitivity of bio-behavioral measures indicative of depressive symptoms post MCAO. Results: About 56% of the rats developed significant depressive-like behavioral disruptions as a result of MCAO compared with 4% in the sham-operated control rats. A pattern of a depressive-like behavioral response was common to all affected MCAO animals, characterized by significantly more escape failures and reduced number of total avoidance shuttles, a significant elevation in immobility duration, and reduced sucrose preference. Significant downregulations of BDNF protein levels in the hippocampal sub-regions, frontal cortex, and hypothalamus were observed in all affected MCAO animals. Conclusion: The UFC analysis supports the behavioral analysis and thus, lends validity to our results.

Suppose that a colleague proposed a fantastic experiment: to introduce human stem cells into a neonatal mouse so that its entire brain developed into “human-like” neuronal structures. The colleague claimed it would still be a mouse, and that its chimeric brain would be nothing like a “human” one. It would not, as a result, have a moral status beyond its nonhuman animal origins. Thus, the “human neuron mouse” would allow scientists to tinker with human-like neurology in ways that would be precluded if it were a human being, and that would promise to lead to substantial understanding of the destructive and incurable brain diseases that befall humanity. The colleague does admit, however, that for reasons of comparative fidelity, experiments in human patients would be scientifically preferable, although in this case, neither ethically justified nor legally permitted. For that reason, it might be desirable to create a human brain in a nonhuman primate, where it would be more likely that significant human-like neuronal development would occur, but still could not become a person. This article explores the significance of a “human neuron chimpanzee,” and suggests that contradictions in the design of the experiment make it unethical to proceed in either murine or primate models.