scholarly journals Delayed Demyelination and Impaired Remyelination in Aged Mice in the Cuprizone Model

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 945 ◽  
Author(s):  
Stefan Gingele ◽  
Florian Henkel ◽  
Sandra Heckers ◽  
Thiemo M. Moellenkamp ◽  
Martin W. Hümmert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Animal Models ◽  
Corpus Callosum ◽  
Mature Adult ◽  
Aged Mice ◽  
Adult Mice ◽  
Regenerative Therapies ◽  
Young Mice

To unravel the failure of remyelination in multiple sclerosis (MS) and to test promising remyelinating treatments, suitable animal models like the well-established cuprizone model are required. However, this model is only standardized in young mice. This does not represent the typical age of MS patients. Furthermore, remyelination is very fast in young mice, hindering the examination of effects of remyelination-promoting agents. Thus, there is the need for a better animal model to study remyelination. We therefore aimed to establish the cuprizone model in aged mice. 6-month-old C57BL6 mice were fed with different concentrations of cuprizone (0.2–0.6%) for 5–6.5 weeks. De- and remyelination in the medial and lateral parts of the corpus callosum were analyzed by immunohistochemistry. Feeding aged mice 0.4% cuprizone for 6.5 weeks resulted in the best and most reliable administration scheme with virtually complete demyelination of the corpus callosum. This was accompanied by a strong accumulation of microglia and near absolute loss of mature oligodendrocytes. Subsequent remyelination was initially robust but remained incomplete. The remyelination process in mature adult mice better represents the age of MS patients and offers a better model for the examination of regenerative therapies.

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 Age-dependent cardiac function during experimental sepsis: effect of pharmacological activation of AMP-activated protein kinase by AICAR

2018 ◽  
Vol 315 (4) ◽  
pp. H826-H837 ◽  
Author(s):  
Yu Inata ◽  
Giovanna Piraino ◽  
Paul W. Hake ◽  
Michael O’Connor ◽  
Patrick Lahni ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Peroxisome Proliferator ◽  
Mature Adult ◽  
Adult Mice ◽  
Age Dependent ◽  
Cardioprotective Effects ◽  
Amp Activated Protein Kinase ◽  
Young Mice

Age represents a major risk factor for multiple organ failure, including cardiac dysfunction, in patients with sepsis. AMP-activated protein kinase (AMPK) is a crucial regulator of energy homeostasis that controls mitochondrial biogenesis by activation of peroxisome proliferator-activated receptor-γ coactivator-1α and disposal of defective organelles by autophagy. We investigated whether AMPK dysregulation contributes to age-dependent cardiac injury in young (2–3 mo) and mature adult (11–13 mo) male mice subjected to sepsis by cecal ligation and puncture and whether AMPK activation by 5-amino-4-imidazole carboxamide riboside affords cardioprotective effects. Plasma proinflammatory cytokines and myokine follistatin were similarly elevated in vehicle-treated young and mature adult mice at 18 h after sepsis. However, despite equivalent troponin I and T levels compared with similarly treated young mice, vehicle-treated mature adult mice exhibited more severe cardiac damage by light and electron microscopy analyses with more marked intercellular edema, inflammatory cell infiltration, and mitochondrial derangement. Echocardiography revealed that vehicle-treated young mice exhibited left ventricular dysfunction after sepsis, whereas mature adult mice exhibited a reduction in stroke volume without apparent changes in load-dependent indexes of cardiac function. At molecular analysis, phosphorylation of the catalytic subunits AMPK-α1/α2 was associated with nuclear translocation of peroxisome proliferator-activated receptor-γ coactivator-1α in vehicle-treated young but not mature adult mice. Treatment with 5-amino-4-imidazole carboxamide riboside ameliorated cardiac architecture derangement in mice of both ages. These cardioprotective effects were associated with attenuation of the systemic inflammatory response and amelioration of cardiac dysfunction in young mice only, not in mature adult animals. NEW & NOTEWORTHY Our data suggest that sepsis-induced cardiac dysfunction manifests with age-dependent characteristics, which are associated with a distinct regulation of AMP-activated protein kinase-dependent metabolic pathways. Consistent with this age-related deterioration, pharmacological activation of AMP-activated protein kinase may afford cardioprotective effects allowing a partial recovery of cardiac function in young but not mature age.

scholarly journals Age-dependent changes of p53 and p63 immunoreactivities in the mouse hippocampus

2019 ◽  
Vol 35 (1) ◽  
Author(s):  
Tae-Kyeong Lee ◽  
Young Eun Park ◽  
Cheol Woo Park ◽  
Bora Kim ◽  
Jae-Chul Lee ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Granule Cells ◽  
Normal Aging ◽  
Aged Mice ◽  
Adult Mice ◽  
Fluoro Jade B ◽  
Neuronal Distribution ◽  
P53 Immunoreactivity ◽  
Young Mice

Abstract P53 and its family member p63 play important roles in cellular senescence and organismal aging. In this study, p53 and p63 immunoreactivity were examined in the hippocampus of young, adult and aged mice by using immunohistochemistry. In addition, neuronal distribution and degeneration was examined by NeuN immunohistochemistry and fluoro-Jade B fluorescence staining. Strong p53 immunoreactivity was mainly expressed in pyramidal and granule cells of the hippocampus in young mice. p53 immunoreactivity in the pyramidal and granule cells was significantly reduced in the adult mice. In the aged mice, p53 immunoreactivity in the pyramidal and granule cells was more significantly decreased. p63 immunoreactivity was strong in the pyramidal and granule cells in the young mice. p63 immunoreactivity in these cells was apparently and gradually decreased with age, showing that p63 immunoreactivity in the aged granule cells was hardly shown. However, numbers of pyramidal neurons and granule cells were not significantly decreased in the aged mice with normal aging. Taken together, this study indicates that there are no degenerative neurons in the hippocampus during normal aging, showing that p53 and p63 immunoreactivity in hippocampal neurons was progressively reduced during normal aging, which might be closely related to the normal aging processes.

scholarly journals Enhanced inflammation in aged mice following infection with Streptococcus pneumoniae is associated with decreased IL-10 and augmented chemokine production

2015 ◽  
Vol 308 (6) ◽  
pp. L539-L549 ◽  
Author(s):  
Andrew E. Williams ◽  
Ricardo J. José ◽  
Jeremy S. Brown ◽  
Rachel C. Chambers
Keyword(s):  
Streptococcus Pneumoniae ◽  
Young Adult ◽  
Inflammatory Responses ◽  
Severe Pneumonia ◽  
Chemokine Production ◽  
Aged Mice ◽  
Adult Mice ◽  
The Impact ◽  
Bacterial Outgrowth ◽  
Young Mice

Streptococcus pneumoniae is the most common cause of severe pneumonia in the elderly. However, the impact of aging on the innate inflammatory response to pneumococci is poorly defined. We compared the innate immune response in old vs. young adult mice following infection with S. pneumoniae. The accumulation of neutrophils recovered from bronchoalveolar lavage fluid and lung homogenates was increased in aged compared with young adult mice, although bacterial outgrowth was similar in both age groups, as were markers of microvascular leak. Aged mice had similar levels of IL-1β, TNF, IFN-γ, IL-17, and granulocyte colony-stimulating factor following S. pneumoniae infection, compared with young mice, but increased levels of the chemokines CXCL9, CXCL12, CCL3, CCL4, CCL5, CCL11, and CCL17. Moreover, levels of IL-10 were significantly lower in aged animals. Neutralization of IL-10 in infected young mice was associated with increased neutrophil recruitment but no decrease in bacterial outgrowth. Furthermore, IL-10 neutralization resulted in increased levels of CCL3, CCL5, and CXCL10. We conclude that aging is associated with enhanced inflammatory responses following S. pneumoniae infection as a result of a compromised immunomodulatory cytokine response.

Interhemispheric transfer evaluation in multiple sclerosis 1The authors would like to thank Claude-Alain Hauert and Christoph Michel for their assistance in the evaluation of motor tapping and Michel Habib for his suggestions and comments. This work was supported by a grant from the Swiss Society of Multiple Sclerosis.

2000 ◽  
Vol 59 (3) ◽  
pp. 150-158 ◽  
Author(s):  
Nadia Ortiz ◽  
Michael Reicherts ◽  
Alan J. Pegna ◽  
Encarni Garran ◽  
Michel Chofflon ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Corpus Callosum ◽  
Lexical Decision ◽  
Dichotic Listening ◽  
Neurological Impairment ◽  
Interhemispheric Transfer ◽  
Decision Task ◽  
Swiss Society ◽  
Listening Test ◽  
Relapsing Remitting

Patients suffering from Multiple Sclerosis (MS) have frequently been found to suffer from damage to callosal fibers. Investigations have shown that this damage is associated with signs of hemisphere disconnections. The aim of our study was to provide evidence for the first signs of interhemispheric dysfunction in a mildly disabled MS population. Therefore, we explored whether the Interhemispheric Transfer (IT) deficit is multi-modal and sought to differentiate two MS evolution forms, on the basis of an interhemispheric disconnection index. Twenty-two patients with relapsing-remitting form of MS (RRMS) and 14 chronic-progressive (CPMS) were compared with matched controls on four tasks: a tachistoscopic verbal and non-verbal decision task, a dichotic listening test, cross tactile finger localization and motor tapping. No overall impairment was seen. The dichotic listening and lexical decision tasks were the most sensitive to MS. In addition, CPMS patients' IT was more impaired and was related to the severity of neurological impairment. The different sizes of the callosal fibers, which determine their vulnerability, may explain the heterogeneity of transfer through the Corpus Callosum. Therefore, evaluation of IT may be of value as an index of evolution in MS.

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.

The Voltage-Gated Sodium Channel Nav1.2 Contributes to Neurodegeneration in an Animal Model of Multiple Sclerosis

2016 ◽  
Vol 47 (S 01) ◽  
Author(s):  
W. Fazeli ◽  
B. Schattling ◽  
B. Engeland ◽  
M. Friese ◽  
D. Isbrand
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Sodium Channel ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated

Cell-based Tolerogenic Therapy, Experience from Animal Models of Multiple Sclerosis, Type 1 Diabetes and Rheumatoid Arthritis

2017 ◽  
Vol 23 (18) ◽  
Author(s):  
Ivana Stojanovic ◽  
Mirjana Dimitrijevic ◽  
Marta Vives-Pi ◽  
Maria Jose Mansilla ◽  
Irma Pujol-Autonell ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Multiple Sclerosis ◽  
Type 1 Diabetes ◽  
Animal Models

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.

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