scholarly journals Characterization of the Kynurenine Pathway and Quinolinic Acid Production in Macaque Macrophages

2013 ◽  
Vol 6 ◽  
pp. IJTR.S11789 ◽  
Author(s):  
Chai K. Lim ◽  
Margaret M.C. Yap ◽  
Stephen J. Kent ◽  
Gabriel Gras ◽  
Boubekeur Samah ◽  
...  

The kynurenine pathway (KP) and one of its end-products, the excitotoxin quinolinic acid (QUIN), are involved in the pathogenesis of several major neuroinflammatory brain diseases. A relevant animal model to study KP metabolism is now needed to assess whether intervention in this pathway may improve the outcome of such diseases. Humans and macaques share a very similar genetic makeup. In this study, we characterized the KP metabolism in macaque primary macrophages of three different species in comparison to human cells. We found that the KP profiles in simian macrophages were very similar to those in humans when challenged with inflammatory cytokines. Further, we found that macaque macrophages are capable of producing a pathophysiological concentration of QUIN. Our data validate the simian model as a relevant model to study the human cellular KP metabolism in the context of inflammation.

PLoS ONE ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. e0209964 ◽  
Author(s):  
Bianca de Moraes Fracasso ◽  
Juliana Oliveira Rangel ◽  
Alessandra Gonçalves Machado ◽  
Fernanda Severo Curuja ◽  
Amanda Lopes ◽  
...  

2021 ◽  
Author(s):  
Alesa Hughson Netzley ◽  
Ryan D Hunt ◽  
Josue Franco-Arellano ◽  
Nicole Arnold ◽  
Kirk A Munoz ◽  
...  

Brain injuries that are induced by external forces are particularly challenging to model experimentally. In recent decades, the domestic pig has been gaining popularity as a highly relevant animal model to address the pathophysiological mechanisms and the biomechanics associated with head injuries. Understanding cognitive, motor, and sensory aspects of pig behavior throughout development is crucial for evaluating cognitive and motor deficits after injury. We have developed a comprehensive battery of tests to characterize the behavior and physiological function of the Yucatan minipig throughout maturation. Behavioral testing included assessments of learning and memory, executive functions, circadian rhythms, gait analysis, and level of motor activity. We applied traditional behavioral apparatus and analysis methods, as well as state-of-the-art sensor technologies to report on motion and activity, and artificial intelligent approaches to analyze behavior. We studied pigs from 16 weeks old through sexual maturity at 35 weeks old. The results show multidimensional characterization of minipig behavior, and how it develops and changes with age. This animal model may capitulate the biomechanical consideration and phenotype of head injuries in the developing brain and can drive forward the field of understanding pathophysiological mechanisms and developing new therapies to accelerate recovery in children who have suffered head trauma.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alesa H. Netzley ◽  
Ryan D. Hunt ◽  
Josue Franco-Arellano ◽  
Nicole Arnold ◽  
Ana I. Vazquez ◽  
...  

AbstractBrain injuries induced by external forces are particularly challenging to model experimentally. In recent decades, the domestic pig has been gaining popularity as a highly relevant animal model to address the pathophysiological mechanisms and the biomechanics associated with head injuries. Understanding cognitive, motor, and sensory aspects of pig behavior throughout development is crucial for evaluating cognitive and motor deficits after injury. We have developed a comprehensive battery of tests to characterize the behavior and physiological function of the Yucatan minipig throughout maturation. Behavioral testing included assessments of learning and memory, executive functions, circadian rhythms, gait analysis, and level of motor activity. We applied traditional behavioral apparatus and analysis methods, as well as state-of-the-art sensor technologies to report on motion and activity, and artificial intelligent approaches to analyze behavior. We studied pigs from 16 weeks old through sexual maturity at 35 weeks old. The results show multidimensional characterization of minipig behavior, and how it develops and changes with age. This animal model may capitulate the biomechanical consideration and phenotype of head injuries in the developing brain and can drive forward the field of understanding pathophysiological mechanisms and developing new therapies to accelerate recovery in children who have suffered head trauma.


2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Bianca Fracasso ◽  
Juliana O Rangel ◽  
Virgílio Olsen ◽  
Amanda Phaelante ◽  
Fernanda Curuja ◽  
...  

Advanced glycation end products (AGE) are molecules produced by oxidative and inflammatory metabolism. Studies have shown that increased AGE levels worse the prognosis of the cardiovascular diseases. However, there is no characterization of AGE generation in a representative animal model of myocardial infarction (MI). Thus, our goal was to characterize the AGE formation in plasma and cardiac tissue in an animal model of MI. Male Wistar rats (3 month-old) were divided in 2 groups: Sham (n = 15) and MI (n = 14) and followed by 12 week. MI was induced by left anterior descending coronary artery (LAD) permanent ligation and the animals were stratified in 2 groups according to ejection fraction (EF) median at 2 days post-MI. MI induced 47% and 29% increase in heart weight/final body weight ratio in MIlowEF MIhighEF group, respectively. There was no significant difference among the groups in the plasma levels of reactive free amines, fluorescents AGE, Nε-(Carboxymethyl)lysine (CML) and Nε-(Carboxyethyl)lysine (CEL) in a 12-week follow-up. However, a significant decrease in the levels of yellowish-brown colored AGEs was revealed in MIlowEF group when compared to Sham. In the cardiac tissue homogenate there was no difference in the amounts of reactive free amines and carbonyl protein among the groups. Our results suggest that a widely employed animal model of MI partially agrees with the human manifestation of the ischemic heart disease concerning the AGEs metabolism. Thus, its use must be employed with caution when studying AGEs signaling or anti-AGE drugs.


Author(s):  
G. C. Smith ◽  
R. L. Heberling ◽  
S. S. Kalter

A number of viral agents are recognized as and suspected of causing the clinical condition “gastroenteritis.” In our attempts to establish an animal model for studies of this entity, we have been examining the nonhuman primate to ascertain what viruses may be found in the intestinal tract of “normal” animals as well as animals with diarrhea. Several virus types including coronavirus, adenovirus, herpesvirus, and picornavirus (Table I) were detected in our colony; however, rotavirus, astrovirus, and calicivirus have not yet been observed. Fecal specimens were prepared for electron microscopy by procedures reported previously.


2001 ◽  
Vol 268 (6) ◽  
pp. 1876-1887
Author(s):  
Markus Spaniol ◽  
Hilary Brooks ◽  
Lucas Auer ◽  
Arthur Zimmermann ◽  
Marc Solioz ◽  
...  

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.


2009 ◽  
Vol 191 (7) ◽  
pp. 2033-2041 ◽  
Author(s):  
Meriyem Aktas ◽  
Franz Narberhaus

ABSTRACT Agrobacterium tumefaciens requires phosphatidylcholine (PC) in its membranes for plant infection. The phospholipid N-methyltransferase PmtA catalyzes all three transmethylation reactions of phosphatidylethanolamine (PE) to PC via the intermediates monomethylphosphatidylethanolamine (MMPE) and dimethylphosphatidylethanolamine (DMPE). The enzyme uses S-adenosylmethionine (SAM) as the methyl donor, converting it to S-adenosylhomocysteine (SAH). Little is known about the activity of bacterial Pmt enzymes, since PC biosynthesis in prokaryotes is rare. In this article, we present the purification and in vitro characterization of A. tumefaciens PmtA, which is a monomeric protein. It binds to PE, the intermediates MMPE and DMPE, the end product PC, and phosphatidylglycerol (PG) and phosphatidylinositol. Binding of the phospholipid substrates precedes binding of SAM. We used a coupled in vitro assay system to demonstrate the enzymatic activity of PmtA and to show that PmtA is inhibited by the end products PC and SAH and the antibiotic sinefungin. The presence of PG stimulates PmtA activity. Our study provides insights into the catalysis and control of a bacterial phospholipid N-methyltransferase.


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