scholarly journals Cuprizone feed formulation influences the extent of demyelinating disease pathology

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lillian M. Toomey ◽  
Melissa Papini ◽  
Brittney Lins ◽  
Alexander J. Wright ◽  
Andrew Warnock ◽  
...  

AbstractCuprizone is a copper-chelating agent that induces pathology similar to that within some multiple sclerosis (MS) lesions. The reliability and reproducibility of cuprizone for inducing demyelinating disease pathology depends on the animals ingesting consistent doses of cuprizone. Cuprizone-containing pelleted feed is a convenient way of delivering cuprizone, but the efficacy of these pellets at inducing demyelination has been questioned. This study compared the degree of demyelinating disease pathology between mice fed cuprizone delivered in pellets to mice fed a powdered cuprizone formulation at an early 3 week demyelinating timepoint. Within rostral corpus callosum, cuprizone pellets were more effective than cuprizone powder at increasing astrogliosis, microglial activation, DNA damage, and decreasing the density of mature oligodendrocytes. However, cuprizone powder demonstrated greater protein nitration relative to controls. Furthermore, mice fed control powder had significantly fewer mature oligodendrocytes than those fed control pellets. In caudal corpus callosum, cuprizone pellets performed better than cuprizone powder relative to controls at increasing astrogliosis, microglial activation, protein nitration, DNA damage, tissue swelling, and reducing the density of mature oligodendrocytes. Importantly, only cuprizone pellets induced detectable demyelination compared to controls. The two feeds had similar effects on oligodendrocyte precursor cell (OPC) dynamics. Taken together, these data suggest that demyelinating disease pathology is modelled more effectively with cuprizone pellets than powder at 3 weeks. Combined with the added convenience, cuprizone pellets are a suitable choice for inducing early demyelinating disease pathology.

2021 ◽  
pp. 202-203
Author(s):  
Andrew McKeon

A 65-year-old woman sought care for a 6-month history of confusion and emotional disturbance that was initially ascribed to stress. She then had development of headaches over several weeks, which prompted brain magnetic resonance imaging with contrast. Imaging showed a mass emanating bilaterally from the splenium of the corpus callosum with heterogeneous T1 postgadolinium enhancement. Neurologic examination indicated left homonymous hemianopia, but she was otherwise normal. She had neither alexia nor other language deficit that may appear with a splenial corpus callosum lesion. A biopsy of the brain mass was performed. Histologic analysis of the biopsy specimen revealed glioblastoma multiforme. Corticosteroid treatment was prescribed, which relieved her headache. Radiation therapy and chemotherapy (temozolomide) were recommended. No further follow-up information was available. In neurologic clinical practice, a large corpus callosum–based lesion is sometimes encountered. The localization of such lesions is not specific for any one diagnosis, but radiologic characteristics can aid clinical decision making. Although the radiologic appearance of a lesion spreading out into both hemispheres from the corpus callosum can indicate butterfly glioma, the differential diagnosis also includes tumefactive demyelinating disease and lymphoma, which can also have a callosal localization and produce mass effect.


Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 903 ◽  
Author(s):  
Jiajia Wang ◽  
Xiaoxiao Wang ◽  
Yufeng He ◽  
Lijie Jia ◽  
Chung S. Yang ◽  
...  

Melatonin is a well-documented antioxidant. Physicochemical analysis using the density functional theory suggests that melatonin is a copper chelating agent; however, experimental evidence is still in demand. The present study investigated the influence of melatonin on reactive oxygen species (ROS) generated from polyphenol autoxidation in the presence of copper. Surprisingly, we found that melatonin paradoxically enhanced ROS formation in a redox system containing low concentrations of copper and quercetin (Que) or (−)-epigallocatechin-3-gallate (EGCG), due to reduction of cupric to cuprous ion by melatonin. Addition of DNA to this system inhibited ROS production, because DNA bound to copper and inhibited copper reduction by melatonin. When melatonin was added to a system containing high concentrations of copper and Que or EGCG, it diminished hydroxyl radical formation as expected. Upon addition of DNA to high concentrations of copper and Que, this pro-oxidative system generated ROS and caused DNA damage. The DNA damage was not prevented by typical scavengers of hydroxyl radical DMSO or mannitol. Under these conditions, melatonin or bathocuproine disulfonate (a copper chelator) protected the DNA from damage by chelating copper. When melatonin was administered intraperitoneally to mice, it inhibited hepatotoxicity and DNA damage evoked by EGCG plus diethyldithiocarbamate (a copper ionophore). Overall, the present study demonstrates the pro-oxidant and antioxidant activities of melatonin in the redox system of copper and polyphenols. The pro-oxidant effect is inhibited by the presence of DNA, which prevents copper reduction by melatonin. Interestingly, in-vivo melatonin protects against copper/polyphenol-induced DNA damage probably via acting as a copper-chelating agent rather than a hydroxyl radical scavenger. Melatonin with a dual function of scavenging hydroxyl radical and chelating copper is a more reliable DNA guardian than antioxidants that only have a single function of scavenging hydroxyl radical.


PLoS Biology ◽  
2017 ◽  
Vol 15 (8) ◽  
pp. e2001993 ◽  
Author(s):  
Balint Nagy ◽  
Anahit Hovhannisyan ◽  
Ruxandra Barzan ◽  
Ting-Jiun Chen ◽  
Maria Kukley

2021 ◽  
Author(s):  
Haipeng Zhou ◽  
Siliang Lu ◽  
Ke Li ◽  
Yinxiang Yang ◽  
Caiyan Hu ◽  
...  

Abstract Oligodendrocyte precursor cells (OPCs), which can differentiate into myelinating oligodendrocytes during embryonic development, are an important potential source for myelin repair or regeneration. To date, OPCs from human sources (hOPCs) remain limited. In this study, we aimed to evaluate the safety and remyelination capacity of hOPCs developed in our laboratory by transplanting them into the lateral ventricles of Sprague–Dawley rats of different ages. The toxicity, biodistribution, and tumor formation abilities of the injected hOPCs were examined by evaluating rats’ vital signs, developmental indicators, neural reflexes, along with hematological, immunological, and pathological assessments. In addition, the hOPCs were transplanted into the corpus callosum of shiverer mice to verify cell myelination efficacy. Overall, our results showed that transplanted hOPCs into young mice showed no toxicity against their organ function or immune system, engrafted only in the brain, and caused no tissue proliferation or tumor formation. In terms of efficacy, the transplanted hOPCs formed myelin in the corpus callosum, alleviated the trembling phenotype of shiverer mice, and promoted normal development. The transplantation of hOPCs is safe and can effectively form myelin in the brain, thereby providing a theoretical basis for the future clinical transplantation of hOPCs.


2019 ◽  
Vol 7 (1) ◽  
pp. 6
Author(s):  
Ivon Dewi Setianingrum ◽  
Ketut Suardita ◽  
Ari Subiyanto ◽  
Dian Agustin Wahjuningrum

Background: Cleanliness of cavity is considered important for a restoration. Smear layer formed after cavity preparation should be removed in order not to disrupt the bond adhesion between restorative materials and dental cavities. Saponins contained in mangosteen pericarp (Garcinia mangostana L.) have surfactant properties that can eliminate the smear layer assessed. 6% citric acid is a chelating agent which can eliminate the inorganic particles of the smear layer. Until now, the research on the differences of 0,78% saponin from mangosteen pericarp extract and 6% citric acid for cleanliness of cavity has never been done. Purpose: To see the differences between 0,78% saponin from mangosteen pericarp extract and 6% citric acid as cavity cleanser. Method: Eighteen human teeth with complete crown, no caries,  and no fractures were randomized in 3 groups (n≥6), in this experiment use (n=6). The cavity was prepared using wheels bur for hand use instrument. After instrumentation, each cavity on the first group used  0,78% saponin from mangosteen pericarp extract as cavity cleanser, the second group used 6% citric acid as cavity cleanser, and the control group used aquadest. Then, the teeth were split to be observed on Scanning Electron Microscope (SEM). Result: For Mann- Whitney test there were significant differences just between 078% saponin from mangosteen pericarp extract with 6% citric acid, and 6% citric acid with aquadest, but not for 0,78% saponin from mangosteen pericarp extract with aquadest. Median value of 6% citric acid showed 2,000 which is the smallest value compared to the value of the other groups. Conclusion: The cleanliness of cavity with 6% citric acid is better than that with 0,78%  saponin from mangosteen pericarp extract. 


2018 ◽  
Vol 40 (1) ◽  
pp. 54-63 ◽  
Author(s):  
Masae Naruse ◽  
Koji Shibasaki ◽  
Hiroya Shimauchi-Ohtaki ◽  
Yasuki Ishizaki

Neuroblasts derived from neural stem cells (NSCs) in the subventricular zone (SVZ) migrate along the rostral migratory stream into the olfactory bulb to generate interneurons under normal physiological conditions. When demyelination occurs, NSCs or neural progenitor cells (NPCs) in the SVZ provide newly formed oligodendrocytes to demyelinated lesions. The plasticity of NSC/NPC lineages may tend to oligodendrogenesis under the influence of demyelinated lesions. The mechanisms, however, still remain unknown. This study revealed that focal demyelination in the corpus callosum caused activation of the microglia, not only at the site of demyelination but also in the SVZ, and dramatically increased the generation of oligodendrocyte progenitor cells (OPCs) in the SVZ. Furthermore, the inhibition of microglial activation by minocycline treatment decreased OPC generation in the SVZ, suggesting that microglial activation in the SVZ, induced by the focal demyelination in the corpus callosum, regulates NSC/NPC lineage plasticity in situ. In contrast to the findings regarding demyelination in the corpus callosum, inducing focal demyelination in the internal capsule did not induce either microglial activation or OPC generation in the SVZ. These results suggest that the mechanism of OPC generation in the SVZ after inducing demyelinating lesions could be different across the demyelinated regions.


Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 552 ◽  
Author(s):  
Zihao Yuan ◽  
Peipei Chen ◽  
Tingting Zhang ◽  
Bin Shen ◽  
Ling Chen

Williams-Beuren syndrome (WBS) is caused by microdeletions of 28 genes and is characterized by cognitive disorder and hypotrophic corpus callosum (CC). Nsun5 gene, which encodes cytosine-5 RNA methyltransferase, is located in the deletion loci of WBS. We have reported that single-gene knockout of Nsun5 (Nsun5-KO) in mice impairs spatial cognition. Herein, we report that postnatal day (PND) 60 Nsun5-KO mice showed the volumetric reduction of CC with a decline in the number of myelinated axons and loose myelin sheath. Nsun5 was highly expressed in callosal oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs) from PND7 to PND28. The numbers of OPCs and OLs in CC of PND7-28 Nsun5-KO mice were significantly reduced compared to wild-type littermates. Immunohistochemistry and Western blot analyses of myelin basic protein (MBP) showed the hypomyelination in the CC of PND28 Nsun5-KO mice. The Nsun5 deletion suppressed the proliferation of OPCs but did not affect transition of radial glial cells into OPCs or cell cycle exit of OPCs. The protein levels, rather than transcriptional levels, of CDK1, CDK2 and Cdc42 in the CC of PND7 and PND14 Nsun5-KO mice were reduced. These findings point to the involvement of Nsun5 deletion in agenesis of CC observed in WBS.


1994 ◽  
Vol 77 (6) ◽  
pp. 1347-1352
Author(s):  
Ellen Jan De Vries ◽  
Richard C Bas ◽  
Henny Kuil

Abstract A specific liquid chromatographic method was developed for determination of nifursol in premixes and turkey feeds. Nifursol is extracted from test sample into tetrahydrofuran. Butylhydroxytoluene is added to prevent degradation of nifursol. The extract is diluted with tetrahydrofuran–water (50 + 50, v/v); an aliquot is injected onto a Zorbax ODS column. The mobile phase is water-acetonitrile (525 + 475, v/v) adjusted to an apparent pH of 3.5 with formic acid and ammonia. The wavelength of detection is 380 nm. The system can separate nifursol from dimetridazole and ronidazole. The method is specific; has linearity of more than one order of magnitude; and has a limit of quantitation in the 1–2 ppm range. Recovery averaged 98% or more, and the reproducibility had a coefficient of variation of better than 2.5% in pelleted feed.


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