Presence of an acute phase response in sheep with clinical classical scrapie

Meling, Siv; Bårdsen, Kjetil; Ulvund, Martha J.

doi:10.1186/1746-6148-8-113

Cited by 23 publications

(24 citation statements)

References 49 publications

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“…pSTAT3 and NF-B have been shown to affect transcription at the promoters controlling many of the genes described (i.e., Cxcl10, Ccl4, and A2m) (72)(73)(74)(75)(76), and together they also strongly influence the expression of acute-phase proteins, such as haptoglobin, ceruloplasmin, ␣ 1 -antichymotrypsin, and serum amyloid A (75,77), which are increased in the serum and brain during scrapie infection (unpublished data) (41,78,79). Moreover, components of the NF-B complex, like RelA, can interact directly with STAT3 to alter transcriptional activity (80)(81)(82).…”

Section: Discussionmentioning

confidence: 97%

Prion Infection of Mouse Brain Reveals Multiple New Upregulated Genes Involved in Neuroinflammation or Signal Transduction

Carroll

Striebel

Race

et al. 2015

J Virol

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Gliosis is often a preclinical pathological finding in neurodegenerative diseases, including prion diseases, but the mechanisms facilitating gliosis and neuronal damage in these diseases are not understood. To expand our knowledge of the neuroinflammatory response in prion diseases, we assessed the expression of key genes and proteins involved in the inflammatory response and signal transduction in mouse brain at various times after scrapie infection. In brains of scrapie-infected mice at pre-and postclinical stages, we identified 15 previously unreported differentially expressed genes related to inflammation or activation of the STAT signal transduction pathway. Levels for the majority of differentially expressed genes increased with time postinfection. In quantitative immunoblotting experiments of STAT proteins, STAT1␣, phosphorylated-STAT1␣ (pSTAT1␣), and pSTAT3 were increased between 94 and 131 days postinfection (p.i.) in brains of mice infected with strain 22L. Furthermore, a select group of STAT-associated genes was increased preclinically during scrapie infection, suggesting early activation of the STAT signal transduction pathway. Comparison of inflammatory markers between mice infected with scrapie strains 22L and RML indicated that the inflammatory responses and gene expression profiles in the brains were strikingly similar, even though these scrapie strains infect different brain regions. The endogenous interleukin-1 receptor antagonist (IL-1Ra), an inflammatory marker, was newly identified as increasing preclinically in our model and therefore might influence scrapie pathogenesis in vivo. However, in IL1Ra-deficient or overexpressor transgenic mice inoculated with scrapie, neither loss nor overexpression of IL-1Ra demonstrated any observable effect on gliosis, protease-resistant prion protein (PrPres) formation, disease tempo, pathology, or expression of the inflammatory genes analyzed. IMPORTANCEPrion infection leads to PrPres deposition, gliosis, and neuroinflammation in the central nervous system before signs of clinical illness. Using a scrapie mouse model of prion disease to assess various time points postinoculation, we identified 15 unreported genes that were increased in the brains of scrapie-infected mice and were associated with inflammation and/or JAK-STAT activation. Comparison of mice infected with two scrapie strains (22L and RML), which have dissimilar neuropathologies, indicated that the inflammatory responses and gene expression profiles in the brains were similar. Genes that increased prior to clinical signs might be involved in controlling scrapie infection or in facilitating damage to host tissues. We tested the possible role of the endogenous IL-1Ra, which was increased at 70 days p.i. In scrapie-infected mice deficient in or overexpressing IL-1Ra, there was no observable effect on gliosis, PrPres formation, disease tempo, pathology, or expression of inflammatory genes analyzed. P rion diseases are infectious progressive neurodegenerative disorders that can affect both h...

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Section: Discussionmentioning

confidence: 97%

Prion Infection of Mouse Brain Reveals Multiple New Upregulated Genes Involved in Neuroinflammation or Signal Transduction

Carroll

Striebel

Race

et al. 2015

J Virol

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“…Reference values of serum haptoglobin (Hp) and serum amyloid A (SAA) have been determined for pigs, horses, ponies, camels, cows and goats. However, only a few studies have analysed the APPs in sheep (Arslan, Cenesiz, Nisbet, & Yazici, ; Dow, Rogers‐Niemana, Holáskováa, Elsasserb, & Daileya, ; Melling, Bårdsen, & Ulvund, ; Miglio et al, , ; Peetsalu, Tummeleht, Kuks, & Orro, ; Yang et al, ). The APPs have been estimated in neonatal lambs (Peetsalu et al, ), during the pregnancy of ewes, but only in the first six weeks of pregnancy (Dow et al, ), in the period from 60 to 140 days of pregnancy and postpartum, and during the three‐month period of lactation (Miglio et al, ) therefore, they have not been determined strictly in the periparturient period.…”

Section: Introductionmentioning

confidence: 99%

Acute‐phase proteins, cortisol and haematological parameters in ewes during the periparturient period

Greguła-Kania

Kosior-Korzecka

Patkowski

et al. 2020

Reprod Domestic Animals

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Numerous subclinical diseases in sheep occur in the periparturient period and involve inflammatory processes; therefore, determining markers, such as acute‐phase proteins (APPs), can allow an early diagnosis. Therefore, the objective of the present study was to assess changes in the plasma concentration of APPs and cortisol in clinically healthy ewes in the periparturient period for use in future studies. At the same time, haematological parameters were monitored. We showed that plasma APPs and cortisol concentrations were significantly higher in pregnant ewes than before insemination. A gradual increase in the SAA concentration was observed from the 14th day before to the day of parturition, while Hp was reduced from 2 weeks before up to 2 weeks after delivery. A significant increase in the Fb concentration was detected from the 14th day before to the 1st week after delivery. The cortisol concentration did not undergo significant changes in the periparturient period. We found an increase in the SAA and Fb concentrations and decrease in Hp in the periparturient period. The direction of the change in APPs of healthy ewes in the current study may be related to their distinct regulatory mechanisms during pregnancy. The APPs are usually altered during infection, inflammation, neoplasia, stress and trauma; therefore, knowing their reference values could help lead to an early diagnosis of subclinical forms of some diseases and pregnancy complications in ewes. The haematological analysis showed that ewes in late pregnancy and postpartum compared to dry period were under metabolic stress related to pregnancy and lactation.

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“…As this was the first study in a mouflon herd, no suitable studies were found for relevant comparison. Based on the results obtained from the research of Hp in small ruminants (Kostro et al 2009;Meling et al 2012), we can deliberate that Hp could be the APP that best reflects pathological states; however, in order to obtain more complete and valuable information it is advisable to perform APP profiles including another APP, such as SAA or AGP.…”

Section: Discussionmentioning

confidence: 99%

Serum concentration of haptoglobin in European mouflon (Ovis musimon L.) from a game reserve

et al. 2015

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Acute phase proteins are used as markers of inflammation and sub-clinical disease, and are considered potential biomarkers for animal health and welfare. The objective of this study was to analyse haptoglobin as the main positive acute phase protein in the mouflon. A total of 30 clinically healthy mouflon of different age and sex, reared in a game reserve, were used for this study. Haptoglobin was determined in blood serum by colorimetric assay with a commercially accessible kit. The mean value of haptoglobin in the herd was 0.215 ± 0.068 mg/ml. There was no significant difference between animals divided by sex: male 0.228 ± 0.073 mg/ml, female 0.202 ± 0.062 mg/ml. The mean value in young animals was higher than the mean value in the adults 0.260 ± 0.081 mg/ml and 0.201 ± 0.059 mg/ml, respectively (P < 0.05). This work was designed to identify the baseline concentration of haptoglobin in a clinically healthy population, thus allowing the comparison of welfare and general health status of the herds or different structured groups within the game reserve. This is the first similar study of haptoglobin as a biomarker in the mouflon.

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Presence of an acute phase response in sheep with clinical classical scrapie

Cited by 23 publications

References 49 publications

Prion Infection of Mouse Brain Reveals Multiple New Upregulated Genes Involved in Neuroinflammation or Signal Transduction

Prion Infection of Mouse Brain Reveals Multiple New Upregulated Genes Involved in Neuroinflammation or Signal Transduction

Acute‐phase proteins, cortisol and haematological parameters in ewes during the periparturient period

Serum concentration of haptoglobin in European mouflon (Ovis musimon L.) from a game reserve

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