Effects of early crush on aging wild type and Connexin 32 knockout mice: Evidence for a neuroprotective state in CMT1X mouse nerve

2021 ◽  
Author(s):  
Alejandro Peinado ◽  
Samantha L. Asche‐ Godin ◽  
Mona M. Freidin ◽  
Charles K. Abrams
Keyword(s):  
Knockout Mice ◽  
Connexin 32 ◽  
Wild Type

scholarly journals IL-17F depletion accelerates chitosan conduit guided peripheral nerve regeneration

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Feixiang Chen ◽  
Weihuang Liu ◽  
Qiang Zhang ◽  
Ping Wu ◽  
Ao Xiao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Knockout Mice ◽  
Inflammatory Markers ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Wild Type ◽  
Anti Inflammatory

AbstractPeripheral nerve injury is a serious health problem and repairing long nerve deficits remains a clinical challenge nowadays. Nerve guidance conduit (NGC) serves as the most promising alternative therapy strategy to autografts but its repairing efficiency needs improvement. In this study, we investigated whether modulating the immune microenvironment by Interleukin-17F (IL-17F) could promote NGC mediated peripheral nerve repair. Chitosan conduits were used to bridge sciatic nerve defect in IL-17F knockout mice and wild-type mice with autografts as controls. Our data revealed that IL-17F knockout mice had improved functional recovery and axonal regeneration of sciatic nerve bridged by chitosan conduits comparing to the wild-type mice. Notably, IL-17F knockout mice had enhanced anti-inflammatory macrophages in the NGC repairing microenvironment. In vitro data revealed that IL-17F knockout peritoneal and bone marrow derived macrophages had increased anti-inflammatory markers after treatment with the extracts from chitosan conduits, while higher pro-inflammatory markers were detected in the Raw264.7 macrophage cell line, wild-type peritoneal and bone marrow derived macrophages after the same treatment. The biased anti-inflammatory phenotype of macrophages by IL-17F knockout probably contributed to the improved chitosan conduit guided sciatic nerve regeneration. Additionally, IL-17F could enhance pro-inflammatory factors production in Raw264.7 cells and wild-type peritoneal macrophages. Altogether, IL-17F may partially mediate chitosan conduit induced pro-inflammatory polarization of macrophages during nerve repair. These results not only revealed a role of IL-17F in macrophage function, but also provided a unique and promising target, IL-17F, to modulate the microenvironment and enhance the peripheral nerve regeneration.

Ascorbic acid and CoQ10 ameliorate the reproductive ability of superoxide dismutase 1-deficient female mice†

2019 ◽  
Author(s):  
Naoki Ishii ◽  
Takujiro Homma ◽  
Jaeyong Lee ◽  
Hikaru Mitsuhashi ◽  
Ken-ichi Yamada ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Superoxide Dismutase ◽  
Coenzyme Q10 ◽  
Knockout Mice ◽  
Knockout Mouse ◽  
Superoxide Dismutase 1 ◽  
Wild Type ◽  
Positive Effects ◽  
Reproductive Ability ◽  
Ascorbic Acid Supplementation

Abstract Superoxide dismutase 1 suppresses oxidative stress within cells by decreasing the levels of superoxide anions. A dysfunction of the ovary and/or an aberrant production of sex hormones are suspected causes for infertility in superoxide dismutase 1-knockout mice. We report on attempts to rescue the infertility in female knockout mice by providing two antioxidants, ascorbic acid and/or coenzyme Q10, as supplements in the drinking water of the knockout mice after weaning and on an investigation of their reproductive ability. On the first parturition, 80% of the untreated knockout mice produced smaller litter sizes compared with wild-type mice (average 2.8 vs 7.3 pups/mouse), and supplementing with these antioxidants failed to improve these litter sizes. However, in the second parturition of the knockout mice, the parturition rate was increased from 18% to 44–75% as the result of the administration of antioxidants. While plasma levels of progesterone at 7.5 days of pregnancy were essentially the same between the wild-type and knockout mice and were not changed by the supplementation of these antioxidants, sizes of corpus luteum cells, which were smaller in the knockout mouse ovaries after the first parturition, were significantly ameliorated in the knockout mouse with the administration of the antioxidants. Moreover, the impaired vasculogenesis in uterus/placenta was also improved by ascorbic acid supplementation. We thus conclude that ascorbic acid and/or coenzyme Q10 are involved in maintaining ovarian and uterus/placenta homeostasis against insults that are augmented during pregnancy and that their use might have positive effects in terms of improving female fertility.

scholarly journals Activation of microglia induces symptoms of Parkinson’s disease in wild-type, but not in IL-1 knockout mice

2013 ◽  
Vol 10 (1) ◽  
Author(s):  
Sachiko Tanaka ◽  
Atsuko Ishii ◽  
Hirokazu Ohtaki ◽  
Seiji Shioda ◽  
Takemi Yoshida ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Knockout Mice ◽  
Wild Type

scholarly journals Food restriction by intermittent fasting induces diabetes and obesity and aggravates spontaneous atherosclerosis development in hypercholesterolaemic mice

2013 ◽  
Vol 111 (6) ◽  
pp. 979-986 ◽  
Author(s):  
Gabriel G. Dorighello ◽  
Juliana C. Rovani ◽  
Christopher J. F. Luhman ◽  
Bruno A. Paim ◽  
Helena F. Raposo ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Plasma Levels ◽  
Food Restriction ◽  
Ldl Receptor ◽  
Intermittent Fasting ◽  
Wild Type ◽  
Obesity And Diabetes ◽  
Ad Libitum ◽  
Atherosclerosis Development ◽  
Ldl Receptor Knockout Mice

Different regimens of food restriction have been associated with protection against obesity, diabetes and CVD. In the present study, we hypothesised that food restriction would bring benefits to atherosclerosis- and diabetes-prone hypercholesterolaemic LDL-receptor knockout mice. For this purpose, 2-month-old mice were submitted to an intermittent fasting (IF) regimen (fasting every other day) over a 3-month period, which resulted in an overall 20 % reduction in food intake. Contrary to our expectation, epididymal and carcass fat depots and adipocyte size were significantly enlarged by 15, 72 and 68 %, respectively, in the IF mice compared with the ad libitum-fed mice. Accordingly, plasma levels of leptin were 50 % higher in the IF mice than in the ad libitum-fed mice. In addition, the IF mice showed increased plasma levels of total cholesterol (37 %), VLDL-cholesterol (195 %) and LDL-cholesterol (50 %). As expected, in wild-type mice, the IF regimen decreased plasma cholesterol levels and epididymal fat mass. Glucose homeostasis was also disturbed by the IF regimen in LDL-receptor knockout mice. Elevated levels of glycaemia (40 %), insulinaemia (50 %), glucose intolerance and insulin resistance were observed in the IF mice. Systemic inflammatory markers, TNF-α and C-reactive protein, were significantly increased and spontaneous atherosclerosis development were markedly increased (3-fold) in the IF mice. In conclusion, the IF regimen induced obesity and diabetes and worsened the development of spontaneous atherosclerosis in LDL-receptor knockout mice. Although being efficient in a wild-type background, this type of food restriction is not beneficial in the context of genetic hypercholesterolaemia.

scholarly journals Nutritional Effects on Host Response to Lung Infections with Mucoid Pseudomonas aeruginosa in Mice

2004 ◽  
Vol 72 (3) ◽  
pp. 1479-1486 ◽  
Author(s):  
Anna M. van Heeckeren ◽  
Mark Schluchter ◽  
Lintong Xue ◽  
Juan Alvarez ◽  
Steven Freedman ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Docosahexaenoic Acid ◽  
Knockout Mice ◽  
Host Response ◽  
Inflammatory Responses ◽  
Liquid Diet ◽  
Wild Type ◽  
Agarose Beads ◽  
Lung Infections

ABSTRACT In cystic fibrosis, a recessive genetic disease caused by defects in the cystic fibrosis conductance regulator (CFTR), the main cause of death is lung infection and inflammation. Nutritional deficits have been proposed to contribute to the excessive host inflammatory response in both humans and Cftr-knockout mice. Cftr-knockout mice and gut-corrected Cftr-knockout mice expressing human CFTR primarily in the gut were challenged with Pseudomonas aeruginosa-laden agarose beads; they responded similarly with respect to bronchoalveolar lavage cell counts and levels of the acute-phase cytokines tumor necrosis factor alpha, interleukin-1β (IL-1β), and IL-6. Wild-type mice fed the liquid diet used to prevent intestinal obstruction in Cftr-knockout mice had inflammatory responses to P. aeruginosa-laden agarose beads similar to those of wild-type mice fed an enriched solid diet, so dietary effects are unlikely to account for differences between wild-type mice and mice with cystic fibrosis. Finally, since cystic fibrosis patients and Cftr-knockout mice have an imbalance in fatty acids (significantly lower-than-normal levels of docosahexaenoic acid), the effects of specific supplementation with docosahexaenoic acid of wild-type and Cftr-knockout mice on their inflammatory responses to P. aeruginosa-laden agarose beads were tested. There were no significant differences (P = 0.35) in cumulative survival rates between Cftr-knockout mice and wild-type mice provided with either the liquid diet Peptamen or Peptamen containing docosahexaenoic acid. In conclusion, diet and docosahexaenoic acid imbalances alone are unlikely to explain the differences in the host response to lung infections with mucoid P. aeruginosa between mice with cystic fibrosis and their wild-type counterparts.

Effects of ketamine on acute somatic nociception in wild-type and N-methyl-d-aspartate (NMDA) receptor ɛ1 subunit knockout mice

2006 ◽  
Vol 50 (6) ◽  
pp. 741-747 ◽  
Author(s):  
Andrey B. Petrenko ◽  
Tomohiro Yamakura ◽  
Ahmed R. Askalany ◽  
Tatsuro Kohno ◽  
Kenji Sakimura ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Knockout Mice ◽  
Wild Type

Abstract 292: The Role of the ATF6 Branch of the ER Stress Response in the Endocrine Heart

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Erik A Blackwood ◽  
Christopher C Glembotski
Keyword(s):  
Stress Response ◽  
Er Stress ◽  
Knockout Mice ◽  
Ex Vivo ◽  
Proteolytic Cleavage ◽  
Isolated Perfused Heart ◽  
Wild Type ◽  
Atrial Myocytes ◽  
Perfused Heart ◽  
Er Stress Response

Rationale: Atrial natriuretic peptide (ANP) is stored in the heart in large dense core granules of atrial myocytes as a biologically inactive precursor, pro-ANP. Hemodynamic stress and atrial stretch stimulate coordinate secretion and proteolytic cleavage of pro-ANP to its bioactive form, ANP, which promotes renal salt excretion and vasodilation, which, together contribute to decreasing blood pressure. While the ATF6 branch of the ER stress response has been studied in ventricular tissue mouse models of myocardial ischemia and pathological hypertrophy, roles for ATF6 and ER stress on the endocrine function of atrial myocytes have not been studied. Objective/Methods: To address this gap in our knowledge, we knocked down ATF6 in primary cultured neonatal rat atrial myocytes (NRAMs) using a chemical inhibitor of the proteolytic cleavage site enabling ATF6 activation and siRNA and measured ANP expression and secretion basally and in response to alpha- adrenergic agonist stimulation using phenylephrine. We also compared the ANP secretion from wild- type mice and ATF6 knockout mice in an ex vivo Langendorff model of the isolated perfused heart. Results: ATF6 knockdown in NRAMs significantly impaired basal and phenylephrine-stimulated ANP secretion. ATF6 knockout mice displayed lower levels of ANP in atrial tissue at baseline as well as after phenylephrine treatment. Similarly, in the ex vivo isolated perfused heart model, less ANP was detected in effluent of ATF6 knockout hearts compared to wild-type hearts. Conclusions: The ATF6 branch of the ER stress response is necessary for efficient co-secretional processing of pro-ANP to ANP and for agonist-stimulated ANP secretion from atrial myocytes. As ANP is secreted in a regulated manner in response to a stimulus and pro-ANP is synthesized and packaged through the classical secretory pathway, we posit that ATF6 is required for adequate expression, folding, trafficking, processing and secretion of biologically active ANP from the endocrine heart.

scholarly journals Preoperative administration of the 5-HT4 receptor agonist prucalopride reduces intestinal inflammation and shortens postoperative ileus via cholinergic enteric neurons

Gut ◽  
2018 ◽  
Vol 68 (8) ◽  
pp. 1406-1416 ◽  
Author(s):  
Nathalie Stakenborg ◽  
Evelien Labeeuw ◽  
Pedro J Gomez-Pinilla ◽  
Sebastiaan De Schepper ◽  
Raymond Aerts ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Postoperative Ileus ◽  
Intestinal Inflammation ◽  
Electrical Field Stimulation ◽  
Enteric Neurons ◽  
Postoperative Treatment ◽  
Wild Type ◽  
Clinical Recovery ◽  
Preoperative Administration

ObjectivesVagus nerve stimulation (VNS), most likely via enteric neurons, prevents postoperative ileus (POI) by reducing activation of alpha7 nicotinic receptor (α7nAChR) positive muscularis macrophages (mMφ) and dampening surgery-induced intestinal inflammation. Here, we evaluated if 5-HT4 receptor (5-HT4R) agonist prucalopride can mimic this effect in mice and human.DesignUsing Ca2+ imaging, the effect of electrical field stimulation (EFS) and prucalopride was evaluated in situ on mMφ activation evoked by ATP in jejunal muscularis tissue. Next, preoperative and postoperative administration of prucalopride (1–5 mg/kg) was compared with that of preoperative VNS in a model of POI in wild-type and α7nAChR knockout mice. Finally, in a pilot study, patients undergoing a Whipple procedure were preoperatively treated with prucalopride (n=10), abdominal VNS (n=10) or sham/placebo (n=10) to evaluate the effect on intestinal inflammation and clinical recovery of POI.ResultsEFS reduced the ATP-induced Ca2+ response of mMφ, an effect that was dampened by neurotoxins tetrodotoxin and ω-conotoxin and mimicked by prucalopride. In vivo, prucalopride administered before, but not after abdominal surgery reduced intestinal inflammation and prevented POI in wild-type, but not in α7nAChR knockout mice. In humans, preoperative administration of prucalopride, but not of VNS, decreased Il6 and Il8 expression in the muscularis externa and improved clinical recovery.ConclusionEnteric neurons dampen mMφ activation, an effect mimicked by prucalopride. Preoperative, but not postoperative treatment with prucalopride prevents intestinal inflammation and shortens POI in both mice and human, indicating that preoperative administration of 5-HT4R agonists should be further evaluated as a treatment of POI.Trial registration numberNCT02425774.

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