Induction of a Mutant Dyskerin in Adult Mice Causes a Transient Increase in ROS Levels and Altered Expression of Specific Antioxidant Enzymes

2013 ◽  
Vol 65 ◽  
pp. S147-S148
Author(s):  
Dara Akosua Reeves
Author(s):  
JM Radley ◽  
SL Ellis

In effective thrombopoies is has been inferred to occur in several disease sates from considerations of megakaryocyte mass and platelet kinetics. Microscopic examination has demonstrated increased numbers of megakaryocytes, with a typical forms particularly pronounced, in primary myelofibrosis. It has not been documented if megakaryocyte ever fail to reach maturity in non-pathological situations. A major difficulty of establishing this is that the number of megakaryocytes normally present in the marrow is extremely low. A large transient increase in megakaryocytopoiesis can how ever be induced in mice by an injection of 5-fluorouracil. We have utilised this treatment and report here evidence for in effective thrombopoies is in healthy mice.Adult mice were perfused (2% glutaraldehyde in 0.08M phosphate buffer, pH 7.4) 8 days following an injection of 5-fluorouracil (150mg/kg). Femurs were subsequently decalcified in 10% neutral E.D.T.A. and embedded in Spurrs resin. Transverse sections of marrow revealed many megakaryocytes at various stages of maturity. Occasional megakaryocytes (less than 1%) were found to be under going degeneration prior to achieving full maturation and releasing cytoplasm as platelets. These cells were characterized by a peripheral rim of dense cytoplasm which enveloped a mass of organelles and vacuoles (Fig. 1). Numerous microtubules were foundaround and with in the organelle-rich zone (Fig 2).


2018 ◽  
Vol 115 (25) ◽  
pp. E5736-E5745 ◽  
Author(s):  
Yaara Tabib ◽  
Nora S. Jaber ◽  
Maria Nassar ◽  
Tal Capucha ◽  
Gabriel Mizraji ◽  
...  

AXL, a member of the TYRO3, AXL, and MERTK (TAM) receptor tyrosine kinase family, has been shown to play a role in the differentiation and activation of epidermal Langerhans cells (LCs). Here, we demonstrate that growth arrest-specific 6 (GAS6) protein, the predominant ligand of AXL, has no impact on LC differentiation and homeostasis. We thus examined the role of protein S (PROS1), the other TAM ligand acting primarily via TYRO3 and MERTK, in LC function. Genetic ablation of PROS1 in keratinocytes resulted in a typical postnatal differentiation of LCs; however, a significant reduction in LC frequencies was observed in adult mice due to increased apoptosis. This was attributed to altered expression of cytokines involved in LC development and tissue homeostasis within keratinocytes. PROS1 was then excised in LysM+ cells to target LCs at early embryonic developmental stages, as well as in adult monocytes that also give rise to LCs. Differentiation and homeostasis of LCs derived from embryonic precursors was not affected following Pros1 ablation. However, differentiation of LCs from bone marrow (BM) precursors in vitro was accelerated, as was their capability to reconstitute epidermal LCs in vivo. These reveal an inhibitory role for PROS1 on BM-derived LCs. Collectively, this study highlights a cell-specific regulation of LC differentiation and homeostasis by TAM signaling.


Zygote ◽  
2017 ◽  
Vol 25 (3) ◽  
pp. 296-303 ◽  
Author(s):  
Maria Cristina Budani ◽  
Erminia Carletti ◽  
Gian Mario Tiboni

SummaryThis study was undertaken to evaluate whether cigarette smoke is associated with changes in the expression of antioxidant enzymes in granulosa cells of women undergoing IVF treatments. For this aim, the expression of three antioxidant enzymes (SOD1, SOD2 and catalase) in non-smokers (n = 20) and smokers (n = 20) was analyzed. There was a statistically significant overexpression of SOD2 and catalase mRNA levels in smokers in comparison with non-smokers. Cigarette smoking was associated with a lower fertilization rate, implantation rate and pregnancy rate in comparison with non-smokers. There was no effect on retrieved oocytes number, metaphase II oocytes number, quality of embryos transferred and live birth rate. These findings suggest that cigarette smoke initiates oxidative stress in granulosa cells.


Endocrinology ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 2319-2330 ◽  
Author(s):  
Cheng Wang ◽  
Shyamal K. Roy

We examined the expression and hormonal regulation of E-cadherin (CDH1) and N-cadherin (CDH2) with respect to primordial follicle formation. Hamster Cdh1 and Cdh2 cDNA and amino acid sequences were more than 90% similar to those of the mouse, rat, and human. Although CDH1 expression remained exclusively in the oocytes during neonatal ovary development, CDH2 expression shifted from the oocytes to granulosa cells of primordial follicles on postnatal day (P)8. Subsequently, strong CDH2 expression was restricted to granulosa cells of growing follicles. Cdh2 mRNA levels in the ovary decreased from embryonic d 13 through P10 with a transient increase on P7, which was the day before the appearance of primordial follicles. Cdh1 mRNA levels decreased from embryonic d 13 through P3 and then showed a transient increase on P8, coinciding with the formation of primordial follicles. CDH1 and CDH2 expression were consistent with that of mRNA. Neutralization of FSH in utero impaired primordial follicle formation with an associated decrease in Cdh2 mRNA and CDH2, but an increase in Cdh1 mRNA and CDH1 expression. The altered expression was reversed by equine chorionic gonadotropin treatment on P1. Whereas a CDH2 antibody significantly reduced the formation of primordial and primary follicles in vitro, a CDH1 antibody had the opposite effect. This is the first evidence to suggest that primordial follicle formation requires a differential spatiotemporal expression and action of CDH1 and CDH2. Further, FSH regulation of primordial follicle formation may involve the action of CDH1 and CDH2.


Plant Science ◽  
2004 ◽  
Vol 166 (2) ◽  
pp. 323-331 ◽  
Author(s):  
Larissa Menezes-Benavente ◽  
Felipe Karam Teixeira ◽  
Claire Lessa Alvim Kamei ◽  
Márcia Margis-Pinheiro

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 384
Author(s):  
Giovanni Provenzano ◽  
Angela Gilardoni ◽  
Marika Maggia ◽  
Mattia Pernigo ◽  
Paola Sgadò ◽  
...  

Impaired function of GABAergic interneurons, and the subsequent alteration of excitation/inhibition balance, is thought to contribute to autism spectrum disorders (ASD). Altered numbers of GABAergic interneurons and reduced expression of GABA receptors has been detected in the brain of ASD subjects and mouse models of ASD. We previously showed a reduced expression of GABAergic interneuron markers parvalbumin (PV) and somatostatin (SST) in the forebrain of adult mice lacking the Engrailed2 gene (En2-/- mice). Here, we extended this analysis to postnatal day (P) 30 by using in situ hybridization, immunohistochemistry, and quantitative RT-PCR to study the expression of GABAergic interneuron markers in the hippocampus and somatosensory cortex of En2-/- and wild type (WT) mice. In addition, GABA receptor subunit mRNA expression was investigated by quantitative RT-PCR in the same brain regions of P30 and adult En2-/- and WT mice. As observed in adult animals, PV and SST expression was decreased in En2-/- forebrain of P30 mice. The expression of GABA receptor subunits (including the ASD-relevant Gabrb3) was also altered in young and adult En2-/- forebrain. Our results suggest that GABAergic neurotransmission deficits are already evident at P30, confirming that neurodevelopmental defects of GABAergic interneurons occur in the En2 mouse model of ASD.


2020 ◽  
Vol 29 (17) ◽  
pp. 2936-2950
Author(s):  
Alexey V Shevelkin ◽  
Chantelle E Terrillion ◽  
Yuto Hasegawa ◽  
Olga A Mychko ◽  
Yan Jouroukhin ◽  
...  

Abstract Our understanding of the contribution of genetic risk factors to neuropsychiatric diseases is limited to abnormal neurodevelopment and neuronal dysfunction. Much less is known about the mechanisms whereby risk variants could affect the physiology of glial cells. Our prior studies have shown that a mutant (dominant-negative) form of a rare but highly penetrant psychiatric risk factor, Disrupted-In-Schizophrenia-1 (DISC1), impairs metabolic functions of astrocytes and leads to cognitive dysfunction. In order to overcome the limitations of the mutant DISC1 model and understand the putative regional properties of astrocyte DISC1, we assessed whether knockdown of Disc1 (Disc1-KD) in mature mouse astrocytes of the prefrontal cortex (PFC) or the hippocampus would produce behavioral abnormalities that could be attributed to astrocyte bioenergetics. We found that Disc1-KD in the hippocampus but not PFC impaired trace fear conditioning in adult mice. Using the innovative deep learning approach and convolutional deep neural networks (cDNNs), ResNet50 or ResNet18, and single cell-based analysis, we found that Disc1-KD decreased the spatial density of astrocytes associated with abnormal levels and distribution of the mitochondrial markers and the glutamate transporter, GLAST. Disc1-KD in astrocytes also led to decreased expression of the glutamatergic and increased expression of the GABA-ergic synaptic markers, possibly via non-apoptotic activation of caspase 3 in neurons located within the individual territories of Disc1-KD astrocytes. Our results indicate that altered expression of DISC1 in astrocytes could impair astrocyte bioenergetics, leading to abnormalities in synaptic neurotransmission and cognitive function in a region-dependent fashion.


2013 ◽  
Vol 8 (Suppl 1) ◽  
pp. P15
Author(s):  
Barbara D’Orio ◽  
Luana Barone ◽  
Anna Fracassi ◽  
Francesca Fanelli ◽  
Sara Sepe ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kira Kleszka ◽  
Tristan Leu ◽  
Theresa Quinting ◽  
Holger Jastrow ◽  
Sonali Pechlivanis ◽  
...  

Abstract Sufficient tissue oxygenation is required for regular brain function; thus oxygen supply must be tightly regulated to avoid hypoxia and irreversible cell damage. If hypoxia occurs the transcription factor complex hypoxia-inducible factor (HIF) will accumulate and coordinate adaptation of cells to hypoxia. However, even under atmospheric O2 conditions stabilized HIF-2α protein was found in brains of adult mice. Mice with a neuro-specific knockout of Hif-2α showed a reduction of pyramidal neurons in the retrosplenial cortex (RSC), a brain region responsible for a range of cognitive functions, including memory and navigation. Accordingly, behavioral studies showed disturbed cognitive abilities in these mice. In search of the underlying mechanisms for the specific loss of pyramidal cells in the RSC, we found deficits in migration in neural stem cells from Hif-2α knockout mice due to altered expression patterns of genes highly associated with neuronal migration and positioning.


Author(s):  
John J. Wolosewick

Classically, the male germinal epithelium is depicted as synchronously developing uninucleate spermatids conjoined by intercellular bridges. Recently, binucleate and multinucleate spermatids from human and mouse testis have been reported. The present paper describes certain developmental events in one type of binucleate spermatid in the seminiferous epithelium of the mouse.Testes of adult mice (ABP Jax) were removed from the animals after cervical dislocation and placed into 2.5% glutaraldehyde/Millonig's phosphate buffer (pH 7.2). Testicular capsules were gently split and separated, exposing the tubules. After 15 minutes the tissue was carefully cut into cubes (approx. 1mm), fixed for an additional 45 minutes and processed for electron microscopy.


Sign in / Sign up

Export Citation Format

Share Document