scholarly journals Neu1 deficiency induces abnormal emotional behavior in zebrafish

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asami Ikeda ◽  
Mayu Komamizu ◽  
Akito Hayashi ◽  
Chiharu Yamasaki ◽  
Keiji Okada ◽  
...  
Keyword(s):  
Bone Dysplasia ◽  
Preference Test ◽  
Sialic Acids ◽  
Emotional Behavior ◽  
Facial Dysmorphism ◽  
Wild Type ◽  
White Region ◽  
Neu1 Sialidase ◽  
Black Region ◽  
Pituitary Adrenal Axis

AbstractNEU1 sialidase hydrolyzes sialic acids from glycoconjugates in lysosomes. Deficiency of NEU1 causes sialidosis with symptoms including facial dysmorphism, bone dysplasia, and neurodegeneration. However, the effects of NEU1 deficiency on emotional activity have not been explored. Here, we conducted the behavioral analysis using Neu1-knockout zebrafish (Neu1-KO). Neu1-KO zebrafish showed normal swimming similar to wild-type zebrafish (WT), whereas shoaling was decreased and accompanied by greater inter-fish distance than WT zebrafish. The aggression test showed a reduced aggressive behavior in Neu1-KO zebrafish than in WT zebrafish. In the mirror and 3-chambers test, Neu1-KO zebrafish showed more interest toward the opponent in the mirror and multiple unfamiliar zebrafish, respectively, than WT zebrafish. Furthermore, Neu1-KO zebrafish also showed increased interaction with different fish species, whereas WT zebrafish avoided them. In the black–white preference test, Neu1-KO zebrafish showed an abnormal preference for the white region, whereas WT zebrafish preferred the black region. Neu1-KO zebrafish were characterized by a downregulation of the anxiety-related genes of the hypothalamic–pituitary–adrenal axis and upregulation of lamp1a, an activator of lysosomal exocytosis, with their brains accumulating several sphingoglycolipids. This study revealed that Neu1 deficiency caused abnormal emotional behavior in zebrafish, possibly due to neuronal dysfunction induced by lysosomal exocytosis.

scholarly journals MUC1 ectodomain is a flagellin-targeting decoy receptor and biomarker operative during Pseudomonas aeruginosa lung infection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Avelino C. Verceles ◽  
Pavan Bhat ◽  
Zain Nagaria ◽  
Destiny Martin ◽  
Harsh Patel ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bronchoalveolar Lavage Fluid ◽  
Wild Type Strain ◽  
Lavage Fluid ◽  
Airway Epithelial ◽  
Wild Type ◽  
Epithelial Surface ◽  
Decoy Receptor ◽  
Neu1 Sialidase

AbstractWe previously reported that flagellin-expressing Pseudomonas aeruginosa (Pa) provokes NEU1 sialidase-mediated MUC1 ectodomain (MUC1-ED) desialylation and MUC1-ED shedding from murine lungs in vivo. Here, we asked whether Pa in the lungs of patients with ventilator-associated pneumonia might also increase MUC1-ED shedding. The levels of MUC1-ED and Pa-expressed flagellin were dramatically elevated in bronchoalveolar lavage fluid (BALF) harvested from Pa-infected patients, and each flagellin level, in turn, predicted MUC1-ED shedding in the same patient. Desialylated MUC1-ED was only detected in BALF of Pa-infected patients. Clinical Pa strains increased MUC1-ED shedding from cultured human alveolar epithelia, and FlaA and FlaB flagellin-expressing strains provoked comparable levels of MUC1-ED shedding. A flagellin-deficient isogenic mutant generated dramatically reduced MUC1-ED shedding compared with the flagellin-expressing wild-type strain, and purified FlaA and FlaB recapitulated the effect of intact bacteria. Pa:MUC1-ED complexes were detected in the supernatants of alveolar epithelia exposed to wild-type Pa, but not to the flagellin-deficient Pa strain. Finally, human recombinant MUC1-ED dose-dependently disrupted multiple flagellin-driven processes, including Pa motility, Pa biofilm formation, and Pa adhesion to human alveolar epithelia, while enhancing human neutrophil-mediated Pa phagocytosis. Therefore, shed desialylated MUC1-ED functions as a novel flagellin-targeting, Pa-responsive decoy receptor that participates in the host response to Pa at the airway epithelial surface.

scholarly journals Determination of Sialic Acids in Liver and Milk Samples of Wild-type and CMAH Knock-out Mice.

10.3791/56030 ◽  
2017 ◽  
Author(s):  
Cui Cao ◽  
Wen J. Wang ◽  
Ying Y. Huang ◽  
Hong L. Yao ◽  
Louis P. Conway ◽  
...  
Keyword(s):  
Sialic Acids ◽  
Wild Type ◽  
Knock Out ◽  
Milk Samples ◽  
Knock Out Mice

scholarly journals Toll-Like Receptor 9 Expression in Murine and Human Adrenal Glands and Possible Implications during Inflammation

2007 ◽  
Vol 92 (7) ◽  
pp. 2773-2783 ◽  
Author(s):  
Nguyen Tran ◽  
Alexander Koch ◽  
Reinhard Berkels ◽  
Olaf Boehm ◽  
Paula A. Zacharowski ◽  
...  
Keyword(s):  
Adrenal Glands ◽  
Hypothalamic Pituitary Adrenal Axis ◽  
Western World ◽  
Wild Type ◽  
Bacterial Dna ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Axis ◽  
Cpg Oligodeoxynucleotide ◽  
Pituitary Adrenal Axis

Abstract Context: Sepsis is a leading cause of death in the Western world and can be associated with failure of the hypothalamic-pituitary-adrenal axis. A coordinated response of the adrenal and immune system is of vital importance for survival during sepsis. Within the immune response, Toll-like receptors (TLRs) play a crucial role by recognizing pathogen-associated molecules such as bacterial DNA. TLR-9 can detect motifs of unmethylated cytosine-phosphate-guanine (CpG) dinucleotides (CpG-DNA) being present in bacterial DNA. Objective: We investigated whether TLR-9 is expressed in human and murine adrenal glands and whether its activation is associated with an adrenal response. Design: Human fetal and adult adrenal glands; wild-type, C57BL/6 and TLR-9 deficient (TLR-9−/−) mice; and in vitro cell line models were used in the study. Setting: The study took place at a university hospital. Results: TLR-9 is expressed in human and murine adrenal glands, as well as in in vitro cell lines (Y-1 and NCI-H295R cells). CpG-oligodeoxynucleotide challenge caused a 3-fold increase in plasma levels of corticosterone in wild-type mice. This effect was not observed in TLR-9−/− mice. Furthermore, CpG-oligodeoxynucleotide challenge resulted in a strong release of several inflammatory cytokines, such as TNF-α, and IL-1β, -6, -10, and -12 in vivo as well as in vitro. Again, this effect was not present in TLR-9−/− mice. Conclusions: TLR-9 is present in both murine and human adrenal glands. TLR-9 stimulation led to a corticosterone and inflammatory cytokine response. TLR-9 may play a role in the regulation of the hypothalamic-pituitary-adrenal axis during conditions in which bacterial DNA is present.

scholarly journals Depression-/Anxiety-Like Behavior Alterations in Adult Slit2 Transgenic Mice

2021 ◽  
Vol 14 ◽  
Author(s):  
Guilan Huang ◽  
Sheng Wang ◽  
Jie Yan ◽  
Changxi Li ◽  
Jianwen Feng ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Hippocampal Neurons ◽  
Preference Test ◽  
Tail Suspension Test ◽  
The Body ◽  
Cellular Migration ◽  
Inflammatory Factors ◽  
Wild Type ◽  
Adult Mice ◽  
Age Related

Background: Slit2 is a member of the Slit family of secreted glycoproteins that plays highly conserved roles in neuronal axon guidance and cellular migration. Our previous experimental results showed Alzheimer's disease-like alterations and increased permeability of the blood–brain barrier in Slit2-overexpressing transgenic (Slit2-Tg) mice aged 8–9 months. Nevertheless, relatively little is known about behavioral alterations in adult Slit2-Tg mice (2–6 months of age). To observe the age-related behavioral effects of Slit2 overexpression in adult mice, we performed a battery of behavioral tests with adult Slit2-Tg mice at 2–6 months of age.Results: The body weight of Slit2-Tg mice was lower than that of the wild-type mice from 15 weeks of age. Compared with the control mice, depression-like behaviors were found in Slit2-Tg mice from 15 to 21 weeks of age in the sucrose preference test, although Slit2-Tg mice were hyperactive in the tail suspension test. The anxiety-like behaviors were found in Slit2-Tg mice in the open field test, as well as increased locomotor activity. The anxiety-like behaviors were also found in adult Slit2-Tg mice in the elevated plus maze. Compared to wild-type mice at 23 weeks old, impairment of the hippocampal neurons were found in Slit2-Tg mice at the same age in hematoxylin–eosin staining (H&E), including some eccentric dispersion and expansion of neuronal bodies. In addition, the messenger RNA (mRNA) expression of TNF-α was elevated in the hippocampus of adult Slit2-Tg mice.Conclusions: Slit2 overexpression causes depression-/anxiety-like behaviors in adult mice that may be related to an increase in inflammatory factors and damage to hippocampal neurons.

scholarly journals Establishment and characterization of Neu1-knockout zebrafish and its abnormal clinical phenotypes

2020 ◽  
Author(s):  
Keiji Okada ◽  
Ryo Takase ◽  
Yurie Hamaoka ◽  
Akinobu Honda ◽  
Asami Ikeda ◽  
...  
Keyword(s):  
Animal Model ◽  
Plasma Membrane ◽  
Sialic Acid ◽  
Danio Rerio ◽  
Cancer Metastasis ◽  
Expression Patterns ◽  
Wild Type ◽  
Fish Embryo ◽  
Neu1 Sialidase

Mammalian sialidase Neu1 is involved in various physiological functions, including cell adhesion, differentiation, cancer metastasis, and diabetes through lysosomal catabolism and desialylation of glycoproteins at the plasma membrane. Various animal models have been established to further explore the functions of vertebrate Neu1. The present study focused on zebrafish (Danio rerio) belonging to Cypriniformes as an experimental animal model with neu1 gene deficiency. The results revealed that the zebrafish Neu1 desialyzed both a2-3 and a2-6 sialic acid linkages from oligosaccharides and glycoproteins at pH 4.5, and it is highly conserved with other fish species and mammalian Neu1. Further, Neu1-knockout zebrafish (Neu1-KO) was established through CRISPR/Cas9 genome editing. Neu1-KO fish exhibited slight abnormal embryogenesis with the accumulation of pleural effusion; however, no embryonic lethality was observed. Although Neu1-KO fish were able to be maintained as homozygous, they showed smaller body length and weight than the wild type (WT) fish, and muscle atrophy and curvature of the vertebra were observed in adult Neu1-KO fish (8 months). The expression patterns of myod and myog transcription factors regulating muscle differentiation varied between Neu1-KO and WT fish embryo. Expression of lysosomal-related genes, including ctsa,lamp1a, and tfeb were upregulated in adult Neu1-KO muscle as compared to WT. Furthermore, the expression pattern of genes involved in bone remodeling (runx2a, runx2b, and mmp9) was decreased in Neu1-KO fish. These phenotypes were quite similar to those of Neu1-KO mice and human sialidosis patients, indicating the effectiveness of the established Neu1-KO zebrafish for the study of vertebrate Neu1 sialidase.

scholarly journals Sialylation on O-glycans protects platelets from clearance by liver Kupffer cells

2017 ◽  
Vol 114 (31) ◽  
pp. 8360-8365 ◽  
Author(s):  
Yun Li ◽  
Jianxin Fu ◽  
Yun Ling ◽  
Tadayuki Yago ◽  
J. Michael McDaniel ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Kupffer Cell ◽  
Kupffer Cells ◽  
Essential Role ◽  
Sialic Acids ◽  
Hematopoietic Cell ◽  
Primary Cells ◽  
Wild Type ◽  
Specific Loss ◽  
Lectin Receptor

Most platelet membrane proteins are modified by mucin-type core 1-derived glycans (O-glycans). However, the biological importance of O-glycans in platelet clearance is unclear. Here, we generated mice with a hematopoietic cell-specific loss of O-glycans (HC C1galt1−/−). These mice lack O-glycans on platelets and exhibit reduced peripheral platelet numbers. Platelets from HC C1galt1−/− mice show reduced levels of α-2,3-linked sialic acids and increased accumulation in the liver relative to wild-type platelets. The preferential accumulation of HC C1galt1−/− platelets in the liver was reduced in mice lacking the hepatic asialoglycoprotein receptor [Ashwell–Morell receptor (AMR)]. However, we found that Kupffer cells are the primary cells phagocytosing HC C1galt1−/− platelets in the liver. Our results demonstrate that hepatic AMR promotes preferential adherence to and phagocytosis of desialylated and/or HC C1galt1−/− platelets by the Kupffer cell through its C-type lectin receptor CLEC4F. These findings provide insights into an essential role for core 1 O-glycosylation of platelets in their clearance in the liver.

scholarly journals Virulence Traits of a Serogroup C Meningococcus and IsogeniccssAMutant, Defective in Surface-Exposed Sialic Acid, in a Murine Model of Meningitis

2019 ◽  
Vol 87 (4) ◽  
Author(s):  
Roberta Colicchio ◽  
Chiara Pagliuca ◽  
Susanna Ricci ◽  
Elena Scaglione ◽  
Denis Grandgirard ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Corpus Callosum ◽  
Type Strain ◽  
Wild Type Strain ◽  
Lethal Dose ◽  
Sialic Acids ◽  
Wild Type ◽  
Knockout Mutant ◽  
Content Type

ABSTRACTIn serogroup CNeisseria meningitidis, thecssA(siaA) gene codes for an UDP-N-acetylglucosamine 2-epimerase that catalyzes the conversion of UDP-N-acetyl-α-d-glucosamine intoN-acetyl-d-mannosamine and UDP in the first step in sialic acid biosynthesis. This enzyme is required for the biosynthesis of the (α2→9)-linked polysialic acid capsule and for lipooligosaccharide (LOS) sialylation. In this study, we have used a reference serogroup C meningococcal strain and an isogeniccssAknockout mutant to investigate the pathogenetic role of surface-exposed sialic acids in a model of meningitis based on intracisternal inoculation of BALB/c mice. Results confirmed the key role of surface-exposed sialic acids in meningococcal pathogenesis. The 50% lethal dose (LD50) of the wild-type strain 93/4286 was about four orders of magnitude lower than that of thecssAmutant. Compared to the wild-type strain, the ability of this mutant to replicate in brain and spread systemically was severely impaired. Evaluation of brain damage evidenced a significant reduction in cerebral hemorrhages in mice infected with the mutant in comparison with the levels in those challenged with the wild-type strain. Histological analysis showed the typical features of bacterial meningitis, including inflammatory cells in the subarachnoid, perivascular, and ventricular spaces especially in animals infected with the wild type. Noticeably, 80% of mice infected with the wild-type strain presented with massive bacterial localization and accompanying inflammatory infiltrate in thecorpus callosum, indicating high tropism of meningococci exposing sialic acids toward this brain structure and a specific involvement of thecorpus callosumin the mouse model of meningococcal meningitis.

scholarly journals Serotonin stimulates GnRH secretion through the c-Src-PLC γ1 pathway in GT1–7 hypothalamic cells

2006 ◽  
Vol 190 (3) ◽  
pp. 581-591 ◽  
Author(s):  
Hyeon Soo Kim ◽  
Sanatombi Yumkham ◽  
Jang Hyun Choi ◽  
Gi Hoon Son ◽  
Kyungjin Kim ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Kinase Inhibitor ◽  
Hormone Secretion ◽  
Dependent Manner ◽  
Wild Type ◽  
Hypothalamic Cells ◽  
Src Homology ◽  
Interfering Rna ◽  
Pituitary Adrenal Axis

Serotonin is a neurotransmitter that alters the hypothalamic-pituitary-adrenal axis. To date, however, the molecular mechanisms underlying the role of serotonin in hormone secretion have remained largely unclear. In this study, we report that serotonin activates phospholipase C (PLC) γ1 in an Src-dependent manner in hypothalamic GT1–7 cells, and that pretreatment with either 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazole [3, 4-d] pyrimidine, an Src-kinase inhibitor, or U73122, a PLC inhibitor, attenuates the serotonin-induced increase in calcium levels. Also, PLC γ1 binds to c-Src through the Src-homology (SH) 223 domain upon serotonin treatment. Moreover, calcium increase is alleviated in the cells transientlyexpressing SH223 domain-deleted PLC γ1 or lipase inactive mutant PLC γ1, as compared with cells transfected with wild-type PLC γ1. Furthermore, the inhibition of the activities of either PLC or Src results in a significant diminution of the serotonin-induced release of gonadotropin-releasing hormone (GnRH). In addition, the results of our small-interfering RNA experiment confirm that endogenous PLC γ1 is a prerequisite for serotonin-mediated signaling pathways. Taken together, our findings demonstrate that serotonin stimulates the release of GnRH through the Src-PLC γ1 pathway, via the modulation of intracellular calcium levels.

scholarly journals A case of acrodysostosis: a rare primary bone dysplasia

2018 ◽  
Vol 6 (6) ◽  
pp. 2165
Author(s):  
Roopal Vasava ◽  
Bhargav Tank ◽  
Abhilasha Jain
Keyword(s):  
Case Report ◽  
Rare Disease ◽  
Skeletal Dysplasia ◽  
Bone Dysplasia ◽  
Female Child ◽  
Facial Dysmorphism ◽  
Radiological Features ◽  
Primary Bone ◽  
Hands And Feet ◽  
Nasal Hypoplasia

Acrodysostosis is a rare skeletal dysplasia characterized by brachydactyly, facial dysostosis and nasal hypoplasia. Diagnostic approach to this disorder is based on clinical, radiological and hormonal assays. We present a case of 11-year-old female child who presented with the complaint of short stubby hands and feet since birth and facial dysmorphism. Her skeletal survey revealed typical radiographic features of acrodysostosis. Hormonal assays did not reveal any significant abnormality. In this case report, we would like to highlight the clinical and radiological features of this disorder which could be helpful in diagnosis of this rare disease.

scholarly journals Role ofTannerella forsythiaNanH Sialidase in Epithelial Cell Attachment

2010 ◽  
Vol 79 (1) ◽  
pp. 393-401 ◽  
Author(s):  
Kiyonobu Honma ◽  
Elina Mishima ◽  
Ashu Sharma
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Outer Membrane ◽  
Type Strain ◽  
Wild Type Strain ◽  
Sialic Acids ◽  
Slight Reduction ◽  
Deficient Mutant ◽  
Wild Type ◽  
Sialidase Activity

ABSTRACTTannerella forsythiais a Gram-negative oral anaerobe which contributes to the development of periodontitis, an inflammatory disease of the tooth-supporting tissues leading to tooth loss. The mechanisms by which this bacterium colonizes the oral cavity are poorly understood. The bacterium has been shown to express two distinct sialidases, namely, SiaHI and NanH, with the latter being the major sialidase. Bacterial sialidases can play roles in pathogenesis by cleaving sialic acids on host glycoproteins, destroying their integrity, and/or unmasking hidden epitopes on host surfaces for colonization. In the present study, we investigated the roles of the SiaHI and NanH sialidases by generating and characterizing specific deletion mutants. Our results showed that the NanH deficiency resulted in a total loss of sialidase activity associated with the outer-membrane and secreted fractions. On the other hand, the SiaHI deficiency resulted in only a slight reduction in the total sialidase activity, with no significant differences in the levels of sialidase activity in the outer membrane or secreted fractions compared to that in the wild-type strain. The results demonstrated that NanH is both surface localized and secreted. The NanH-deficient mutant but not the SiaHI-deficient mutant was significantly attenuated in epithelial cell binding and invasion abilities compared to the wild-type strain. Moreover, the NanH-deficient mutant alone was impaired in cleaving surface sialic acids on epithelial cells. Thus, our study suggests that NanH sialidase might play roles in bacterial colonization by exposing sialic acid-hidden epitopes on epithelial cells.

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