scholarly journals MicroRNA-138 Overexpression Alters Aβ42 Levels and Behavior in Wildtype Mice

2021 ◽  
Vol 14 ◽  
Author(s):  
Emmanuelle Boscher ◽  
Claudia Goupil ◽  
Serena Petry ◽  
Rémi Keraudren ◽  
Andréanne Loiselle ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Early Onset ◽  
Cultured Cells ◽  
Neurodegenerative Disorder ◽  
Gene Dosage ◽  
Copy Number Variations ◽  
Object Recognition Test ◽  
Microrna Genes ◽  
Aβ Production

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by changes in cognitive and behavioral functions. With the exception or rare mutations in PSEN and APP genes causing early-onset autosomal dominant AD (EOADAD), little is known about the genetic factors that underlie the vast majority (>95%) of early onset AD (EOAD) cases. We have previously identified copy number variations (CNVs) in microRNA genes in patients with EOAD, including a duplication of the MIR-138-2 gene. Overexpression of miR-138 in cultured cells increased Aβ production and tau phosphorylation, similar to what is seen in AD brain. In this study, we sought to determine if miR-138 overexpression could recapitulate certain features of disease in vivo in non-transgenic mice. A mild overexpression of pre-miR-138 in the brain of C57BL/6J wildtype mice altered learning and memory in a novel object recognition test and in the Barnes Maze. Increased levels of anxiety were also observed in the open-field test. MiR-138 upregulation in vivo caused an increase in endogenous Aβ42 production as well as changes in synaptic and inflammation markers. Tau expression was significantly lower with no overt effects on phosphorylation. We finally observed that Sirt1, a direct target of miR-138 involved in Aβ production, learning and memory as well as anxiety, is decreased following miR-138 overexpression. In sum, this study further strengthens a role for increased gene dosage of MIR-138-2 gene in modulating AD risk, possibly by acting on different biological pathways. Further studies will be required to better understand the role of CNVs in microRNA genes in AD and related neurodegenerative disorders.

scholarly journals Biallelic SQSTM1 mutations in early-onset, variably progressive neurodegeneration

Neurology ◽  
2018 ◽  
Vol 91 (4) ◽  
pp. e319-e330 ◽  
Author(s):  
Valentina Muto ◽  
Elisabetta Flex ◽  
Zachary Kupchinsky ◽  
Guido Primiano ◽  
Hamid Galehdari ◽  
...  
Keyword(s):  
Protein Function ◽  
Early Onset ◽  
Structural Integrity ◽  
Neurodegenerative Disorder ◽  
Homozygosity Mapping ◽  
Autophagic Flux ◽  
Exon 2

ObjectiveTo characterize clinically and molecularly an early-onset, variably progressive neurodegenerative disorder characterized by a cerebellar syndrome with severe ataxia, gaze palsy, dyskinesia, dystonia, and cognitive decline affecting 11 individuals from 3 consanguineous families.MethodsWe used whole-exome sequencing (WES) (families 1 and 2) and a combined approach based on homozygosity mapping and WES (family 3). We performed in vitro studies to explore the effect of the nontruncating SQSTM1 mutation on protein function and the effect of impaired SQSTM1 function on autophagy. We analyzed the consequences of sqstm1 down-modulation on the structural integrity of the cerebellum in vivo using zebrafish as a model.ResultsWe identified 3 homozygous inactivating variants, including a splice site substitution (c.301+2T>A) causing aberrant transcript processing and accelerated degradation of a resulting protein lacking exon 2, as well as 2 truncating changes (c.875_876insT and c.934_936delinsTGA). We show that loss of SQSTM1 causes impaired production of ubiquitin-positive protein aggregates in response to misfolded protein stress and decelerated autophagic flux. The consequences of sqstm1 down-modulation on the structural integrity of the cerebellum in zebrafish documented a variable but reproducible phenotype characterized by cerebellum anomalies ranging from depletion of axonal connections to complete atrophy. We provide a detailed clinical characterization of the disorder; the natural history is reported for 2 siblings who have been followed up for >20 years.ConclusionsThis study offers an accurate clinical characterization of this recently recognized neurodegenerative disorder caused by biallelic inactivating mutations in SQSTM1 and links this phenotype to defective selective autophagy.

Ultrastructural Correlations between Clonal Human Tumor Colonies and in Vivo Neoplasms

1982 ◽  
Vol 40 ◽  
pp. 210-211
Author(s):  
M.J. Murphy ◽  
R.R. Price ◽  
J.C. Sloman
Keyword(s):  
Cultured Cells ◽  
Human Tumor ◽  
Cell Type ◽  
Tumor Mass ◽  
Initial Cell ◽  
Cloning Assay ◽  
Human Tumor Cloning ◽  
The Relationship

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.

The Infection of Cells by Bullet-Shaped Viruses

1969 ◽  
Vol 27 ◽  
pp. 372-373
Author(s):  
Frederick A. Murphy ◽  
Alyne K. Harrison ◽  
Sylvia G. Whitfield
Keyword(s):  
Electron Microscopy ◽  
Physical Properties ◽  
Host Cell ◽  
Thin Section ◽  
Cultured Cells ◽  
Cell Infection ◽  
Thin Section Electron Microscopy ◽  
Section Electron ◽  
Section Electron Microscopy

The bullet-shaped viruses are currently classified together on the basis of similarities in virion morphology and physical properties. Biologically and ecologically the member viruses are extremely diverse. In searching for further bases for making comparisons of these agents, the nature of host cell infection, both in vivo and in cultured cells, has been explored by thin-section electron microscopy.

Preparation of cultured astrocytes for x-ray microanalysis

1989 ◽  
Vol 47 ◽  
pp. 988-989
Author(s):  
N.K.R. Smith ◽  
K.E. Hunter ◽  
P. Mobley ◽  
L.P. Felpel
Keyword(s):  
Cultured Cells ◽  
Elemental Content ◽  
Elemental Distribution ◽  
Sprague Dawley ◽  
X Ray ◽  
Cultured Astrocytes ◽  
Freeze Dried ◽  
Ultimate Objective

Electron probe energy dispersive x-ray microanalysis (XRMA) offers a powerful tool for the determination of intracellular elemental content of biological tissue. However, preparation of the tissue specimen , particularly excitable central nervous system (CNS) tissue , for XRMA is rather difficult, as dissection of a sample from the intact organism frequently results in artefacts in elemental distribution. To circumvent the problems inherent in the in vivo preparation, we turned to an in vitro preparation of astrocytes grown in tissue culture. However, preparations of in vitro samples offer a new and unique set of problems. Generally, cultured cells, growing in monolayer, must be harvested by either mechanical or enzymatic procedures, resulting in variable degrees of damage to the cells and compromised intracel1ular elemental distribution. The ultimate objective is to process and analyze unperturbed cells. With the objective of sparing others from some of the same efforts, we are reporting the considerable difficulties we have encountered in attempting to prepare astrocytes for XRMA.Tissue cultures of astrocytes from newborn C57 mice or Sprague Dawley rats were prepared and cultured by standard techniques, usually in T25 flasks, except as noted differently on Cytodex beads or on gelatin. After different preparative procedures, all samples were frozen on brass pins in liquid propane, stored in liquid nitrogen, cryosectioned (0.1 μm), freeze dried, and microanalyzed as previously reported.

In silico and In vivo Evaluation of Oxidative Stress Inhibitors Against Parkinson`s Disease using the C. elegans Model

2020 ◽  
Vol 23 (8) ◽  
pp. 814-826
Author(s):  
Pradeep Hanumanthappa ◽  
Arpitha Ashok ◽  
Inderjit Prakash ◽  
Carmel I. Priya ◽  
Julie Zinzala ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Neurodegenerative Disorder ◽  
In Vivo Evaluation ◽  
Neuroprotective Effects ◽  
Ample Evidence ◽  
C Elegans ◽  
Rational Drug ◽  
Cullin 3 ◽  
Anti Oxidant

Background: Parkinson’s disease ranks second, after Alzheimer’s as the major neurodegenerative disorder, for which no cure or disease-modifying therapies exist. Ample evidence indicate that PD manifests as a result of impaired anti-oxidative machinery leading to neuronal death wherein Cullin-3 has ascended as a potential therapeutic target for diseases involving damaged anti-oxidative machinery. Objective: The design of target specific inhibitors for the Cullin-3 protein might be a promising strategy to increase the Nrf2 levels and to decrease the possibility of “off-target” toxic properties. Methods: In the present study, an integrated computational and wet lab approach was adopted to identify small molecule inhibitors for Cullin-3. The rational drug designing process comprised homology modeling and derivation of the pharmacophore for Cullin-3, virtual screening of Zinc natural compound database, molecular docking and Molecular dynamics based screening of ligand molecules. In vivo validations of an identified lead compound were conducted in the PD model of C. elegans. Results and Discussion: Our strategy yielded a potential inhibitor; (Glide score = -12.31), which was evaluated for its neuroprotective efficacy in the PD model of C. elegans. The inhibitor was able to efficiently defend against neuronal death in PD model of C. elegans and the neuroprotective effects were attributed to its anti-oxidant activities, supported by the increase in superoxide dismutase, catalase and the diminution of acetylcholinesterase and reactive oxygen species levels. In addition, the Cullin-3 inhibitor significantly restored the behavioral deficits in the transgenic C. elegans. Conclusion: Taken together, these findings highlight the potential utility of Cullin-3 inhibition to block the persistent neuronal death in PD. Further studies focusing on Cullin-3 and its mechanism of action would be interesting.

Electromagnetic field in Alzheimer’s disease: a literature review of recent preclinical and clinical studies

2020 ◽  
Vol 17 ◽  
Author(s):  
Reem Habib Mohamad Ali Ahmad ◽  
Marc Fakhoury ◽  
Nada Lawand
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
In Vivo Studies ◽  
Key Factors ◽  
Potential Benefits ◽  
Preclinical And Clinical Studies ◽  
The Brain

: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the progressive loss of neurons leading to cognitive and memory decay. The main signs of AD include the irregular extracellular accumulation of amyloidbeta (Aβ) protein in the brain and the hyper-phosphorylation of tau protein inside neurons. Changes in Aβ expression or aggregation are considered key factors in the pathophysiology of sporadic and early-onset AD and correlate with the cognitive decline seen in patients with AD. Despite decades of research, current approaches in the treatment of AD are only symptomatic in nature and are not effective in slowing or reversing the course of the disease. Encouragingly, recent evidence revealed that exposure to electromagnetic fields (EMF) can delay the development of AD and improve memory. This review paper discusses findings from in vitro and in vivo studies that investigate the link between EMF and AD at the cellular and behavioural level, and highlights the potential benefits of EMF as an innovative approach for the treatment of AD.

Role of MicroRNA Genes miR-1000 and miR-375 in Forming Olfactory Conditional Memory in Drosophila melanogaster

MicroRNA ◽  
2020 ◽  
Vol 09 ◽  
Author(s):  
Sadniman Rahman ◽  
Chaity Modak ◽  
Mousumi Akter ◽  
Mohammad Shamimul Alam
Keyword(s):  
Learning And Memory ◽  
Short Term Memory ◽  
Memory Loss ◽  
Memory Formation ◽  
Neural Integration ◽  
Significant Difference ◽  
Locomotion Speed ◽  
Microrna Genes ◽  
With Memory

Background: Learning and memory is basic aspects in neurogenetics as most of the neurological disorders start with dementia or memory loss. Several genes associated with memory formation have been discovered. MicroRNA genes miR-1000 and miR-375 were reported to be associated with neural integration and glucose homeostasis in some insects and vertebrates. However, neuronal function of these genes is yet to be established in D. melanogaster. Objective: Possible role of miR-1000 and miR-375 in learning and memory formation in this fly has been explored in the present study. Methods: Both appetitive and aversive olfactory conditional learning were tested in the miR-1000 and miR-375 knockout (KO) strains and compared with wild one. Five days old third instar larvae were trained by allowing them to be associated with an odor with reward (fructose) or punishment (salt). Then, the larvae were tested to calculate their preferences to the odor trained with. Learning index (LI) values and larval locomotion speed were calculated for all strains. Results: No significant difference was observed for larval locomotion speed in mutant strains. Knockout strain of miR-1000 showed significant deficiency in both appetitive and aversive memory formation whereas miR-375 KO strain showed a significantly lower response only in appetitive one. Conclusion: The results of the present study indicate important role played by these two genes in forming short-term memory in D. melanogaster.

EPA-enriched ethanolamine plasmalogen and EPA-enriched phosphatidylethanolamine enhance BDNF/TrkB/CREB signaling and inhibit neuronal apoptosis in vitro and in vivo

2020 ◽  
Vol 11 (2) ◽  
pp. 1729-1739 ◽  
Author(s):  
Hongxia Che ◽  
Lingyu Zhang ◽  
Lin Ding ◽  
Wancui Xie ◽  
Xiaoming Jiang ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Neuronal Apoptosis ◽  
Memory Deficit ◽  
Ethanolamine Plasmalogen ◽  
Learning And Memory Deficit

Our previous study showed that EPA-enriched ethanolamine plasmalogen (EPA-pPE) exerted more significant effects than EPA-enriched phosphatidylethanolamine (EPA-PE) in improving learning and memory deficit.

In vivo study of the angiogenesis potential of bone marrow-derived mesenchymal stem cell aggregates in their niche like environment

2021 ◽  
pp. 039139882110255
Author(s):  
Sara Anajafi ◽  
Azam Ranjbar ◽  
Monireh Torabi-Rahvar ◽  
Naser Ahmadbeigi
Keyword(s):  
Tissue Engineering ◽  
Bone Marrow ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cultured Cells ◽  
Morphological Evidence ◽  
Cell Aggregates ◽  
Plla Scaffold ◽  
Significant Difference

Background: Sufficient blood vessel formation in bioengineered tissues is essential in order to keep the viability of the organs. Impaired development of blood vasculatures results in failure of the implanted tissue. The cellular source which is seeded in the scaffold is one of the crucial factors involved in tissue engineering methods. Materials and methods: Considering the notable competence of Bone Marrow derived Mesenchymal Stem Cell aggregates for tissue engineering purposes, in this study BM-aggregates and expanded BM-MSCs were applied without any inductive agent or co-cultured cells, in order to investigate their own angiogenesis potency in vivo. BM-aggregates and BM-MSC were seeded in Poly-L Lactic acid (PLLA) scaffold and implanted in the peritoneal cavity of mice. Result: Immunohistochemistry results indicated that there was a significant difference ( p < 0.050) in CD31+ cells between PLLA scaffolds contained cultured BM-MSC; PLLA scaffolds contained BM-aggregates and empty PLLA. According to morphological evidence, obvious connections with recipient vasculature and acceptable integration with surroundings were established in MSC and aggregate-seeded scaffolds. Conclusion: Our findings revealed cultured BM-MSC and BM-aggregates, capacity in order to develop numerous connections between PLLA scaffold and recipient’s vasculature which is crucial to the survival of tissues, and considerable tendency to develop constructs containing CD31+ endothelial cells which can contribute in vessel’s tube formation.

scholarly journals Eap1p, an Adhesin That Mediates Candida albicans Biofilm Formation In Vitro and In Vivo

2007 ◽  
Vol 6 (6) ◽  
pp. 931-939 ◽  
Author(s):  
Fang Li ◽  
Michael J. Svarovsky ◽  
Amy J. Karlsson ◽  
Joel P. Wagner ◽  
Karen Marchillo ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cell Adhesion ◽  
Biofilm Formation ◽  
Fungal Infections ◽  
Gene Dosage ◽  
Venous Catheter ◽  
Flow Chamber ◽  
Dependent Manner

ABSTRACT Candida albicans is the leading cause of systemic fungal infections in immunocompromised humans. The ability to form biofilms on surfaces in the host or on implanted medical devices enhances C. albicans virulence, leading to antimicrobial resistance and providing a reservoir for infection. Biofilm formation is a complex multicellular process consisting of cell adhesion, cell growth, morphogenic switching between yeast form and filamentous states, and quorum sensing. Here we describe the role of the C. albicans EAP1 gene, which encodes a glycosylphosphatidylinositol-anchored, glucan-cross-linked cell wall protein, in adhesion and biofilm formation in vitro and in vivo. Deleting EAP1 reduced cell adhesion to polystyrene and epithelial cells in a gene dosage-dependent manner. Furthermore, EAP1 expression was required for C. albicans biofilm formation in an in vitro parallel plate flow chamber model and in an in vivo rat central venous catheter model. EAP1 expression was upregulated in biofilm-associated cells in vitro and in vivo. Our results illustrate an association between Eap1p-mediated adhesion and biofilm formation in vitro and in vivo.

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