scholarly journals Manipulation of microbiota reveals altered myelination and white matter plasticity in a model of Huntington disease

2018 ◽  
Author(s):  
Carola I. Radulescu ◽  
Marta Garcia-Miralles ◽  
Harwin Sidik ◽  
Costanza Ferrari Bardile ◽  
Nur Amirah Binte Mohammad Yusof ◽  
...  
Keyword(s):  
Huntington Disease ◽  
Wild Type ◽  
Germ Free ◽  
Bidirectional Communication ◽  
The Family ◽  
Specific Pathogen ◽  
Myelin Thickness ◽  
Related Proteins ◽  
The Impact ◽  
Free Status

ABSTRACTStructural and molecular myelination deficits represent early pathological features of Huntington disease (HD). Recent evidence from germ-free (GF) animals suggests a role for microbiota-gut-brain bidirectional communication in the regulation of myelination. In this study, we aimed to investigate the impact of microbiota on myelin plasticity and oligodendroglial population dynamics in the mixed-sex BACHD mouse model of HD. Ultrastructural analysis of myelin in the corpus callosum revealed alterations of myelin thickness in BACHD GF compared to specific-pathogen free (SPF) mice, whereas no differences were observed between wild-type (WT) groups. In contrast, myelin compaction was altered in all groups when compared to WT SPF animals. Levels of myelin-related proteins were generally reduced, and the number of mature oligodendrocytes was decreased in the prefrontal cortex under GF compared to SPF conditions, regardless of genotype. Minor differences in commensal bacteria at the family and genera levels were found in the gut microbiota of BACHD and WT animals housed in standard living conditions. Our findings indicate complex effects of a germ-free status on myelin-related characteristics, and highlight the adaptive properties of myelination as a result of environmental manipulation.

Abnormal Spinal Cord Myelination due to Oligodendrocyte Dysfunction in a Model of Huntington’s Disease

2021 ◽  
pp. 1-8
Author(s):  
Costanza Ferrari Bardile ◽  
Harwin Sidik ◽  
Reynard Quek ◽  
Nur Amirah Binte Mohammad Yusof ◽  
Marta Garcia-Miralles ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Oligodendrocyte Progenitor Cells ◽  
Wild Type ◽  
Specific Expression ◽  
Relative Contribution ◽  
Related Proteins ◽  
The Impact ◽  
Cervical Area

Background: The relative contribution of grey matter (GM) and white matter (WM) degeneration to the progressive brain atrophy in Huntington’s disease (HD) has been well studied. The pathology of the spinal cord in HD is comparatively less well documented. Objective: We aim to characterize spinal cord WM abnormalities in a mouse model of HD and evaluate whether selective removal of mutant huntingtin (mHTT) from oligodendroglia rescues these deficits. Methods: Histological assessments were used to determine the area of GM and WM in the spinal cord of 12-month-old BACHD mice, while electron microscopy was used to analyze myelin fibers in the cervical area of the spinal cord. To investigate the impact of inactivation of mHTT in oligodendroglia on these measures, we used the previously described BACHDxNG2Cre mouse line where mHTT is specifically reduced in oligodendrocyte progenitor cells. Results: We show that spinal GM and WM areas are significantly atrophied in HD mice compared to wild-type controls. We further demonstrate that specific reduction of mHTT in oligodendroglial cells rescues the atrophy of spinal cord WM, but not GM, observed in HD mice. Inactivation of mHTT in oligodendroglia had no effect on the density of oligodendroglial cells but enhanced the expression of myelin-related proteins in the spinal cord. Conclusion: Our findings demonstrate that the myelination abnormalities observed in brain WM structures in HD extend to the spinal cord and suggest that specific expression of mHTT in oligodendrocytes contributes to such abnormalities.

scholarly journals Microbial Colonization in Adulthood Shapes the Intestinal Macrophage Compartment

2019 ◽  
Vol 13 (9) ◽  
pp. 1173-1185 ◽  
Author(s):  
Franziska Schmidt ◽  
Katja Dahlke ◽  
Arvind Batra ◽  
Jacqueline Keye ◽  
Hao Wu ◽  
...  
Keyword(s):  
Intestinal Wall ◽  
Functional Restoration ◽  
Microbial Colonization ◽  
Germ Free ◽  
Adult Mice ◽  
Immune Mediated ◽  
Complete Restoration ◽  
Specific Pathogen ◽  
Intestinal Macrophage ◽  
The Impact

Abstract Background and Aims Contact with distinct microbiota early in life has been shown to educate the mucosal immune system, hence providing protection against immune-mediated diseases. However, the impact of early versus late colonization with regard to the development of the intestinal macrophage compartment has not been studied so far. Methods Germ-free mice were colonized with specific-pathogen-free [SPF] microbiota at the age of 5 weeks. The ileal and colonic macrophage compartment were analysed by immunohistochemistry, flow cytometry, and RNA sequencing 1 and 5 weeks after colonization and in age-matched SPF mice, which had had contact with microbiota since birth. To evaluate the functional differences, dextran sulfate sodium [DSS]-induced colitis was induced, and barrier function analyses were undertaken. Results Germ-free mice were characterized by an atrophied intestinal wall and a profoundly reduced number of ileal macrophages. Strikingly, morphological restoration of the intestine occurred within the first week after colonization. In contrast, ileal macrophages required 5 weeks for complete restoration, whereas colonic macrophages were numerically unaffected. However, following DSS exposure, the presence of microbiota was a prerequisite for colonic macrophage infiltration. One week after colonization, mild colonic inflammation was observed, paralleled by a reduced inflammatory response after DSS treatment, in comparison with SPF mice. This attenuated inflammation was paralleled by a lack of TNFα production of LPS-stimulated colonic macrophages from SPF and colonized mice, suggesting desensitization of colonized mice by the colonization itself. Conclusions This study provides the first data indicating that after colonization of adult mice, the numeric, phenotypic, and functional restoration of the macrophage compartment requires the presence of intestinal microbiota and is time dependent.

scholarly journals Transcriptome Analysis of Trichothecene-Induced Gene Expression in Barley

2007 ◽  
Vol 20 (11) ◽  
pp. 1364-1375 ◽  
Author(s):  
Jayanand Boddu ◽  
Seungho Cho ◽  
Gary J. Muehlbauer
Keyword(s):  
Cell Death ◽  
Defense Response ◽  
Type Strain ◽  
Wild Type Strain ◽  
Loss Of Function ◽  
Wild Type ◽  
Genes Encoding ◽  
Basal Defense ◽  
Related Proteins ◽  
The Impact

Fusarium head blight, caused primarily by Fusarium graminearum, is a major disease problem on barley (Hordeum vulgare L.). Trichothecene mycotoxins produced by the fungus during infection increase the aggressiveness of the fungus and promote infection in wheat (Triticum aestivum L.). Loss-of-function mutations in the TRI5 gene in F. graminearum result in the inability to synthesize trichothecenes and in reduced virulence on wheat. We examined the impact of pathogen-derived trichothecenes on virulence and the transcriptional differences in barley spikes infected with a trichothecene-producing wild-type strain and a loss-of-function tri5 trichothecene nonproducing mutant. Disease severity, fungal biomass, and floret necrosis and bleaching were reduced in spikes inoculated with the tri5 mutant strain compared with the wild-type strain, indicating that the inability to synthesize trichothecenes results in reduced virulence in barley. We detected 63 transcripts that were induced during trichothecene accumulation, including genes encoding putative trichothecene detoxification and transport proteins, ubiquitination-related proteins, programmed cell death-related proteins, transcription factors, and cytochrome P450s. We also detected 414 gene transcripts that were designated as basal defense response genes largely independent of trichothecene accumulation. Our results show that barley exhibits a specific response to trichothecene accumulation that can be separated from the basal defense response. We propose that barley responds to trichothecene accumulation by inducing at least two general responses. One response is the induction of genes encoding trichothecene detoxification and transport activities that may reduce the impact of trichothecenes. The other response is to induce genes encoding proteins associated with ubiquitination and cell death which may promote successful establishment of the disease.

Subtle Impact of Akt1 and Akt3 on Exploratory Behavior in Gene Targeted Mice

2015 ◽  
Vol 223 (3) ◽  
pp. 173-180 ◽  
Author(s):  
Christina Leibrock ◽  
Michael Hierlmeier ◽  
Undine E. Lang ◽  
Florian Lang
Keyword(s):  
Forced Swimming Test ◽  
Open Field Test ◽  
Wild Type ◽  
Average Speed ◽  
Closed Area ◽  
Light Area ◽  
Swimming Test ◽  
The Impact ◽  
Center Area ◽  
Dark Transition

Abstract. The present study explored the impact of Akt1 and Akt3 on behavior. Akt1 (akt1-/-) and Akt3 (akt3-/-) knockout mice were compared to wild type (wt) mice. The akt1-/- mice, akt3-/- mice, and wt mice were similar in most parameters of the open-field test. However, the distance traveled in the center area was slightly but significantly less in akt3-/- mice than in wt mice. In the light/dark transition test akt1-/- mice had significantly lower values than wt mice and akt3-/- mice for distance traveled, number of rearings, rearing time in the light area, as well as time spent and distance traveled in the entrance area. They were significantly different from akt3-/- mice in the distance traveled, visits, number of rearings, rearing time in the light area, as well as time spent, distance traveled, number of rearings, and rearing time in the entrance area. In the O-maze the time spent, and the visits to open arms, as well as the number of protected and unprotected headdips were significantly less in akt1-/- mice than in wt mice, whereas the time spent in closed arms was significantly more in akt1-/- mice than in wt mice. Protected and unprotected headdips were significantly less in akt3-/- mice than in wt mice. In closed area, akt3-/- mice traveled a significantly larger distance at larger average speed than akt1-/- mice. No differences were observed between akt1-/- mice, akt3-/- mice and wt-type mice in the time of floating during the forced swimming test. In conclusion, akt1-/- mice and less so akt3-/ mice display subtle changes in behavior.

Adolescents' Perceptions of The Impact of Caregiving on The Family

2007 ◽  
Author(s):  
Sharon B. Hamill ◽  
Tayari Shorter ◽  
Sarah Singleton ◽  
Carrie Page ◽  
Tabitha Pierce
Keyword(s):  
The Family ◽  
The Impact

The effect of brain vitalization activity on dementia incidence in elderly at Budi Luhur Nursing Home of Yogyakarta, Kasongan, Bantul

2020 ◽  
Vol 1 (3) ◽  
pp. 43-50
Author(s):  
Firstyono Miftahul Aziz ◽  
Suratini Suratini
Keyword(s):  
Nursing Home ◽  
The Elderly ◽  
Control Group ◽  
P Value ◽  
Sampling System ◽  
Randomized Sampling ◽  
Care For The Elderly ◽  
Dementia Incidence ◽  
The Family ◽  
The Impact

For some people, dementia is considered as a disease that is common in elderly, regardless the impact of dementia. Taking care for the elderly with dementia brings stress for the family. It can cause and increase the family burden. Brain vitalization gymnastics is one of the methods to improve memory. The study aims to investigate the effect of brain vitalization activity on dementia incidence in elderly at Budi Luhur Nursing Home of Yogyakarta. The study used Quasi Experimental with Pretest-Posttest control group and randomized sampling system. The samples were taken randomly as many as 26 respondents and were divided into two groups namely 13 respondents of experimental group and 13 respondents of control group. The statistical test used Wilcoxon Match Pairs Test. The result showed that Wilcoxon Match pairs test obtained p value 0,003, which is smaller than 0,005. There is an effect of brain vitalization activity on dementia incidence in elderly at Budi Luhur Nursing Home of Yogyakarta

The Impact of Parole Upon the Family

1961 ◽  
Vol 3 (3) ◽  
pp. 291-297
Author(s):  
Patrick Deehy
Keyword(s):  
The Family ◽  
The Impact

Modulation of Hepatic MRP3/ABCC3 by Xenobiotics and Pathophysiological Conditions: Role in Drug Pharmacokinetics

2019 ◽  
Vol 26 (7) ◽  
pp. 1185-1223 ◽  
Author(s):  
Carolina I. Ghanem ◽  
Jose E. Manautou
Keyword(s):  
Abc Transporters ◽  
Basolateral Membrane ◽  
Clinical Use ◽  
Nucleotide Analogs ◽  
Synthetic Drugs ◽  
The Family ◽  
Hepatic Transporter ◽  
Related Proteins ◽  
Drug Pharmacokinetics ◽  
Conjugated Metabolites

Liver transporters play an important role in the pharmacokinetics and disposition of pharmaceuticals, environmental contaminants, and endogenous compounds. Among them, the family of ATP-Binding Cassette (ABC) transporters is the most important due to its role in the transport of endo- and xenobiotics. The ABCC sub-family is the largest one, consisting of 13 members that include the cystic fibrosis conductance regulator (CFTR/ABCC7); the sulfonylurea receptors (SUR1/ABCC8 and SUR2/ABCC9) and the multidrug resistanceassociated proteins (MRPs). The MRP-related proteins can collectively confer resistance to natural, synthetic drugs and their conjugated metabolites, including platinum-containing compounds, folate anti-metabolites, nucleoside and nucleotide analogs, among others. MRPs can be also catalogued into "long" (MRP1/ABCC1, -2/C2, -3/C3, -6/C6, and -7/C10) and "short" (MRP4/C4, -5/C5, -8/C11, -9/C12, and -10/C13) categories. While MRP2/ABCC2 is expressed in the canalicular pole of hepatocytes, all others are located in the basolateral membrane. In this review, we summarize information from studies examining the changes in expression and regulation of the basolateral hepatic transporter MPR3/ABCC3 by xenobiotics and during various pathophysiological conditions. We also focus, primarily, on the consequences of such changes in the pharmacokinetic, pharmacodynamic and/or toxicity of different drugs of clinical use transported by MRP3.

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