Role of gastrointestinal microflora in nitrogen and mineral balances in young mice fed on autoclaved and irradiated diets.

Experiments were carried out to assess the role of naturally acquired antibody-specific immunoregulation in the immunodeficiency of aged individuals. It was found that greater than 50% of the primary dinitrophenyl-specific BALB/c B cells did not respond in carrier-primed 2-yr-old BALB/c adoptive hosts as compared with similarly primed younger recipients. Similar suppression was observed in carrier-primed younger BALB/c mice that had received 4 x 10(7) spleen cells from 2-yr-old BALB/c mice, as opposed to those that had received 4 x 10(7) spleen cells from younger mice. This diminution in responsiveness was noted only for syngeneic BALB/c B cells because B cells of strains differing from BALB/c in the heavy chain allotype-idiotype locus were not suppressed. These findings indicate that old, but not young, mice had developed the capacity to suppress primary B cells bearing receptors expressing much of the syngeneic antibody repertoire. This suppression may play an important causative role in the relatively poor humoral immune responsiveness of aged individuals.

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Regulation of Appetite and Gastrointestinal Microflora: Role of a Fecal Anorexigenic Substance (FS-.T)

Bifidobacteria and Microflora ◽

10.12938/bifidus1982.12.1_25 ◽

1993 ◽

Vol 12 (1) ◽

pp. 25-30 ◽

Cited By ~ 1

Author(s):

Tomi T. TSUDA ◽

Tomoichi OHKUBO ◽

Michio TSUDA ◽

Masaichi YAMAMURA ◽

Nobuhiko OHNISHI

Keyword(s):

Gastrointestinal Microflora

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Dicer Ablations in Bone Marrow Niche Impair Hematopoietic Progenitor/Stem Cells and Induce Myelodysplasia in Young Mice but Are Dispensable for Adult Hematopoiesis

Blood ◽

10.1182/blood.v126.23.1196.1196 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1196-1196 ◽

Cited By ~ 1

Author(s):

Bijender Kumar ◽

Mayra Garcia ◽

Guido Marcucci ◽

Ching-Cheng Chen

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Embryonic Development ◽

Bone Marrow Niche ◽

Hematopoietic Progenitors ◽

Mirna Processing ◽

Adult Mice ◽

Hsc Niche ◽

Young Mice

Abstract MicroRNAs (miRNAs) regulate hematopoietic cell fate and their global down-regulation by Dicer1 deletion promotes tumorigenesis in a cancer-cell-autonomous manner (Kumar M.S. et al, 2007). Raajimakers MH et al. (2010) using neonatal Osterix specific dicer deletion showed altered hematopoiesis and developed myelodysplasia. However, there is no study illustrating the role of the ablation of bone marrow (BM) niche specific miRNA processing machinery in the adult mice. Since expression and functions of different mesenchymal and osteoprogenitors vary from embryonic development to adulthood, studying the dicer ablation in adult mice may provide more insight about the role of miRNA processing in adult mice niche. Here we investigate whether adult Osterix expressing cells play a similar role in the HSC niche compared to fetal Osterix expressing cells. We crossed Osx-GFP-tTA-Cre recombinase mice with mice with floxed Dicer1 allele. Crossing generated Osx- GFP-tTA-Cre+Dicerfl/+ (OCDfl/+control) and Osx-GFP- tTA-Cre+ Dicerfl/fl (OCDfl/fl mutant) mice. Osx-GFP-tTA-Cre expression was either activated during embryonic development (young dicer KO) or suppressed using tetracycline until mice were 6 weeks of age (adult dicer KO). We found young dicer KO mice had reduced weight (p=0.0031), leukopenia, anemia, reduced mature CD19+B220- B lymphocytes (p=0.0034) and increased CD11b+Gr- monocytes and CD11b+Gr+ neutrophils (p=0.02 and p=0.04 respectively) in peripheral blood compared to OCDfl/+ control aged littler mates. The leucocytes and platelets showed dysplastic changes suggestive of myelodysplasia and had extra-medullary hematopoiesis. Adult dice KO, on the other hand, show no leukemia development 6 months after Cre activation. The number of BM hematopoietic progenitors (Lin-Sca1+ c-Kit+ cells, LSK) and long term hematopoietic stem cells (LT-HSCs, LSK CD150+CD48+ cells) in young dicer KO mice were significantly reduced compared to age matched control (OCDfl/+ control) mice. We observed increased Annexin V positive LSK, LT-HSCs and megakaryocytes erythroid progenitors (MEP) in the young dicer KO mice indicating increased apoptosis. Adult dicer KO mice didn't have significant changes in apoptosis in different hematopoietic progenitors. In young dicer KO mice, BM derived LSK and LT-HSCs showed increased cycling (SG2M phase, p=0.0133) and less quiescenece (Go phase, p=0.013). However LT-HSC from adult dicer KO didn't show any difference in cell cycling (p=0.18 and 0.09 respectively). Together these results indicate that while Osterix expressing cells in fetal and young mice give rise to a variety of HSC niche supporting cells the adult expression is limited to more mature osteoblast that are not absolutely essential for HSC maintenance. Our study provides the rationale for further exploration of the complexity in hierarchy of activity within niche constituting mesenchymal stroma progenitors and their role in different developmental stages to maintain hematopoiesis. Disclosures No relevant conflicts of interest to declare.

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Beneficial effects of tamoxifen on leptin sensitivity in young mice fed a high fat diet: Role of estrogen receptor α and cytokines

Life Sciences ◽

10.1016/j.lfs.2020.117384 ◽

2020 ◽

Vol 246 ◽

pp. 117384

Author(s):

Zeinab Farhadi ◽

Mohammad Khaksari ◽

Hossein Azizian ◽

Abbas Mortazaeizadeh ◽

Mohammad Shabani ◽

...

Keyword(s):

Estrogen Receptor ◽

High Fat Diet ◽

Estrogen Receptor Α ◽

High Fat ◽

Beneficial Effects ◽

Leptin Sensitivity ◽

Young Mice

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Cytoplasmic mislocalization and mitochondrial colocalization of TDP-43 are common features between normal aged and young mice

Experimental Biology and Medicine ◽

10.1177/1535370220914253 ◽

2020 ◽

Vol 245 (17) ◽

pp. 1584-1593 ◽

Cited By ~ 1

Author(s):

Pichet Termsarasab ◽

Thananan Thammongkolchai ◽

Ju Gao ◽

Luwen Wang ◽

Jingjing Liang ◽

...

Keyword(s):

Neurodegenerative Disorders ◽

Neuronal Loss ◽

Critical Factor ◽

Brain Regions ◽

Normal Aging ◽

Age Related ◽

Wide Range ◽

Cytoplasmic Accumulation ◽

Young Mice

Transactive response DNA binding protein 43 (TDP-43) pathologies have been well recognized in various neurodegenerative disorders including frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Alzheimer’s disease (AD). However, there have been limited studies on whether there are any TDP-43 alterations in normal aging. We investigated TDP-43 distribution in different brain regions in normal aged ( n = 3 for 26- or 36-month-old) compared to young ( n = 3 for 6- or 12-month-old) mice. In both normal aged and young mice, TDP-43 and phosphorylated TDP-43 (pTDP-43) demonstrated a unique pattern of distribution in neurons in some specific brain regions including the pontine nuclei, thalamus, CA3 region of the hippocampus, and orbital cortex. This pattern was demonstrated on higher magnification of high-resolution double fluorescence images and confocal microscopy as mislocalization of TDP-43 and pTDP-43, characterized by neuronal nuclear depletion and cytoplasmic accumulation in these brain regions, as well as colocalization between TDP-43 or pTDP-43 and mitochondria, similar to what has been described previously in neurodegenerative disorders. All these findings were identical in both normal aged and young mice. In summary, TDP-43 and pTDP-43 mislocalization from nucleus to cytoplasm and their colocalization with mitochondria in the specific brain regions are present not only in aging, but also in young healthy states. Our findings provide a new insight for the role of TDP-43 proteinopathy in health and diseases, and that aging may not be a critical factor for the development of TDP-43 proteinopathy in subpopulations of neurons. Impact statement Despite increasing evidence implicating the important role of TDP-43 in the pathogenesis of a wide range of age-related neurodegenerative diseases, there is limited study of TDP-43 proteinopathy and its association with mitochondria during normal aging. Our findings of cytoplasmic accumulation of TDP-43 that is highly colocalized with mitochondria in neurons in selective brain regions in young animals in the absence of neuronal loss provide a novel insight into the development of TDP-43 proteinopathy and its contribution to neuronal loss.

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Role of the gastrointestinal microflora in amygdalin (laetrile)-induced cyanide toxicity

Biochemical Pharmacology ◽

10.1016/0006-2952(80)90504-3 ◽

1980 ◽

Vol 29 (3) ◽

pp. 301-304 ◽

Cited By ~ 54

Author(s):

John H. Carter ◽

Martha A. McLafferty ◽

Peter Goldman

Keyword(s):

Cyanide Toxicity ◽

Gastrointestinal Microflora

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Abstract 1485: Ischemic Postconditioning’s Protection Is Lost In Aged And Stat3-deficient Mice

Circulation ◽

10.1161/circ.116.suppl_16.ii_306-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Kerstin Boengler ◽

Astrid Buechert ◽

Yvonne Heinen ◽

Denise Hilfiker-Kleiner ◽

Gerd Heusch ◽

...

Keyword(s):

List Type ◽

Area At Risk ◽

Lower Efficiency ◽

Age Related ◽

Transcription 3 ◽

Phosphorylated Stat3 ◽

Deficient Mice ◽

Mediated Reduction ◽

Young Mice

The cardioprotection by ischemic preconditioning is lost in aged wildtype (WT) mice and in STAT3-deficient mice (signal transducer and activator of transcription 3). The aim of the present study was to analyze whether or not ischemic postconditioning (iPo) is effective in aged WT mice hearts, and whether or not it is dependent on the presence of STAT3. Young (3 months) and aged (>13 months) C57Bl6/J female mice underwent 30 min of ischemia and 2 h reperfusion (I/R) without or with iPo (3 cycles of 10 s ischemia and 10 s reperfusion (iPo3) or 5 cycles of 5 s ischemia and 5 s reperfusion (iPo5) at the beginning of reperfusion). In young mice hearts, iPo3 and iPo5 reduced the infarct size (IS, % of the area at risk) to a similar extent from 65.8±2.8 (n=11) to 50.7±2.8 (3×10, n=10, p<0.05) and to 49.8±3.8 (5×5, n=10, p<0.05). In contrast, in aged WT hearts IS was similar following I/R and iPo3 (60.1±3.2, n=10 vs. 66.4±3.0, n=7), but was reduced by iPo5 (46.5±4.2, n=7, p<0.05). Western blot analysis on right ventricular protein extracts from aged WT mice hearts indicated a reduction of phosphorylated STAT3 (Ser727) to 72.0±7.6% (n=19, p<0.05) and of total STAT3 to 72.1±5.5% (n=27, p<0.05) of that in young WT mice, which was set as 100% (n=18). In young mice (3 months) with a cardiomyocyte-restricted deletion of STAT3 (STAT3-KO) only iPo3 failed to reduce IS compared to I/R (62.2±3.5, n=5 vs. 64.4±3.1, n=8), whereas the stronger stimulus iPo5 once again significantly reduced IS (55.0±2.8, n=9, p<0.05). In conclusion, lower efficiency of iPO protection against I/R in aged mice hearts was associated with a reduced cardiac expression of STAT3. In line with a crucial role of STAT3 for iPO protection in I/R, STAT3-KO mice displayed also an attenuated susceptibility for iPO mediated protection in I/R. Thus age mediated reduction of cardiac STAT3 expression may contribute to the age-related reduced efficienty of iPo to protect from I/R injury.

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