Young ICR Research Articles

Spontaneous type II cell-derived bronchioloalveolar adenoma in a young ICR mouse.

Although pulmonary adenomas have been reported in ICR mice, spontaneous adenomas have not been reported in mice aged ≤10 weeks. Here, we report a well-circumscribed nodule (1 mm × 1 mm) in the peripheral lesion of the left lateral lobe of a 10-week-old male ICR mouse. Histopathologic evaluation revealed a well-demarcated nodule compressing the surrounding tissue. The neoplastic cells were polygonal with indistinct cellular borders, round/oval nuclei and abundant cytoplasm. These characteristics led to the diagnosis of type II cell-derived bronchioloalveolar adenoma. Given that they are generally observed in aged laboratory animals, this case represents a rare manifestation of a spontaneous tumor in young laboratory mice before puberty.

DietaryAdvancedGlycationEnd Products-InducedCognitive Impairment in Aged ICR Mice: Protective Role of Quercetin.

Dietary advanced glycation products (dAGEs) have been reported to induce cognitive impairment while quercetin possesses potential neuroprotective effects. The aim is to explore whether dAGEs would induce similar cognitive impairment from both young and aged ICR mice, and the protective effects of quercetin. A total of 32 aged ICR mice (15-month-old) and 16 young ICR mice (3-month-old) are randomly assigned into the following six groups: Young mice control group, young mice fed with AGEs diet group, old mice control group, old mice fed with AGEs diet group, old mice with quercetin supplemented diet group, old mice fed with AGE diet supplemented with quercetin group. Dietary AGEs induced cognitive impairment only in aged, but not in young, ICR mice, while quercetin intervention is capable of reversing dAGEs-induced cognitive dysfunction. This may be since quercetin 1) increased miR-219, miR-15a, and miR-132 expression, inhibited p-ERK1/2, and tau phosphorylation; and 2) improved gut microbiota richness and diversity, inhibited phylum Tenericutes and Proteobacteria, and elevated butyric acid from cecum. Prolonged application of quercetin may be beneficial in the elderly, especially for those with high consumption of dAGEs.

Study of Jianpi Mixture on Intestinal Microbiota of Diarrhea Irritable Bowel Syndrome Mice.

To investigate the differences in intestinal microbiota between diarrhea irritable bowel syndrome mice (IBS-D) and healthy mice and to explore the effects of Jianpi mixture on intestinal microbes' changes in IBS-D mice based on 16S rDNA sequencing analysis. 48 young ICR male mice were randomly divided into four groups (n = 12): (1) control group, (2) IBS-D group fed with distilled water, (3) IBS-D group fed with lactic acid bacteria compound, and (4) IBS-D group fed with Jianpi mixture for 14 days. At the end of the treatment period, 5 mice were randomly selected from each group, and then the changes in intestinal microbiota in the mice before and after treatment were analyzed by 16S rDNA high-throughput gene sequencing. Compared with the control group, the species richness and species diversity of intestinal microbiota in feces and intestinal mucosa of IBS-D mice were decreased (P < 0.05); IBS-D mice showed changes in composition of and in ratio of the intestinal microbiota in feces and intestinal mucosa at the level of phylum, class, order, family, genus, and species. Treatment with Jianpi mixture increased the species diversity of intestinal microbiota in IBS-D mice (P < 0.05) and the abundance of beneficial bacteria (P < 0.05) and decreased the abundance of harmful bacteria (P < 0.05) at the level of phylum and genus. Compared with healthy mice, the species richness and species diversity of intestinal microbiota of IBS-D mice are decreased. The intervention with Jianpi mixture can improve its diversity and regulate the equilibrium between beneficial and harmful bacteria.

Reduction of Type IV Collagen by Upregulated miR-29 in Normal Elderly Mouse and klotho-Deficient, Senescence-Model Mouse

MicroRNA (miRNA), a small non-coding RNA that functions as a mediator in gene silencing, plays important roles in gene regulation in various vital functions and activities. Here we show that the miR-29 members are upregulated in klotho-deficient [klotho(−/−)] mice, a senescence-model animal, and also in normal elderly ICR mice relative to wild-type littermates and young ICR mice. In addition, levels of type IV collagen, a major component of basement membranes and a putative target of miR-29, were lower in klotho(−/−) and elderly ICR mice than in wild-type littermates and young ICR mice. RNA degradation mediated by miR-29 may participate in the suppression of type IV collagen, both in vivo and in vitro. Taken together, our current findings suggest that the miR-29 upregulated in aging may be involved in the downregulation of type IV collagen, leading to a possible weakening of the basal membrane in senescent tissues, and miR-29 may be a useful molecular marker of senescence.

Cumulus cell CoQ10 synthesis and mitochondrial function in aged mice: effect of CoQ10 supplementation

Older infertility patients have reduced oocyte mitochondrial production of ATP, which limits normal oocyte chromosomal disjunction and subsequent embryo development. Coenzyme Q10 (CoQ10) is a crucial substrate in the electron transport chain of mitochondria. The cumulus cells (CC), which nourish the oocyte, can produce and deliver CoQ10 to the oocyte like other substrates including cholesterol. The objective of the present study was to evaluate whether CoQ10 synthesis and mitochondrial activity in CC is altered with aging in mice, and if CoQ10 supplementation would improve CC mitochondrial function. Case-control study. 10 aged (12 months) and 10 young ICR mice (2-3 months) were superovulated and retrieved oocytes were stripped of CC. Another 10 aged mice were injected with coQ10 in oil (70 mg/week SC for 12 weeks). The CC from each oocyte were counted and examined by TUNEL for apoptosis, by RT-PCR for genes in the CoQ10 synthesis pathway, and by mitotracker green and red for mitochondrial content and activity. The number of CC per oocyte was decreased with aging (3050±236 young vs 1472±143 aged; P<0.001) and was abrogated (2218±276) in the aged-CoQ10 treated group. We saw a significant increase in apoptotic CC with aging (9.3% young vs 14.2% old; P<0.05, that was completely reversed by CoQ10 (6.9%). The expression of coQ10 synthesis genes was reduced in the aged compared to young animals, with significant reduction in Coq6 and Pdss2 (P<0.008 and P<0.013, respectively). Preliminary results showed reduced levels of CC mitochondrial content and activity with aging. Reduced CoQ10 synthesis gene expression was found in CC and was associated with decreased CC number, increased apoptosis, and decreased mitochondrial energy. Our results support reduced substrate synthesis in CC as a factor in reproductive aging in mammals. We are presently analyzing expression of CoQ10 synthesis genes in CC of older women undergoing IVF/ICSI and measuring coQ10 levels in follicular fluid.

The use of mitochondrial nutrients to improve the outcome of infertility treatment in older patients

We present a hypothesis emphasizing the role of mitochondrial dysfunction in reproductive senescence and suggesting the use of mitochondrial nutrients as an adjuvant treatment in older patients with infertility.

An Animal Model for Studying the Pathogenesis of Chikungunya Virus Infection

Newborn and 14-day-old mice inoculated subcutaneously with chikungunya virus (CHIKV) developed lethargy, difficulty walking, dragging of hind limbs, and reduced weight gain within 7-10 days after infection (PI). During the initial 6-7 days PI, the animals had viremia; high levels (10(6)-10(8) PFU) of CHIKV were also present in leg muscle. The virus persisted in muscle for several days after viremia disappeared. The major histopathologic changes were in skeletal muscle, which were focal necrosis and inflammation, followed by fibrosis and dystrophic calcification. Some mice also showed dystrophic calcification in the joint cartilage, but there were few deaths, and most of the animals eventually recovered. CHIKV antigen was shown by immunohistochemistry in the muscle for several weeks after infection. Based on the clinical and pathologic similarities with CHIKV infection in humans, young ICR and CD-1 mice offer a useful and realistic model for further study of the pathogenesis and treatment of CHIKV infection.

Regional transport of TNF-alpha across the blood-brain barrier in young ICR and young and aged SAMP8 mice.

The blood-brain barrier (BBB) controls the exchange of regulatory substances, including tumor necrosis factor-alpha (TNF), between the brain and the blood. Transport across the BBB of some regulatory substances is altered with aging. Here, we measured the blood to brain unidirectional influx rate (Ki) for whole brain and 10 brain regions for radioactively labeled TNF in three groups of mice: young (2 mo old) ICR (the standard outbred albino laboratory mouse also termed CD-1), young SAMP8 (a strain which develops impaired learning and memory with aging that correlates with an age-related increase in brain levels of amyloid beta protein), and aged (17 mo) SAMP8 mice. In ICR mice, the hypothalamus had the fastest (1.73 microl/g-min) and the parietal cortex the slowest (0.189 microl/g-min) rates of uptake, a regional difference of about 9 fold. No differences in transport into whole brain or brain regions occurred between the ICR and young SAMP8, showing a lack of differences between strains. Transport was higher for the occipital cortex, midbrain, and striatum in aged SAMP8 mice. These results show blood-borne TNF enters some regions of the brain much more readily than others and TNF transport is increased into some brain regions of the SAMP8 mice at an age when learning and memory are impaired.

Regional Variations in the Transport of Interleukin-1α across the Blood-Brain Barrier in ICR and Aging SAMP8 Mice

Objectives: The blood-brain barrier (BBB) transports blood-borne interleukin-1α (IL-1) into the brain by a saturable process. Here, we determined whether all regions of the brain could transport IL-1 and whether transport differed between ICR and SAMP8 mice, a strain which overexpresses amyloid beta protein (Aβ) with aging. Methods: We used multiple-time regression analysis to measure the unidirectional influx rate (transport rate) of radioactively labeled IL-1 for 10 brain regions in young (2 months old) ICR mice and in young and aged (17 months old) SAMP8 mice. We also used radioactively labeled sucrose and albumin to determine whether the BBB was disrupted in aged SAMP8 mice. Results: In young ICR mice, eight of the 10 brain regions transported IL-1, with the pons-medulla having the fastest transport rate (0.584 ± 0.163 µl/g·min), but no statistically significant differences occurred among regions. In SAMP8 mice, only four regions transported IL-1. In young SAMP8 mice, the pons-medulla transported IL-1 faster than any other region (0.642 ± 0.197 µl/g·min), a rate that was significantly different (p < 0.01) from each of the other regions. Aged SAMP8 mice had a similar regional transport pattern to young SAMP8 mice, but there were no statistically significant differences among the four transporting regions. Sucrose and albumin spaces were not increased in aged SAMP8 mice, demonstrating an intact BBB. Conclusions: The smaller number of regions transporting IL-1 in SAMP8 mice as compared to ICR mice demonstrates a genetic influence on transport which could alter the ability of blood-borne IL-1 to directly affect brain functions. No evidence of BBB disruption was found in the aged SAMP8 mice from this colony.

Production of term offspring by in vitro fertilization using old mouse spermatozoa.

We successfully produced offspring of old male BDF1 mice using in vitro fertilization. Although 7 old male mice (33 months of age) were infertile and revealed frequent degeneration in the seminiferous epithelia, 4 of them had spermatozoa in the caudae epididymides. The IVF rate of their sperm with eggs from young ICR mice was very high (82.0%). The production rate of offspring was also satisfactory (61.6%). The present study indicates that the IVF method is useful for producing offspring of aged male mice.