Experimental Animals
Online ISSN : 1881-7122
Print ISSN : 1341-1357
ISSN-L : 0007-5124
Advance online publication
Displaying 1-19 of 19 articles from this issue
  • Naoshige ONO, Joji HORIKOSHI, Takeshi IZAWA, Kazuhiro NISHIYAMA, Miyuu ...
    Article type: Original
    Article ID: 23-0094
    Published: 2023
    Advance online publication: December 06, 2023
    JOURNAL OPEN ACCESS ADVANCE PUBLICATION

    IL-19 is a member of IL-10 family and is mainly produced by macrophages. Acute pancreatitis (AP) is an inflammatory disease characterized by acinar cell injury and necrosis. In the present study, the role of IL-19 in AP and AP-associated lung injury in mice was explored using L-arginine-induced pancreatitis. Experimental pancreatitis was induced by intraperitoneal injection of L-arginine in wild-type (WT) and IL-19 gene deficient (IL-19 KO) mice. In L-arginine treated mice, the serum amylase level was significantly increased in IL-19 KO mice, and interstitial edema, analyzed using hematoxylin and eosin (H&E)-stained sections, was aggravated mildly in IL-19 KO mice compared to WT mice. Compared to WT mice treated with L-arginine, mRNA expression of tumor necrosis factor (TNF)-α was significantly upregulated in IL-19 KO mice treated with L-arginine. In WT mice, IL-19 mRNA was equally expressed in the pancreas of both control and L-arginine treated mice. The condition of lung alveoli in WT and IL-19 KO mice treated with L-arginine was then evaluated. In mice with L-arginine-induced pancreatitis, alveolar area was remarkedly decreased, and expression of lung myeloperoxidase was significantly increased in IL-19 KO mice compared to WT mice. In the lungs, mRNA expressions of IL-6 and inducible nitric oxide synthase were significantly increased in IL-19 KO mice compared to WT mice. In summary, IL-19 was proposed to alleviate L-arginine-induced pancreatitis by regulating TNF-α production and to protect against AP-related lung injury by inhibiting neutrophil migration.

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  • Haiqing ZHANG, Jiyao QIN, Zunlin ZHOU, Juan YANG, Hao HUANG, Xiaoyan Y ...
    Article type: Original
    Article ID: 23-0092
    Published: 2023
    Advance online publication: November 29, 2023
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    Transmembrane protein (TMEM230) is located in secretory/recycling vesicles, including synaptic vesicles in neurons. However, the functional relationship between TMEM230 and epilepsy is still a mystery. The aims of this study were to investigate the expression of TMEM230 in patients with temporal lobe epilepsy (TLE) and two different mice models of chronic epilepsy, and to determine the probable roles of TMEM230 in epilepsy. Our results showed that TMEM230 expression was increased in the temporal neocortex of epileptic patients and the hippocampus and cortex of epileptic mice compared with that in the control tissues. Moreover, TMEM230 was mainly expressed in the neurons in both humans and mice epileptic brain. TMEM230 co-localized with glutamate vesicular transporter 1 (VGLUT-1), but not with vesicular GABA transporter (VGAT). Mechanistically, coimmunoprecipitation confirmed that TMEM230 interacted with VGLUT-1, but not with VGAT in the hippocampus of epileptic mice. Lentivirus mediated overexpression of TMEM230 increased mice susceptibility to epilepsy and behavioural phenotypes of epileptic seizures during the kainite (KA)-induced chronic phase of epileptic seizures and the pentylenetetrazole (PTZ) kindling process, whereas lentivirus-mediated TMEM230 downregulation had the opposite effect. These results shed light on the functions of TMEM230 in neurons, suggesting that TMEM230 may play a critical role in the regulation of epileptic activity via influencing excitatory neurotransmission.

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  • Rui DAI, Yun XIANG, Rui FANG, Hai-Han ZHENG, Qing-Song ZHAO, Yan WANG
    Article type: Original
    Article ID: 23-0068
    Published: 2023
    Advance online publication: November 10, 2023
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    Asthma is the most common chronic disease in the respiratory system of children caused by abnormal immunity that responses to common antigens. Lonicerin exerts anti-inflammatory activity in other inflammatory models through targeting enhancer of zeste homolog 2 (EZH2) that is related to asthma. We sought to explore the role and mechanism of lonicerin in regulating allergic airway inflammation. Mice were intraperitoneally injected 10 μg ovalbumin (OVA) on postnatal day 5 (P5) and P10, and then inhaled 3% aerosolized OVA for 10 min every day on P18–20, to establish asthmatic mice model. Lonicerin (10 or 30 mg/kg) was given to mice by intragastric administration on P16–P20. Notably, the administration of lonicerin amended infiltration of inflammatory cells and mucus hypersecretion. OVA-specific IgE level, inflammatory cell count and inflammatory cytokines in asthmatic mice were reduced after lonicerin treatment. Moreover, it suppressed the activity of EZH2 and activation of nuclear factor-kappa B (NF-ĸB) as evidenced by decreasing tri-methylation of histone H3 at lysine 27 and reducing nuclear translocation of NF-κB p65. In a word, Lonicerin may attenuate asthma by inhibiting EZH2/NF-κB signaling pathway.

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  • Ryota TOCHINAI, Koichi KIMURA, Takeru SAIKA, Wataru FUJII, Hiroyuki MO ...
    Article type: Original
    Article ID: 23-0087
    Published: 2023
    Advance online publication: November 01, 2023
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    Duchenne muscular dystrophy (DMD) is an X-linked recessive myopathy caused by dystrophin mutations. Inevitable progressive cardiomyopathy is a current leading cause of premature death although respiratory management has improved the prognosis of patients with DMD. Recent evidence shows that reducing the heart rate is expected as one of the promising strategies for heart failure treatment, but administering a sufficient dose of β-blocker for patients with DMD with tachycardia is difficult because of their low blood pressure (BP). Thus, this study aimed to clarify the role of ivabradine, which suppresses cardiac sinus node pacemakers without decreasing BP, in ameliorating cardiomyopathy progression in a rat model with DMD. A trans-oral single ivabradine administration demonstrated a declined dose-dependent heart rate without any significant BP reduction. Trans-gastric repeated administrations of 5 mg/kg of ivabradine twice a day for 3 months showed ameliorated cardiomyopathy in DMD rats based on echocardiography and histopathological observations (left ventricular dysfunction, right ventricular dysfunction, and myocardial fibrosis) as compared with vehicle administration. Our finding indicates that ivabradine is expected as another treatment choice for patients with DMD having tachycardia.

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  • Yanqiang CHEN, Cong ZHANG, Liming ZHAO, Rong CHEN, Peipei ZHANG, Junxi ...
    Article type: Original
    Article ID: 23-0070
    Published: 2023
    Advance online publication: October 14, 2023
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    Excessive neuroinflammation mediated by microglia has a detrimental effect on the progression of ischemic stroke. Eriocalyxin B (EriB) was found with a neuroprotective effect in mice with Parkinson’s disease by suppressing the microglial overactivation. This study aims to investigate the roles of EriB in permanent middle cerebral artery occlusion (pMCAO) mice. The pMCAO was induced by intraluminal filament method in internal carotidartery of mice, which underwent an immediately intraperitoneal injection of EriB (10 mg/kg) post surgery. The behavior score, 2,3,5-triphenyltetrazole chloride staining, Nissl staining, TUNEL, immunohistochemistry, immunofluorescence, PCR, ELISA and immunoblotting revealed that EriB administration reduced brain infarct and neuron death, ameliorated neuroinflammation and microglia overactivation in pMCAO mice, manifested by alterations of TUNEL-positive cell numbers, ionized calcium binding adaptor molecule 1 (Iba-1)-positive cell numbers, expression of tumor necrosis factor-α, interleukin (IL)-6, IL-1β, inducible nitric oxide synthase and arginase 1. In addition, EriB suppressed ischemia-induced activation of nuclear factor kappa B (NF-κB) signaling in brain penumbra, suggesting the involvement of NF-κB in EriB function. In conclusions, EriB exerted anti-inflammatory effects in ischemia stroke through regulating NF-κB signaling pathway, which may provide insights into the neuroprotective effect of EriB on the treatment of ischemic stroke.

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  • Kohei KAWAKAMI, Hiroyuki MATSUO, Naoyo KAJITANI, Ken-ichi MATSUMOTO
    Article type: Original
    Article ID: 23-0069
    Published: 2023
    Advance online publication: October 12, 2023
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    Genetic and environmental factors interact in a complex manner in the pathogenesis of essential hypertension in humans. Oxidative stress is considered one of the more important environmental factors. We used the spontaneously hypertensive rat (SHR) model to test whether continuous feeding with the antioxidant tempol reduces maternal oxidative stress during pregnancy and potentially contributes to the prevention of cardiovascular disease onset. Pregnant female rats were divided into control and tempol-treated groups. Tempol was continuously administered in the drinking water. The administration period lasted approximately 40 days from the confirmation of a vaginal plug until birth of the pups and their subsequent weaning. The blood pressure (BP) of each adult female was measured three times during pregnancy and post parturition. Milk was collected three times in the immediate postpartum period from nursing mother rats. Markers of oxidative stress were measured: 8-hydroxyl-2′-deoxyguanosine (8-OHdG) levels in milk during the experimental period, 8-OHdG levels and corticosterone levels in urine of adult and neonatal rats. The urinary level of 8-OHdG in the tempol-treated group was significantly lower than in the control group. Corticosterone levels were significantly lower in urine of neonatal rats from the tempol-treated group compared to the control group. 8-OHdG and corticosterone levels in milk of the tempol-treated group were significantly greater than in the control group. This study demonstrates that continuous administration of tempol to pregnant SHRs reduced maternal oxidative stress and contributed to reduced oxidative stress in neonatal rats.

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  • Zhen LI, Mengfan HE, Danqing DAI, Xiaofei GAO, Huazheng LIANG, Lize XI ...
    Article type: Original
    Article ID: 23-0065
    Published: 2023
    Advance online publication: September 27, 2023
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    Postoperative complications, such as perioperative neurocognitive disorders (PND), have become a major issue affecting surgical outcomes. However, the mechanism of PND remains unclear, and stable animal models of middle-aged PND are lacking. S-adenosylmethionine (SAM), a cystathionine beta-synthase (CBS) allosteric activator, can reduce the level of plasma homocysteine and prevent the occurrence of PND. However, the time and resource-intensive process of constructing models of PND in elderly animals have limited progress in PND research and innovative therapy development. The present study aimed to construct a stable PND model in middle-aged CAMKII-Cre:CBSfl/fl mice whose CBS was specifically knocked out in CAMKII positive neurons. Behavioral tests showed that these middle-aged mice displayed cognitive deficits which were aggravated by exploratory laparotomy under isoflurane anesthesia. Compared with typical PND mice which were 18-month-old, these middle-aged mice showed similar cognitive deficits after undergoing exploratory laparotomy under isoflurane anesthesia. Though there was no significant difference in the number of neurons in either the hippocampus or the cortex, a significant increase in numbers of microglia and astrocytes in the hippocampus was observed. These indicate that middle-aged CAMKII-Cre:CBSfl/fl mice can be used as a new PND model for mechanistic studies and therapy development for PND.

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  • Tohru MIYATA, Akira SHOGATSUDANI, Ayaka IGARASHI, Haruna TSUTIYA, Kyou ...
    Article type: Original
    Article ID: 23-0074
    Published: 2023
    Advance online publication: September 12, 2023
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    This study compared differences in exercise capacity as well as muscle glycogen content and degradation, and mitochondrial enzyme activity between C57BL/6J and BALB/cA mice. In exercise tests, grip strength was higher in BALB/cA mice. In Rotarod and Inverted screen test, C57BL/6J mice had significantly longer exercise durations and showed differences in motor function and muscle endurance time. Glycogen in the liver and muscle of C57BL/6J mice was significantly decreased after 20 minutes of swimming. Muscle glycogen content in BALB/cA mice was higher than in C57BL/6J, but swimming induced no decrease in glycogen content. Glycogen phosphorylase in muscle was inactive in the absence of AMP, and its activity increased in a concentration-dependent manner with the addition of AMP in C57BL/6J mice. In BALB/cA mice, phosphorylase activity was increased by AMP, but not further increased by higher concentrations of AMP. The citrate synthase activity in muscle did not differ between C57BL/6J and BALB/cA mice. The results of this study suggested that the reactivity of muscle glycogen phosphorylase to AMP differs among strains of mice and affects glycogen availability during exercise.

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  • Satsuki TAKASHIMA, Eiichi OKAMURA, Yusuke ICHIYAMA, Kiyoto NISHI, Akio ...
    Article type: Original
    Article ID: 23-0105
    Published: 2023
    Advance online publication: September 01, 2023
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    Exocyst is an octameric protein complex implicated in exocytosis. The exocyst complex is highly conserved among mammalian species, but the physiological function of each subunit in exocyst remains unclear. Previously, we identified exocyst complex 3-like (Exoc3l) as a gene abundantly expressed in embryonic endothelial cells and implicated in the process of angiogenesis in human umbilical cord endothelial cells. Here, to reveal the physiological roles of Exoc3l during development, we generated Exoc3l knockout (KO) mice by genome editing with CRISPR/Cas9. Exoc3l KO mice were viable and showed no significant phenotype in embryonic angiogenesis or postnatal retinal angiogenesis. Exoc3l KO mice also showed no significant alteration in cholesterol homeostasis or insulin secretion, although several reports suggest an association of Exoc3l with these processes. Despite the implied roles, Exoc3l KO mice exhibited no apparent phenotype in vascular development, cholesterol homeostasis, or insulin secretion.

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  • Yu LEI, Yu CHEN, Shuhui WANG, Zhuoying LIN, Ping HAN, Dean TIAN, Han W ...
    Article type: Original
    Article ID: 23-0053
    Published: 2023
    Advance online publication: August 31, 2023
    JOURNAL OPEN ACCESS ADVANCE PUBLICATION

    The incidence of autoimmune hepatitis (AIH) has increased significantly worldwide. The present study aims to explore the protective effect of L-lysine supplementation against AIH and to investigate its potential underlying mechanisms. A chronic experimental AIH mouse model was established by repeated tail vein injection of human cytochrome P450 2D6 (CYP2D6) plasmid. Starting from day 14 of the modeling, mice in the CYP2D6-AIH +L-lysine group were given 200 μl of purified water containing 10 mg/kg L-lysine by gavage until day27, once a day, and mice in the healthy control group and model group were given an equal volume of purified water by gavage. Our results showed that L-lysine supplementation partially reversed the liver injury mediated by CYP2D6 overexpression. These effects were consistent with the restraining impacts of L-lysine supplementation on decreasing pro-inflammatory cytokines expression level and CD4+ and CD8+ T lymphocytes infiltration, as well as curbing hepatic oxidative stress. Furthermore, L-lysine supplement relieved liver fibrosis in the context of AIH. In conclusion, L-lysine supplementation attenuates CYP2D6-induced immune liver injury in mice, which may serve as a novel nutrition support approach for AIH.

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  • Nozomi FUJISAWA, Tomochika MATSUSHITA, Saori MATSUO, Mayumi HIRANUMA, ...
    Article type: Original
    Article ID: 23-0017
    Published: 2023
    Advance online publication: August 29, 2023
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    Animals frequently eat less after test-article treatment in non-clinical toxicological studies, and it can be difficult to distinguish test article-derived toxicities from secondary changes related to this reduced food intake. Therefore, in this study, we restricted the food intake of cynomolgus monkeys (Cambodian, male, n=2 or 3, 4-year ± 3-month-old) to 25% of control for two weeks, and evaluated its effect on toxicological parameters (general conditions, body weight, electrocardiography, urinalysis, hematology, blood chemistry, bone marrow analysis, pathological examination). After 2 weeks, these monkeys exhibited decreases in bone marrow erythropoiesis (e.g. decreases in reticulocytes and bone marrow erythrocytes), glycogenesis induction (e.g. increase in AST), and malnutrition (e.g. decrease in triglyceride and systemic adipocytes atrophy). Additionally, histopathological analysis revealed granuloma and inflammatory cell infiltration in coronary fat, which had never been found in previous food restriction studies using other animal species. These findings will enable researchers to more accurately evaluate the toxicological risks of test-articles that simultaneously induce food intake reduction.

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  • Hong-Bo YANG, Ying LI, Xiu-Hai LI, Qing-Ming YAN, Xian-Zhang HAN, Jian ...
    Article type: Original
    Article ID: 23-0041
    Published: 2023
    Advance online publication: August 12, 2023
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    Spinal cord injury (SCI) is a devastating disease characterized by neuronal apoptosis. Gli-similar 3 (GLIS3), a transcriptional factor, was involved in cell apoptosis and associated with the transcription of downstream target genes related to neuronal function. However, the function of GLIS3 in SCI remains unknown. Therefore, we used the mouse model of SCI to explore the role of GLIS3 in SCI. The results showed that GLIS3 expression was significantly increased in spinal cord tissues of SCI mice, and GLIS3 overexpression promoted the functional recovery, reserved histological changes, and inhibited neuronal apoptosis after SCI. Through online tools, the potential target genes of GLIS3 were analyzed and we found that Mps One Binder Kinase Activator 1b (MOB1b) had a strong association with SCI among these genes. MOB1b is a core component of Hippo signaling pathway, which was reported to inhibit cell apoptosis. MOB1b expression was significantly increased in mice at 7 days post-SCI and GLIS3 overexpression further increased its expression. Dual-luciferase reporter assay revealed that GLIS3 bound to the promoter of MOB1b and promoted its transcription. In conclusion, our findings reveal that the compensatory increase of GLIS3 promotes functional recovery after SCI through inhibiting neuronal apoptosis by transcriptionally regulating MOB1b. Our study provides a novel target for functional recovery after SCI.

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  • Denisa NANUSHAJ, Masamitsu KONO, Hideki SAKATANI, Daichi MURAKAMI, Mun ...
    Article type: Original
    Article ID: 23-0001
    Published: 2023
    Advance online publication: August 03, 2023
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    Streptococcus pneumoniae can cause mortality in infant, elderly, and immunocompromised individuals owing to invasion of bacteria to the lungs, the brain, and the blood. In building strategies against invasive infections, it is important to achieve greater understanding of how the pneumococci are able to survive in the host. Toll-like receptors (TLRs), critically important components in the innate immune system, have roles in various stages of the development of infectious diseases. Endosomal TLRs recognize nucleic acids of the pathogen, but the impact on the pneumococcal diseases of immune responses from signaling them remains unclear. To investigate their role in nasal colonization and invasive disease with/without influenza co-infection, we established a mouse model of invasive pneumococcal diseases directly developing from nasal colonization. TLR9 KO mice had bacteremia more frequently than wildtype in the pneumococcal mono-infection model, while the occurrence of bacteremia was higher among TLR3 KO mice after infection with influenza in advance of pneumococcal inoculation. All TLR KO strains showed poorer survival than wildtype after the mice had bacteremia. The specific and protective role of TLR3 and TLR9 was shown in developing bacteremia with/without influenza co-infection respectively, and all nucleic sensing TLRs would contribute equally to protecting sepsis after bacteremia.

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  • Hideyuki KOBAYASHI, Ayami TACHI, Sumihiko HAGITA
    Article type: Original
    Article ID: 23-0048
    Published: 2023
    Advance online publication: July 28, 2023
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    Idiopathic pulmonary fibrosis (IPF) is a poor prognosis disease that affects approximately 5 million people worldwide, and the detailed mechanisms underlying the pathogenesis of IPF remain unclear. Bleomycin-induced pulmonary fibrosis has been widely used as a representative animal model of IPF that induces fibrosis in lung tissue. The lungs of rodent consist of five lobes and each bronchus enters each lobe of the lung at a different bifurcation angle, path length, and diameter. The method of administration of bleomycin is considered as important thing to establish appropriate animal models. We conducted a time-dependent histopathological study to examine how pulmonary fibrosis develops in each lung lobe when bleomycin is intratracheally sprayed in ICR mice. And we then explored the suitable points for evaluation of anti-fibrotic agents in this model. As a result, we found that homogeneous fibrosis was induced in the 5 lobes of the lungs following initial inflammation. The expression of TGF-β1 and pSmad2 was observed from Day 1, and their positivity increased until Day 21. In conclusion, we have observed a detailed time course of histological changes in bleomycin-induced pulmonary fibrosis in ICR mice using the aerosolization technique. We found that our protocol can induce a highly homogeneous lesion in the lung and that the most suitable time point to assess anti-fibrotic agents is 14 days after treatment in this model.

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  • Mariko MAEKAWA, Tatsuya MAEKAWA, Tomohiko SASASE, Takeshi WAKASHIMA, A ...
    Article type: Original
    Article ID: 22-0168
    Published: 2023
    Advance online publication: July 21, 2023
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    Diabetic nephropathy (DN), included in diabetic kidney disease (DKD), is a primary driver of end-stage renal disease (ESRD) leading to dialysis treatment. To develop new therapeutic drugs to prevent ESRD and avoid dialysis treatment, insight into DKD pathophysiology and animal models suitable for drug efficacy testing are needed. In this study, transcriptome analysis of kidneys from 26-week-old and 35-week-old uninephrectomized (UNX) db/db mice was used to identify the pathways that affect the deterioration of renal function in db/db mice. Differentially expressed genes suggested that there was increased interferon (IFN)-γ signaling during the 26 to 35-week period. Modules that changed between 26 and 35 weeks of age extracted by weighted gene co-expression network analysis (WGCNA) suggested increased the tumor necrosis factor (TNF)-α and nuclear factor-kappa B (NF-κB) signaling pathway in component cells of glomeruli. The protein-protein interaction (PPI) network analysis identified Cxcl16 as a hub gene for those signaling pathways, and it was shown that the pathways in this module changed when the glomerular filtration rate decreased in patients with DN. These results suggested the possibility that signaling mediated by Cxcl16 induced by IFN-γ and TNF-α between 26 and 35 weeks of age leads to renal fibrosis, resulting in severe disease. Drugs that target such pathways can be options for developing drugs for DN. We also think that the uninephrectomized db/db mouse can be used as an animal model of severe DKD and to evaluate efficacy in patients with diabetic nephropathy.

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  • Chengjie HE, Jingyi PENG, Jiayi JIN, Wanwen SHAO, Yongxin ZHENG, Liuxu ...
    Article type: Original
    Article ID: 22-0022
    Published: 2023
    Advance online publication: July 18, 2023
    JOURNAL OPEN ACCESS ADVANCE PUBLICATION

    Non-human primates are important research models for basic vision research, preclinical pathogenesis and treatment studies due to strong similarities in retinal structure and function with humans. We compared retinal parameters between healthy normal rhesus macaques (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis) by optical coherence tomography and electroretinography. The retinal parameters of 10 male rhesus macaques and 10 male cynomolgus macaques were compared. The Heldelberg Spectralis® HRA+OCT and Roland multifocal electrophysiometer were used to analyze retinal morphology, multifocal electroretinogram (mfERG), and full-filed electroretinogram (ff-ERG). Mean retinal thickness was lowest in the central fovea of macaques and did not differ significantly between species, but the retinal thickness of the nerve fiber ganglion cell layer and the inner plexiform layer were significantly different. The amplitude density of the N1 wave is lower in rhesus macaques than in cynomolgus macaques in ring and quadrant areas between species. Dark-adapted 3.0 oscillatory potentials (reflection of amacrine cells’ activity) and light-adapted 30hz flicker ERG (a sensitive cone-pathway-driven response) waveforms of the ff-ERG were similar in both species while the time reached peaks in dark-adapted 0.01 ERG (the rod-driven response of bipolar cells) and dark-adapted 3.0 ERG (combined rod and cone system responses) as well as the implicit time of a-wave and b-wave in light-adapted 3.0 ERG (the single-flash cone response) really differed. This study provides normative retinal parameters for nonhuman primate research on basic and clinical ophthalmology, as well as a reference for researchers in the appropriate selection of rhesus or cynomolgus macaques as models for ophthalmology studies.

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  • Naoto MUROMACHI, Junji ISHIDA, Kazuyuki NOGUCHI, Tomoki AKIYAMA, Syuns ...
    Article type: Original
    Article ID: 23-0071
    Published: 2023
    Advance online publication: July 18, 2023
    JOURNAL OPEN ACCESS ADVANCE PUBLICATION

    The interconnection of heart performance and kidney function plays an important role for maintaining homeostasis through a variety of physiological crosstalk between these organs. It has been suggested that acute or chronic dysfunction in one organ causes dysregulation in another one, like patients with cardiorenal syndrome. Despite its growing recognition as global health issues, still little is known on pathophysiological evaluation between the two organs. Previously, we established a preclinical murine model with cardiac hypertrophy and fibrosis, and impaired kidney function with renal enlargement and increased urinary albumin levels induced by co-treatment with vasopressor angiotensin II (A), unilateral nephrectomy (N), and salt loading (S) (defined as ANS treatment) for 4 weeks. However, how both tissues, heart and kidney, are initially affected by ANS treatment during the progression of tissue damages remains to be determined. Here, at one week after ANS treatment, we found that cardiac function in ANS-treated mice (ANS mice) are sustained despite hypertrophy. On the other hand, kidney dysfunction is evident in ANS mice, associated with high blood pressure, enlarged glomeruli, increased levels of urinary albumin and urinary neutrophil gelatinase-associated lipocalin, and reduced creatinine clearance. Our results suggest that cardiorenal tissues become damaged at one week after ANS treatment and that ANS mice are useful as a model causing transition from early to late-stage damages of cardiorenal tissues.

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  • Keisuke SHIMADA, Yonggang LU, Masahito IKAWA
    Article type: Original
    Article ID: 23-0055
    Published: 2023
    Advance online publication: July 10, 2023
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    Mammalian sperm flagellum contains the midpiece characterized by a mitochondrial sheath that packs tightly around the axoneme and outer dense fibers. Mitochondria are known as the “powerhouse” of the cell, and produce ATP through the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). However, the contribution of the TCA cycle and OXPHOS to sperm motility and male fertility is less clear. Cytochrome c oxidase (COX) is an oligomeric complex localized within the mitochondrial inner membrane, and the terminal enzyme of the mitochondrial electron transport chain in eukaryotes. Both COX6B2 and COX8C are testis-enriched COX subunits whose functions in vivo are poorly studied. Here, we generated Cox6b2 and Cox8c knockout (KO) mice using the CRISPR/Cas9 system. We examined their fertility and sperm mitochondrial function to determine the significance of testis-enriched COX subunits in male fertility. The mating test revealed that disrupting COX6B2 induces male subfertility, while disrupting COX8C does not affect male fertility. Cox6b2 KO spermatozoa showed low sperm motility, but mitochondrial function was normal according to oxygen consumption rates. Therefore, low sperm motility seems to cause subfertility in Cox6b2 KO male mice. These results also indicate that testis-enriched COX, COX6B2 and COX8C, are not essential for OXPHOS in mouse spermatozoa.

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  • Gisele Henrique Cardoso MARTINS, Juliete PALANDI, Vitória Helena Kuhn ...
    Article type: Review
    Article ID: 19-0140
    Published: 2020
    Advance online publication: March 23, 2020
    JOURNAL OPEN ACCESS ADVANCE PUBLICATION
    This article released online on March 23, 2020 as advance publication was withdrawn from consideration for publication in Experimental Animals at author’s request.
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