Publications by authors named "Mitsuru Kuwamura"

188 Publications

Properties of macrophages and lymphocytes appearing in rat renal fibrosis followed by repeated injection of cisplatin.

J Vet Med Sci 2021 Jul 22. Epub 2021 Jul 22.

Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University.

Properties of macrophages and lymphocytes appearing in renal fibrosis remains to be investigated. F344 rats were injected once a week with cisplatin (2 mg/kg body weight) for 8 weeks and examined at post-final injection weeks 1, 3, 6, 9, and 12. Rats developed progressive renal fibrosis at weeks 1 to 6 as fibrosis-progress phase, and subsequent amelioration at weeks 9 and 12. CD68 M1-macrophages and major histocompatibility complex (MHC) class II macrophages remarkably increased persistently, whereas CD163 M2-macrophages slightly increased. MHC class II/CD68 and MHC class II/CD163 macrophages were present, indicating that MHC class II macrophages might have both functions of M1- and M2-macrophages. In the fibrosis-progress phase, Interleukin (IL)-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ for M1-factors, and transforming growth factor (TGF)-β1 and IL-10 for M2-factors tended to increase; tissue injury by M1 and fibrosis by M2 might have occurred simultaneously. Lots of CD4 and CD8 T cells appeared in close relation with MHC class II macrophages, and mainly CD4 T cells formed aggregations. In the lymphocyte aggregates collected by laser microdissection, expression of IL-17A (for Th17 cells) and forkhead box P3 (FoxP3) (for Treg) significantly increased at weeks 1 and 6, respectively; presumably, Th17 cells might be involved in tissue injury, whereas Treg might be related to fibrosis amelioration. These results suggested that macrophages and T cells may contribute interrelatedly to renal fibrosis.
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http://dx.doi.org/10.1292/jvms.21-0341DOI Listing
July 2021

Canine induced pluripotent stem cell maintenance under feeder-free and chemically-defined conditions.

Mol Reprod Dev 2021 06 19;88(6):395-404. Epub 2021 May 19.

Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan.

Canine induced pluripotent stem cells (ciPSCs) provide a platform for regenerative veterinary medicine, disease modeling, and drug discovery. However, in the conventional method, ciPSCs are maintained using chemically-undefined media containing unknown animal components under on-murine embryonic fibroblast feeder conditions, which were reported to modify cell surface of iPSCs and increases the risk of immune rejection when the cells are transplanted into patients. Moreover, in the conventional method, ciPSCs are mechanically passaged, which requires much time and effort. Therefore, the large-scale expansion of ciPSCs is difficult, which should be resolved for using ciPSCs in clinical application and research. Here, it was shown that StemFit® AK02N and iMatrix-511 could maintain the pluripotency of ciPSCs using conventional culture method. Furthermore, it was demonstrated that the feeder-free and chemically-defined ciPSC culture systems using StemFit® AK02N and iMatrix-511 could stably maintain and allow the easy expansion of ciPSCs generated using N2B27 and StemFit® AK02N, without causing karyotype abnormalities. ciPSCs expressed several pluripotency markers and formed teratomas, including cells derived from three germ layers.
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http://dx.doi.org/10.1002/mrd.23478DOI Listing
June 2021

Analyses of hemorrhagic diathesis in high-iron diet-fed rats.

J Toxicol Pathol 2021 Jan 24;34(1):33-41. Epub 2020 Oct 24.

Laboratory of Veterinary Pathology, Osaka Prefecture University, 1-58 Rinku-Orai-Kita, Izumisano, Osaka 598-8531, Japan.

Iron overload has been well recognized to cause oxidant-mediated cellular/tissue injury; however, little is known about the effects of iron overload on the blood coagulation system. We encountered an unexpected bleeding tendency in rats fed a high-iron diet in a set of studies using iron-modified diets. In this study, we investigated the mechanism of hemorrhagic diathesis induced by dietary iron overload in rats. Six-week-old F344/DuCrlCrlj male rats were fed a standard (containing 0.02% iron) or a high-iron diet (containing 1% iron) for 6 weeks and were then sampled for hematological, blood biochemical, coagulation, and pathological examinations. Serum and liver iron levels increased in rats fed the high-iron diet (Fe group) and serum transferrin was almost saturated with iron. However, serum transaminase levels did not increase. Moreover, plasma prothrombin time and activated partial thromboplastin time were significantly prolonged, regardless of the presence of hemorrhage. The activity of clotting factors II and VII (vitamin K-dependent coagulation factors) decreased significantly, whereas that of factor VIII was unaltered. Blood platelet levels were not influenced by dietary iron overload, suggesting that the bleeding tendency in iron-overloaded rats is caused by secondary hemostasis impairment. In addition, hemorrhage was observed in multiple organs in rats fed diets containing more than 0.8% iron. Our results suggest that iron overload can increase the susceptibility of coagulation abnormalities caused by latent vitamin K insufficiency.
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http://dx.doi.org/10.1293/tox.2020-0004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890162PMC
January 2021

Immunophenotypical Characterization of M1/M2 Macrophages and Lymphocytes in Cisplatin-Induced Rat Progressive Renal Fibrosis.

Cells 2021 Jan 28;10(2). Epub 2021 Jan 28.

Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku-Ourai-Kita, Izumisano City, Osaka 598-8531, Japan.

Renal fibrosis is regarded as the common final pathway leading to chronic kidney diseases; macrophages and myofibroblasts play important roles in the development of fibrosis. F344 rats were injected once with cisplatin (CDDP; 6 mg/kg BW) for renal lesions. Here, immunophenotypical characteristics of macrophages and lymphocytes in CDDP-induced rat renal lesions were investigated histopathologically; the CDDP-induced renal lesions consisted of tissue damage at the early-stage, worsen the damage and commencement of interstitial fibrosis at the mid-stage, and progressive fibrosis at the late stage; the KIM-1 expression and α-SMA myofibroblast area reflected renal tubular damage/abnormal regeneration and renal interstitial fibrosis, respectively. CD68 M1 macrophages began to increase at the mid-stage, with increased mRNA expressions of M1-related cytokines (INF-γ, TNF-α and IL-6), and then slightly decreased at the late-stage. CD163 M2 macrophages showed a gradually increased number at the mid- and late-stages, accompanied by increased TGF-β1 mRNA expression (a fibrogenic factor). Double immunofluorescence using fibrotic samples at the late-stage revealed that 62.0-78.0% of CD68 M1 macrophages co-expressed CD163, indicating that M1/M2 macrophages may contribute to progressive renal fibrosis in cooperation; further, MHC class II-expressing macrophages had a tendency towards M1 polarization, whereas CD204-expressing macrophages towards M2 polarization. In addition, CD4 and CD8 T cells were increased at the late-stage. Collectively, progressive renal interstitial fibrosis may be developed by complicated mechanisms that arose via interaction of M1/M2 macrophages (inflammatory for M1 and anti-inflammatory for M2) and T cells reacting to CD4 (for helper) and CD8 (for cytotoxicity). This study would provide some information on the pathogenesis of renal fibrosis based on inflammatory cells.
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http://dx.doi.org/10.3390/cells10020257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911194PMC
January 2021

Deficiency of the RIβ subunit of protein kinase A causes body tremor and impaired fear conditioning memory in rats.

Sci Rep 2021 Jan 21;11(1):2039. Epub 2021 Jan 21.

Laboratory of Animal Nutrition, Department of Animal Science, Faculty of Agriculture, Tokyo University of Agriculture, 1737 Funako, Atsugi, Kanagawa, 243-0034, Japan.

The RIβ subunit of cAMP-dependent protein kinase (PKA), encoded by Prkar1b, is a neuronal isoform of the type I regulatory subunit of PKA. Mice lacking the RIβ subunit exhibit normal long-term potentiation (LTP) in the Schaffer collateral pathway of the hippocampus and normal behavior in the open-field and fear conditioning tests. Here, we combined genetic, electrophysiological, and behavioral approaches to demonstrate that the RIβ subunit was involved in body tremor, LTP in the Schaffer collateral pathway, and fear conditioning memory in rats. Genetic analysis of WTC-furue, a mutant strain with spontaneous tremors, revealed a deletion in the Prkar1b gene of the WTC-furue genome. Prkar1b-deficient rats created by the CRISPR/Cas9 system exhibited body tremor. Hippocampal slices from mutant rats showed deficient LTP in the Schaffer collateral-CA1 synapse. Mutant rats also exhibited decreased freezing time following contextual and cued fear conditioning, as well as increased exploratory behavior in the open field. These findings indicate the roles of the RIβ subunit in tremor pathogenesis and contextual and cued fear memory, and suggest that the hippocampal and amygdala roles of this subunit differ between mice and rats and that rats are therefore beneficial for exploring RIβ function.
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http://dx.doi.org/10.1038/s41598-021-81515-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820254PMC
January 2021

Involvement of neutrophils in rat livers by low-dose thioacetamide administration.

J Vet Med Sci 2021 Mar 20;83(3):390-396. Epub 2021 Jan 20.

Laboratory of Veterinary Pathology, Osaka Prefecture University, 1-58 Rinku-Ourai-Kita, Izumisano-shi, Osaka 598-8531, Japan.

The administration with high dose (close to LD) of thioacetamide (TAA), a hepatotoxicant used widely to induce experimental liver lesions, develops hepatocellular necrosis and subsequent inflammation (mainly M1-/M2-macrophages without neutrophil infiltration) in rats. We analyzed rat livers treated with a low dose TAA (50 mg/kg/body weight) at 6, 12, 18, 24 and 48 hr. The lesions in the affected centrilobular areas consisted of slight hepatocyte degeneration at 12 hr, and inflammatory cell infiltration at 18 and 24 hr; the lesions recovered until 48 hr. Translocation of intranuclei to cytoplasm of HMGB1, a representative molecule of damage-associated molecular patterns, was seen in some hepatocytes mainly at 6, 12, and 18 hr. As an interesting finding, at 12 hr, myeloperoxidase-positive neutrophil infiltration was observed in the affected centrilobular area. Additionally, CD68 M1-/CD163 M2-macrophages increased consistently at 12 to 48 hr. CXCL1, a chemokine for induction of neutrophils, began to increase at 6 hr and gradually increased at 12, 18 and 24 hr, apparently corresponding to the appearance of neutrophils. Collectively, the present findings at the low dose TAA indicated that along with M1-/M2-macrophages, neutrophils were characteristically seen, which might be elicited by cytoplasmic translocation of HMGB1 from nuclei. These finding would be useful for evaluation of hepatotoxicity at the early stages.
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http://dx.doi.org/10.1292/jvms.20-0581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025423PMC
March 2021

Appearance of Heterogeneous Macrophages During Development of Isoproterenol-Induced Rat Myocardial Fibrosis.

Toxicol Pathol 2021 07 5;49(5):1048-1061. Epub 2021 Jan 5.

Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Sciences, 194887Osaka Prefecture University, Izumisano City, Osaka, Japan.

Macrophages appearing in lesions are polarized toward M1 (for inflammation) and M2 (for anti-inflammation/fibrosis) types. We analyzed immunophenotypes of macrophages appearing in myocardial lesion in rats injected once with isoproterenol (10 mg/kg body weight). Inflammation following myocardial necrosis on day 1 was seen with a peak on days 3 and 5, and thereafter, reparative fibrosis developed on days 7 to 28. CD68 M1 macrophages were seen in the early stages of injury and inflammatory on days 1 to 7, and thereafter, CD163 M2 macrophages increased in the late stages of fibrosis on days 7 to 28. There was the polarization of M1 and M2 macrophages. The kinetics of macrophages reacting to Iba-1 and Galectin-3 was similar to that of M1 macrophages, indicating that Iba1- and Gal-3-positive macrophages might have functions of M1 type. Double immunofluorescence revealed that CD204- and MHC class II-positive macrophages are polarized toward M1 and M2 types, respectively. CCR2 messenger RNA expression is transiently elevated on day 1. Since CCR2 is a marker of blood monocytes, M1 macrophages might be recruited from blood monocytes. Collectively, macrophages expressing heterogeneous immunophenotypes participate in myocardial fibrosis. These findings would be useful for understanding the pathogenesis of myocardial fibrosis and analyzing myocardial toxicity.
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http://dx.doi.org/10.1177/0192623320982526DOI Listing
July 2021

Efficient Reprogramming of Canine Peripheral Blood Mononuclear Cells into Induced Pluripotent Stem Cells.

Stem Cells Dev 2021 01 24;30(2):79-90. Epub 2020 Dec 24.

Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan.

Forced coexpression of the transcription factors , , , and reprograms somatic cells into pluripotent stem cells (PSCs). Such induced PSCs (iPSCs) can generate any cell type of the adult body or indefinitely proliferate without losing their potential. Accordingly, iPSCs can serve as an unlimited cell source for the development of various disease models and regenerative therapies for animals and humans. Although canine peripheral blood mononuclear cells (PBMCs) can be easily obtained, they have a very low iPSC reprogramming efficiency. In this study, we determined the reprogramming efficiency of canine PBMCs under several conditions involving three types of media supplemented with small-molecule compounds. We found that canine iPSCs (ciPSCs) could be efficiently generated from PBMCs using N2B27 medium supplemented with leukemia inhibitory factor (LIF), basic fibroblast growth factor (bFGF), and a small-molecule cocktail (Y-27632, PD0325901, CHIR99021, A-83-01, Forskolin, and l-ascorbic acid). We generated five ciPSC lines that could be maintained in StemFit medium supplemented with LIF. The SeVdp(KOSM)302L vectors were appropriately silenced in four ciPSC lines. Of the two lines characterized, both were positive for alkaline phosphatase activity and expressed pluripotency markers, including the , , and transcripts, as well as the octamer-binding transcription factor (OCT) 3/4 and NANOG proteins, and the SSEA-1 carbohydrate antigen. The ciPSCs could form embryoid bodies and differentiate into the three germ layers, as indicated by marker gene and protein expression. Furthermore, one ciPSC line formed teratomas comprising several tissues from every germ layer. Our ciPSC lines maintained a normal karyotype even after multiple passages. Moreover, our new reprogramming method was able to generate ciPSCs from multiple donor PBMCs. In conclusion, we developed an easy and efficient strategy for the generation of footprint-free ciPSCs from PBMCs. We believe that this strategy can be useful for disease modeling and regenerative medicine in the veterinary field.
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http://dx.doi.org/10.1089/scd.2020.0084DOI Listing
January 2021

Acetaminophen-Induced Rat Hepatotoxicity Based on M1/M2-Macrophage Polarization, in Possible Relation to Damage-Associated Molecular Patterns and Autophagy.

Int J Mol Sci 2020 Nov 26;21(23). Epub 2020 Nov 26.

Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58 Rinku-Ourai-Kita, Izumisano City, Osaka 598-8531, Japan.

Overdose of acetaminophen (APAP), an antipyretic drug, is an important cause of liver injury. However, the mechanism in the rat model remains undetermined. We analyzed APAP-induced hepatotoxicity using rats based on M1/M2-macrophage functions in relation to damage-associated molecular patterns (DAMPs) and autophagy. Liver samples from six-week-old rats injected with APAP (1000 mg/kg BW, ip, once) after 15 h fasting were collected at hour 10, and on days 1, 2, 3, and 5. Liver lesions consisting of coagulation necrosis and inflammation were seen in the affected centrilobular area on days 1 and 2, and then, recovered with reparative fibrosis by day 5. Liver exudative enzymes increased transiently on day 1. CD68 M1-macrophages increased significantly on days 1 and 2 with increased mRNAs of M1-related cytokines such as IFN-g and TNF-α, whereas CD163 M2-macrophages appeared later on days 2 and 3. Macrophages reacting to MHC class II and Iba1 showed M1-type polarization, and CD204 macrophages tended to be polarized toward M2-type. At hour 10, interestingly, HMGB1 (representative DAMPs) and its related signals, TLR-9 and MyD88, as well as LC3B autophagosomes began to increase. Collectively, the pathogenesis of rat APAP hepatotoxicity, which is the first, detailed report for a rat model, might be influenced by macrophage functions of M1 type for tissue injury/inflammation and M2-type for anti-inflammatory/fibrosis; particularly, M1-type may function in relation to DAMPs and autophagy. Understanding the interplayed mechanisms would provide new insight into hepato-pathogenesis and contribute to the possible development of therapeutic strategies.
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http://dx.doi.org/10.3390/ijms21238998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730394PMC
November 2020

Effects of dexamethasone on hepatic macrophages in normal livers and thioacetamide-induced acute liver lesions in rats.

J Toxicol Pathol 2020 Oct 31;33(4):237-246. Epub 2020 Jul 31.

Veterinary Pathology, Osaka Prefecture University, 1-58 Rinku-Ourai-Kita, Izumisano City, Osaka 598-8531, Japan.

Resident and infiltrative macrophages play important roles in the development of pathological lesions. M1/M2 macrophage polarization with respective CD68 and CD163 expression remains unclear in chemically induced liver injury. This study was aimed at investigating the influence of macrophages on normal and chemically induced liver injury. For this, dexamethasone (DX), an immunosuppressive drug, was administered in normal rats and thioacetamide (TAA)-treated rats. Liver samples were collected and analyzed with immunohistochemical methods. Repeated injections of DX (0.5 or 1.0 mg/kg BW) for 3, 7 and 11 days reduced the number of CD163 positive hepatic resident macrophages (Kupffer cells) in normal livers, while increasing AST and ALT levels. In TAA (300 mg/kg BW)-treated rats injected with DX (0.5 mg/kg BW) pretreatment, the number of M1 and M2 macrophages showed a significant decrease compared with that of TAA-treated rats without DX treatment. Additionally, reparative fibrosis resulting from hepatocyte injury induced by TAA injection was suppressed by DX pretreatment. Our data suggested that macrophages could influence not only normal hepatic homeostasis (reflected by AST and ALT levels) but also chemically induced hepatic lesion development (reduced reparative fibrosis).
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http://dx.doi.org/10.1293/tox.2020-0016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677630PMC
October 2020

PHF24 is expressed in the inhibitory interneurons in rats.

Exp Anim 2021 Feb 29;70(1):137-143. Epub 2020 Oct 29.

Laboratory of Veterinary Pathology, Osaka Prefecture University, 1-58 Ourai-kita, Izumisano, Osaka 598-8531, Japan.

Noda epileptic rat (NER) is a mutant model for epilepsy that exhibits spontaneous generalized tonic-clonic seizure. Epileptogenesis of NER remains to be elucidated; but it is detected an insertion of an endogenous retrovirus sequence in intron 2 of the PHD finger protein 24 (Phf24) gene, encoding Gαi-interacting protein (GINIP). Phf24 is a strong candidate gene for epileptogenesis in NER. PHF24 modulates GABA signaling through interacting with Gαi protein. To clarify the epileptogenesis of NER, we investigated a distribution of PHF24-expressing cells in the central nerve system (CNS). While broad expression of PHF24 was observed in the CNS, characteristic expression was noted in the periglomerular layer of the olfactory bulb and the lamina II of the spinal cord in the control rats. These cells showed co-expression with calbindin or calretinin, inhibitory interneuron markers. In the olfactory bulb, 15.6% and 41.2% of PHF24-positive neurons co-expressed calbindin and calretinin, respectively. Immunoelectron microscopy revealed that PHF24 was located in the presynaptic terminals, synaptic membranes and cytoplasmic matrix of neuronal soma. Our data suggested PHF24 is expressed in the inhibitory interneurons and may play important roles in modulation of the GABA signaling.
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http://dx.doi.org/10.1538/expanim.20-0105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887615PMC
February 2021

Characterization of Immature Myofibroblasts of Stellate Cell or Mesenchymal Cell Origin in D-Galactosamine-Induced Liver Injury in Rats.

Vet Pathol 2021 01 15;58(1):80-90. Epub 2020 Oct 15.

13311Osaka Prefecture University, Izumisano City, Osaka, Japan.

Lesions of D-galactosamine (D-GalN)-induced hepatotoxicity resemble those of human acute viral hepatitis. This study investigated hepatic mesenchymal cells including hepatic stellate cells (HSCs) and myofibroblasts in D-GalN-induced hepatotoxicity. Rats, injected with D-GalN (800 mg/kg body weight, once, intraperitoneally) were examined on post single injection (PSI) at 8 hours and days 1 to 5. Lesions consisting of hepatocyte necrosis and reparative fibrosis were present diffusely or focally within the hepatic lobules on PSI days 1 and 2, and then the injury recovered on PSI days 3 and 5. Myofibroblasts expressing vimentin, desmin, and α-smooth muscle actin (α-SMA) were present in the lesions. Double immunofluorescence showed that myofibroblasts reacted simultaneously to vimentin/α-SMA, desmin/α-SMA, and desmin/vimentin; furthermore, myofibroblasts reacting to vimentin, desmin, and α-SMA also co-expressed glial fibrillary acidic protein (GFAP), a marker of HSCs. Additionally, GFAP-expressing myofibroblasts reacted to nestin and A3 (both are markers of immature mesenchymal cells). Cells reacting to Thy-1, a marker for immature mesenchymal cells, also appeared in fibrotic lesions. In agreement with the myofibroblastic appearance, mRNAs of fibrosis-related factors (TGF-β1, PDGF-β, TNF-α, Timp2, and Mmp2) increased mainly on PSI days 1 and 2. Myofibroblasts with expression of various cytoskeletal proteins were present in diffuse or focal hepatic lesions, and they might be derived partly from immature HSCs and from immature mesenchymal cells.
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http://dx.doi.org/10.1177/0300985820963097DOI Listing
January 2021

Dietary Iron Overload Differentially Modulates Chemically-Induced Liver Injury in Rats.

Nutrients 2020 Sep 11;12(9). Epub 2020 Sep 11.

Laboratory of Veterinary Pathology, Osaka Prefecture University, 1-58 Rinku Orai Kita, Osaka 598-8531, Japan.

Hepatic iron overload is well known as an important risk factor for progression of liver diseases; however, it is unknown whether it can alter the susceptibility to drug-induced hepatotoxicity. Here we investigate the pathological roles of iron overload in two single-dose models of chemically-induced liver injury. Rats were fed a high-iron (Fe) or standard diet (Cont) for four weeks and were then administered with allyl alcohol (AA) or carbon tetrachloride (CCl). Twenty-four hours after administration mild mononuclear cell infiltration was seen in the periportal/portal area (Zone 1) in Cont-AA group, whereas extensive hepatocellular necrosis was seen in Fe-AA group. Centrilobular (Zone 3) hepatocellular necrosis was prominent in Cont-CCl group, which was attenuated in Fe-CCl group. Hepatic lipid peroxidation and hepatocellular DNA damage increased in Fe-AA group compared with Cont-AA group. Hepatic caspase-3 cleavage increased in Cont-CCl group, which was suppressed in Fe-CCl group. Our results showed that dietary iron overload exacerbates AA-induced Zone-1 liver injury via enhanced oxidative stress while it attenuates CCl-induced Zone-3 liver injury, partly via the suppression of apoptosis pathway. This study suggested that susceptibility to drugs or chemical compounds can be differentially altered in iron-overloaded livers.
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http://dx.doi.org/10.3390/nu12092784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551424PMC
September 2020

Assessment of biomarkers influencing treatment success on small intestinal lymphoma in dogs.

Vet Comp Oncol 2021 Mar 21;19(1):123-131. Epub 2020 Sep 21.

Veterinary Medical Center, College of Life, Environmental and Advanced Sciences, Osaka Prefecture University, Osaka, Japan.

This study aimed to determine a reliable therapeutic biomarker for localized small intestinal lymphoma (SIL) in dogs based on clinical and histopathological features. We retrospectively investigated 84 dogs with localized SIL, including 36 dogs receiving surgery and 48 dogs receiving chemotherapy. The dogs receiving surgery were divided into two subgroups: 18 dogs (group 1) with overall survival (OS) <120 days (median OS) and 18 dogs (group 2) with OS ≥120 days. Correspondingly, the dogs receiving chemotherapy were divided into 24 dogs (group 3) with OS <98 days (median OS) and 24 dogs (group 4) with OS ≥98 days. Clinical, haematological, histopathological and immunohistochemical analyses were comparatively evaluated among the four subgroups. There was no significant difference in OS between the surgery and chemotherapy groups. In dogs receiving surgery, the rate of Ki67-positive cells was significantly increased in group 1 compared to group 2 and showed no significant difference between groups 3 and 4. In dogs receiving chemotherapy, the rate of O6-methylguanine-DNA methyltransferase (MGMT) was significantly higher in group 3 than in group 4 and showed no significant difference between groups 1 and 2. Additionally, our data showed that OS in dogs with higher Ki67 expression might be significantly increased by chemotherapy than by surgery, that of those with higher MGMT expression might be significantly increased by surgery than by chemotherapy, and Ki67 and MGMT were independent of each other. Indices of Ki67 and MGMT are suggested therapeutic biomarkers to determine the optimal first-line treatment for localized SIL in dogs.
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http://dx.doi.org/10.1111/vco.12653DOI Listing
March 2021

Deficiency of interleukin-19 exacerbates lipopolysaccharide/D-galactosamine-induced acute liver failure.

J Vet Med Sci 2020 Oct 11;82(10):1450-1455. Epub 2020 Aug 11.

Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences, Izumisano, Osaka 598-8531, Japan.

Interleukin (IL)-19 is a cytokine clustered in the IL-20 cytokine superfamily with both anti-inflammatory and pro-inflammatory aspects depending on the etiology of inflammatory disease. The function of IL-19 has been evaluated in cutaneous and inflammatory bowel diseases, but has not been studied in liver diseases. Here, we examined the effect of IL-19 on acute liver failure (ALF) using two mouse models of ALF: lipopolysaccharide and D-galactosamine (LPS/GalN)-induced model and concanavalin A (ConA)-induced model. In the LPS/GalN-induced ALF model, which is mainly caused by the innate immune response of liver macrophages, IL-19 knockout (KO) mice showed increased plasma level of liver deviation enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) compared with wild-type (WT) mice. In histopathology of liver sections, IL-19 KO mice exacerbated liver injury with marked hemorrhagic lesions and hepatocellular death in the liver compared with WT mice. In this model, mRNA expressions of pro-inflammatory chemokines, CCL2 and CCL5 were increased in liver tissue from IL-19 KO mice compared with WT mice. Moreover, the mRNA expressions of IL-19 and its receptor subunit were induced in liver tissue by LPS/GalN administration. However, there is no difference in liver injury between WT and IL-19KO in the ConA-induced ALF model induced by CD4 T cell activation. These data suggest that IL-19 has a protective effect against inflammation-mediated liver injury, which is dependent on the etiology.
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http://dx.doi.org/10.1292/jvms.20-0344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653317PMC
October 2020

Generation of knockout rabbits with X-linked severe combined immunodeficiency (X-SCID) using CRISPR/Cas9.

Sci Rep 2020 06 19;10(1):9957. Epub 2020 Jun 19.

Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan.

Severe immunodeficient mice are widely used to examine human and animal cells behaviour in vivo. However, mice are short-lived and small in size; while large animals require specific large-scale equipment. Rabbits are also commonly employed as experimental models and are larger than mice or rats, easy to handle, and suitable for long-term observational and pre-clinical studies. Herein, we sought to develop and maintain stable strains of rabbits with X-linked severe combined immunodeficiency (X-SCID) via the CRISPR/Cas9 system targeting Il2rg. Consequently, X-SCID rabbits presented immunodeficient phenotypes including the loss of T and B cells and hypoplasia of the thymus. Further, these rabbits exhibited a higher success rate with engraftments upon allogeneic transplantation of skin tissue than did wild type controls. X-SCID rabbits could be stably maintained for a minimum of four generations. These results indicate that X-SCID rabbits are effective animals for use in a non-rodent model of severe immunodeficiency.
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http://dx.doi.org/10.1038/s41598-020-66780-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305219PMC
June 2020

Participation of Somatic Stem Cells, Labeled by a Unique Antibody (A3) Recognizing both N-glycan and Peptide, to Hair Follicle Cycle and Cutaneous Wound Healing in Rats.

Int J Mol Sci 2020 May 27;21(11). Epub 2020 May 27.

Laboratory of Veterinary Pathology, Osaka Prefecture University, Izumisano City, Osaka 598-0048, Japan.

A monoclonal antibody (A3) was generated by using rat malignant fibrous histiocytoma (MFH) cells as the antigen. Generally, MFH is considered to be a sarcoma derived from undifferentiated mesenchymal cells. Molecular biological analyses using the lysate of rat MFH cells revealed that A3 is a conformation specific antibody recognizing both -glycan and peptide. A3-labeled cells in bone marrow were regarded as somatic stem cells, because the cells partly coexpressed CD90 and CD105 (both immature mesenchymal markers). In the hair follicle cycle, particularly the anagen, the immature epithelial cells (suprabasal cells) near the bulge and some immature mesenchymal cells in the disassembling dermal papilla and regenerating connective tissue sheath/hair papilla reacted to A3. In the cutaneous wound-healing process, A3-labeled epithelial cells participated in re-epithelialization in the wound bed, and apparently, the labeled cells were derived from the hair bulge; in addition, A3-labeled immature mesenchymal cells in the connective tissue sheath of hair follicles at the wound edge showed the expansion of the A3 immunolabeling. A3-labeled immature epithelial and mesenchymal cells contributed to morphogenesis in the hair cycle and tissue repair after a cutaneous wound. A3 could become a unique antibody to identify somatic stem cells capable of differentiating both epithelial and mesenchymal cells in rat tissues.
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http://dx.doi.org/10.3390/ijms21113806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312608PMC
May 2020

Generation of Footprint-Free Canine Induced Pluripotent Stem Cells from Peripheral Blood Mononuclear Cells Using Sendai Virus Vector.

Mol Reprod Dev 2020 06 19;87(6):663-665. Epub 2020 May 19.

Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka, Japan.

Using auto-erasable Sendai virus vector, we generated ciPSC line. After several passages, virus was not present in ciPSCs by RT-PCR. ciPSCs from canine PBMCs had pluripotent state, differentiated all three germ layers in vitro, and had normal 78 XX karyotype. These results proved that PBMCs were one of the good cell sources to generate ciPSC lines from companion and patient dogs.
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http://dx.doi.org/10.1002/mrd.23349DOI Listing
June 2020

Hepatocellular necrosis with prominent regenerative reactions in a zonisamide administrated dog.

J Vet Med Sci 2020 Jun 3;82(6):704-706. Epub 2020 Apr 3.

Laboratory of Veterinary Pathology, Osaka Prefecture University, Izumisano, Osaka 598-8531, Japan.

A 16 years old neutered male Miniature Dachshund with 1-year history of repetitive administration of zonisamide for treatment of epileptic seizure was presented for vomiting, anorexia and diarrhea. Serum biochemistry showed a markedly elevated ALP level. The dog died 6 days after the presentation and a necropsy was performed. Histopathologically, random, focal to extensive necrosis, formation of regenerative hepatocellular nodules surrounded by fibrous septa and proliferation of bile ducts were seen in the liver. From these findings, the hepatic lesion was diagnosed as hepatocellular necrosis with prominent regenerative reactions due to the chronic persistent liver injury. Hepatic lesions were considered to be induced by zonisamide, based on the history of continuous administration, and clinical and histopathological findings.
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http://dx.doi.org/10.1292/jvms.20-0045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324810PMC
June 2020

An aortic body carcinoma with sarcomatoid morphology and chondroid metaplasia in a French Bulldog.

J Vet Med Sci 2020 May 12;82(5):576-579. Epub 2020 Mar 12.

Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano, Osaka 598-8531, Japan.

An 11-year-old female French Bulldog was presented with a mass at the base of the heart, detected by X-ray and echocardiography. Clinical abnormality included abdominal retention by ascites. Radiation therapy was performed for 5 weeks. The mass volume didn't change during the radiotherapy. The condition became worse and the dog died 6 months after the initial presentation and necropsy was performed. Grossly, the mass, 12.5 × 6.5 × 6.0 cm in size, was found at the base of the heart. Histopathological examination revealed that cardiac mass was composed of alveolar, bundle and diffuse proliferation of neoplastic cells. Most of the neoplastic cells showed a spindle morphology; in some areas small round or polyhedral neoplastic cells were observed. Occasional cartilage metaplasia was seen multifocal in the mass, and it was surrounded by the sarcomatoid proliferation. Electron microscopy revealed a few neuroendocrine granules in the cytoplasm of spindle and polyhedral neoplastic cells. Metastatic cells in the lungs which had not irradiated demonstrated typical morphology of aortic body tumors. Based on these findings, the case was diagnosed as an aortic body carcinoma with sarcomatoid morphology and chondroid metaplasia.
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http://dx.doi.org/10.1292/jvms.20-0016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273586PMC
May 2020

Participation of Somatic Stem Cells, Recognized by a Unique A3 Antibody, in Mucosal Epithelial Regeneration in Dextran Sulfate Sodium (DSS)-Induced Rat Colonic Lesions.

Toxicol Pathol 2020 06 3;48(4):560-569. Epub 2020 Mar 3.

Laboratory of Veterinary Pathology, Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan.

A3, generated as a monoclonal antibody against rat malignant fibrous histiocytoma cells, recognizes somatic stem cells in rats. We analyzed the distribution of A3-positive cells in dextran sulfate sodium (DSS)-induced colonic lesions consisting of regenerating mucosa and fibrosis. Male 6-week-old F344 rats were administered 5% DSS in drinking water for 5 to 7 days, and lesions at recovery stage were also examined. In untreated control adult colons, A3-positive cells are localized around the crypts where stem cell niche is formed. Histopathologically, in colons of DSS-administered rats, mucosal atrophy, inflammatory cell infiltration, and fibrosis were observed in the lamina propria; thereafter, mucosal epithelia were desquamated, and crypts were decreased gradually with decrease in surrounding A3-positive cells. At the early recovery stage, crypts showed regeneration with reappearance of A3-positive cells. Interestingly, A3-positive cells aggregated in desquamated mucosa surface of fibrosis. Aggregated A3-positive cells coexpressed with vimentin, Thy-1, and partly CK19 but did not react simultaneously with α-SMA. Likely, aggregated A3-positive cells may be rescue cells with nature of both mesenchymal and epithelial cells to maintain self-renewal after injury in the colon. A3 antibody would become a useful tool to investigate the participation of stem cells in rat colonic lesions.
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http://dx.doi.org/10.1177/0192623320906817DOI Listing
June 2020

Characterization of Macrophages and Myofibroblasts Appearing in Dibutyltin Dichloride-Induced Rat Pancreatic Fibrosis.

Toxicol Pathol 2020 04 3;48(3):509-523. Epub 2020 Jan 3.

Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano City, Osaka, Japan.

Macrophages and myofibroblasts are important in fibrogenesis. The cellular characteristics in pancreatic fibrosis remain to be investigated. Pancreatic fibrosis was induced in F344 rats by a single intravenous injection of dibutyltin dichloride. Histopathologically, the induced pancreatic fibrosis was divided into 3 grades (1+, 2+, and 3+), based on collagen deposition. Immunohistochemically, CD68-expressing M1 macrophages increased with grade and CD163-expressing M2 macrophages also increased later than M1 macrophage appearance. Double immunofluorescence showed that there were macrophages coexpressing CD68 and CD163, suggesting a possible shift from M1 to M2 types; similarly, increased major histocompatibility complex class II- and CD204-expressing macrophages were polarized toward M1 and M2 types, respectively. These findings indicated the participation of M1- and M2-polarized macrophages. Mesenchymal cells staining positive for vimentin, desmin, and α-smooth muscle actin (α-SMA) increased with grade. There were mesenchymal cells coexpressing vimentin/α-SMA, desmin/α-SMA, and glial fibrillary acidic protein (GFAP)/α-SMA; Thy-1-expressing immature mesenchymal cells also increased in fibrotic lesions. Because α-SMA expression is a reliable marker for myofibroblasts, α-SMA-expressing pancreatic myofibroblasts might be originated from GFAP-expressing pancreatic stellate cells or Thy-1-expressing immature mesenchymal cells; the myofibroblasts could simultaneously express cytoskeletal proteins such as vimentin and desmin. The present findings would provide useful information for analyses based on features of macrophages and myofibroblasts in chemically induced pancreatic fibrosis.
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http://dx.doi.org/10.1177/0192623319893310DOI Listing
April 2020

Diffuse leiomyomatosis with circumferential thickening of the gastrointestinal wall, resembling human diffuse leiomyomatosis, in a young miniature dachshund.

J Vet Med Sci 2020 Feb 18;82(2):139-142. Epub 2019 Dec 18.

Laboratory of Veterinary Pathology, Osaka Prefecture University, 1-58 Rinku-Ourai-Kita, Izumisano, Osaka 598-8531, Japan.

Leiomyoma is the most common mesenchymal tumor in the gastrointestinal (GI) tract. Leiomyomas usually have a single or multinodular mass of various sizes, and affected animals can develop alimentary symptoms depending on the location and size. A 3-year old female miniature dachshund died after a history of refractory rectal prolapse, esophagectasis and aspiration pneumonia. At necropsy, the GI wall at the gastroesophageal and anorectal junctions was circumferentially thickened. Histologically, both GI lesions were composed of bundles of well-differentiated smooth muscles without mass formation or invasive growth. The neoplastic cells had little cellular atypia and low proliferative activity, and were positive for α-smooth muscle actin. The lesions were diagnosed as diffuse leiomyomatosis with circumferential thickening of the GI wall and has not been described in the veterinary literature.
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http://dx.doi.org/10.1292/jvms.19-0453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041974PMC
February 2020

[The role of iron overload in the progression of nonalcoholic steatohepatitis (NASH)].

Nihon Yakurigaku Zasshi 2019 ;154(2):61-65

Laboratory of Veterinary Pathology, Division of Veterinary Science, Osaka Prefecture University Graduate School of Life and Environmental Sciences.

Non-alcoholic steatohepatitis (NASH), one of the most common chronic liver diseases (CLD), is getting the most important cause of cirrhosis and hepatocellular carcinoma. Iron is an essential micronutrient for organisms. Once excess iron is accumulated in vital organs, dysfunctions of these organs can occur via the generation of reactive oxygen species. Hepatic iron overload is often seen in CLD patients. In NASH patients, iron accumulation in the liver is positively correlated with histological severity. Thus iron overload can contribute to progression of nonalcoholic fatty liver disease (NAFLD) to NASH. In a rat model of NASH, feeding of high-fat and high-iron diet increases hepatic inflammation with increased hepatic cytokine expression compared with feeding of high-fat diet only. In this model, iron is intensely accumulated in Kupffer cells/macrophages within the lesion, raising the possibility that iron-laden Kupffer cells/macrophages can play a key role in the enhancement of hepatic inflammation in NASH condition. On the other hand, in a rat model of liver cirrhosis, dietary iron overload clearly abrogates the development and progression of liver cirrhosis induced by repeated administration of thioacetamide (TAA). These findings suggest that iron overload can promote or suppress chronic liver diseases depending on the tissue microenvironment. Here we review and introduce the recent findings on the pathological roles of iron overload in the development and progression of NAFLD/NASH.
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http://dx.doi.org/10.1254/fpj.154.61DOI Listing
August 2019

Pathological characteristics of Ccdc85c knockout rats: a rat model of genetic hydrocephalus.

Exp Anim 2020 Jan 23;69(1):26-33. Epub 2019 Jul 23.

Laboratory of Veterinary Pathology, Graduate School of Agriculture and Biological Sciences, Osaka Prefecture University, 1-58 Rinku Orai-Kita, Izumisano, Osaka 598-8531, Japan.

Spontaneous hhy mice show hydrocephalus and subcortical heterotopia, and a mutation in the Ccdc85c gene has been identified. To contribute to the comparison of the role of Ccdc85c in different species, we established a Ccdc85c KO rat and investigated its pathological phenotypes. Ccdc85c KO rats were produced by genomic engineering using transcription activator-like effector nuclease (TALEN). The KO rats had an approximately 350-bp deletion in Ccdc85c and lacked CCDC85C protein expression. The KO rats showed non-obstructive hydrocephalus, subcortical heterotopia, and intracranial hemorrhage. The KO rats had many pathological characteristics similar to those in hhy mice. These results indicate that CCDC85C plays an important role in cerebral development in rats, and the function of CCDC85C in the cerebrum are similar in rats and mice.
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http://dx.doi.org/10.1538/expanim.19-0005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004802PMC
January 2020

Muscle weakness and impaired motor coordination in hyperpolarization-activated cyclic nucleotide-gated potassium channel 1-deficient rats.

Exp Anim 2020 Jan 9;69(1):11-17. Epub 2019 Jul 9.

Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.

Hyperpolarization-activated cyclic nucleotide-gated potassium channel 1 (HCN1) contribute to spontaneous rhythmic activity in different tissues, including the heart and brain. Deficiency in HCN1 function is associated with sick sinus syndrome in mice and epilepsy in humans. We recently developed Hcn1-deficient rats and found that they exhibit absence epilepsy. While rearing Hcn1-deficient rats, we noticed loose muscle tension and abnormal gait. We therefore evaluated the muscle strength and motor functions of Hcn1-deficient rats. When subjected to the wire hang test, Hcn1-deficient rats fell down more easily than control F344 rats. Grip strength of Hcn1-deficient rats was significantly smaller than F344 rats. In the inclined plane test, they exhibited a smaller maximum angle. In the rotarod test, the latency to fall was shorter for Hcn1-deficient rats than F344 rats. In the footprint analysis, Hcn1-deficient rats exhibited smaller step length and wider step width than F344 rats. Instead of poor motor coordination ability and muscle weakness, Hcn1-deficient rats exhibited normal electromyograms, muscle histology, and deep tendon reflex. These findings suggest that HCN1 channels contribute to motor coordination and muscle strength, and that the muscle weakness of Hcn1-deficient rats results from the involvement not of the peripheral but of the central nervous system.
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http://dx.doi.org/10.1538/expanim.19-0067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004805PMC
January 2020

Hepatic Myoepithelial Carcinoma in a Dog: Immunohistochemical Comparison With Other Canine Hepatic Carcinomas.

Vet Pathol 2019 11 6;56(6):889-894. Epub 2019 Jun 6.

Laboratory of Veterinary Pathology, Osaka Prefecture University, Izumisano, Osaka, Japan.

An 11-year-old female miniature Dachshund dog presented with a solid, soft, gray mass on the hepatic lateral left lobe. Histologically, the mass consisted of neoplastic proliferation of cells with round nuclei and eosinophilic and vacuolated cytoplasm arranged in alveolar, trabecular, and solid patterns. Immunohistochemically, the neoplastic cells were positive for pancytokeratin (CK AE1/AE3), CK5, CK14, vimentin, Sox9, and myoepithelial markers (α-smooth muscle actin, p63, and calponin). The morphological and immunohistochemical findings indicated a diagnosis of myoepithelial carcinoma. We conducted immunohistochemical studies on other representative canine hepatic tumors. Although the myoepithelial phenotype was not observed in the hepatocellular carcinoma, some tumor cells in cholangiocarcinoma showed immunohistochemical features of myoepithelium, suggesting that some neoplastic cells in cholangiocarcinoma may have the potential to differentiate into myoepithelial cells. To our knowledge, this is the first report in veterinary medicine of a hepatic carcinoma with a myoepithelial phenotype.
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http://dx.doi.org/10.1177/0300985819854439DOI Listing
November 2019

Downregulation of aspartoacylase during the progression of myelin breakdown in the dmy mutant rat with mitochondrial magnesium channel MRS2 defect.

Brain Res 2019 09 14;1718:169-175. Epub 2019 May 14.

Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.

Objective: The dmy rat is an autosomal recessive mutant that exhibits severe rapid myelin breakdown throughout the central nervous system at 7-8 weeks of age. The dmy rat has a point mutation in Mrs2 gene, which encodes an essential component of the major electrophoretic Mg influx system in the mitochondria. However, it remains unknown how mitochondrial dysfunction leads to the myelin breakdown.

Methods: We focused on the aspartoacylase (ASPA) and mitochondrion-related metabolites to clarify the mechanism of myelin pathology in dmy rats. Aspa mRNA was significantly decreased in both the gray matter and the ventral white matter of spinal cord in the dmy rats from 4 to 8 weeks of age. Very faint immunohistochemical expression for ASPA was noted in the gray and white matter of the affected dmy rats at 8 weeks. Liquid chromatography mass spectrometry revealed no different amount of N-acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A (CoA) in neurons, in the brain and spinal cord between the dmy and control rats.

Conclusion: Our results indicated that the pyruvate dehydrogenase activity might be reduced due to the loss of Mg transport activity in the mitochondria of the dmy rats, suggesting acetyl CoA production might be reduced. The number of oligodendrocytes was well preserved until 7 weeks. It is intriguing that prior to the myelin destruction at 7-8 weeks, disrupted expression of Aspa mRNA and ASPA protein undergoes from early stage of myelinogenesis. These data indicate that ASPA expression would be a useful index to evaluate a function of oligodendrocyte in the dmy rat.
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http://dx.doi.org/10.1016/j.brainres.2019.05.017DOI Listing
September 2019

Late onset of cerebellar cortical degeneration in a Magellanic penguin (Spheniscus magellanicus).

J Vet Med Sci 2019 May 5;81(5):750-752. Epub 2019 Apr 5.

Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Science, Osaka Prefecture University, Izumisano, Osaka 598-8531, Japan.

An 8-year-old female Magellanic penguin (Spheniscus magellanicus) started to show epilepsy-like seizures. Subsequent magnetic resonance imaging (MRI) examinations did not reveal any responsible lesions. The neurological symptoms worsened at the age of 10. This penguin became recumbent and died 6 months later after the apparition of the recumbency. At necropsy, only multiple yellowish necrotic lesions in the air sacs and lungs were found. Histopathological evaluation of the brain showed a marked loss of Purkinje cells and many hypertrophied parvalbumin-positive basket/stellate cells were seen in the cerebellar cortex. Calbindin immunohistochemistry demonstrated disrupted arrangement of dendrites in the Purkinje cells. This case was diagnosed as cerebellar cortical degeneration with a very late onset and a slow progression in a Magellanic penguin.
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http://dx.doi.org/10.1292/jvms.19-0089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541849PMC
May 2019

Spontaneous peripheral neuritis in two electric eels (Electrophorus electricus).

J Vet Med Sci 2019 May 5;81(5):744-746. Epub 2019 Mar 5.

Laboratory of Veterinary Pathology, Osaka Prefecture University, Izumisano, Osaka 598-8531, Japan.

This study represents cases with spontaneous neuritis of peripheral nerves in electric eels. Two electric eels were presented with abnormal swimming behavior and loss of appetite. Electric eels had extensive histopathologic lesions in the splenic and cardiac nerves. The lesions were characterized by swelling of neuronal cells, central chromatolysis and marked inflammatory cell infiltration consisting mainly of lymphocytes around the affected nerves. To the best of our knowledge, this is the first case report of spontaneous neuritis of peripheral nerves in electric eels.
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http://dx.doi.org/10.1292/jvms.18-0751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541840PMC
May 2019
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