A high-fat, low–carbohydrate diet (KD) or calorie restriction in the form of every-other-day fasting (EODF) results in ketone body metabolism with an increasing β-hydroxybutyrate (βOHB) level. Previous studies have supported that a KD and EODF have a neuroprotective effect. However, the βOHB levels in the cerebrospinal fluid (CSF) resulting from a KD and EODF remain unknown. The aim of this study was to detect βOHB levels in rats fed a KD, EODF diet, and every-other-day ketogenic diet (EODKD) and to compare the serum βOHB level with the CSF βOHB level. Twenty-four male Sprague-Dawley rats were randomly divided into KD, EODF, EODKD, and standard diet (SD) groups. A customized food with a ratio of carbohydrates to fats of 1:4 was used in the KD and EODKD groups. The βOHB level was measured using ELISA kits in 200 µl serum and 100 µl CSF samples for each rat after feeding for 2 weeks. The KD, EODF, and EODKD resulted in a significant increase in βOHB levels in both the serum and CSF. The βOHB levels in the EODKD group were the highest. The CSF βOHB level was, on average, 69% of the serum βOHB level. There was a positive correlation between the overall βOHB levels in serum and that in cerebrospinal fluid. This study demonstrated that the KD, EODF, and EODKD resulted in ketone body metabolism, as the βOHB levels increased significantly compared with those resulting from the standard diet. Our results suggested that the serum βOHB level was an indicator of the CSF βOHB level, and that the EODKD was an effective diet to enhance ketogenic metabolism.
{"title":"β hydroxybutyrate levels in serum and cerebrospinal fluid under ketone body metabolism in rats","authors":"Xiaomeng Wang, Qi Liu, Jian Zhou, Xiuhua Wu, Qingan Zhu","doi":"10.1538/expanim.16-0090","DOIUrl":"https://doi.org/10.1538/expanim.16-0090","url":null,"abstract":"A high-fat, low–carbohydrate diet (KD) or calorie restriction in the form of every-other-day fasting (EODF) results in ketone body metabolism with an increasing β-hydroxybutyrate (βOHB) level. Previous studies have supported that a KD and EODF have a neuroprotective effect. However, the βOHB levels in the cerebrospinal fluid (CSF) resulting from a KD and EODF remain unknown. The aim of this study was to detect βOHB levels in rats fed a KD, EODF diet, and every-other-day ketogenic diet (EODKD) and to compare the serum βOHB level with the CSF βOHB level. Twenty-four male Sprague-Dawley rats were randomly divided into KD, EODF, EODKD, and standard diet (SD) groups. A customized food with a ratio of carbohydrates to fats of 1:4 was used in the KD and EODKD groups. The βOHB level was measured using ELISA kits in 200 µl serum and 100 µl CSF samples for each rat after feeding for 2 weeks. The KD, EODF, and EODKD resulted in a significant increase in βOHB levels in both the serum and CSF. The βOHB levels in the EODKD group were the highest. The CSF βOHB level was, on average, 69% of the serum βOHB level. There was a positive correlation between the overall βOHB levels in serum and that in cerebrospinal fluid. This study demonstrated that the KD, EODF, and EODKD resulted in ketone body metabolism, as the βOHB levels increased significantly compared with those resulting from the standard diet. Our results suggested that the serum βOHB level was an indicator of the CSF βOHB level, and that the EODKD was an effective diet to enhance ketogenic metabolism.","PeriodicalId":75961,"journal":{"name":"Jikken dobutsu. Experimental animals","volume":"66 1","pages":"177 - 182"},"PeriodicalIF":0.0,"publicationDate":"2017-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1538/expanim.16-0090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43527172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniele Masselli Rodrigues, J. C. Moreira, M. Lancellotti, R. Gilioli, M. Corat
Murine norovirus (MNV) is a single-stranded positive-sense RNA virus of the Caliciviridae family. MNV has been reported to infect laboratory mice with the ability to cause lethal infections in strains lacking components of the innate immune response. Currently, MNV is considered the most prevalent infectious agent detected in laboratory mouse facilities. In this study, mice in 22 laboratory animal facilities within Brazil were analyzed for MNV infection. Using primers targeting a conserved region of the viral capsid, MNV was detected by RT-PCR in 137 of 359 mice from all 22 facilities. Nucleotide sequencing and phylogenetic analysis of the capsid region from the viral genome showed identity ranging from 87% to 99% when compared to reported MNV sequences. In addition, RAW264.7 cells inoculated with a mouse fecal suspension displayed cytopathic effect after the fifth passage. This study represents the first report of MNV in mouse colonies in Brazilian laboratory animal facilities, emphasizing the relevance of a health surveillance program in such environments.
{"title":"Murine norovirus infection in Brazilian animal facilities","authors":"Daniele Masselli Rodrigues, J. C. Moreira, M. Lancellotti, R. Gilioli, M. Corat","doi":"10.1538/expanim.16-0027","DOIUrl":"https://doi.org/10.1538/expanim.16-0027","url":null,"abstract":"Murine norovirus (MNV) is a single-stranded positive-sense RNA virus of the Caliciviridae family. MNV has been reported to infect laboratory mice with the ability to cause lethal infections in strains lacking components of the innate immune response. Currently, MNV is considered the most prevalent infectious agent detected in laboratory mouse facilities. In this study, mice in 22 laboratory animal facilities within Brazil were analyzed for MNV infection. Using primers targeting a conserved region of the viral capsid, MNV was detected by RT-PCR in 137 of 359 mice from all 22 facilities. Nucleotide sequencing and phylogenetic analysis of the capsid region from the viral genome showed identity ranging from 87% to 99% when compared to reported MNV sequences. In addition, RAW264.7 cells inoculated with a mouse fecal suspension displayed cytopathic effect after the fifth passage. This study represents the first report of MNV in mouse colonies in Brazilian laboratory animal facilities, emphasizing the relevance of a health surveillance program in such environments.","PeriodicalId":75961,"journal":{"name":"Jikken dobutsu. Experimental animals","volume":"66 1","pages":"115 - 124"},"PeriodicalIF":0.0,"publicationDate":"2016-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1538/expanim.16-0027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67291314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Yamada, T. Koike, T. Nakagawa, Nobue Kuniyoshi, Yu Ying, H. Itabe, A. Yamashita, Y. Asada, M. Shiomi
In order to examine their suitability for studies on coronary atherosclerosis, we evaluated the features of coronary atherosclerotic plaques in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits, a spontaneous animal model for coronary atherosclerosis and myocardial infarction. Coronary segments of the hearts of 187 WHHLMI rabbits (10–29 months old) were sectioned serially and stained histopathologically and immunohistologically. Progression of coronary lesions was prominent in rabbits that had died suddenly. The degree of coronary lesions of females was higher than that of males. Various types of atherosclerotic lesions were observed in the coronary arteries, such as plaques with a large lipid core covered by a thin fibrous cap, fatty streaks, early and advanced fibroatheromas, fibrous lesions, and advanced lesions with calcium accumulation and the vasa vasorum. In rabbits that had died suddenly, the frequencies of fibroatheromas or advanced lesions were higher than those of rabbits euthanized. Matrix metalloproteinase (MMP)-positive macrophages were detected in gaps among endothelial cells at the plaque surface, beneath the fibrous cap of thin-capped fibroatheromas, and at the bottom of the intimal plaques in which the tunica media was attenuated. Immunohistological results suggest that MMP-positive macrophages are involved in the initiation, progression, and destabilization of coronary plaques, in addition to vascular remodeling, even in WHHLMI rabbits. In conclusion, coronary lesions in WHHLMI rabbits resemble human atherosclerotic lesions, and thus, the WHHLMI rabbit is a suitable animal model for studies on human coronary plaques.
{"title":"Morphological features of coronary plaques in WHHLMI rabbits (Oryctolagus cuniculus), an animal model for familial hypercholesterolemia","authors":"S. Yamada, T. Koike, T. Nakagawa, Nobue Kuniyoshi, Yu Ying, H. Itabe, A. Yamashita, Y. Asada, M. Shiomi","doi":"10.1538/expanim.16-0078","DOIUrl":"https://doi.org/10.1538/expanim.16-0078","url":null,"abstract":"In order to examine their suitability for studies on coronary atherosclerosis, we evaluated the features of coronary atherosclerotic plaques in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits, a spontaneous animal model for coronary atherosclerosis and myocardial infarction. Coronary segments of the hearts of 187 WHHLMI rabbits (10–29 months old) were sectioned serially and stained histopathologically and immunohistologically. Progression of coronary lesions was prominent in rabbits that had died suddenly. The degree of coronary lesions of females was higher than that of males. Various types of atherosclerotic lesions were observed in the coronary arteries, such as plaques with a large lipid core covered by a thin fibrous cap, fatty streaks, early and advanced fibroatheromas, fibrous lesions, and advanced lesions with calcium accumulation and the vasa vasorum. In rabbits that had died suddenly, the frequencies of fibroatheromas or advanced lesions were higher than those of rabbits euthanized. Matrix metalloproteinase (MMP)-positive macrophages were detected in gaps among endothelial cells at the plaque surface, beneath the fibrous cap of thin-capped fibroatheromas, and at the bottom of the intimal plaques in which the tunica media was attenuated. Immunohistological results suggest that MMP-positive macrophages are involved in the initiation, progression, and destabilization of coronary plaques, in addition to vascular remodeling, even in WHHLMI rabbits. In conclusion, coronary lesions in WHHLMI rabbits resemble human atherosclerotic lesions, and thus, the WHHLMI rabbit is a suitable animal model for studies on human coronary plaques.","PeriodicalId":75961,"journal":{"name":"Jikken dobutsu. Experimental animals","volume":"76 1","pages":"145 - 157"},"PeriodicalIF":0.0,"publicationDate":"2016-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1538/expanim.16-0078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67291480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chunhua Yin, Lumei Kang, Ch Lai, Jing-yong Zhou, Bin Shi, Lei Zhang, Hongping Chen
Leptin is secreted predominantly by adipocytes and exerts its role mainly by interaction with the long form of leptin receptor (LEPR_V2). It has been identified that LEPR_V2 is widely distributed in various tissues, including the anterior pituitary. Cross-talk between leptin and estrogens has been indentified. Estrogen is known to modulate the tissue-specific expression of LEPR_V2 and leptin in ovariectomized (OVX) rats, a model of postmenopausal condition. Our previous data showed that 17β-estradiol (E2) up-regulated the expression of LEPR_V2 protein and mRNA in rat dorsal root ganglion (DRG) in an estrogen receptor alpha (ERα)-dependent manner. But it is still unclear whether estrogen can regulate leptin signalling in the pituitary of OVX rats. In the present study, we found that ovariectomy decreased the expressions of LEPR_V2. Administration of E2 increased the expressions of LEPR_V2 in a dose-dependent manner. In addition, E2 improved LEPR_V2, STAT3, and SOCS3 protein levels in OVX rats. The effects of exogenous E2 were attenuated by ICI 182,780, a specific estrogen receptors antagonist. However, E2 did not change the Lepr_v1, a type of short form of leptin receptor (LEPR), or leptin mRNA levels. Thus, E2 plays a crucial role in regulating pituitary sensitivity to leptin in OVX rats. Our findings implied that exogenous E2 had potential roles in modification of the function of pituitary in postmenopausal women.
{"title":"Effects of 17β-estradiol on leptin signaling in anterior pituitary of ovariectomized rats","authors":"Chunhua Yin, Lumei Kang, Ch Lai, Jing-yong Zhou, Bin Shi, Lei Zhang, Hongping Chen","doi":"10.1538/expanim.16-0087","DOIUrl":"https://doi.org/10.1538/expanim.16-0087","url":null,"abstract":"Leptin is secreted predominantly by adipocytes and exerts its role mainly by interaction with the long form of leptin receptor (LEPR_V2). It has been identified that LEPR_V2 is widely distributed in various tissues, including the anterior pituitary. Cross-talk between leptin and estrogens has been indentified. Estrogen is known to modulate the tissue-specific expression of LEPR_V2 and leptin in ovariectomized (OVX) rats, a model of postmenopausal condition. Our previous data showed that 17β-estradiol (E2) up-regulated the expression of LEPR_V2 protein and mRNA in rat dorsal root ganglion (DRG) in an estrogen receptor alpha (ERα)-dependent manner. But it is still unclear whether estrogen can regulate leptin signalling in the pituitary of OVX rats. In the present study, we found that ovariectomy decreased the expressions of LEPR_V2. Administration of E2 increased the expressions of LEPR_V2 in a dose-dependent manner. In addition, E2 improved LEPR_V2, STAT3, and SOCS3 protein levels in OVX rats. The effects of exogenous E2 were attenuated by ICI 182,780, a specific estrogen receptors antagonist. However, E2 did not change the Lepr_v1, a type of short form of leptin receptor (LEPR), or leptin mRNA levels. Thus, E2 plays a crucial role in regulating pituitary sensitivity to leptin in OVX rats. Our findings implied that exogenous E2 had potential roles in modification of the function of pituitary in postmenopausal women.","PeriodicalId":75961,"journal":{"name":"Jikken dobutsu. Experimental animals","volume":"66 1","pages":"159 - 166"},"PeriodicalIF":0.0,"publicationDate":"2016-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1538/expanim.16-0087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67291802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The aryl hydrocarbon receptor (AHR) is a pivotal chemical sensor that transduces extrinsic and intrinsic signals into cellular responses. AHR was originally thought to be involved in not only drug metabolism but also carcinogenic and toxicological responses against environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbons. However, recent studies demonstrate that the AHR plays multiple intrinsic roles in host defense and homeostasis as well, including immunity, stem cell maintenance, and cell differentiation, upon binding with an increasing number of newly defined dietary, cellular, and microbe-derived ligands. In addition, AHR is a convergence point for several signaling cascades, which may be involved in the diverse diseases caused by binding of the persistent ligand TCDD with extremely high affinity to AHR. A comprehensive understanding of physiological and pathological processes initiated by endogenous AHR agonists and antagonists may allow for the therapeutic regulation of AHR activity. Thus, the AHR can be a valuable diagnostic marker and therapeutic target for human diseases.
{"title":"The aryl hydrocarbon receptor: a multifunctional chemical sensor for host defense and homeostatic maintenance","authors":"K. Kawajiri, Y. Fujii‐Kuriyama","doi":"10.1538/expanim.16-0092","DOIUrl":"https://doi.org/10.1538/expanim.16-0092","url":null,"abstract":"The aryl hydrocarbon receptor (AHR) is a pivotal chemical sensor that transduces extrinsic and intrinsic signals into cellular responses. AHR was originally thought to be involved in not only drug metabolism but also carcinogenic and toxicological responses against environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polycyclic aromatic hydrocarbons. However, recent studies demonstrate that the AHR plays multiple intrinsic roles in host defense and homeostasis as well, including immunity, stem cell maintenance, and cell differentiation, upon binding with an increasing number of newly defined dietary, cellular, and microbe-derived ligands. In addition, AHR is a convergence point for several signaling cascades, which may be involved in the diverse diseases caused by binding of the persistent ligand TCDD with extremely high affinity to AHR. A comprehensive understanding of physiological and pathological processes initiated by endogenous AHR agonists and antagonists may allow for the therapeutic regulation of AHR activity. Thus, the AHR can be a valuable diagnostic marker and therapeutic target for human diseases.","PeriodicalId":75961,"journal":{"name":"Jikken dobutsu. Experimental animals","volume":"66 1","pages":"75 - 89"},"PeriodicalIF":0.0,"publicationDate":"2016-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1538/expanim.16-0092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67291523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Satoki Ichimura, Shun-ichi Sasaki, T. Murata, R. Fukumura, Y. Gondo, S. Ikegawa, T. Furuichi
Camurati-Engelmann disease (CED) is a rare sclerosing bone disorder in humans with autosomal dominant inheritance. Mutations in the gene (TGFB1) that encodes transforming growth factor-β1 (TGF-β1) are causative for CED. TGF-β1 signaling is enhanced by the CED-causing mutations. In this study, we performed Tgfb1 mutation screening in an ENU-mutagenized mouse genomic DNA library. We identified a missense mutation in which cysteine was substituted by serine at position 225 (p.C225S), that corresponded to the CED-causing mutation (p.C225R). TGF-β1 mutant protein carrying p.C225S was secreted normally into the extracellular space. Reporter gene assays showed that the p.C225S mutants enhanced TGF-β signaling at the same level as p.C225R mutants. We generated p.C225S homozygous mice and confirmed that the mature TGF-β1 levels in the culture supernatants of the calvarial cells from the homozygotes were significantly higher than those from wild-type mice. Although the skull and femur are sclerotic in CED, these phenotypes were not observed in p.C225S homozygous mice. These results suggest that human and mouse bone tissue react differently to TGF-β1. These findings are useful to pharmacological studies using mouse models in developing drugs that will target TGF-β signaling.
{"title":"An ENU-induced p.C225S missense mutation in the mouse Tgfb1 gene does not cause Camurati-Engelmann disease-like skeletal phenotypes","authors":"Satoki Ichimura, Shun-ichi Sasaki, T. Murata, R. Fukumura, Y. Gondo, S. Ikegawa, T. Furuichi","doi":"10.1538/expanim.16-0085","DOIUrl":"https://doi.org/10.1538/expanim.16-0085","url":null,"abstract":"Camurati-Engelmann disease (CED) is a rare sclerosing bone disorder in humans with autosomal dominant inheritance. Mutations in the gene (TGFB1) that encodes transforming growth factor-β1 (TGF-β1) are causative for CED. TGF-β1 signaling is enhanced by the CED-causing mutations. In this study, we performed Tgfb1 mutation screening in an ENU-mutagenized mouse genomic DNA library. We identified a missense mutation in which cysteine was substituted by serine at position 225 (p.C225S), that corresponded to the CED-causing mutation (p.C225R). TGF-β1 mutant protein carrying p.C225S was secreted normally into the extracellular space. Reporter gene assays showed that the p.C225S mutants enhanced TGF-β signaling at the same level as p.C225R mutants. We generated p.C225S homozygous mice and confirmed that the mature TGF-β1 levels in the culture supernatants of the calvarial cells from the homozygotes were significantly higher than those from wild-type mice. Although the skull and femur are sclerotic in CED, these phenotypes were not observed in p.C225S homozygous mice. These results suggest that human and mouse bone tissue react differently to TGF-β1. These findings are useful to pharmacological studies using mouse models in developing drugs that will target TGF-β signaling.","PeriodicalId":75961,"journal":{"name":"Jikken dobutsu. Experimental animals","volume":"66 1","pages":"137 - 144"},"PeriodicalIF":0.0,"publicationDate":"2016-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1538/expanim.16-0085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67291697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katsuyoshi Kumagai, M. Takanashi, Shin-ichiro Ohno, M. Kuroda, K. Sudo
Targeted mutant mice generated on a C57BL/6 background are powerful tools for analysis of the biological functions of genes, and gene targeting technologies using mouse embryonic stem (ES) cells have been used to generate such mice. Recently, a bacterial artificial chromosome (BAC) recombineering system was established for the construction of targeting vectors. However, gene retrieval from BACs for the generation of gene targeting vectors using this system remains difficult. Even when construction of a gene targeting vector is successful, the efficiency of production of targeted mutant mice from ES cells derived from C57BL/6 mice are poor. Therefore, in this study, we first improved the strategy for the retrieval of genes from BACs and their transfer into a DT-A plasmid, for the generation of gene targeting vectors using the BAC recombineering system. Then, we attempted to generate targeted mutant mice from ES cell lines derived from C57BL/6 mice, by culturing in serum-free medium. In conclusion, we established an improved strategy for the efficient generation of targeted mutant mice on a C57BL/6 background, which are useful for the in vivo analysis of gene functions and regulation.
{"title":"An improved Red/ET recombineering system and mouse ES cells culture conditions for the generation of targeted mutant mice","authors":"Katsuyoshi Kumagai, M. Takanashi, Shin-ichiro Ohno, M. Kuroda, K. Sudo","doi":"10.1538/expanim.16-0075","DOIUrl":"https://doi.org/10.1538/expanim.16-0075","url":null,"abstract":"Targeted mutant mice generated on a C57BL/6 background are powerful tools for analysis of the biological functions of genes, and gene targeting technologies using mouse embryonic stem (ES) cells have been used to generate such mice. Recently, a bacterial artificial chromosome (BAC) recombineering system was established for the construction of targeting vectors. However, gene retrieval from BACs for the generation of gene targeting vectors using this system remains difficult. Even when construction of a gene targeting vector is successful, the efficiency of production of targeted mutant mice from ES cells derived from C57BL/6 mice are poor. Therefore, in this study, we first improved the strategy for the retrieval of genes from BACs and their transfer into a DT-A plasmid, for the generation of gene targeting vectors using the BAC recombineering system. Then, we attempted to generate targeted mutant mice from ES cell lines derived from C57BL/6 mice, by culturing in serum-free medium. In conclusion, we established an improved strategy for the efficient generation of targeted mutant mice on a C57BL/6 background, which are useful for the in vivo analysis of gene functions and regulation.","PeriodicalId":75961,"journal":{"name":"Jikken dobutsu. Experimental animals","volume":"66 1","pages":"125 - 136"},"PeriodicalIF":0.0,"publicationDate":"2016-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1538/expanim.16-0075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67291845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Epidemiological and experimental data have indicated the beneficial and adverse effects of estrogenic replacement therapy. In the present study, we explored the effect of ethinylestradiol (EE) and 17β-estradiol (E2) on screening tests, prothrombin time (PT) and activated partial thromboplastin time (APTT), as well as the activity of coagulation factors (FVII, FX, FXI, and FXII) in male Wistar rats. Animals were injected subcutaneously during three consecutive days with EE or E2 (1, 3, 10, and 30 mg/kg) and propylene glycol (0.3 ml; vehicle, V). EE produced significant increments (P<0.05) on PT (8, 13, 15, and 10%) and APTT (32, 35, and 28%), whereas E2 did not show any effect. EE diminished the activity of factors VII (−10, −13, and −10%) and X (−10, −9, −15, and −14%; P<0.05), and E2 (1 mg/kg) produced a modest increment (8%; P<0.05) on FX only. E2 (10 mg/kg) showed a diminution of 9% (P<0.05), while EE did not produce any response on factor XII. EE diminished (−15, −14, −19, and −17%) but E2 augmented (10, 14, 24, and 24%) factor XI activity (P<0.05). Our findings suggest that EE and E2 produce different effects on coagulation and that EE seems to act across an inhibitory mechanism of coagulation factor activity in the present experimental model.
{"title":"Inhibitory effect of ethinylestradiol on coagulation factors in rats","authors":"Y. Franco-Murillo, R. Jaimez","doi":"10.1538/expanim.16-0084","DOIUrl":"https://doi.org/10.1538/expanim.16-0084","url":null,"abstract":"Epidemiological and experimental data have indicated the beneficial and adverse effects of estrogenic replacement therapy. In the present study, we explored the effect of ethinylestradiol (EE) and 17β-estradiol (E2) on screening tests, prothrombin time (PT) and activated partial thromboplastin time (APTT), as well as the activity of coagulation factors (FVII, FX, FXI, and FXII) in male Wistar rats. Animals were injected subcutaneously during three consecutive days with EE or E2 (1, 3, 10, and 30 mg/kg) and propylene glycol (0.3 ml; vehicle, V). EE produced significant increments (P<0.05) on PT (8, 13, 15, and 10%) and APTT (32, 35, and 28%), whereas E2 did not show any effect. EE diminished the activity of factors VII (−10, −13, and −10%) and X (−10, −9, −15, and −14%; P<0.05), and E2 (1 mg/kg) produced a modest increment (8%; P<0.05) on FX only. E2 (10 mg/kg) showed a diminution of 9% (P<0.05), while EE did not produce any response on factor XII. EE diminished (−15, −14, −19, and −17%) but E2 augmented (10, 14, 24, and 24%) factor XI activity (P<0.05). Our findings suggest that EE and E2 produce different effects on coagulation and that EE seems to act across an inhibitory mechanism of coagulation factor activity in the present experimental model.","PeriodicalId":75961,"journal":{"name":"Jikken dobutsu. Experimental animals","volume":"66 1","pages":"107 - 113"},"PeriodicalIF":0.0,"publicationDate":"2016-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1538/expanim.16-0084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67291552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ectothermic animals rely on behavioral thermoregulation due to low capacity of heat production and storage. Previously, lizards were shown to achieve ‘fever’ during microbial infection by increasing their preferred body temperature (PBT) behaviorally, thereby attaining a relatively high survival rate. The purpose of this study was to investigate whether domesticated lizards pursued ‘behavioral hypothermia’ induced by a hypometabolic agent 3-iodothyronamine (T1AM). We found that treatment with 8.0 mg/kg T1AM caused a lizard species, the leopard gecko (Eublepharis macularius), to decrease its ventilation and oxygen consumption rates 0.64- and 0.76-fold, respectively, compared to those of the control (P<0.05). The lizards, habituated at an ambient temperature of 30 ± 0.5°C, also showed a significant decrease in the PBT range over a freely accessible thermal gradient between 5°C and 45°C. The upper limit of the PBT in the treated lizards lowered from 31.9°C to 30.6°C, and the lower limit from 29.5°C to 26.3°C (P<0.001). These findings demonstrate that the treated lizards pursued behavioral hypothermia in conjunction with hypoventilation and hypometabolism. Because prior studies reported a similar hypometabolic response in T1AM-injected laboratory mice, the domesticated lizards, as a part of the vertebrate phylogeny, may be a useful laboratory model for biological and pharmacological researches such as drug potency test.
{"title":"Behavioral hypothermia of a domesticated lizard under treatment of the hypometabolic agent 3-iodothyronamine","authors":"Kyoungbong Ha, H. Shin, H. Ju, C. Chung, I. Choi","doi":"10.1538/expanim.16-0070","DOIUrl":"https://doi.org/10.1538/expanim.16-0070","url":null,"abstract":"Ectothermic animals rely on behavioral thermoregulation due to low capacity of heat production and storage. Previously, lizards were shown to achieve ‘fever’ during microbial infection by increasing their preferred body temperature (PBT) behaviorally, thereby attaining a relatively high survival rate. The purpose of this study was to investigate whether domesticated lizards pursued ‘behavioral hypothermia’ induced by a hypometabolic agent 3-iodothyronamine (T1AM). We found that treatment with 8.0 mg/kg T1AM caused a lizard species, the leopard gecko (Eublepharis macularius), to decrease its ventilation and oxygen consumption rates 0.64- and 0.76-fold, respectively, compared to those of the control (P<0.05). The lizards, habituated at an ambient temperature of 30 ± 0.5°C, also showed a significant decrease in the PBT range over a freely accessible thermal gradient between 5°C and 45°C. The upper limit of the PBT in the treated lizards lowered from 31.9°C to 30.6°C, and the lower limit from 29.5°C to 26.3°C (P<0.001). These findings demonstrate that the treated lizards pursued behavioral hypothermia in conjunction with hypoventilation and hypometabolism. Because prior studies reported a similar hypometabolic response in T1AM-injected laboratory mice, the domesticated lizards, as a part of the vertebrate phylogeny, may be a useful laboratory model for biological and pharmacological researches such as drug potency test.","PeriodicalId":75961,"journal":{"name":"Jikken dobutsu. Experimental animals","volume":"66 1","pages":"99 - 105"},"PeriodicalIF":0.0,"publicationDate":"2016-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1538/expanim.16-0070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67291051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jeng-Rung Chen, S. Lim, Sin-Cun Chung, Yee-Fun Lee, Yueh-Jan Wang, G. Tseng, Tsyr-Jiuan Wang
Behavioral adaptations during motherhood are aimed at increasing reproductive success. Alterations of hormones during motherhood could trigger brain morphological changes to underlie behavioral alterations. Here we investigated whether motherhood changes a rat’s sensory perception and spatial memory in conjunction with cortical neuronal structural changes. Female rats of different statuses, including virgin, pregnant, lactating, and primiparous rats were studied. Behavioral test showed that the lactating rats were most sensitive to heat, while rats with motherhood and reproduction experience outperformed virgin rats in a water maze task. By intracellular dye injection and computer-assisted 3-dimensional reconstruction, the dendritic arbors and spines of the layer III and V pyramidal neurons of the somatosensory cortex and CA1 hippocampal pyramidal neurons were revealed for closer analysis. The results showed that motherhood and reproductive experience increased dendritic spines but not arbors or the lengths of the layer III and V pyramidal neurons of the somatosensory cortex and CA1 hippocampal pyramidal neurons. In addition, lactating rats had a higher incidence of spines than pregnant or primiparous rats. The increase of dendritic spines was coupled with increased expression of the glutamatergic postsynaptic marker protein (PSD-95), especially in lactating rats. On the basis of the present results, it is concluded that motherhood enhanced rat sensory perception and spatial memory and was accompanied by increases in dendritic spines on output neurons of the somatosensory cortex and CA1 hippocampus. The effect was sustained for at least 6 weeks after the weaning of the pups.
{"title":"Reproductive experience modified dendritic spines on cortical pyramidal neurons to enhance sensory perception and spatial learning in rats","authors":"Jeng-Rung Chen, S. Lim, Sin-Cun Chung, Yee-Fun Lee, Yueh-Jan Wang, G. Tseng, Tsyr-Jiuan Wang","doi":"10.1538/expanim.16-0061","DOIUrl":"https://doi.org/10.1538/expanim.16-0061","url":null,"abstract":"Behavioral adaptations during motherhood are aimed at increasing reproductive success. Alterations of hormones during motherhood could trigger brain morphological changes to underlie behavioral alterations. Here we investigated whether motherhood changes a rat’s sensory perception and spatial memory in conjunction with cortical neuronal structural changes. Female rats of different statuses, including virgin, pregnant, lactating, and primiparous rats were studied. Behavioral test showed that the lactating rats were most sensitive to heat, while rats with motherhood and reproduction experience outperformed virgin rats in a water maze task. By intracellular dye injection and computer-assisted 3-dimensional reconstruction, the dendritic arbors and spines of the layer III and V pyramidal neurons of the somatosensory cortex and CA1 hippocampal pyramidal neurons were revealed for closer analysis. The results showed that motherhood and reproductive experience increased dendritic spines but not arbors or the lengths of the layer III and V pyramidal neurons of the somatosensory cortex and CA1 hippocampal pyramidal neurons. In addition, lactating rats had a higher incidence of spines than pregnant or primiparous rats. The increase of dendritic spines was coupled with increased expression of the glutamatergic postsynaptic marker protein (PSD-95), especially in lactating rats. On the basis of the present results, it is concluded that motherhood enhanced rat sensory perception and spatial memory and was accompanied by increases in dendritic spines on output neurons of the somatosensory cortex and CA1 hippocampus. The effect was sustained for at least 6 weeks after the weaning of the pups.","PeriodicalId":75961,"journal":{"name":"Jikken dobutsu. Experimental animals","volume":"66 1","pages":"61 - 74"},"PeriodicalIF":0.0,"publicationDate":"2016-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1538/expanim.16-0061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67291406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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