scholarly journals Pathological mechanism of secondary-progressive multiples sclerosis and its animal model

2016 ◽  
Vol 39 (2) ◽  
pp. 103-113 ◽  
Author(s):  
Shinji OKI
Keyword(s):  
Animal Model ◽  
Secondary Progressive ◽  
Pathological Mechanism

scholarly journals Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy

2020 ◽  
Author(s):  
Bo Jin ◽  
Haiming Shi ◽  
Zhu Jun ◽  
Bangwei Wu ◽  
Quzhen Geshang
Keyword(s):  
Animal Model ◽  
Cardiovascular Diseases ◽  
Cardiac Function ◽  
Dilated Cardiomyopathy ◽  
Cardiac Remodeling ◽  
Therapeutic Strategy ◽  
Volume Fraction ◽  
Pathological Process ◽  
Cardiac Myosin ◽  
Pathological Mechanism

Abstract Background: Autophagy plays a crucial role in the pathological process of cardiovascular diseases. However, little is known about the pathological mechanism underlying autophagy regulation in dilated cardiomyopathy (DCM). Methods: We explored whether up-regulating autophagy could improve cardiac function in mice with experimental DCM through the mTOR-4EBP1 pathway. Animal model of DCM was established in BALB/c mice by immunization with porcine cardiac myosin. Both up- or down-regulation of autophagy were studied by administration of rapamycin or 3-MA in parallel. Morphology, Western blotting, and echocardiography were applied to confirm the pathological mechanisms. Results: Autophagy was activated and autophagosomes were significantly increased in the rapamycin group. The collagen volume fraction (CVF) was decreased in the rapamycin group compared with the DCM group (9.21 ± 0.82 % vs 14.38 ± 1.24 %, P<0.01). The expression of p-mTOR and p-4EBP1 were significantly decreased in rapamycin-induced autophagy activation, while the levels were increased by down-regulating autophagy with 3-MA. In the rapamycin group, the LVEF and FS were significantly increased compared with the DCM group (54.12 ± 6.48 % vs 45.29 ± 6.68 %, P <0.01; 26.89 ± 4.04 % vs 22.17 ± 2.82 %, P <0.05). As the inhibitor of autophagy, 3-MA aggravated the progress of maladaptive cardiac remodeling and declined cardiac function in DCM mice. Conclusions: The study indicated a possible mechanism for improving cardiac function in mice with experimental DCM by up-regulating autophagy via the mTOR-4EBP1 pathway, which could be a promising therapeutic strategy for DCM.

scholarly journals Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy

2019 ◽  
Author(s):  
Bo Jin ◽  
Haiming Shi ◽  
Zhu Jun ◽  
Bangwei Wu ◽  
Quzhen Geshang
Keyword(s):  
Animal Model ◽  
Cardiovascular Diseases ◽  
Cardiac Function ◽  
Dilated Cardiomyopathy ◽  
Cardiac Remodeling ◽  
Therapeutic Strategy ◽  
Volume Fraction ◽  
Pathological Process ◽  
Cardiac Myosin ◽  
Pathological Mechanism

Abstract Background: Autophagy plays a crucial role in the pathological process of cardiovascular diseases. However, little is known about the pathological mechanism underlying autophagy regulation in dilated cardiomyopathy (DCM).Methods: We explored whether up-regulating autophagy could improve cardiac function in mice with experimental DCM through the mTOR-4EBP1 pathway. Animal model of DCM was established in BALB/c mice by immunization with porcine cardiac myosin. Both up- or down-regulation of autophagy were studied by administration of rapamycin or 3-MA in parallel. Morphology, Western blotting, and echocardiography were applied to confirm the pathological mechanisms.Results: Autophagy was activated and autophagosomes were significantly increased in the rapamycin group. The collagen volume fraction (CVF) was decreased in the rapamycin group compared with the DCM group (9.21 ± 0.82 % vs 14.38 ± 1.24 %, P<0.01). The expression of p-mTOR and p-4EBP1 were significantly decreased in rapamycin-induced autophagy activation, while the levels were increased by down-regulating autophagy with 3-MA. In the rapamycin group, the LVEF and FS were significantly increased compared with the DCM group (54.12 ± 6.48 % vs 45.29 ± 6.68 %, P<0.01; 26.89 ± 4.04 % vs 22.17 ± 2.82 %, P<0.05). As the inhibitor of autophagy, 3-MA aggravated the progress of maladaptive cardiac remodeling and declined cardiac function in DCM mice.Conclusions: The study indicated a possible mechanism for improving cardiac function in mice with experimental DCM by up-regulating autophagy via the mTOR-4EBP1 pathway, which could be a promising therapeutic strategy for DCM.

scholarly journals Dynamic urine proteome changes in a rat model of simvastatin-induced skeletal muscle injury.

2021 ◽  
Author(s):  
Jing Wei ◽  
Yuhang Huan ◽  
Ziqi Heng ◽  
Chenyang Zhao ◽  
Youhe Gao
Keyword(s):  
Animal Model ◽  
Side Effects ◽  
Rat Model ◽  
Muscle Injury ◽  
Urine Proteome ◽  
Data Independent Acquisition ◽  
Pathological Mechanism ◽  
Hematoxylin And Eosin ◽  
Biochemical Analyses ◽  
Proteome Changes

Background: Statin-associated muscle symptoms (SAMS) are the main side effects of statins. Currently, there are no effective biomarkers for accurate clinical diagnosis. Urine is not subject to homeostatic control and therefore accumulates early changes, making it an ideal biomarker source. We therefore examined urine proteome changes associated with SAMS in an animal model. Methods: Here, we established a SAMS rat model by intragastric intubation with simvastatin (80 mg/kg). Biochemical analyses and hematoxylin and eosin (H&E) staining were used to evaluate the degree of muscle injury. The urine proteome on days 3, 6, 9 and 14 was profiled using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) with the data-independent acquisition (DIA) method. Results: Differential proteins on day 14 of SAMS were mainly associated with glycolysis/gluconeogenesis, pyruvate metabolism, metabolism of reactive oxygen species and apoptosis, all of which were reported to be associated with the pathological mechanism of SAMS. Among the 14 differentially expressed proteins on day 3, FIBG, OSTP and CRP were associated with muscle damage, while EHD1, CUBN and FINC were associated with the pathogenic mechanisms of SAMS. MYG and PRVA increased dramatically compared with CK elevation in serum on day 14 of SAMS. Conclusions: Our preliminary results indicated that the urine proteome can reflect early changes in the SAMS rat model, providing the potential for monitoring drug side effects in future clinical research. Keywords: Urine proteome, statin-associated muscle symptoms, animal model, biomarkers

scholarly journals Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy

2020 ◽  
Author(s):  
Bo Jin ◽  
Haiming Shi ◽  
Zhu Jun ◽  
Bangwei Wu ◽  
Quzhen Geshang
Keyword(s):  
Animal Model ◽  
Cardiovascular Diseases ◽  
Cardiac Function ◽  
Dilated Cardiomyopathy ◽  
Cardiac Remodeling ◽  
Therapeutic Strategy ◽  
Volume Fraction ◽  
Pathological Process ◽  
Cardiac Myosin ◽  
Pathological Mechanism

Abstract Background: Autophagy plays a crucial role in the pathological process of cardiovascular diseases. However, little is known about the pathological mechanism underlying autophagy regulation in dilated cardiomyopathy (DCM).Methods: We explored whether up-regulating autophagy could improve cardiac function in mice with experimental DCM through the mTOR-4EBP1 pathway. Animal model of DCM was established in BALB/c mice by immunization with porcine cardiac myosin. Both up- or down-regulation of autophagy were studied by administration of rapamycin or 3-MA in parallel. Morphology, Western blotting, and echocardiography were applied to confirm the pathological mechanisms.Results: Autophagy was activated and autophagosomes were significantly increased in the rapamycin group. The collagen volume fraction (CVF) was decreased in the rapamycin group compared with the DCM group (9.21 ± 0.82 % vs 14.38 ± 1.24 %, P<0.01). The expression of p-mTOR and p-4EBP1 were significantly decreased in rapamycin-induced autophagy activation, while the levels were increased by down-regulating autophagy with 3-MA. In the rapamycin group, the LVEF and FS were significantly increased compared with the DCM group (54.12 ± 6.48 % vs 45.29 ± 6.68 %, P<0.01; 26.89 ± 4.04 % vs 22.17 ± 2.82 %, P<0.05). As the inhibitor of autophagy, 3-MA aggravated the progress of maladaptive cardiac remodeling and declined cardiac function in DCM mice.Conclusions: The study indicated a possible mechanism for improving cardiac function in mice with experimental DCM by up-regulating autophagy via the mTOR-4EBP1 pathway, which could be a promising therapeutic strategy for DCM.

Ultrastructural investigation of spontaneous pituitary gonadotroph cell adenomas in aging Sprague-Dawley rats

1983 ◽  
Vol 41 ◽  
pp. 702-703
Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs
Keyword(s):  
Electron Microscopy ◽  
Animal Model ◽  
Epoxy Resin ◽  
Immunoelectron Microscopy ◽  
Tumor Type ◽  
Gonadal Function ◽  
Sprague Dawley ◽  
Male And Female ◽  
Reticulin Fibers ◽  
Sprague Dawley Rats

Gonadotroph cell adenomas of the pituitary are infrequent in human patients and are not invariably associated with altered gonadal function. To date, no animal model of this tumor type exists. Herein, we describe spontaneous gonadotroph cell adenomas in old male and female Sprague-Dawley rats by histology, immunocytology and electron microscopy.The material consisted of the pituitaries of 27 male and 38 female Sprague Dawley rats, all 26 months of age or older, removed at routine autopsy. Sections of formal in-fixed, paraffin-embedded tissue were stained with hematoxylin-phloxine-saffron (HPS), the PAS method and the Gordon-Sweet technique for the demonstration of reticulin fibers. For immunostaining, sections were exposed to anti-rat β-LH, anti-ratβ-TSH, anti-rat PRL, anti-rat GH and anti-rat ACTH 1-39. For electron microscopy, tissue was fixed in 2.5% glutaraldehyde, postfixed in 1% OsO4 and embedded in epoxy-resin. Tissue fixed in 10% formalin, embedded in epoxy resin without osmification, was used for immunoelectron microscopy.

Electron Microscopic Detection and Characterization of Nonhuman Primate Enteric Viruses

1982 ◽  
Vol 40 ◽  
pp. 306-307
Author(s):  
G. C. Smith ◽  
R. L. Heberling ◽  
S. S. Kalter
Keyword(s):  
Electron Microscopy ◽  
Animal Model ◽  
Nonhuman Primate ◽  
Clinical Condition ◽  
Intestinal Tract ◽  
Enteric Viruses ◽  
Electron Microscopic ◽  
Microscopic Detection

A number of viral agents are recognized as and suspected of causing the clinical condition “gastroenteritis.” In our attempts to establish an animal model for studies of this entity, we have been examining the nonhuman primate to ascertain what viruses may be found in the intestinal tract of “normal” animals as well as animals with diarrhea. Several virus types including coronavirus, adenovirus, herpesvirus, and picornavirus (Table I) were detected in our colony; however, rotavirus, astrovirus, and calicivirus have not yet been observed. Fecal specimens were prepared for electron microscopy by procedures reported previously.

Neurofilaments and Paired Helical Filaments

1985 ◽  
Vol 43 ◽  
pp. 740-743
Author(s):  
J. Metuzals
Keyword(s):  
Animal Model ◽  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Giant Axon ◽  
Paired Helical Filaments ◽  
Squid Giant Axon ◽  
In Vitro Experiments ◽  
Thin Sections ◽  
Structural Relationships

It has been demonstrated that the neurofibrillary tangles in biopsies of Alzheimer patients, composed of typical paired helical filaments (PHF), consist also of typical neurofilaments (NF) and 15nm wide filaments. Close structural relationships, and even continuity between NF and PHF, have been observed. In this paper, such relationships are investigated from the standpoint that the PHF are formed through posttranslational modifications of NF. To investigate the validity of the posttranslational modification hypothesis of PHF formation, we have identified in thin sections from frontal lobe biopsies of Alzheimer patients all existing conformations of NF and PHF and ordered these conformations in a hypothetical sequence. However, only experiments with animal model preparations will prove or disprove the validity of the interpretations of static structural observations made on patients. For this purpose, the results of in vitro experiments with the squid giant axon preparations are compared with those obtained from human patients. This approach is essential in discovering etiological factors of Alzheimer's disease and its early diagnosis.

Membrane-associated microtubular areays induced in proximal myelinated processes of dorsal root ganglia by large doses of vitamin B6

1986 ◽  
Vol 44 ◽  
pp. 368-369
Author(s):  
V.J. Montpetit ◽  
S. Dancea ◽  
L. Tryphonas ◽  
D.F. Clapin
Keyword(s):  
Animal Model ◽  
Endoplasmic Reticulum ◽  
Dorsal Root Ganglia ◽  
Rough Endoplasmic Reticulum ◽  
Dorsal Root ◽  
Vitamin B6 ◽  
Morphological Changes ◽  
Model System ◽  
Sensory Nerves ◽  
Peripheral Sensory

Very large doses of pyridoxine (vitamin B6) are neurotoxic in humans, selectively affecting the peripheral sensory nerves. We have undertaken a study of the morphological and biochemical aspects of pyridoxine neurotoxicity in an animal model system. Early morphological changes in dorsal root ganglia (DRG) associated with pyridoxine megadoses include proliferation of neurofilaments, ribosomes, rough endoplasmic reticulum, and Golgi complexes. We present in this report evidence of the formation of unique aggregates of microtubules and membranes in the proximal processes of DRG which are induced by high levels of pyridoxine.

Paired helical filaments (PHF) in rats: An experimental animal model for Alzheimer's disease

1987 ◽  
Vol 45 ◽  
pp. 842-843
Author(s):  
V.J.A. Montpetit ◽  
S. Dancea ◽  
S.W. French ◽  
D.F. Clapin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Paired Helical Filaments ◽  
Ethanol Intoxication ◽  
Drg Neurons ◽  
Critical Difference ◽  
Suitable Animal Model ◽  
The Central Nervous System ◽  
Chronic Ethanol Intoxication

A continuing problem in Alzheimer research is the lack of a suitable animal model for the disease. The absence of neurofibrillary tangles of paired helical filaments is the most critical difference in the processes by which the central nervous system ages in most species other than man. However, restricting consideration to single phenomena, one may identify animal models for specific aspects of Alzheimer's disease. Abnormal fibers resembling PHF have been observed in dorsal root ganglia (DRG) neurons of rats in a study of chronic ethanol intoxication and spontaneously in aged rats. We present in this report evidence that PHF-like filaments occur in ethanol-treated rats of young age. In control animals lesions similar in some respects to our observations of cytoskeletal pathology in pyridoxine induced neurotoxicity were observed.Male Wistar BR rats (Charles River Labs) weighing 350 to 400 g, were implanted with a single gastrostomy cannula and infused with a liquid diet containing 30% of total calories as fat plus ethanol or isocaloric dextrose.

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