Displaying publications 81 - 100 of 686 in total

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  1. Fahmy MEA, Abdel-Aal AA, Hassan SI, Shalaby MA, Esmat M, Abdel Shafi IR, et al.
    Trop Biomed, 2023 Mar 01;40(1):115-123.
    PMID: 37356011 DOI: 10.47665/tb.40.1.018
    Toxoplasma gondii, the etiologic agent of toxoplasmosis, infects about 30 - 50% of the world population. The currently available anti-Toxoplasma agents have serious limitations. The present study aimed to investigate the effects of two antimalarials; buparvaquone (BPQ) and chloroquine (CQ), on immunocompromised mice with chronic cerebral toxoplasmosis, using spiramycin as a reference drug. The assessed parameters included the estimation of mortality rates (MR) among mice of the different study groups, in addition to the examination of the ultrastructural changes in the brain tissues by transmission electron microscopy. The results showed that only CQ treatment could decrease the MR significantly with zero deaths, while both spiramycin and BPQ caused an insignificant reduction of MR compared to the infected non-treated group. All the used drugs decreased the number of mature ruptured cysts significantly compared to the infected non-treated group, while only CQ increased the number of atrophic and necrotic cysts significantly. Furthermore, both spiramycin and BPQ improved the microvasculopathy and neurodegeneration accompanying the infection with different degrees of reactive astrocytosis and neuronal damage with the best results regarding the repair of the microvascular damage with less active glial cells, and normal neurons in the CQ-treated group. In conclusion, this study sheds light on CQ and its excellent impact on treating chronic cerebral toxoplasmosis in an immunocompromised mouse model.
    Matched MeSH terms: Disease Models, Animal
  2. Tan FHP, Azzam G, Najimudin N, Shamsuddin S, Zainuddin A
    Mol Neurobiol, 2023 Aug;60(8):4716-4730.
    PMID: 37145377 DOI: 10.1007/s12035-023-03368-x
    Alzheimer's disease (AD) is the most common neurological ailment worldwide. Its process comprises the unique aggregation of extracellular senile plaques composed of amyloid-beta (Aβ) in the brain. Aβ42 is the most neurotoxic and aggressive of the Aβ42 isomers released in the brain. Despite much research on AD, the complete pathophysiology of this disease remains unknown. Technical and ethical constraints place limits on experiments utilizing human subjects. Thus, animal models were used to replicate human diseases. The Drosophila melanogaster is an excellent model for studying both physiological and behavioural aspects of human neurodegenerative illnesses. Here, the negative effects of Aβ42-expression on a Drosophila AD model were investigated through three behavioural assays followed by RNA-seq. The RNA-seq data was verified using qPCR. AD Drosophila expressing human Aβ42 exhibited degenerated eye structures, shortened lifespan, and declined mobility function compared to the wild-type Control. RNA-seq revealed 1496 genes that were differentially expressed from the Aβ42-expressing samples against the control. Among the pathways that were identified from the differentially expressed genes include carbon metabolism, oxidative phosphorylation, antimicrobial peptides, and longevity-regulating pathways. While AD is a complicated neurological condition whose aetiology is influenced by a number of factors, it is hoped that the current data will be sufficient to give a general picture of how Aβ42 influences the disease pathology. The discovery of molecular connections from the current Drosophila AD model offers fresh perspectives on the usage of this Drosophila which could aid in the discovery of new anti-AD medications.
    Matched MeSH terms: Disease Models, Animal
  3. Boahen A, Chew SY, Neela VK, Than LTL
    Probiotics Antimicrob Proteins, 2023 Dec;15(6):1681-1699.
    PMID: 36881331 DOI: 10.1007/s12602-023-10050-0
    Vaginal dysbiosis advocates burgeoning of devious human vaginal pathobionts like Candida species that possess multiple virulence properties and metabolic flexibility to cause infections. Inevitably, antifungal resistance may emerge due to their innate nature (e.g., biofilm formation), which assists in their virulence as well as the formation of persister cells after dispersal. In consequence, the phenomenon of biofilm involvement in vulvovaginal candidiasis (VVC) and its recurrence is becoming paramount. Lactic acid bacteria and their derivatives have proven to be hostile to Candida species. Here, we throw more light on the potency of the derivatives, i.e., cell-free supernatant (CFS) produced by an indigenously isolated vaginal Lactobacillus strain, Limosilactobacillus reuteri 29A. In the present study, we investigated the antibiofilm and antagonistic effects of L. reuteri 29A CFS, against biofilms of Candida species and in murine model of vulvovaginal candidiasis. In our in vitro biofilm study, the CFS disrupted and inhibited preformed biofilms of C. albicans and C. glabrata. Scanning electron microscopy displayed the destruction of preformed biofilms and impediment of C. albicans morphogenesis by the CFS. Gas chromatography-mass spectrometry analysis showed multiple key compounds that may act singly or synergistically. In vivo, the CFS showed no collateral damage to uninfected mice; the integrity of infected vaginal tissues was restored by the administration of the CFS as seen from the cytological, histopathological, and electron microscopical analyses. The results of this study document the potential use of CFS as an adjuvant or prophylactic option in addressing vaginal fungal infections.
    Matched MeSH terms: Disease Models, Animal
  4. Shirmanova MV, Lukina MM, Sirotkina MA, Shimolina LE, Dudenkova VV, Ignatova NI, et al.
    Int J Mol Sci, 2024 Jan 30;25(3).
    PMID: 38338976 DOI: 10.3390/ijms25031703
    This work was aimed at the complex analysis of the metabolic and oxygen statuses of tumors in vivo after photodynamic therapy (PDT). Studies were conducted on mouse tumor model using two types of photosensitizers-chlorin e6-based drug Photoditazine predominantly targeted to the vasculature and genetically encoded photosensitizer KillerRed targeted to the chromatin. Metabolism of tumor cells was assessed by the fluorescence lifetime of the metabolic redox-cofactor NAD(P)H, using fluorescence lifetime imaging. Oxygen content was assessed using phosphorescence lifetime macro-imaging with an oxygen-sensitive probe. For visualization of the perfused microvasculature, an optical coherence tomography-based angiography was used. It was found that PDT induces different alterations in cellular metabolism, depending on the degree of oxygen depletion. Moderate decrease in oxygen in the case of KillerRed was accompanied by an increase in the fraction of free NAD(P)H, an indicator of glycolytic switch, early after the treatment. Severe hypoxia after PDT with Photoditazine resulted from a vascular shutdown yielded in a persistent increase in protein-bound (mitochondrial) fraction of NAD(P)H. These findings improve our understanding of physiological mechanisms of PDT in cellular and vascular modes and can be useful to develop new approaches to monitoring its efficacy.
    Matched MeSH terms: Disease Models, Animal
  5. Cheng SH, Ismail A, Anthony J, Ng OC, Hamid AA, Barakatun-Nisak MY
    PMID: 26713097 DOI: 10.1155/2015/405615
    Objectives. Optimizing glycemic control is crucial to prevent type 2 diabetes related complications. Cosmos caudatus is reported to have promising effect in improving plasma blood glucose in an animal model. However, its impact on human remains ambiguous. This study was carried out to evaluate the effectiveness of C. caudatus on glycemic status in patients with type 2 diabetes. Materials and Methods. In this randomized controlled trial with two-arm parallel-group design, a total of 101 subjects with type 2 diabetes were randomly allocated to diabetic-ulam or diabetic controls for eight weeks. Subjects in diabetic-ulam group consumed 15 g of C. caudatus daily for eight weeks while diabetic controls abstained from taking C. caudatus. Both groups received the standard lifestyle advice. Results. After 8 weeks of supplementation, C. caudatus significantly reduced serum insulin (-1.16 versus +3.91), reduced HOMA-IR (-1.09 versus +1.34), and increased QUICKI (+0.05 versus -0.03) in diabetic-ulam group compared with the diabetic controls. HbA1C level was improved although it is not statistically significant (-0.76% versus -0.37%). C. caudatus was safe to consume. Conclusions. C. caudatus supplementation significantly improves insulin resistance and insulin sensitivity in patients with type 2 diabetes.
    Matched MeSH terms: Disease Models, Animal
  6. Anjum A, Cheah YJ, Yazid MD, Daud MF, Idris J, Ng MH, et al.
    Biol Res, 2022 Dec 09;55(1):38.
    PMID: 36494836 DOI: 10.1186/s40659-022-00407-0
    BACKGROUND: Excitotoxicity-induced in vivo injury models are vital to reflect the pathophysiological features of acute spinal cord injury (SCI) in humans. The duration and concentration of chemical treatment controls the extent of neuronal cell damage. The extent of injury is explained in relation to locomotor and behavioural activity. Several SCI in vivo methods have been reported and studied extensively, particularly contusion, compression, and transection models. These models depict similar pathophysiology to that in humans but are extremely expensive (contusion) and require expertise (compression). Chemical excitotoxicity-induced SCI models are simple and easy while producing similar clinical manifestations. The kainic acid (KA) excitotoxicity model is a convenient, low-cost, and highly reproducible animal model of SCI in the laboratory. The basic impactor approximately cost between 10,000 and 20,000 USD, while the kainic acid only cost between 300 and 500 USD, which is quite cheap as compared to traditional SCI method.

    METHODS: In this study, 0.05 mM KA was administered at dose of 10 µL/100 g body weight, at a rate of 10 µL/min, to induce spinal injury by intra-spinal injection between the T12 and T13 thoracic vertebrae. In this protocol, detailed description of a dorsal laminectomy was explained to expose the spinal cord, following intra-spinal kainic acid administration at desired location. The dose, rate and technique to administer kainic acid were explained extensively to reflect a successful paraplegia and spinal cord injury in rats. The postoperative care and complication post injury of paraplegic laboratory animals were also explained, and necessary requirements to overcome these complications were also described to help researcher.

    RESULTS: This injury model produced impaired hind limb locomotor function with mild seizure. Hence this protocol will help researchers to induce spinal cord injury in laboratories at extremely low cost and also will help to determine the necessary supplies, methods for producing SCI in rats and treatments designed to mitigate post-injury impairment.

    CONCLUSIONS: Kainic acid intra-spinal injection at the concentration of 0.05 mM, and rate 10 µL/min, is an effective method create spinal injury in rats, however more potent concentrations of kainic acid need to be studied in order to create severe spinal injuries.

    Matched MeSH terms: Disease Models, Animal
  7. Parsi S, Pandamooz S, Heidari S, Naji M, Morfini G, Ahmadiani A, et al.
    Neuroscience, 2015 Jan 22;284:99-106.
    PMID: 25270904 DOI: 10.1016/j.neuroscience.2014.09.045
    Alzheimer's disease (AD) is characterized by progressive and irreversible cognitive and memory impairment. The discovery of familial forms of AD (fAD) in association with specific gene mutations facilitated the generation of numerous rodent models. These models in turn proved valuable for the study of molecular mechanisms underlying AD pathogenesis, and facilitated translational research and preclinical drug development. This study aimed to introduce a new rat model of AD simulating some aspects of the sporadic cases of disease.
    Matched MeSH terms: Disease Models, Animal*
  8. Rufus P, Mohamed N, Shuid AN
    Curr Drug Targets, 2013 Dec;14(14):1689-93.
    PMID: 24354584
    Osteoporosis is a metabolic bone disorder that affects both men and women worldwide. It causes low bone mass and therefore increases bone susceptibility to fracture when bone undergoes a minor trauma. Lack of estrogen is the principal cause of osteoporosis. Estrogen, calcium, calcitonin, vitamin D and several antioxidants help in the prevention of osteoporosis. In order to effectively treat osteoporosis, there has been an extended research on the biological activities of traditional medicines since synthetic medicines possess several side effects that reduce their efficacy. Therefore, there is a need to develop new treatment alternatives for osteoporosis. This review centres on the scientific researches carried out on the evaluation of Chinese traditional medicines in the treatment of osteoporosis. Various plants like Achyranthes bidentata, Davallia formosana, polygonatum sibiricum, Cibotium barometz, Er-Zhi-Wan, Curculigo orchioides and a combined treatment of Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan) with alendronate proved active in preventing post-menopausal osteoporosis.
    Matched MeSH terms: Disease Models, Animal*
  9. Ming-Tatt L, Khalivulla SI, Akhtar MN, Lajis N, Perimal EK, Akira A, et al.
    Pharmacol. Biochem. Behav., 2013 Dec;114-115:58-63.
    PMID: 24201054 DOI: 10.1016/j.pbb.2013.10.019
    The present study investigated the analgesic effect of a novel synthetic cyclohexanone derivative, 2,6-bis-4-(hydroxyl-3-methoxybenzilidine)-cyclohexanone or BHMC in a mouse model of chronic constriction injury-induced neuropathic pain. It was demonstrated that intraperitoneal administration of BHMC (0.03, 0.1, 0.3 and 1.0mg/kg) exhibited dose-dependent inhibition of chronic constriction injury-induced neuropathic pain in mice, when evaluated using Randall-Selitto mechanical analgesiometer. It was also demonstrated that pretreatment of naloxone (non-selective opioid receptor blocker), nor-binaltorphimine (nor-BNI, selective κ-opioid receptor blocker), but not β-funaltrexamine (β-FN, selective μ-opioid receptor blocker) and naltrindole hydrochloride (NTI, selective δ-opioid receptor blocker), reversed the anti-nociceptive effect of BHMC. In addition, the analgesic effect of BHMC was also reverted by pretreatment of 1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one (ODQ, soluble guanosyl cyclase blocker) and glibenclamide (ATP-sensitive potassium channel blocker) but not Nω-nitro-l-arginine (l-NAME, a nitric oxide synthase blocker). Taken together, the present study demonstrated that the systemic administration of BHMC attenuated chronic constriction, injury-induced neuropathic pain. We also suggested that the possible mechanisms include κ-opioid receptor activation and nitric oxide-independent cyclic guanosine monophosphate activation of ATP-sensitive potassium channel opening.
    Matched MeSH terms: Disease Models, Animal*
  10. Mitra NK, Goh TE, Bala Krishnan T, Nadarajah VD, Vasavaraj AK, Soga T
    Int J Clin Exp Pathol, 2013;6(8):1505-15.
    PMID: 23923068
    Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease of idiopathic etiology. Glutamate excitotoxicity is one of the proposed hypotheses causing progressive death of motor neurons. We aimed to develop an experimental animal model of this disease to enhance the knowledge of pathophysiological mechanism of ALS. Male Wistar rats were infused with Kainic acid (KA) intra-cisternally for 5 days at the dosage of 50 fmol/day and 150 fmol/day. Locomotor activity, sensory function and histological changes in cervical and lumbar sections of spinal cord were evaluated. Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Protein (NFP) were used as immunohistochemical marker for reactive astrogliosis and neuronal damage respectively. Specific Superoxide Dismutase (SOD) activity of spinal cord was estimated. The locomotor activity in the parameter of observed mean action time remained reduced on 14(th) day after administration of KA. Spinal motor neurons under Nissl stain showed pyknosis of nucleus and vacuolation of neuropil. GFAP expression increased significantly in the lumbar section of the spinal cord with high dose of KA treatment (p<0.05). NFP was expressed in axonal fibres around the neurons in KA-treated rats. A significant increase in specific SOD activity in both cervical and lumbar sections of the spinal cord was found with low dose of KA treatment (p<0.05). This study concludes that spinal cord damage with some features similar to ALS can be produced by low dose intra-cisternal administration of KA.
    Matched MeSH terms: Disease Models, Animal*
  11. Zulfahmi S, Yazan LS, Ithnin H, Armania N
    Exp. Toxicol. Pathol., 2013 Nov;65(7-8):1083-9.
    PMID: 23726752 DOI: 10.1016/j.etp.2013.04.004
    Cervical cancer is the most common gynecological cancer and one of the major causes of female cancer-related death worldwide particularly in developing countries. Thus far, there are a few in vivo models have been developed in investigating this type of cancer. In this study, we induced cervical cancer in Balb/c mice by exploiting the carcinogenic property of diestylstilbestrol (DES). The Balb/c pregnant mice were given subcutaneous (SC) injection of 67μg/kg body weight of DES on GD 13, and the mice gave birth approximately at gestation day 19-22. Female offspring were reared and the body weight was recorded once weekly. The female offspring were sacrificed at age of 5 months. Upon termination, blood was collected in a plain tube via cardiac puncture and the reproductive tracts were collected and weighed. The reproductive tract sections were stained using H&E for observation of pathological changes. The progression of disease state was monitored by measuring the level of serum interleukin (IL-6) using the Mouse IL-6 ELISA Assay Kit (BD OptEIA™, USA). All parameters were compared with Not-induced group. The outcome of this study demonstrated a significant difference in body weight gain, reproductive organ weight, diameter of cervix and the level of serum IL-6 in the Induced group as compared to the Not-induced group (P<0.05). Histopathological findings revealed the presence of adenosis only in the Induced group. It shows that DES could be employed as an agent to induce cervical carcinogenesis in animal model. In addition to that, new potential anti-cancer agents from various sources could be further evaluated using this technique.
    Matched MeSH terms: Disease Models, Animal*
  12. Sambanthamurthi R, Tan Y, Sundram K, Hayes KC, Abeywardena M, Leow SS, et al.
    Br J Nutr, 2011 Dec;106(11):1664-75.
    PMID: 21736778 DOI: 10.1017/S0007114511002133
    It is well established that plant phenolics elicit various biological activities, with positive effects on health. Palm oil production results in large volumes of aqueous by-products containing phenolics. In the present study, we describe the effects of oil palm phenolics (OPP) on several degenerative conditions using various animal models. OPP reduced blood pressure in a NO-deficient rat model, protected against ischaemia-induced cardiac arrhythmia in rats and reduced plaque formation in rabbits fed an atherogenic diet. In Nile rats, a spontaneous model of the metabolic syndrome and type 2 diabetes, OPP protected against multiple aspects of the syndrome and diabetes progression. In tumour-inoculated mice, OPP protected against cancer progression. Microarray studies on the tumours showed differential transcriptome profiles that suggest anti-tumour molecular mechanisms involved in OPP action. Thus, initial studies suggest that OPP may have potential against several chronic disease outcomes in mammals.
    Matched MeSH terms: Disease Models, Animal*
  13. Mannerås L, Fazliana M, Wan Nazaimoon WM, Lönn M, Gu HF, Ostenson CG, et al.
    J Ethnopharmacol, 2010 Feb 3;127(2):346-51.
    PMID: 19883744 DOI: 10.1016/j.jep.2009.10.032
    New options are needed to prevent and treat metabolic disorders associated with polycystic ovary syndrome (PCOS). Labisia pumila var. alata (LPva)-a Malaysian herb thought to have phytoestrogenic effects-has shown promise in reducing body weight gain in ovariectomized rats. In this study, we investigated the effect of LPva on body composition and metabolic features in female rats treated continuously with dihydrotestosterone, starting before puberty, to induce PCOS.
    Matched MeSH terms: Disease Models, Animal*
  14. Sulaiman MR, Zakaria ZA, Abdul Rahman A, Mohamad AS, Desa MN, Stanslas J, et al.
    Biol Res Nurs, 2010 Jan;11(3):293-301.
    PMID: 19689990 DOI: 10.1177/1099800409343311
    The current study was performed to evaluate the antinociceptive and antiedematogenic properties of andrographolide isolated from the leaves of Andrographis paniculata using two animal models. Antinociceptive activity was evaluated using the acetic acid- induced writhing and the hot-plate tests, while antiedematogenic activity was measured using the carrageenan-induced paw edema test. Subcutaneous (s.c.) administration of andrographolide (10, 25, and 50 mg/kg) did not affect the motor coordination of the experimental animals but produced significant (p < .05) antinociceptive activity when assessed using both tests. However, 2 mg/kg naloxone failed to affect the 25 mg/kg andrographolide activity in both tests, indicating that the activity was modulated via nonopioid mechanisms. Furthermore, andrographolide showed significant (p < .05) antiedematogenic activity. In conclusion, the results obtained suggest that andrographolide has antinociceptive and antiedematogenic activities; it may be useful for treating pain and inflammation once human studies are conducted.
    Matched MeSH terms: Disease Models, Animal*
  15. Zamri-Saad M, Effendy WM, Maswati MA, Salim N, Sheikh-Omar AR
    Br. Vet. J., 1996 Jul;152(4):453-8.
    PMID: 8791853
    A model of pneumonic pasteurellosis has been established in goats using Pasteurella multocida harvested from pneumonic lungs of goats (types A and D), rabbits (type A) and sheep (type D). The resultant infections were acute, subacute or chronic. The gross and histological lesions of the subacute and chronic infections were typical of pneumonic pasteurellosis. P. multocida type D produced significantly (P < 0.01) more severe lesions when compared with other isolates. There were strong correlations between the clinical signs and the severity of lesions.
    Matched MeSH terms: Disease Models, Animal*
  16. Surin J
    PMID: 8525399
    There are few small animals models for filariasis, even more so for onchocerciasis. Therefore it is difficult to test under drug screening conditions large numbers of potentially macrofilaricidal compounds. One way around this difficulty is to use mice infected with Trichinella spiralis which by reason of anatomical location in the host would show some correlation in antinematode activity between the test and target organisms. This study investigated the activity of 16 compounds against the immature larval stage of T. spiralis. All the nine benzimidazole compounds (albendazole, flubendazole, mebendazole, oxfendazole, oxibendazole 780118, 780120, 790163, and 790392) were active, the most potent being oxfendazole. The benzothiazoles (CGP21306, CGP20376, CGP21833 and CGP24588A) also indicated some anti-nematode activity together with 35vr, an imidazopyridine, but not as marked as the benzimidazole group. However, the organic arsenical compounds (Mel Ga and Mel Ni) showed little activity and this was at a rather highly toxic level. The prospects of using the Trichinella-mouse model as a primary screen to test for potential macrofilaricides are discussed.
    Matched MeSH terms: Disease Models, Animal*
  17. Leong YK, Awang A
    Microbiol. Immunol., 1990;34(2):153-62.
    PMID: 2161071
    Rotaviral infections in cynomolgus monkeys (Macaca fasicularis) were studied to ascertain its suitability as a model of infection and diarrhea caused by group A human rotaviruses. Formula-fed monkeys were used as they could be observed closely. Experimental rotaviral infection of cynomolgus monkeys was age-dependent; only young monkeys were readily infected. Formula-fed newborns were readily infected with cell-culture-adapted human (WA) and simian (SA11) viruses and with a rotavirus from a human fecal specimen. However, diarrhea was detected only in very young animals. A number of rotaviral shedding patterns as a function of time were observed. Although there was no typical viral shedding pattern which represented exclusive association of viral infection with diarrhea, the initial level of viral excretion and the maximum level of viral shedding attained were much higher in animals with diarrhea. Seroconversion occurred in less than half of the inoculated animals. The presence of maternal rotaviral antibodies did not prevent infection or diarrhea.
    Matched MeSH terms: Disease Models, Animal*
  18. Choong MF, Mak JW
    Trop. Med. Parasitol., 1991 Mar;42(1):71-2.
    PMID: 1675809
    The Presbytis cristata--Brugia malayi model, now established as a reliable non-human primate model for the experimental screening of potential filaricides, was monitored at monthly intervals for changes in the liver and renal function tests and also for alkaline phosphatase levels during infection. Animals infected with 200-400 infective larvae became patient at 50-90 days post-infection and geometric mean microfilarial counts were above 1000 per ml from the fourth month onwards. There were no significant changes in the biochemical parameters monitored throughout the period of observation. This is an important observation as any changes seen in these parameters during experimental drug studies can be attributed to drug reaction or toxicity and this will be invaluable in decision making as to drug safety.
    Matched MeSH terms: Disease Models, Animal*
  19. Lee HC, Md Yusof HH, Leong MP, Zainal Abidin S, Seth EA, Hewitt CA, et al.
    Int J Neurosci, 2019 Sep;129(9):871-881.
    PMID: 30775947 DOI: 10.1080/00207454.2019.1580280
    Aims: The JAK-STAT signalling pathway is one of the key regulators of pro-gliogenesis process during brain development. Down syndrome (DS) individuals, as well as DS mouse models, exhibit an increased number of astrocytes, suggesting an imbalance of neurogenic-to-gliogenic shift attributed to dysregulated JAK-STAT signalling pathway. The gene and protein expression profiles of JAK-STAT pathway members have not been characterised in the DS models. Therefore, we aimed to profile the expression of Jak1, Jak2, Stat1, Stat3 and Stat6 at different stages of brain development in the Ts1Cje mouse model of DS. Methods: Whole brain samples from Ts1Cje and wild-type mice at embryonic day (E)10.5, E15, postnatal day (P)1.5; and embryonic cortex-derived neurospheres were collected for gene and protein expression analysis. Gene expression profiles of three brain regions (cerebral cortex, cerebellum and hippocampus) from Ts1Cje and wild-type mice across four time-points (P1.5, P15, P30 and P84) were also analysed. Results: In the developing mouse brain, none of the Jak/Stat genes were differentially expressed in the Ts1Cje model compared to wild-type mice. However, Western blot analyses indicated that phosphorylated (p)-Jak2, p-Stat3 and p-Stat6 were downregulated in the Ts1Cje model. During the postnatal brain development, Jak/Stat genes showed complex expression patterns, as most of the members were downregulated at different selected time-points. Notably, embryonic cortex-derived neurospheres from Ts1Cje mouse brain expressed lower Stat3 and Stat6 protein compared to the wild-type group. Conclusion: The comprehensive expression profiling of Jak/Stat candidates provides insights on the potential role of the JAK-STAT signalling pathway during abnormal development of the Ts1Cje mouse brains.
    Matched MeSH terms: Disease Models, Animal*
  20. Yanagisawa D, Ibrahim NF, Taguchi H, Morikawa S, Tomiyama T, Tooyama I
    Molecules, 2021 Mar 04;26(5).
    PMID: 33806326 DOI: 10.3390/molecules26051362
    Recent evidence suggests that the formation of soluble amyloid β (Aβ) aggregates with high toxicity, such as oligomers and protofibrils, is a key event that causes Alzheimer's disease (AD). However, understanding the pathophysiological role of such soluble Aβ aggregates in the brain in vivo could be difficult due to the lack of a clinically available method to detect, visualize, and quantify soluble Aβ aggregates in the brain. We had synthesized a novel fluorinated curcumin derivative with a fixed keto form, named as Shiga-Y51, which exhibited high selectivity to Aβ oligomers in vitro. In this study, we investigated the in vivo detection of Aβ oligomers by fluorine-19 (19F) magnetic resonance imaging (MRI) using Shiga-Y51 in an APP/PS1 double transgenic mouse model of AD. Significantly high levels of 19F signals were detected in the upper forebrain region of APP/PS1 mice compared with wild-type mice. Moreover, the highest levels of Aβ oligomers were detected in the upper forebrain region of APP/PS1 mice in enzyme-linked immunosorbent assay. These findings suggested that 19F-MRI using Shiga-Y51 detected Aβ oligomers in the in vivo brain. Therefore, 19F-MRI using Shiga-Y51 with a 7 T MR scanner could be a powerful tool for imaging Aβ oligomers in the brain.
    Matched MeSH terms: Disease Models, Animal*
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