Displaying publications 81 - 100 of 662 in total

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  1. 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*
  2. 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*
  3. 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*
  4. 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*
  5. 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*
  6. 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*
  7. 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*
  8. 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*
  9. 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*
  10. 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*
  11. 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*
  12. 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*
  13. 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*
  14. 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*
  15. Mohamad Isa II, Abu Bakar S, Md Tohid SF, Mat Jais AM
    J Ethnopharmacol, 2016 Dec 24;194:469-474.
    PMID: 27732902 DOI: 10.1016/j.jep.2016.10.033
    ETHNOPHARMACOLOGICAL RELEVANCE: Haruan, Channa striatus, is a freshwater fish which has been well-known locally to accelerate wound healing during post-operative and post-partum periods. The fish extract also has potent anti-inflammatory and analgesic properties.

    AIM OF THE STUDY: To assess topical anti-inflammatory effect of Haruan cream on 12-0-tetradecanoylphorbol-13-acetate (TPA)-induced chronic-like dermatitis in mice.

    MATERIALS AND METHODS: Male ICR mice were randomized into six groups of five mice each: acetone (vehicle), TPA alone (negative control), three Haruan treatment groups (Haruan 1%, Haruan 5% and Haruan 10%) and hydrocortisone 1% (positive control). Briefly, both surfaces of mouse ears were applied with TPA (2.5μg/20μl acetone) for five times on alternate days and with Haruan or hydrocortisone 1% cream for the last three days. Mouse ear thickness was measured 24h after final treatment with the cream and the ears were harvested for further histological analysis and gene expression studies of TNF-α by real-time reverse transcriptase-polymerase chain reaction (RT-qPCR).

    RESULTS: Topical application of Haruan cream had reduced the mouse ear thickness 18.1-28%) with comparable effect to the positive control. In addition, histopathological comparison had shown evident reduction in various parameters of cutaneous inflammation including dermal oedema, inflammatory cells infiltration and proliferation of epidermal keratinocytes. Furthermore, TPA application had resulted in the up-regulation of TNF-α gene expression by 353-fold, which was subsequently down-regulated by the Haruan cream (34- to 112-fold).

    CONCLUSION: Haruan is an effective topical anti-inflammatory agent in this mouse model of chronic-like dermatitis, thus suggesting its potential as a non-steroidal treatment option for chronic inflammatory dermatoses.

    Matched MeSH terms: Disease Models, Animal*
  16. Okamura T, Tsujimura Y, Soma S, Takahashi I, Matsuo K, Yasutomi Y
    J Gen Virol, 2016 Dec;97(12):3413-3426.
    PMID: 27902330 DOI: 10.1099/jgv.0.000641
    Simian immunodeficiency virus (SIV) infection models in cynomolgus macaques are important for analysis of the pathogenesis of immunodeficiency virus and for studies on the efficacy of new vaccine candidates. However, very little is known about the pathogenesis of SIV or simian human immunodeficiency virus (SHIV) in cynomolgus macaques from different Asian countries. In the present study, we analysed the infectivity and pathogenicity of CCR5-tropic SIVmac and those of dual-tropic SHIV89.6P inoculated into cynomolgus macaques in Indonesian, Malaysian or Philippine origin. The plasma viral loads in macaques infected with either SIVmac239 or SHIV89.6P were maintained at high levels. CD4+ T cell levels in macaques infected with SIVmac239 gradually decreased. All of the macaques infected with SHIV89.6P showed greatly reduced CD4+ T-cell numbers within 6 weeks of infection. Eight of the 11 macaques infected with SIVmac239 were killed due to AIDS symptoms after 2-4.5 years, while four of the five macaques infected with SHIV89.6P were killed due to AIDS symptoms after 1-3.5 years. We also analysed cynomolgus macaques infected intrarectally with repeated low, medium or high doses of SIVmac239, SIVmac251 or SHIV89.6P. Infection was confirmed by quantitative RT-PCR at more than 5000, 300 and 500 TCID50 for SIVmac239, SIVmac251 and SHIV89.6P, respectively. The present study indicates that cynomolgus macaques of Asian origin are highly susceptible to SIVmac and SHIV infection by both intravenous and mucosal routes. These models will be useful for studies on virus pathogenesis, vaccination and therapeutics against human immunodeficiency virus/AIDS.
    Matched MeSH terms: Disease Models, Animal*
  17. El-Desouky S, Taalab YM, El-Gamal M, Mohamed W, Salama M
    Methods Mol Biol, 2019;2011:451-464.
    PMID: 31273716 DOI: 10.1007/978-1-4939-9554-7_27
    Leigh syndrome (LS) is a common neurodegenerative disease affecting neonates with devastating sequences. One of the characteristic features for LS is the phenotypic polymorphism, which-in part-can be dedicated to variety of genetic causes. A strong correlation with mitochondrial dysfunction has been assumed as the main cause of LS. This was based on the fact that most genetic causes are related to mitochondrial complex I genome. The first animal LS model was designed based on NDUFS4 knockdown. Interestingly, however, this one or others could not recapitulate the whole spectrum of manifestations encountered in different cases of LS. We show in this chapter a new animal model for LS based on silencing of one gene that is reported previously in clinical cases, FOXRED1. The new model carries some differences from previous models in the fact that more histopathological degeneration in dopaminergic system is seen and more behavioral changes can be recognized. FOXRED1 is an interesting gene that is related to complex I assembly, hence, plays important role in different neurodegenerative disorders leading to different clinical manifestations.
    Matched MeSH terms: Disease Models, Animal*
  18. Sanchez-Bezanilla S, Åberg ND, Crock P, Walker FR, Nilsson M, Isgaard J, et al.
    Int J Mol Sci, 2020 Jan 17;21(2).
    PMID: 31963456 DOI: 10.3390/ijms21020606
    Motor impairment is the most common and widely recognised clinical outcome after stroke. Current clinical practice in stroke rehabilitation focuses mainly on physical therapy, with no pharmacological intervention approved to facilitate functional recovery. Several studies have documented positive effects of growth hormone (GH) on cognitive function after stroke, but surprisingly, the effects on motor function remain unclear. In this study, photothrombotic occlusion targeting the motor and sensory cortex was induced in adult male mice. Two days post-stroke, mice were administered with recombinant human GH or saline, continuing for 28 days, followed by evaluation of motor function. Three days after initiation of the treatment, bromodeoxyuridine was administered for subsequent assessment of cell proliferation. Known neurorestorative processes within the peri-infarct area were evaluated by histological and biochemical analyses at 30 days post-stroke. This study demonstrated that GH treatment improves motor function after stroke by 50%-60%, as assessed using the cylinder and grid walk tests. Furthermore, the observed functional improvements occurred in parallel with a reduction in brain tissue loss, as well as increased cell proliferation, neurogenesis, increased synaptic plasticity and angiogenesis within the peri-infarct area. These findings provide new evidence about the potential therapeutic effects of GH in stroke recovery.
    Matched MeSH terms: Disease Models, Animal*
  19. Tan KS, Wang D, Lu Z, Zhang Y, Li S, Lin Y, et al.
    Int J Mol Sci, 2021 Oct 06;22(19).
    PMID: 34639145 DOI: 10.3390/ijms221910806
    Heart failure is the end-stage of all cardiovascular diseases with a ~25% 5-year survival rate, and insufficient mitochondrial energy production to meet myocardial demand is the hallmark of heart failure. Mitochondrial components involved in the regulation of ATP production remain to be fully elucidated. Recently, roles of 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) in the pathophysiological processes of heart diseases have emerged, implicated by evidence that mitochondrial CNPase proteins are associated with mitochondrial integrity under metabolic stress. In this study, a zebrafish heart failure model was established, by employing antisense morpholino oligonucleotides and the CRISPR-Cas9 gene-editing system, which recapitulates heart failure phenotypes including heart dysfunction, pericardial edema, ventricular enlargement, bradycardia, and premature death. The translational implications of CNPase in the pathophysiological process of heart failure were tested in a pressure overload-induced heart hypertrophy model, which was carried out in rats through transverse abdominal aorta constriction (TAAC). AAV9-mediated myocardial delivery of CNPase mitigated the hypertrophic response through the specific hydrolysis of 2'-3'-cyclic nucleotides, supported by the decrease of cardiac hypertrophy and fibrosis, the integrity of mitochondrial ultrastructure, and indicators of heart contractility in the AAV9-TAAC group. Finally, the biometrics of a mitochondrial respiration assay carried out on a Seahorse cellular energy analyzer demonstrated that CNPase protects mitochondrial respiration and ATP production from AngII-induced metabolic stress. In summary, this study provides mechanistic insights into CNPase-2',3'-cyclic nucleotide metabolism that protects the heart from energy starvation and suggests novel therapeutic approaches to treat heart failure by targeting CNPase activity.
    Matched MeSH terms: Disease Models, Animal*
  20. El-Gamal M, Salama M, Collins-Praino LE, Baetu I, Fathalla AM, Soliman AM, et al.
    Neurotox Res, 2021 Jun;39(3):897-923.
    PMID: 33765237 DOI: 10.1007/s12640-021-00356-8
    Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by cardinal motor impairments, including akinesia and tremor, as well as by a host of non-motor symptoms, including both autonomic and cognitive dysfunction. PD is associated with a death of nigral dopaminergic neurons, as well as the pathological spread of Lewy bodies, consisting predominantly of the misfolded protein alpha-synuclein. To date, only symptomatic treatments, such as levodopa, are available, and trials aiming to cure the disease, or at least halt its progression, have not been successful. Wong et al. (2019) suggested that the lack of effective therapy against neurodegeneration in PD might be attributed to the fact that the molecular mechanisms standing behind the dopaminergic neuronal vulnerability are still a major scientific challenge. Understanding these molecular mechanisms is critical for developing effective therapy. Thirty-five years ago, Calne and William Langston (1983) raised the question of whether biological or environmental factors precipitate the development of PD. In spite of great advances in technology and medicine, this question still lacks a clear answer. Only 5-15% of PD cases are attributed to a genetic mutation, with the majority of cases classified as idiopathic, which could be linked to exposure to environmental contaminants. Rodent models play a crucial role in understanding the risk factors and pathogenesis of PD. Additionally, well-validated rodent models are critical for driving the preclinical development of clinically translatable treatment options. In this review, we discuss the mechanisms, similarities and differences, as well as advantages and limitations of different neurotoxin-induced rat models of PD. In the second part of this review, we will discuss the potential future of neurotoxin-induced models of PD. Finally, we will briefly demonstrate the crucial role of gene-environment interactions in PD and discuss fusion or dual PD models. We argue that these models have the potential to significantly further our understanding of PD.
    Matched MeSH terms: Disease Models, Animal*
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