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Fulltext Understanding translational research in schizophrenia: A novel insight into animal models

Malik JA, Yaseen Z, Thotapalli L, Ahmed S, Shaikh MF, Anwar S

Mol Biol Rep, 2023 Apr;50(4):3767-3785.
PMID: 36692676 DOI: 10.1007/s11033-023-08241-7

Schizophrenia affects millions of people worldwide and is a major challenge for the scientific community. Like most psychotic diseases, it is also considered a complicated mental disorder caused by an imbalance in neurotransmitters. Due to the complexity of neuropathology, it is always a complicated disorder. The lack of proper understanding of the pathophysiology makes the disorder unmanageable in clinical settings. However, due to recent advances in animal models, we hope we can have better therapeutic approaches with more success in clinical settings. Dopamine, glutamate, GABA, and serotonin are the neurotransmitters involved in the pathophysiology of schizophrenia. Various animal models have been put forward based on these neurotransmitters, including pharmacological, neurodevelopmental, and genetic models. Polymorphism of genes such as dysbindin, DICS1, and NRG1 has also been reported in schizophrenia. Hypothesis based on dopamine, glutamate, and serotonin are considered successful models of schizophrenia on which drug therapies have been designed to date. New targets like the orexin system, muscarinic and nicotinic receptors, and cannabinoid receptors have been approached to alleviate the negative and cognitive symptoms. The non-pharmacological models like the post-weaning social isolation model (maternal deprivation), the isolation rearing model etc. have been also developed to mimic the symptoms of schizophrenia and to create and test new approaches of drug therapy which is a breakthrough at present in psychiatric disorders. Different behavioral tests have been evaluated in these specific models. This review will highlight the currently available animal models and behavioral tests in psychic disorders concerning schizophrenia.

Matched MeSH terms: Disease Models, Animal
Fulltext Fluorinated curcumin derivative (Shiga-Y6) modulates the level of thioredoxin-interacting protein (TXNIP) in a mouse model of diabetes

Aldoghachi AF, Yanagisawa D, Pahrudin Arrozi A, Abu Bakar ZH, Taguchi H, Ishigaki S, et al.

Biochem Biophys Res Commun, 2024 Jan 29;694:149392.
PMID: 38142581 DOI: 10.1016/j.bbrc.2023.149392

Thioredoxin interacting protein (TXNIP) has emerged as a significant regulator of β-cell mass and loss, rendering it an attractive target for treating diabetes. We previously showed that Shiga-Y6, a fluorinated curcumin derivative, inhibited TXNIP mRNA and protein expression in vitro, raising the question of whether the same effect could be translated in vivo. Herein, we examined the effect of Shiga-Y6 on TNXIP levels and explored its therapeutic potential in a mouse model of diabetes, Akita mice. We intraperitoneally injected Shiga-Y6 (SY6; 30 mg/kg of body weight) or vehicle into 8-week-old Akita mice for 28 consecutive days. On day 29, the mice were euthanized, following which the serum levels of glucose, insulin, and glucagon were measured using ELISA, the expression of TXNIP in pancreatic tissue lysates was determined using western blotting, and the level of β-cell apoptosis was assessed using the TUNEL assay. TXNIP levels in the pancreatic tissue of Akita mice were significantly elevated compared with wild-type (WT) mice. Shiga-Y6 administration for 28 days significantly lowered those levels compared with Akita mice that received vehicle to a level comparable to WT mice. In immunohistochemical analysis, both α- to β-cell ratio and the number of apoptotic β-cells were significantly reduced in SY6-treated Akita mice, compared with vehicle-treated Akita mice. Findings from the present study suggest a potential of Shiga-Y6 as an antidiabetic agent through lowering TXNIP protein levels and ameliorating pancreatic β-cells apoptosis.

Matched MeSH terms: Disease Models, Animal
Antinociceptive Activity of Asiaticoside in Mouse Models of Induced Nociception

Ayumi RR, Shaik Mossadeq WM, Zakaria ZA, Bakhtiar MT, Kamarudin N, Hisamuddin N, et al.

Planta Med, 2020 May;86(8):548-555.
PMID: 32294786 DOI: 10.1055/a-1144-3663

The antinociceptive property of Centella asiatica extracts is known but the analgesic activity of its bioactive constituent asiaticoside has not been reported. We evaluated the antinociceptive activity of orally (p. o.) administered asiaticoside (1, 3, 5, and 10 mg/kg) in mice using the 0.6% acetic acid-induced writhing test, the 2.5% formalin-induced paw licking test, and the hot plate test. The capsaicin- and glutamate-induced paw licking tests were employed to evaluate the involvement of the vanilloid and glutamatergic systems, respectively. Asiaticoside (3, 5, and 10 mg/kg, p. o.) reduced the rate of writhing (p

Matched MeSH terms: Disease Models, Animal
A single targeted gamma-ray irradiation induced an acute modulation of immune cells and related cytokines in EMT6 mouse-bearing tumour model

Hasan N, Hasani NAH, Omar E, Sham FR, Fuad SBSA, Karim MKA, et al.

Cancer Biomark, 2023;38(1):61-75.
PMID: 37522193 DOI: 10.3233/CBM-220268

BACKGROUND: A complicated interplay between radiation doses, tumour microenvironment (TME), and host immune system is linked to the active participation of immune response.
OBJECTIVE: The effects of single targeted 2 Gy and 8 Gy gamma-ray irradiations on the immune cell population (lymphocytes, B-cells, T-cells, neutrophils, eosinophils, and macrophages) in EMT6 mouse-bearing tumour models was investigated.
METHODS: The effects of both irradiation doses in early (96 hours) and acute phase (5 to 11 days) post-irradiation on immune parameters were monitored in blood circulation and TME using flow cytometry. Simultaneously, selected cytokines related to immune cells within the TME were measured using multiplex ELISA.
RESULTS: A temporary reduction in systemic total white blood count (TWBC) resulted from an early phase (96 hours) of gamma-ray irradiation at 2 Gy and 8 Gy compared to sham control group. No difference was obtained in the acute phase. Neutrophils dominated among other immune cells in TME in sham control group. Eosinophils in TME was significantly increased after 8 Gy treatment in acute phase compared to sham control (p< 0.005). Furthermore, the increment of tumour necrosis (TNF)-α, eotaxin and interleukin (IL)-7 (p< 0.05) in both treatment groups and phases were associated with anti-tumour activities within TME by gamma-ray irradiation.
CONCLUSION: The temporary changes in immune cell populations within systemic circulation and TME induced by different doses of gamma-ray irradiation correlated with suppression of several pro-tumorigenic cytokines in mouse-bearing EMT6 tumour models.

Matched MeSH terms: Disease Models, Animal
Adult Endogenous Dopaminergic Neuroregeneration Against Parkinson's Disease: Ideal Animal Models?

Vijayanathan Y, Lim SM, Tan MP, Lim FT, Majeed ABA, Ramasamy K

Neurotox Res, 2021 Apr;39(2):504-532.
PMID: 33141428 DOI: 10.1007/s12640-020-00298-7

Parkinson's disease (PD) is the second most common neurodegenerative disease. The etiology of PD remains an enigma with no available disease modifying treatment or cure. Pharmacological compensation is the only quality of life improving treatments available. Endogenous dopaminergic neuroregeneration has recently been considered a plausible therapeutic strategy for PD. However, researchers have to first decipher the complexity of adult endogenous neuroregeneration. This raises the need of animal models to understand the underlying molecular basis. Mammalian models with highly conserved genetic homology might aid researchers to identify specific molecular mechanisms. However, the scarcity of adult neuroregeneration potential in mammals obfuscates such investigations. Nowadays, non-mammalian models are gaining popularity due to their explicit ability to neuroregenerate naturally without the need of external enhancements, yet these non-mammals have a much diverse gene homology that critical molecular signals might not be conserved across species. The present review highlights the advantages and disadvantages of both mammalian and non-mammalian animal models that can be essentially used to study the potential of endogenous DpN regeneration against PD.

Matched MeSH terms: Models, Animal
Timing of orthodontic tooth movement in bone defects repaired with synthetic scaffolds: A scoping review of animal studies

Tsai MH, Megat Abdul Wahab R, Yazid F

Arch Oral Biol, 2021 Dec;132:105278.
PMID: 34634537 DOI: 10.1016/j.archoralbio.2021.105278

OBJECTIVE: The optimal timing of orthodontic tooth movement (OTM) could allow earlier tooth movements across alveolar bone defects while minimizing the adverse effects. The objective of this scoping systematic review was therefore designed to review pre-clinical animal studies on the ideal protocol for the timing of orthodontic traction across alveolar defects augmented with synthetic scaffolds.
DESIGN: Following the PRISMA-ScR guidelines, three electronic databases were searched (Pubmed, Scopus and Web of Science).
RESULTS: A total of twelve studies were included in the final review that reported on small-animal (rats, guinea pigs, rabbits) and large-animal (dogs and goats) models. Based on the grafting biomaterials, eight papers used cell-free scaffolds, four articles utilised cell-based scaffolds. The timing protocol for the initiation of OTM employed in the studies ranged from immediate to 6 months after surgical grafting. Only four studies included autologous bone graft (gold standard) as positive control. Most papers reported positive results with regards to the rate of OTM and bone augmentation effects while only a few reported side effects such as root resorptions. Overall, the included articles showed a massive heterogeneity in terms of the animal bone defect model characteristics, scaffold materials, study designs, parameters of OTM and methods of analysis.
CONCLUSION: Since there was inadequate evidence to identify the optimal protocol of OTM, optimization of animal bone defect models and outcome measurements is needed to improve the translational ability of future studies.

Matched MeSH terms: Disease Models, Animal
Zebrafish: predictive model for targeted cancer therapeutics from nature

Zulkhernain NS, Teo SH, Patel V, Tan PJ

Curr Cancer Drug Targets, 2014;14(8):764-73.
PMID: 25348017 DOI: 10.2174/1568009614666141028121347

Targeted therapy, the treatment of cancer based on an underlying genetic alteration, is rapidly gaining favor as the preferred therapeutic approach. To date, although natural products represent a rich resource of bio-diverse drug candidates, only a few have been identified to be effective as targeted cancer therapies largely due to the incompatibilities to current high-throughput screening methods. In this article, we review the utility of a zebrafish developmental screen for bioactive natural product-based compounds that target signaling pathways that are intimately shared with those in humans. Any bioactive compound perturbing signaling pathways identified from phenotypic developmental defects in zebrafish embryos provide an opportunity for developing targeted therapies for human cancers. This model provides a promising tool in the search for targeted cancer therapeutics from natural products.

Matched MeSH terms: Disease Models, Animal*
Fulltext Subclinical infection without encephalitis in mice following intranasal exposure to Nipah virus-Malaysia and Nipah virus-Bangladesh

Dups J, Middleton D, Long F, Arkinstall R, Marsh GA, Wang LF

Virol J, 2014;11:102.
PMID: 24890603 DOI: 10.1186/1743-422X-11-102

Nipah virus and Hendra virus are closely related and following natural or experimental exposure induce similar clinical disease. In humans, encephalitis is the most serious outcome of infection and, hitherto, research into the pathogenesis of henipavirus encephalitis has been limited by the lack of a suitable model. Recently we reported a wild-type mouse model of Hendra virus (HeV) encephalitis that should facilitate detailed investigations of its neuropathogenesis, including mechanisms of disease recrudescence. In this study we investigated the possibility of developing a similar model of Nipah virus encephalitis.

Matched MeSH terms: Disease Models, Animal*
Mouse model of intracerebellar haemorrhage

Tijjani Salihu A, Muthuraju S, Aziz Mohamed Yusoff A, Ahmad F, Zulkifli Mustafa M, Jaafar H, et al.

Behav Brain Res, 2016 10 01;312:374-84.
PMID: 27327104 DOI: 10.1016/j.bbr.2016.06.034

The present study aimed to investigate the behavior and neuronal morphological changes in the perihaemorrhagic tissue of the mouse intracerebellar haemorrhage experimental model. Adult male Swiss albino mice were stereotactically infused with collagenase type VII (0.4U/μl of saline) unilaterally in to the cerebellum, following anaesthesia. Motor deficits were assessed using open field and composite score for evaluating the mouse model of cerebellar ataxia at 1, 3, 7, 14 and 21 days after collagenase infusion. The animals were sacrificed at the same time interval for evaluation of perihaematomal neuronal degeneration using haematoxylin and eosin staining and Annexin V-FITC/Propidium iodide assay. At the end of the study, it was found that infusion of 0.4U collagenase produces significant locomotor and ataxic deficit in the mice especially within the first week post surgery, and that this gradually improved within three weeks. Neuronal degeneration evident by cytoplasmic shrinkage and nuclear pyknosis was observed at the perihaematomal area after one day; especially at 3 and 7 days post haemorrhage. By 21 days, both the haematoma and degenerating neurons in the perihaematomal area were phagocytosed and the remaining neuronal cells around the scar tissue appeared normal. Moreover, Annexin-V/propidium iodide-positive cells were observed at the perihaematomal area at 3 and 7 days implying that the neurons likely die via apoptosis. It was concluded that a population of potentially salvageable neurons exist in the perihaematomal area after cerebellar haemorrhage throughout a wide time window that could be amenable to treatment.

Matched MeSH terms: Disease Models, Animal*
Utilizing Zebrafish to Identify Anti-(Lymph)Angiogenic Compounds for Cancer Treatment: Promise and Future Challenges

Okuda KS, Lee HM, Velaithan V, Ng MF, Patel V

Microcirculation, 2016 08;23(6):389-405.
PMID: 27177346 DOI: 10.1111/micc.12289

Cancer metastasis which predominantly occurs through blood and lymphatic vessels, is the leading cause of death in cancer patients. Consequently, several anti-angiogenic agents have been approved as therapeutic agents for human cancers such as metastatic renal cell carcinoma. Also, anti-lymphangiogenic drugs such as monoclonal antibodies VGX-100 and IMC-3C5 have undergone phase I clinical trials for advanced and metastatic solid tumors. Although anti-tumor-associated angiogenesis has proven to be a promising therapeutic strategy for human cancers, this approach is fraught with toxicities and development of drug resistance. This emphasizes the need for alternative anti-(lymph)angiogenic drugs. The use of zebrafish has become accepted as an established model for high-throughput screening, vascular biology, and cancer research. Importantly, various zebrafish transgenic lines have now been generated that can readily discriminate different vascular compartments. This now enables detailed in vivo studies that are relevant to both human physiological and tumor (lymph)angiogenesis to be conducted in zebrafish. This review highlights recent advancements in the zebrafish anti-vascular screening platform and showcases promising new anti-(lymph)angiogenic compounds that have been derived from this model. In addition, this review discusses the promises and challenges of the zebrafish model in the context of anti-(lymph)angiogenic compound discovery for cancer treatment.

Matched MeSH terms: Disease Models, Animal*
Animal model of margosa oil ingestion with Reye-like syndrome. Pathogenesis of microvesicular fatty liver

Sinniah R, Sinniah D, Chia LS, Baskaran G

J Pathol, 1989 Nov;159(3):255-64.
PMID: 2593049

The aetiology and pathogenesis of Reye's syndrome (RS) are incompletely understood. A number of environmental toxins and biological agents, including viruses, have been postulated to cause RS, either acting alone or synergistically. Most investigations have suggested that the primary insult is in the liver mitochondria, leading to a complex biochemical catastrophe, with death from encephalopathy. Margosa oil (MO), a long-chain fatty acid compound, has been shown to cause a Reye-like syndrome with death from hepatoencephalopathy, in children in Malaysia and India. The present time-course study performed in MO-administered mice showed the development of hepatic lesions with many features of RS. MO acts rapidly, within 30 min, on the nuclei of hepatocytes inducing mitoses and binucleated cells. This is followed by mitochondrial injury, with swelling, rarefaction of matrix, loss of dense bodies, pleomorphism, and loss of ribosomes starting at 60 min. There is loss of liver glycogen, and proliferation and hypertrophy of the endoplasmic reticulum (ER), followed by the presence of lipid droplets in the hyaloplasm, and globules within dilated cisterns of the ER. Additional fatty acids from lipolysis of body adipocytes, and fat globules from intestinal MO ingestion further aggravate the liver fatty change. There is evidence of fat globule ingestion by endocytosis into hepatocytes at the level of the sinusoids. The development of microvesicular liver steatosis and glycogen depletion due to involvement of liver cell organelles occur rapidly as in RS.

Matched MeSH terms: Disease Models, Animal*
Experimental infection of the leaf-monkey, Presbytis cristata, with subperiodic Brugia malayi

Mak JW, Choong MF, Suresh K, Lam PL

Parasitol Res, 1990;76(8):689-91.
PMID: 2251244

Presbytis cristata monkeys infected through the inoculation of between 200 and 400 subperiodic Brugia malayi infective larvae (L3) in the right thigh, in both thighs or in the dorsum of the right foot were followed up for varying periods of up to about 8 months after infection. All 148 inoculated animals became patent, with mean prepatent periods being between 66 and 76 days. In animals injected in the thigh, the patterns of microfilaraemia were similar, there being a rapid rise in the geometric mean counts (GMCs) of microfilariae during the first 10-12 weeks of patency, which then plateaued at levels of greater than 1000/ml. Adult worm recovery, expressed as the percentage of the infective dose, was significantly higher in animals injected with 100 L3 in each thigh, being 9.4% as compared with 2.8%-4.8% in other groups. It is therefore recommended that animals should be injected with 100 L3 in each thigh and that the testing of potential filaricides in this model be carried out during the phase of rapid increase in microfilaraemia to ensure that any microfilaricidal effect can easily be detected.

Matched MeSH terms: Disease Models, Animal*
Envisioning the neuroprotective effect of Metformin in experimental epilepsy: A portrait of molecular crosstalk

H S N, Paudel YN, K L K

Life Sci, 2019 Sep 15;233:116686.
PMID: 31348946 DOI: 10.1016/j.lfs.2019.116686

Epilepsy is a neurological disorder characterized by an enduring predisposition to generate and aggravate epileptic seizures affecting around 1% of global population making it a serious health concern. Despite the recent advances in epilepsy research, no disease-modifying treatment able to terminate epileptogenesis have been reported yet reflecting the complexity in understanding the disease pathogenesis. To overcome the current treatment gap against epilepsy, one effective approach is to explore anti-epileptic effects from a drug that are approved to treat non-epileptic diseases. In this regard, Metformin emerged as an ideal candidate which is a first line treatment option for type 2 diabetes mellitus (T2DM), has conferred neuroprotection in several in vivo neurological disorders such as Alzheimer's diseases (AD), Parkinson's disease (PD), Stroke, Huntington's diseases (HD) including epilepsy. In addition, Metformin has ameliorated cognitive alteration, learning and memory induced by epilepsy as well as in animal model of AD. Herein, we review the promising findings demonstrated upon Metformin treatment against animal model of epilepsy however, the precise underlying mechanism of anti-epileptic potential of Metformin is not well understood. However, there is a growing understanding that Metformin demonstrates its anti-epileptic effect mainly via ameliorating brain oxidative damage, activation of AMPK, inhibition of mTOR pathway, downregulation of α-synuclein, reducing apoptosis, downregulation of BDNF and TrkB level. These reflects that Metformin being non-anti-epileptic drug (AED) has a potential to ameliorate the cellular pathways that were impaired in epilepsy reflecting its therapeutical potential against epileptic seizure that might plausibly overcome the limitations of today epilepsy treatment.

Matched MeSH terms: Disease Models, Animal*
Evaluation of the sub-acute toxicity of Acacia catechu Willd seed extract in a Wistar albino rat model

Thangavelu L, Balusamy SR, Shanmugam R, Sivanesan S, Devaraj E, Rajagopalan V, et al.

Regul Toxicol Pharmacol, 2020 Jun;113:104640.
PMID: 32169672 DOI: 10.1016/j.yrtph.2020.104640

Acacia catechu (A. catechu) or Khair (Hindi) is used in several herbal preparations in the Ayurvedic system of medicine in India. Traditionally, this drug is beneficial against several gastrointestinal and stomach related ailments, and leprosy. The present investigation was carried out to evaluate the sub-acute oral toxicity of the ethanolic extract of A. catechu seeds in Wistar albino rats. Results obtained from the quantitative chemical analysis of A. catechu seed extract were compared with commercially available standards. A. catechu seed extract was administered orally at the doses of 250, 500 and 1000 mg/kg b.w. daily for 28 days. General behavior, bodyweight and mortality were examined during the entire study period. At the end of 28 days, hematological and biochemical parameters along with the relative organ weights were determined. It was observed that the extract did not induce death or any significant changes in the body weight, relative weight of vital organs and in hematological parameters for up to a dose of 1000 mg/kg. The oral administration of the plant extract did not produce any significant changes in the levels of glucose. In addition, there were no significant changes in the activity of both hepatotoxic and nephrotoxic marker enzymes in the serum. Oral administration of A. catechu also did not produce any significant changes in the levels of oxidative markers. Furthermore, the findings from the biochemical studies were, well corroborated with the histological findings.

Matched MeSH terms: Models, Animal*
Fulltext A preliminary study of insect succession on a pig carcass in a palm oil plantation in Malaysia

Heo CC, Mohamad AM, Ahmad Firdaus MS, Jeffery J, Baharudin O

Trop Biomed, 2007 Dec;24(2):23-7.
PMID: 18209704 MyJurnal

This preliminary study was carried out in a palm oil plantation in Tanjung Sepat, Selangor in 17 May 2007 by using pig (Sus scrofa) as a carcass model in forensic entomological research. A 3 month old pig (8.5 kg) that died of pneumonio was placed in the field to observe the decomposition stages and the fauna succession of forensically important flies. Observation was made for two weeks; two visits per day and all climatological data were recorded. The first visitor to the pig carcass was a muscid fly, seen within a minute, and followed by ants and spiders. Within half an hour, calliphorid flies came over. On the second day (fresh), few calliphorid and sarcophagid flies were found on the carcass. Two different species of moths were trapped in the hanging net. The first larva mass occurred on the third day (bloated) around the mouthpart, with some L1 and L2 found in the eyes. Reduvid bugs and Staphylinidae beetles were recovered on the fourth day (active decay), and new maggot masses occurred in the eyes and anus. L3 larvae could be found beneath the pig carcass on the fourth day. On the fifth day (active decay), new maggot masses were found on neck, thorax, and hind legs. Advance decay occurred on the sixth day with abundant maggots covering all over the body. The main adult fly population was Chrysomya megacephala (day 2 to day 6), but the larvae population was mainly those of Chrysomya rufifacies (day 4 to day 14). The dry stage began on the eighth day. Hermetia illucens adult was caught on day-13, and a larvae mass of Chrysomya rufifacies was seen burrowing under the soil. This forensic entomological research using pig carcass model was the first record in this country.

Matched MeSH terms: Models, Animal*
Fulltext Safety Assessment of Two New Lactobacillus Strains as Probiotic for Human Using a Rat Model

Shokryazdan P, Faseleh Jahromi M, Liang JB, Kalavathy R, Sieo CC, Ho YW

PLoS One, 2016;11(7):e0159851.
PMID: 27467068 DOI: 10.1371/journal.pone.0159851

Two previously isolated Lactobacillus strains (L. fermentum HM3 from human milk and L. buchneri FD2 from fermented dates), intended as probiotic for human, were assessed for their safety using acute and subacute oral toxicity tests in rats. In addition, their effects on cecal microflora and harmful bacterial enzymes (β-glucuronidase and β-glucosidase) of the tested animals were also determined. The results showed that L. buchneri FD2, L. fermentum HM3, or a mixture of them were safe up to a level of 1010 CFU/kg BW/day in a 14-day or 28-day treatment period. Both strains were well tolerated and there were no observed adverse effects on growth, feed consumption, cellular blood components and vital organs of the treated animals. The Lactobacillus strains were also able to reduce harmful intestinal bacterial enzymes, and decrease pathogenic bacterial populations while increasing beneficial bacterial populations. These results suggest that the two Lactobacillus strains are safe and could be potential probiotic for human.

Matched MeSH terms: Models, Animal*
Lipopolysaccharide-induced memory impairment in rats: a model of Alzheimer's disease

Zakaria R, Wan Yaacob WM, Othman Z, Long I, Ahmad AH, Al-Rahbi B

Physiol Res, 2017 09 22;66(4):553-565.
PMID: 28406691

Alzheimer's disease (AD) is a primary cause of dementia in the middle-aged and elderly worldwide. Animal models for AD are widely used to study the disease mechanisms as well as to test potential therapeutic agents for disease modification. Among the non-genetically manipulated neuroinflammation models for AD, lipopolysaccharide (LPS)-induced animal model is commonly used. This review paper aims to discuss the possible factors that influence rats' response following LPS injection. Factors such as dose of LPS, route of administration, nature and duration of exposure as well as age and gender of animal used should be taken into account when designing a study using LPS-induced memory impairment as model for AD.

Matched MeSH terms: Disease Models, Animal*
Fulltext A Zebrafish Embryo as an Animal Model for the Treatment of Hyperpigmentation in Cosmetic Dermatology Medicine

Lajis AFB

Medicina (Kaunas), 2018 May 25;54(3).
PMID: 30344266 DOI: 10.3390/medicina54030035

For years, clinical studies involving human volunteers and several known pre-clinical in vivo models (i.e., mice, guinea pigs) have demonstrated their reliability in evaluating the effectiveness of a number of depigmenting agents. Although these models have great advantages, they also suffer from several drawbacks, especially involving ethical issues regarding experimentation. At present, a new depigmenting model using zebrafish has been proposed and demonstrated. The application of this model for screening and studying the depigmenting activity of many bioactive compounds has been given great attention in genetics, medicinal chemistry and even the cosmetic industry. Depigmenting studies using this model have been recognized as noteworthy approaches to investigating the antimelanogenic activity of bioactive compounds in vivo. This article details the current knowledge of zebrafish pigmentation and its reliability as a model for the screening and development of depigmenting agents. Several methods to quantify the antimelanogenic activity of bioactive compounds in this model, such as phenotype-based screening, melanin content, tyrosinase inhibitory activity, other related proteins and transcription genes, are reviewed. Depigmenting activity of several bioactive compounds which have been reported towards this model are compared in terms of their molecular structure and possible mode of actions. This includes patented materials with regard to the application of zebrafish as a depigmenting model, in order to give an insight of its intellectual value. At the end of this article, some limitations are highlighted and several recommendations are suggested for improvement of future studies.

Matched MeSH terms: Disease Models, Animal*
Role of dietary fat on obesity-related postmenopausal breast cancer: insights from mouse models and methodological considerations

Tan PY, Teng KT

Breast Cancer, 2021 May;28(3):556-571.
PMID: 33687609 DOI: 10.1007/s12282-021-01233-0

The increasing incidence rate of breast cancer in the last few decades is known to be linked to the upward trend of obesity prevalence worldwide. The consumption of high-fat diet in particular has been correlated with postmenopausal breast cancer risk. The underlying mechanisms, using suitable and reliable experimental mouse model, however, is lacking. The current review aims to discuss the evidence available from mouse models on the effects of dietary fats intake on postmenopausal breast cancer. We will further discuss the biochemical mechanisms involved in the occurrence of postmenopausal breast cancer. In addition, the methodological considerations and their limitations in obesity-related postmenopausal breast cancer, such as choice of mouse models and breast cancer cell lines as well as the study duration will be reviewed. The current review will provide a platform for further development of new xenograft models which may offer the opportunity to investigate the mechanisms of postmenopausal breast cancer in a greater detail.

Matched MeSH terms: Disease Models, Animal*
Fulltext The Use of Large-Particle Aerosol Exposure to Nipah Virus to Mimic Human Neurological Disease Manifestations in the African Green Monkey

Lee JH, Hammoud DA, Cong Y, Huzella LM, Castro MA, Solomon J, et al.

J Infect Dis, 2020 05 11;221(Suppl 4):S419-S430.
PMID: 31687756 DOI: 10.1093/infdis/jiz502

Nipah virus (NiV) is an emerging virus associated with outbreaks of acute respiratory disease and encephalitis. To develop a neurological model for NiV infection, we exposed 6 adult African green monkeys to a large-particle (approximately 12 μm) aerosol containing NiV (Malaysian isolate). Brain magnetic resonance images were obtained at baseline, every 3 days after exposure for 2 weeks, and then weekly until week 8 after exposure. Four of six animals showed abnormalities reminiscent of human disease in brain magnetic resonance images. Abnormalities ranged from cytotoxic edema to vasogenic edema. The majority of lesions were small infarcts, and a few showed inflammatory or encephalitic changes. Resolution or decreased size in some lesions resembled findings reported in patients with NiV infection. Histological lesions in the brain included multifocal areas of encephalomalacia, corresponding to known ischemic foci. In other regions of the brain there was evidence of vasculitis, with perivascular infiltrates of inflammatory cells and rare intravascular fibrin thrombi. This animal model will help us better understand the acute neurological features of NiV infection and develop therapeutic approaches for managing disease caused by NiV infection.

Matched MeSH terms: Disease Models, Animal*

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