Displaying publications 81 - 100 of 161 in total

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  1. Sequence and localization of kcnk10a in the brain of adult zebrafish (Danio rerio)
    Loganathan K, Moriya S, Sivalingam M, Ng KW, Parhar IS
    J. Chem. Neuroanat., 2017 Dec;86:92-99.
    PMID: 29074372 DOI: 10.1016/j.jchemneu.2017.10.004
    kcnk10a has been predicted in zebrafish to be a member of the two-pore domain potassium ion (K+) channel-related K+ (TREK) channel family known as a thermoreceptor. Since reproduction is affected by temperature, Kcnk10a could be involved in the regulation of reproduction. However, expression of kcnk10a in the zebrafish brain and association with reproduction has not been identified. In this study, the full length sequence and localization of kcnk10a in the brain was investigated and gene expressions of the TREK channel family were examined to investigate association with reproduction. We initially identified the full length cDNA sequence of kcnk10a using Rapid Amplification of cDNA Ends and localization in the zebrafish brain using in situ hybridization. Furthermore, we examined the gene expression differences of kcnk2b, kcnk10a and kcnk10b mRNA between genders as well as developmental stages by real-time PCR. The deduced amino acid sequence of the identified kcnk10a mRNA contains highly conserved two pore domains and four transmembrane regions and was higher similarity to zebrafish Kcnk10b than zebrafish Kcnk2a and 2b. kcnk10a mRNA was widely distributed in the brain such as the preoptic area, hypothalamus and the midbrain. kcnk10a mRNA expression exhibited significant difference between mature male and female, and increase during puberty. Kcnk10a could be involved in the regulation of reproductive function.
    Matched MeSH terms: Zebrafish/genetics*; Zebrafish/metabolism*; Zebrafish Proteins/genetics; Zebrafish Proteins/metabolism*; Zebrafish Proteins/chemistry
  2. Trek2a regulates gnrh3 expression under control of melatonin receptor Mt1 and α2-adrenoceptor
    Loganathan K, Moriya S, Parhar IS
    Biochem Biophys Res Commun, 2018 02 12;496(3):927-933.
    PMID: 29395088 DOI: 10.1016/j.bbrc.2018.01.117
    Gonadotrophin-releasing hormone (GnRH) expression is associated with the two-pore domain potassium ion (K+) channel-related K+ (TREK) channel trek2a expression and melatonin levels. We aimed to investigate correlation of trek2a expression with gnrh3 expression, and regulatory mechanisms of trek2a expression by the melatonin receptor Mt1 and α2-adrenoceptor which are regulated by melatonin. trek2a specific siRNA, Mt1 antagonist luzindole and α2-adrenoceptor antagonist prazosin were administered into the adult zebrafish brain and gene expressions were examined by real-time PCR. trek2a specific siRNA administration significantly reduced expression levels of trek2a, gnrh3 and mt1. Luzindole administration suppressed trek2a and gnrh3 expressions. Prazosin administration reduced trek2a and gnrh3 expressions. It is suggested that Trek2a regulates gnrh3 expression under the control of Mt1 and α2-adrenoceptor.
    Matched MeSH terms: Zebrafish; Zebrafish Proteins/metabolism*
  3. Coencapsulation of Gemcitabine and Thymoquinone in Citrem-Phosphatidylcholine Hexosome Nanocarriers Improves In Vitro Cellular Uptake in Breast Cancer Cells
    Loo YS, Zahid NI, Madheswaran T, Ikeno S, Nurdin A, Mat Azmi ID
    Mol Pharm, 2023 Sep 04;20(9):4611-4628.
    PMID: 37587099 DOI: 10.1021/acs.molpharmaceut.3c00333
    Lyotropic liquid crystalline nanoassemblies (LLCNs) are internally self-assembled (ISA)-somes formed by amphiphilic molecules in a mixture comprising a lipid, stabilizer, and/or surfactant and aqueous media/dispersant. LLCNs are unique nanoassemblies with versatile applications in a wide range of biomedical functions. However, they comprise a nanosystem that is yet to be fully explored for targeted systemic treatment of breast cancer. In this study, LLCNs proposed for gemcitabine and thymoquinone (Gem-TQ) co-delivery were prepared from soy phosphatidylcholine (SPC), phytantriol (PHYT), or glycerol monostearate (MYVR) in optimized ratios containing a component of citric and fatty acid ester-based emulsifier (Grinsted citrem) or a triblock copolymer, Pluronic F127 (F127). Hydrodynamic particle sizes determined were below 400 nm (ranged between 96 and 365 nm), and the series of nanoformulations displayed negative surface charge. Nonlamellar phases identified by small-angle X-ray scattering (SAXS) profiles comprise the hexagonal, cubic, and micellar phases. In addition, high entrapment efficiency that accounted for 98.3 ± 0.1% of Gem and 99.5 ± 0.1% of TQ encapsulated was demonstrated by the coloaded nanocarrier system, SPC/citrem/Gem-TQ hexosomes. Low cytotoxicity of SPC-citrem hexosomes was demonstrated in MCF10A cells consistent with hemo- and biocompatibility observed in zebrafish (Danio rerio) embryos for up to 96 h postfertilization (hpf). SPC/citrem/Gem-TQ hexosomes demonstrated IC50 of 24.7 ± 4.2 μM in MCF7 breast cancer cells following a 24 h treatment period with the moderately synergistic interaction between Gem and TQ retained (CI = 0.84). Taken together, biocompatible SPC/citrem/Gem-TQ hexosomes can be further developed as a multifunctional therapeutic nanodelivery approach, plausible for targeting breast cancer cells by incorporation of targeting ligands.
    Matched MeSH terms: Zebrafish
  4. Some aspects of breast feeding in Singapore
    MILLIS J
    Med J Malaya, 1955 Dec;10(2):157-61.
    PMID: 13308616
    Matched MeSH terms: Zebrafish*
  5. Mutated Shiitake extracts inhibit melanin-producing neural crest-derived cells in zebrafish embryo
    Mahmood I, Azfaralariff A, Mohamad A, Airianah OB, Law D, Dyari HRE, et al.
    Comp Biochem Physiol C Toxicol Pharmacol, 2021 Jul;245:109033.
    PMID: 33737223 DOI: 10.1016/j.cbpc.2021.109033
    The ability of natural extracts to inhibit melanocyte activity is of great interest to researchers. This study evaluates and explores the ability of mutated Shiitake (A37) and wildtype Shiitake (WE) extract to inhibit this activity. Several properties such as total phenolic (TPC) and total flavonoid content (TFC), antioxidant activity, effect on cell and component profiling were conducted. While having no significant differences in total phenolic content, mutation resulted in A37 having a TFC content (1.04 ± 0.7 mg/100 ml) compared to WE (0.86 ± 0.9 mg/100 ml). Despite that, A37 extract has lower antioxidant activity (EC50, A37 = 549.6 ± 2.70 μg/ml) than WE (EC50 = 52.8 ± 1.19 μg/ml). Toxicity tests on zebrafish embryos show that both extracts, stop the embryogenesis process when the concentration used exceeds 900 μg/ml. Although both extracts showed pigmentation reduction in zebrafish embryos, A37 extract showed no effect on embryo heartbeat. Cell cycle studies revealed that WE significantly affect the cell cycle while A37 not. Further tests found that these extracts inhibit the phosphorylation of Glycogen synthase kinase 3 β (pGSK3β) in HS27 cell line, which may explain the activation of apoptosis in melanin-producing cells. It was found that from 19 known compounds, 14 compounds were present in both WE and A37 extracts. Interestingly, the presence of decitabine in A37 extract makes it very potential for use in the medical application such as treatment of melanoma, skin therapy and even cancer.
    Matched MeSH terms: Zebrafish/embryology*
  6. Fulltext MicroRNA-6744-5p promotes anoikis in breast cancer and directly targets NAT1 enzyme
    Malagobadan S, Ho CS, Nagoor NH
    Cancer Biol Med, 2020 Feb 15;17(1):101-111.
    PMID: 32296579 DOI: 10.20892/j.issn.2095-3941.2019.0010
    Objective: Anoikis is apoptosis that is induced when cells detach from the extracellular matrix and neighboring cells. As anoikis serves as a regulatory barrier, cancer cells often acquire resistance towards anoikis during tumorigenesis to become metastatic. MicroRNAs (miRNAs) are short strand RNA molecules that regulate genes post-transcriptionally by binding to mRNAs and reducing the expression of its target genes. This study aimed to elucidate the role of a novel miRNA, miR-6744-5p, in regulating anoikis in breast cancer and identify its target gene. Methods: An anoikis resistant variant of the luminal A type breast cancer MCF-7 cell line (MCF-7-AR) was generated by selecting and amplifying surviving cells after repeated exposure to growth in suspension. MiRNA microarray analysis identified a list of dysregulated miRNAs from which miR-6744-5p was chosen for overexpression and knockdown studies in MCF-7. Additionally, the miRNA was also overexpressed in a triple-negative breast cancer cell line, MDA-MB-231, to evaluate its ability to impair the metastatic potential of breast cancer cells. Results: This study showed that overexpression and knockdown of miR-6744-5p in MCF-7 increased and decreased anoikis sensitivity, respectively. Similarly, overexpression of miR-6744-5p in MDA-MB-231 increased anoikis and also decreased tumor cell invasion in vitro and in vivo. Furthermore, NAT1 enzyme was identified and validated as the direct target of miR-6744-5p. Conclusions: This study has proven the ability of miR-6744-5p to increase anoikis sensitivity in both luminal A and triple negative breast cancer cell lines, highlighting its therapeutic potential in treating breast cancer.
    Matched MeSH terms: Zebrafish
  7. Fulltext The Most Developmentally Truncated Fishes Show Extensive Hox Gene Loss and Miniaturized Genomes
    Malmstrøm M, Britz R, Matschiner M, Tørresen OK, Hadiaty RK, Yaakob N, et al.
    Genome Biol Evol, 2018 04 01;10(4):1088-1103.
    PMID: 29684203 DOI: 10.1093/gbe/evy058
    The world's smallest fishes belong to the genus Paedocypris. These miniature fishes are endemic to an extreme habitat: the peat swamp forests in Southeast Asia, characterized by highly acidic blackwater. This threatened habitat is home to a large array of fishes, including a number of miniaturized but also developmentally truncated species. Especially the genus Paedocypris is characterized by profound, organism-wide developmental truncation, resulting in sexually mature individuals of <8 mm in length with a larval phenotype. Here, we report on evolutionary simplification in the genomes of two species of the dwarf minnow genus Paedocypris using whole-genome sequencing. The two species feature unprecedented Hox gene loss and genome reduction in association with their massive developmental truncation. We also show how other genes involved in the development of musculature, nervous system, and skeleton have been lost in Paedocypris, mirroring its highly progenetic phenotype. Further, our analyses suggest two mechanisms responsible for the genome streamlining in Paedocypris in relation to other Cypriniformes: severe intron shortening and reduced repeat content. As the first report on the genomic sequence of a vertebrate species with organism-wide developmental truncation, the results of our work enhance our understanding of genome evolution and how genotypes are translated to phenotypes. In addition, as a naturally simplified system closely related to zebrafish, Paedocypris provides novel insights into vertebrate development.
    Matched MeSH terms: Zebrafish/genetics
  8. Biomarker triterpenoids of Centella asiatica as potential antidepressant agents: Combining in vivo and in silico studies
    Mando Z, Mando H, Afzan A, Shaari K, Hassan Z, Mohamad Taib MNA, et al.
    Behav Brain Res, 2024 May 28;466:114976.
    PMID: 38599249 DOI: 10.1016/j.bbr.2024.114976
    Although there are various treatments available for depression, some patients may experience resistance to treatment or encounter adverse effects. Centella asiatica (C. asiatica) is an ancient medicinal herb used in Ayurvedic medicine for its rejuvenating, neuroprotective and psychoactive properties. This study aims to explore the antidepressant-like effects of the major constituents found in C. asiatica, i.e., asiatic acid, asiaticoside, madecassic acid, and madecassoside at three doses (1.25, 2.5, and 5 mg/kg, i.p), on the behavioural and cortisol level of unpredictable chronic stress (UCS) zebrafish model. Based on the findings from the behavioural study, the cortisol levels in the zebrafish body after treatment with the two most effective compounds were measured using enzyme-linked immunosorbent assay (ELISA). Furthermore, a molecular docking study was conducted to predict the inhibitory impact of the triterpenoid compounds on serotonin reuptake. The in vivo results indicate that madecassoside (1.25, 2.5, and 5 mg/kg), asiaticoside and asiatic acid (5 mg/kg) activated locomotor behaviour. Madecassoside at all tested doses and asiaticoside at 2.5 and 5 mg/kg significantly decreased cortisol levels compared to the stressed group, indicating the potential regulation effect of madecassoside and asiaticoside on the hypothalamic-pituitary-adrenal axis overactivity. This study highlights the potential benefits of madecassoside and asiaticoside in alleviating depressive symptoms through their positive effects on behaviour and the hypothalamic-pituitary-adrenal (HPA)- axis in a chronic unpredictable stress zebrafish model. Furthermore, the in silico study provided additional evidence to support these findings. These promising results suggest that C. asiatica may be a valuable and cost-effective therapeutic option for depression, and further research should be conducted to explore its potential benefits.
    Matched MeSH terms: Zebrafish*
  9. The effects of metallothionein in paraquat-induced Parkinson disease model of zebrafish
    Mohamad Najib NH, Yahaya MF, Das S, Teoh SL
    Int J Neurosci, 2023 Dec;133(8):822-833.
    PMID: 34623211 DOI: 10.1080/00207454.2021.1990916
    INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disease caused by selective degeneration of dopaminergic neurons in the substantia nigra. Metallothionein has been shown to act as a neuroprotectant in various brain injury. Thus, this study aims to identify the effects of full-length human metallothionein 2 peptide (hMT2) in paraquat-induced brain injury in the zebrafish.

    METHODOLOGY: A total of 80 adult zebrafish were divided into 4 groups namely control, paraquat-treated, pre-hMT2-treated, and post-hMT2-treated groups. Fish were treated with paraquat intraperitoneally every 3 days for 15 days. hMT2 were injected intracranially on day 0 (pre-treated group) and day 16 (post-treated group). Fish were sacrificed on day 22 and the brains were collected for qPCR, ELISA and immunohistochemistry analysis.

    RESULTS: qPCR analysis showed that paraquat treatment down-regulated the expression of genes related to dopamine activity and biosynthesis (dat and th1) and neuroprotective agent (bdnf). Paraquat treatment also up-regulated the expression of the mt2, smtb and proinflammatory genes (il-1α, il-1β, tnf-α and cox-2). hMT2 treatment was able to reverse the effects of paraquat. Lipid peroxidation decreased in the paraquat and pre-hMT2-treated groups. However, lipid peroxidation increased in the post-hMT2-treated group. Paraquat treatment also led to a reduction of dopaminergic neurons while their numbers showed an increase following hMT2 treatment.

    CONCLUSION: Paraquat has been identified as one of the pesticides that can cause the death of dopaminergic neurons and affect dopamine biosynthesis. Treatment with exogenous hMT2 could reverse the effects of paraquat in the zebrafish brain.

    Matched MeSH terms: Zebrafish/metabolism
  10. Fulltext Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio)
    Mohd Sakeh N, Md Razip NN, Mohd Ma'in FI, Abdul Bahari MN, Latif N, Akhtar MN, et al.
    Molecules, 2020 Jul 28;25(15).
    PMID: 32731323 DOI: 10.3390/molecules25153403
    Excessive production of melanin implicates hyperpigmentation disorders. Flavokawain A (FLA) and flavokawain B (FLB) have been reported with anti-melanogenic activity, but their melanogenic inhibition and toxicity effects on the vertebrate model of zebrafish are still unknown. In the present study, cytotoxic as well as melanogenic effects of FLA and FLB on cellular melanin content and tyrosinase activity were evaluated in α-MSH-induced B16/F10 cells. Master regulator of microphthalmia-associated transcription factor (Mitf) and the other downstream melanogenic-related genes were verified via quantitative real time PCR (qPCR). Toxicity assessment and melanogenesis inhibition on zebrafish model was further observed. FLA and FLB significantly reduced the specific cellular melanin content by 4.3-fold and 9.6-fold decrement, respectively in α-MSH-induced B16/F10 cells. Concomitantly, FLA significantly reduced the specific cellular tyrosinase activity by 7-fold whilst FLB by 9-fold. The decrement of melanin production and tyrosinase activity were correlated with the mRNA suppression of Mitf which in turn down-regulate Tyr, Trp-1 and Trp-2. FLA and FLB exhibited non-toxic effects on the zebrafish model at 25 and 6.25 µM, respectively. Further experiments on the zebrafish model demonstrated successful phenotype-based depigmenting activity of FLA and FLB under induced melanogenesis. To sum up, our findings provide an important first key step for both of the chalcone derivatives to be further studied and developed as potent depigmenting agents.
    Matched MeSH terms: Zebrafish/metabolism*; Zebrafish Proteins/metabolism
  11. pink1, atp13a2 and uchl1 expressions are affected by inflammation in the brain
    Moriya S, Tan VP, Yee AK, Parhar IS
    Neurosci Lett, 2019 08 24;708:134330.
    PMID: 31201839 DOI: 10.1016/j.neulet.2019.134330
    In Parkinson's disease (PD), several genes have been identified as the PD-related genes, however, the regulatory mechanisms of these gene expressions have not been fully identified. In this study, we investigated the effect of inflammation, one of the major risk factors in PD on expressions of the PD-related genes. Lipopolysaccharide (LPS) was intraperitoneally administered to mature male zebrafish and gene expressions in the brains were examined by real-time PCR. In the inflammation-related genes, expressions of tnfb, il1b and il6 were increased at 2 days post administration in the 10 μg group, and tnfb expression was also increased at 4 days post administration in the 1 μg and 10 μg group. In the PD-related genes, pink1 expression was significantly decreased at 4 days, atp13a2 expression was significantly increased at 7 days, and uchl1 expression was significantly decreased at 7 days. This suggests that pink1, atp13a2 and uchl1 expressions are regulated by inflammation, and this regulatory mechanism might be involved in the progress of PD.
    Matched MeSH terms: Zebrafish; Zebrafish Proteins/genetics; Zebrafish Proteins/metabolism*
  12. Fulltext Bpifcl modulates kiss2 expression under the influence of 11-ketotestosterone in female zebrafish
    Moriya S, Tahsin N, Parhar IS
    Sci Rep, 2017 08 11;7(1):7926.
    PMID: 28801581 DOI: 10.1038/s41598-017-08248-8
    The bactericidal/permeability-increasing (BPI) fold-containing (BPIF) superfamily of genes expressed in the brain are purportedly involved in modulating brain function in response to stress, such as inflammation. Kisspeptin, encoded by kiss, is affected by inflammation in the brain; therefore, BPIF family genes might be involved in the modulation of kisspeptin in the brain. In this study, we investigated the expression of BPIF family C, like (bpifcl) in zebrafish brain and its involvement in kiss2 regulation. The identified, full-length sequence of a bpifcl isoform expressed in the zebrafish brain contained the BPI fold shared by BPIF family members. bpifcl mRNA expression in female zebrafish brains was significantly higher than that in males. Exposure of female zebrafish to 11-ketotestosterone decreased bpifcl and kiss2 mRNA expression. bpifcl knockdown by bpifcl-specific small interfering RNA administration to female zebrafish brain decreased kiss2 mRNA expression. bpifcl expression was widely distributed in the brain, including in the dorsal zone of the periventricular hypothalamus (Hd). Furthermore, bpifcl was also expressed in KISS2 neurons in the Hd. These results suggest that the Bpifcl modulates kiss2 mRNA expression under the influence of testosterone in the Hd of female zebrafish.
    Matched MeSH terms: Zebrafish/genetics*; Zebrafish/physiology*; Zebrafish Proteins/metabolism*
  13. Fabrication of nano-mosquitocides using chitosan from crab shells: Impact on non-target organisms in the aquatic environment
    Murugan K, Anitha J, Dinesh D, Suresh U, Rajaganesh R, Chandramohan B, et al.
    Ecotoxicol Environ Saf, 2016 Oct;132:318-28.
    PMID: 27344400 DOI: 10.1016/j.ecoenv.2016.06.021
    Mosquitoes are arthropods of huge medical and veterinary relevance, since they vector pathogens and parasites of public health importance, including malaria, dengue and Zika virus. Currently, nanotechnology is considered a potential eco-friendly approach in mosquito control research. We proposed a novel method of biofabrication of silver nanoparticles (AgNP) using chitosan (Ch) from crab shells. Ch-AgNP nanocomposite was characterized by UV-vis spectroscopy, FTIR, SEM, EDX and XRD. Ch-AgNP were tested against larvae and pupae of the malaria vector Anopheles stephensi obtaining LC50 ranging from 3.18 ppm (I) to 6.54 ppm (pupae). The antibacterial properties of Ch-AgNP were proved against Bacillus subtilis, Klebsiella pneumoniae and Salmonella typhi, while no growth inhibition was reported in assays conducted on Proteus vulgaris. Concerning non-target effects, in standard laboratory considtions the predation efficiency of Danio rerio zebrafishes was 68.8% and 61.6% against I and II instar larvae of A. stephensi, respectively. In a Ch-AgNP-contaminated environment, fish predation was boosted to 89.5% and 77.3%, respectively. Quantitative analysis of antioxidant enzymes SOD, CAT and LPO from hepatopancreas of fresh water crabs Paratelphusa hydrodromous exposed for 16 days to a Ch-AgNP-contaminated aquatic environment were conducted. Notably, deleterious effects of Ch-AgNP contaminating aquatic enviroment on the non-target crab P. hydrodromous were observed, particularly when doses higher than 8-10ppm are tested. Overall, this research highlights the potential of Ch-AGNP for the development of newer control tools against young instar populations of malaria mosquitoes, also highlighting some risks concerned the employ of nanoparticles in aquatic environments.
    Matched MeSH terms: Zebrafish
  14. Toxicity study on Clinacanthus nutans leaf hexane fraction using Danio rerio embryos
    Murugesu S, Khatib A, Ahmed QU, Ibrahim Z, Uzir BF, Benchoula K, et al.
    Toxicol Rep, 2019;6:1148-1154.
    PMID: 31993329 DOI: 10.1016/j.toxrep.2019.10.020
    Clinacanthus nutans, an herbal shrub belonging to the Acanthaceae family, is traditionally used as a functional food to treat various ailments in Malaysia and Indonesia. Although the polar fraction of this plant shows non-toxic effect, the toxicity of the non-polar extract is not reported so far. The present study aimed to assess the toxic effect and determine the lethal concentration of this non-polar fraction using zebrafish embryos. The n-hexane fraction was partitioned from the crude extract of C. nutans obtained using 80% methanolic solution. After spawning of the adult male and female zebrafish, the eggs were collected, transferred into a 96-well plate and incubated with the n-hexane fraction at concentrations of 15.63 μg/ml, 31.25 μg/ml, 62.5 μg/ml, 125 μg/ml, 250 μg/ml and 500 μg/ml in 2% DMSO. The survival and sublethal endpoint were assessed, the mortality and hatchability rates were calculated based on microscopic observation, while the heartbeat rate was measured using DanioScope software. The median lethal concentration (LC50) of the C. nutans n-hexane fraction, which was determined using probit analysis, was calculated to be 75.49 μg/mL, which is harmful. Moreover, gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of palmitic acid, phytol, hexadecanoic acid, 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol and stigmasterol in the n-hexane fraction.
    Matched MeSH terms: Zebrafish
  15. Role of ambrisentan (selective endothelin-A receptor antagonist) on cigarette smoke exposure induced cognitive impairment in Danio rerio
    Muthuraman A, Nafisa K, Sowmya MS, Arpitha BM, Choedon N, Sandy CD, et al.
    Life Sci, 2019 Mar 04.
    PMID: 30844374 DOI: 10.1016/j.lfs.2019.03.002
    BACKGROUND: Cigarette smoke is exogenous modifiable factors to changes the neurovascular complication. The chronic exposure of cigarette smoke enhances neurocognitive dysfunction.

    AIMS: The present study is focused on evaluating the role of ambrisentan (selective endothelin-A receptor antagonist) on cigarette smoke-induced cognitive impairment in Danio rerio.

    MAIN METHODS: The cognitive dysfunction was developed by cigarette smoke exposure (CSE; 10 min in 25 ml of CSE per day) for five days. The selective endothelin-A receptor antagonist i.e., ambrisentan (2.5 to 5 mg/kg; i.p. for five consecutive days) was used for testing of CSE induced cognitive dysfunction. In addition, treatment of reference drug i.e., donepezil (10 mg/kg; i.p. for five consecutive days) was used for this cognitive function study. The cognitive functions were assessed by light and dark chamber; color recognition; partition preference; horizontal compartment; and T-Maze tests. Further, the CSE induced biomarkers changes of the zebrafish brain samples were estimated.

    KEY FINDINGS: The treatment of ambrisentan showed a potential ameliorative effect against the CSE induced cognitive functions along with attenuation of biochemical changes. The results are comparable to donepezil-treated groups.

    SIGNIFICANCE: Therefore, ambrisentan can be considered for the attenuation of CSE induced impairment neurocognitive functions due to its reduction of free radical scavenging and neuroinflammatory actions as well as regulation of cholinergic neurotransmitter functions.

    Matched MeSH terms: Zebrafish
  16. Fulltext In Silico and In Vitro Methods in the Characterization of Beta-Carotene as Pharmaceutical Material via Acetylcholine Esterase Inhibitory Actions
    Muthuraman A, Ramesh M, Mustaffa F, Nadeem A, Nishat S, Paramakrishnan N, et al.
    Molecules, 2023 May 26;28(11).
    PMID: 37298835 DOI: 10.3390/molecules28114358
    Molecular docking is widely used in the assessment of the therapeutic potential of pharmaceutical agents. The binding properties of beta-carotene (BC) to acetylcholine esterase (AChE) proteins were characterized using the molecular docking method. The mechanism of AChE inhibition was assessed by an experimental in vitro kinetic study. In addition, the role of BC action was tested by the zebrafish embryo toxicity test (ZFET). The results of the docking ability of BC to AChE showed significant ligand binding mode. The kinetic parameter, i.e., the low AICc value shown as the compound was the competitive type of inhibition of AChE. Further, BC also showed mild toxicity at a higher dose (2200 mg/L) in ZFET assessment with changes in biomarkers. The LC50 value of BC is 1811.94 mg/L. Acetylcholine esterase (AChE) plays a pivotal role in the hydrolysis of acetylcholine, which leads to the development of cognitive dysfunction. BC possesses the regulation of acetylcholine esterase (AChE) and acid phosphatase (AP) activity to prevent neurovascular dysfunction. Therefore, the characterization of BC could be used as a pharmaceutical agent for the treatment of cholinergic neurotoxicity-associated neurovascular disorders such as developmental toxicity, vascular dementia, and Alzheimer's disease due to its AChE and AP inhibitory actions.
    Matched MeSH terms: Zebrafish/metabolism
  17. Modeling Parkinson's Disease in Zebrafish
    Najib NHM, Nies YH, Abd Halim SAS, Yahaya MF, Das S, Lim WL, et al.
    CNS Neurol Disord Drug Targets, 2020;19(5):386-399.
    PMID: 32640968 DOI: 10.2174/1871527319666200708124117
    Parkinson's Disease (PD) is one of the most common neurodegenerative disorders that affects the motor system, and includes cardinal motor symptoms such as resting tremor, cogwheel rigidity, bradykinesia and postural instability. Its prevalence is increasing worldwide due to the increase in life span. Although, two centuries since the first description of the disease, no proper cure with regard to treatment strategies and control of symptoms could be reached. One of the major challenges faced by the researchers is to have a suitable research model. Rodents are the most common PD models used, but no single model can replicate the true nature of PD. In this review, we aim to discuss another animal model, the zebrafish (Danio rerio), which is gaining popularity. Zebrafish brain has all the major structures found in the mammalian brain, with neurotransmitter systems, and it also possesses a functional blood-brain barrier similar to humans. From the perspective of PD research, the zebrafish possesses the ventral diencephalon, which is thought to be homologous to the mammalian substantia nigra. We summarize the various zebrafish models available to study PD, namely chemical-induced and genetic models. The zebrafish can complement the use of other animal models for the mechanistic study of PD and help in the screening of new potential therapeutic compounds.
    Matched MeSH terms: Zebrafish*
  18. Fulltext Neuronal connectivity between habenular glutamate-kisspeptin1 co-expressing neurons and the raphe 5-HT system
    Nathan FM, Ogawa S, Parhar IS
    J Neurochem, 2015 Nov;135(4):814-29.
    PMID: 26250886 DOI: 10.1111/jnc.13273
    The habenula, located on the dorsal thalamic surface, is an emotional and reward processing center. As in the mammalian brain, the zebrafish habenula is divided into dorsal (dHb) and ventral (vHb) subdivisions that project to the interpeduncular nucleus and median raphe (MR) respectively. Previously, we have shown that kisspeptin 1 (Kiss1) expressing in the vHb, regulates the serotonin (5-HT) system in the MR. However, the connectivity between the Kiss1 neurons and the 5-HT system remains unknown. To resolve this issue, we generated a specific antibody against zebrafish Kiss1 receptor (Kiss-R1); using this primary antibody we found intense immunohistochemical labeling in the ventro-anterior corner of the MR (vaMR) but not in 5-HT neurons, suggesting the potential involvement of interneurons in 5-HT modulation by Kiss1. Double-fluorescence labeling showed that the majority of habenular Kiss1 neurons are glutamatergic. In the MR region, Kiss1 fibers were mainly seen in close association with glutamatergic neurons and only scarcely within GABAergic and 5-HT neurons. Our findings indicate that the habenular Kiss1 neurons potentially modulate the 5-HT system primarily through glutamatergic neurotransmission via as yet uncharacterized interneurons. The neuropeptide kisspeptin (Kiss1) play a key role in vertebrate reproduction. We have previously shown modulatory role of habenular Kiss1 in the raphe serotonin (5-HT) systems. This study proposed that the habenular Kiss1 neurons modulate the 5-HT system primarily through glutamatergic neurotransmission, which provides an important insight for understanding of the modulation of 5-HT system by the habenula-raphe pathway.
    Matched MeSH terms: Zebrafish; Zebrafish Proteins/genetics; Zebrafish Proteins/metabolism*
  19. Fulltext Kisspeptin1 modulates odorant-evoked fear response via two serotonin receptor subtypes (5-HT1A and 5-HT2) in zebrafish
    Nathan FM, Ogawa S, Parhar IS
    J Neurochem, 2015 Jun;133(6):870-8.
    PMID: 25818845 DOI: 10.1111/jnc.13105
    Kiss1, a neuropeptide predominantly expressed in the habenula, modulates the serotonin (5-HT) system to decrease odorant cue [alarm substance (AS)]-evoked fear behaviour in the zebrafish. The purpose of this study was to assess the interaction of Kiss1 with the 5-HT system as well as to determine the involvement of the 5-HT receptor subtypes in AS-evoked fear. We utilized 0. 28 mg/kg WAY 100635 (WAY), a selective 5-HT1A receptor antagonist, to observe the effects of Kiss1 administration on AS-evoked fear. We found WAY significantly inhibited the anxiolytic effects of Kiss1 (p < 0.001) with an exception of freezing behaviour. Based on this, we utilized 92.79 mg/kg methysergide, a 5-HT1 and 5-HT2 receptor antagonist, and found that methysergide significantly blocked the anxiolytic effects of Kiss1 in the presence of the AS (p < 0.001). From this, we conclude that Kiss1 modulates AS-evoked fear responses mediated by the 5-HT1A and 5-HT2 receptors. Kiss1 peptide intracranially (IC) administrated has been shown to decrease olfactory, alarm substance (AS)-evoked fear response. Blockade of the 5-HT1A receptor utilizing WAY 100635 (0.28 mg/kg) and the 5-HT1 and 5-HT2 receptor utilizing methysergide (92.79 mg/kg) produced increased AS-evoked fear responses that were unable to be overcome even during the recovery period. Blockade of this 5-HT system followed by Kiss1 administration showed that the peptide was unable to recover the anxiolytic effects upon 5-HT1A blocking using WAY 100635 with the exception of freezing behaviour while methysergide significantly blocked all the anxiolytic effects of Kiss1. These findings implicate that Kiss1 could modulate AS-evoked fear responses mediated by 5-HT1A and 5-HT2 receptors.
    Matched MeSH terms: Zebrafish; Zebrafish Proteins/metabolism*
  20. Aggregation, toxicity, and biodegradability study of an ionic liquid-based formulation for effective oil spill remediation
    Nazar M, Ul Hassan Shah M, Ahmad A, Goto M, Zaireen Nisa Yahya W, Moniruzzaman M
    Chemosphere, 2023 Dec;344:140412.
    PMID: 37827466 DOI: 10.1016/j.chemosphere.2023.140412
    Chemical dispersants are extensively used for marine oil spill remediation. However, the increased toxicity and low biodegradability of these dispersants restrict their employment in the marine environment. Hence, in this work, we have developed an eco-friendly formulation composed of an ionic liquid,1-butyl-3-methylimidazolium lauroyl sarcosinate [BMIM][Lausar] and sorbitan monooleate (Span) 80. Micellar and interfacial parameters, dispersion effectiveness, as well as the toxicity and biodegradability of the developed formulation were investigated. Micellar properties confirmed a high degree of synergism among the surfactant molecules and the formation of stable micelle. The dispersion effectiveness, at dispersant-to-oil ratio (DOR) of 1:25 (v/v), against three crude oils (Arab, Ratawi, and Doba) was assessed. We achieved a dispersion effectiveness of 68.49%, 74.05%, and 83.43% for Ratawi, Doba, and Arab crude oil, respectively, using a 70:30 (w/w) ratio of Span 80 to [BMIM][Lausar]. Furthermore, the results obtained from optical microscopy and particle size analysis (PSA) indicated that the oil droplet size decreased with higher DOR. Additionally, acute toxicity experiments were conducted on zebrafish (Danio rerio) using the developed formulation, confirming its non-toxic behavior, with LC50 values of 800 mg/L after 96 h. The formulation also exhibited high biodegradability, with only 25.01% of the original quantity remaining after 28 days. Hence, these results suggest that the new formulation has the potential to be a highly effective and environmentally friendly dispersant for oil spill remediation.
    Matched MeSH terms: Zebrafish
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