Model For Biomedical Research Research Articles

Review of Pseudoloma neurophilia (Microsporidia): A common neural parasite of laboratory zebrafish (Danio rerio).

Zebrafish (Danio rerio) is now the second most used animal model in biomedical research. As with other vertebrate models, underlying diseases and infections often impact research. Beyond mortality and morbidity, these conditions can compromise research end points by producing nonprotocol induced variation within experiments. Pseudoloma neurophilia, a microsporidium that targets the central nervous system, is the most frequently diagnosed pathogen in zebrafish facilities. The parasite undergoes direct, horizontal transmission within populations, and is also maternally transmitted with spores in ovarian fluid and occasionally within eggs. This transmission explains the wide distribution among research laboratories as new lines are generally introduced as embryos. The infection is chronic, and fish apparently never recover following the initial infection. However, most fish do not exhibit outward clinical signs. Histologically, the parasite occurs as aggregates of spores throughout the midbrain and spinal cord and extends to nerve roots. It often elicits meninxitis, myositis, and myodegeneration when it infects the muscle. There are currently no described therapies for the parasite, thus the infection is best avoided by screening with PCR-based tests and removal of infected fish from a facility. Examples of research impacts include reduced fecundity, behavioral changes, transcriptome alterations, and autofluorescent lesions.

Expression and secretion of SPARC, FGF-21 and DCN in bovine muscle cells: Effects of age and differentiation.

Skeletal muscle growth is an economically important trait in the cattle industry. Secreted muscle-derived proteins, referred to as myokines, have important roles in regulating the growth, metabolism, and health of skeletal muscle in human and biomedical research models. Accumulating evidence supports the importance of myokines in skeletal muscle and whole-body health, though little is known about the potential presence and functional significance of these proteins in cattle. This study evaluates and confirms that secreted proteins acidic and rich in cysteine (SPARC), fibroblast growth factor 21 (FGF-21), myostatin (MSTN), and decorin (DCN) are expressed and SPARC, FGF-21, and DCN are secreted by primary bovine satellite cells from 3- (BSC3; n = 3) and 11- (BSC11; n = 3) month -old commercial angus steers. Cells were cultured and collected at zero, 12, 24, and 48 hours to characterize temporal expression and secretion from undifferentiated and differentiated cells. The expression of SPARC was higher in the undifferentiated (p = 0.04) and differentiated (p = 0.07) BSC11 than BSC3. The same was observed with protein secretion from undifferentiated (p <0.0001) BSC11 compared to BSC3. Protein secretion of FGF-21 was higher in undifferentiated BSC11 (p < 0.0001) vs. BSC3. DCN expression was higher in differentiated BSC11 (p = 0.006) vs. BSC3. Comparing undifferentiated vs. differentiated BSC, MSTN expression was higher in differentiated BSC3 (p ≤ 0.001) for 0, 12, and 24 hours and in BSC11 (p ≤ 0.03) for 0, 12, 24, and 48 hours. There is also a change over time for SPARC expression (p ≤ 0.03) in undifferentiated and differentiated BSC and protein secretion (p < 0.0001) in undifferentiated BSC, as well as FGF-21 expression (p = 0.007) in differentiated BSC. This study confirms SPARC, FGF-21, and DCN are secreted, and SPARC, FGF-21, MSTN, and DCN are expressed in primary bovine muscle cells with age and temporal differences.

Addressing the Challenges of Traditional, Complementary, and Integrative Medicine Research: An International Perspective and Proposed Strategies Moving Forward

Traditional, complementary, and integrative medicine (TCIM) encompasses a broad range of healthcare practices beyond conventional Western medicine. Despite its use globally and increased research, many TCIM research challenges persist impeding its progress and integration into clinical practice. Key challenges involve financial constraints, insufficient research training and educational support, and the methodological barriers which arise from a lack of standardization. Financial limitations hinder investment into crucial research limiting both the quantity and quality of TCIM research. Inadequate training in research and educational support limit the development of TCIM research, hindering growth and recognition of TCIM in academic and clinical settings. The inherent dynamic nature of TCIM therapies poses additional challenges for applying standardized biomedical research models. These challenges not only impede the advancement of TCIM research but also perpetuate negative attitudes and biases within the healthcare and research communities. To overcome these challenges, a comprehensive strategy is necessary to increase funding, improve literacy, and the promotion of open science practices in TCIM. Addressing these confounding factors will enable well-informed TCIM research literacy and the development of TCIM skills and facilitate the integration of evidence based TCIM therapies into a more inclusive healthcare domain, ultimately reducing negative attitudes and biases towards TCIM.

Bridging the Gap: Integrating 3D Bioprinting and Microfluidics for Advanced Multi-Organ Models in Biomedical Research

Recent advancements in 3D bioprinting and microfluidic lab-on-chip systems offer promising solutions to the limitations of traditional animal models in biomedical research. Three-dimensional bioprinting enables the creation of complex, patient-specific tissue models that mimic human physiology more accurately than animal models. These 3D bioprinted tissues, when integrated with microfluidic systems, can replicate the dynamic environment of the human body, allowing for the development of multi-organ models. This integration facilitates more precise drug screening and personalized therapy development by simulating interactions between different organ systems. Such innovations not only improve predictive accuracy but also address ethical concerns associated with animal testing, aligning with the three Rs principle. Future directions include enhancing bioprinting resolution, developing advanced bioinks, and incorporating AI for optimized system design. These technologies hold the potential to revolutionize drug development, regenerative medicine, and disease modeling, leading to more effective, personalized, and humane treatments.

In vitro matured oocytes have a higher developmental potential than in vivo matured oocytes after hormonal ovarian stimulation in Callithrix jacchus

BackgroundThe common marmoset, Callithrix jacchus, is an invaluable model in biomedical research. Its use includes genetic engineering applications, which require manipulations of oocytes and production of embryos in vitro. To maximize the recovery of oocytes suitable for embryo production and to fulfil the requirements of the 3R principles to the highest degree possible, optimization of ovarian stimulation protocols is crucial. Here, we compared the efficacy of two hormonal ovarian stimulation approaches: 1) stimulation of follicular growth with hFSH followed by triggering of oocyte maturation with hCG (FSH + hCG) and 2) stimulation with hFSH only (FSH-priming).MethodsIn total, 14 female marmosets were used as oocyte donors in this study. Each animal underwent up to four surgical interventions, with the first three performed as ovum pick-up (OPU) procedures and the last one being an ovariohysterectomy (OvH). In total, 20 experiments were carried out with FSH + hCG stimulation and 18 with FSH-priming. Efficacy of each stimulation protocol was assessed through in vitro maturation (IVM), in vitro fertilization (IVF) and embryo production rates.ResultsEach study group consisted of two subgroups: the in vivo matured oocytes and the oocytes that underwent IVM. Surprisingly, in the absence of hCG triggering some of the oocytes recovered were at the MII stage, moreover, their number was not significantly lower compared to FSH + hCG stimulation (2.8 vs. 3.9, respectively (ns)). While the IVM and IVF rates did not differ between the two stimulation groups, the IVF rates of in vivo matured oocytes were significantly lower compared to in vitro matured ones in both FSH-priming and FSH + hCG groups. In total, 1.7 eight-cell embryos/experiment (OPU) and 2.1 eight-cell embryos/experiment (OvH) were obtained after FSH + hCG stimulation vs. 1.8 eight-cell embryos/experiment (OPU) and 5.0 eight-cell embryos/experiment (OvH) following FSH-priming. These numbers include embryos obtained from both in vivo and in vitro matured oocytes.ConclusionA significantly lower developmental competence of the in vivo matured oocytes renders triggering of the in vivo maturation with hCG as a part of the currently used FSH-stimulation protocol unnecessary. In actual numbers, between 1 and 7 blastocysts were obtained following each FSH-priming. In the absence of further studies, FSH-priming appears superior to FSH + hCG stimulation in the common marmoset under current experimental settings.

Gastric emphysema and pneumatosis intestinalis in two common marmosets with duodenal dilation syndrome

BackgroundCommon marmosets (Callithrix jacchus) are widely used as primate experimental models in biomedical research. Duodenal dilation with chronic vomiting in captive common marmosets is a recently described life-threatening syndrome that is problematic for health control. However, the pathogenesis and cause of death are not fully understood.Case presentationWe report two novel necropsy cases in which captive common marmosets were histopathologically diagnosed with gastric emphysema (GE) and pneumatosis intestinalis (PI). Marmoset duodenal dilation syndrome was confirmed in each case by clinical observation of chronic vomiting and by gross necropsy findings showing a dilated, gas-filled and fluid-filled descending duodenum that adhered to the ascending colon. A diagnosis of GE and PI was made on the basis of the bubble-like morphology of the gastric and intestinal mucosa, with histological examination revealing numerous vacuoles diffused throughout the lamina propria mucosae and submucosa. Immunostaining for prospero homeobox 1 and CD31 distinguished gas cysts from blood and lymph vessels. The presence of hepatic portal venous gas in case 1 and possible secondary bacteremia-related septic shock in case 2 were suggested to be acute life-threatening abdominal processes resulting from gastric emphysema and pneumatosis intestinalis.ConclusionsIn both cases, the gross and histopathological findings of gas cysts in the GI tract walls matched the features of human GE and PI. These findings contribute to clarifying the cause of death in captive marmosets that have died of gastrointestinal diseases.

Biomedical Researchers Should be Taught Statistics Differently than Biostatisticians in Training: Illustration of a Module within a Clinical Research Seminar Course

The predominant model for biomedical research is team science. Two critical members of the team are the clinical investigator and the biostatistician. Typically, the biostatistician performs statistical analyses and the clinical investigator interprets the results. Clinical investigators have different background and interests than biostatisticians, and should be taught statistics differently. Concepts should be phrased in plain language, illustrations should replace mathematical derivations, and underlying statistical concepts should be explicitly named. Consistent with basic principles of constructivism, clinical investigators and biostatisticians will (and should) have different but overlapping mental maps of statistics. Our approach is illustrated through the description of a module within a research seminar course for clinical investigators.

Genetic characterization of a captive marmoset (Callithrix jacchus) colony using genotype-by-sequencing.

The marmoset is a fundamental nonhuman primate model for the study of aging, neurobiology, and many other topics. Genetic management of captive marmoset colonies is complicated by frequent chimerism in the blood and other tissues, a lack of tools to enable cost-effective, genome-wide interrogation of variation, and historic mergers and migrations of animals between colonies. We implemented genotype-by-sequencing (GBS) of hair follicle derived DNA (a minimally chimeric DNA source) of 82 marmosets housed at the Southwest National Primate Research Center (SNPRC). Our primary goals were the genetic characterization of our marmoset population for pedigree verification and colony management and to inform the scientific community of the functional genetic makeup of this valuable resource. We used the GBS data to reconstruct the genetic legacy of recent mergers between colonies, to identify genetically related animals whose relationships were previously unknown due to incomplete pedigree information, and to show that animals in the SNPRC colony appear to exhibit low levels of inbreeding. Of the >99,000 single-nucleotide variants (SNVs) that we characterized, >9800 are located within gene regions known to harbor pathogenic variants of clinical significance in humans. Overall, we show the combination of low-resolution (sparse) genotyping using hair follicle DNA is a powerful strategy for the genetic management of captive marmoset colonies and for identifying potential SNVs for the development of biomedical research models.

Complete Genomic Assembly of Mauritian Cynomolgus Macaque Killer Ig-like Receptor and Natural Killer Group 2 Haplotypes.

Mauritian-origin cynomolgus macaques (MCMs) serve as a powerful nonhuman primate model in biomedical research due to their unique genetic homogeneity, which simplifies experimental designs. Despite their extensive use, a comprehensive understanding of crucial immune-regulating gene families, particularly killer Ig-like receptors (KIR) and NK group 2 (NKG2), has been hindered by the lack of detailed genomic reference assemblies. In this study, we employ advanced long-read sequencing techniques to completely assemble eight KIR and seven NKG2 genomic haplotypes, providing an extensive insight into the structural and allelic diversity of these immunoregulatory gene clusters. Leveraging these genomic resources, we prototype a strategy for genotyping KIR and NKG2 using short-read, whole-exome capture data, illustrating the potential for cost-effective multilocus genotyping at colony scale. These results mark a significant enhancement for biomedical research in MCMs and underscore the feasibility of broad-scale genetic investigations.

Ultrasonography of the neotropical primate female reproductive system.

The Neotropical (e. g., Aotus sp., Callithrix jacchus, Saguinus sp., Saimiri sp., and Sapajus sp.) primates are important models for biomedical research and studies on reproductive physiology and biotechnology. Consequently, studies about gynecological and obstetric ultrasonography are crucial. B-mode ultrasonography is a non-invasive imaging technique that provides real-time bidimensional or three-dimensional/four-dimensional B-mode images. In association with Doppler ultrasonography, B-mode ultrasonography can also be used to monitor the mammalian blood flow to the reproductive tract during important events such as ovulation and gestation. Thus, gynecological and obstetric ultrasonography is essential for establishing the female reproductive anatomical and physiological ovarian and uterine health status, gestational diagnosis, and fetal growth monitoring. For instance, the paper presents and discusses the state-of-the-art gynecological and obstetric ultrasonography in the Neotropical primates, species that are models for biomedical research, and some recent studies on species targets for conservation strategies for wild animal populations.

Gen expression of Bax and Bcl-2 in Cynomolgus monkeys (Macaca fascicularis) as animal model for Papillomavirus study

Cervical cancer is one of the fourth cancers in the world that occurs in women. Papillomavirus infection has been reported as one of the causative agents of cervical cancer. Apoptotic mechanism is one of the signs of cancer. Cynomolgus monkeys have been widely used as animal models in biomedical research because they are similar to humans in terms of genetics, anatomy, and physiology compared to other animals. Previous studies reported that cynomolgus monkeys have undergone spontaneous infection by papillomavirus, but this infection did not show the phenomenon of cervical cancer. This study aimed to evaluate the prediction of papillomavirus-infected cervical cancer through apoptotic mechanisms regulated by Bax and Bcl-2 genes. Gene expression was performed in this study using Real-Time PCR technique. The results showed an increase in Bax and Bcl-2 gene expression in positive group cynomolgus monkeys with papillomavirus infection. Bcl-2 as anti-apoptotic gene expression increased significantly higher than Bax as pro-apoptotic gene. Bax and Bcl-2 have potential as biomarkers to predict the phenomenon of cervical cancer in cynomolgus monkeys with papillomavirus infection.

Alternatives of Animal Models for Biomedical Research: a Comprehensive Review of Modern Approaches.

Biomedical research has long relied on animal models to unravel the intricacies of human physiology and pathology. However, concerns surrounding ethics, expenses, and inherent species differences have catalyzed the exploration of alternative avenues. The contemporary alternatives to traditional animal models in biomedical research delve into three main categories of alternative approaches: in vitro models, in vertebrate models, and in silico models. This unique approach to artificial intelligence and machine learning has been a keen interest to be used in different biomedical research. The main goal of this review is to serve as a guide to researchers seeking novel avenues for their investigations and underscores the importance of considering alternative models in the pursuit of scientific knowledge and medical breakthroughs, including showcasing the broad spectrum of modern approaches that are revolutionizing biomedical research and leading the way toward a more ethical, efficient, and innovative future. Models can insight into cellular processes, developmental biology, drug interaction, assessing toxicology, and understanding molecular mechanisms.

Integrated meta-omics reveals the regulatory landscape involved in lipid metabolism between pig breeds

BackgroundDomesticated pigs serve as an ideal animal model for biomedical research and also provide the majority of meat for human consumption in China. Porcine intramuscular fat content associates with human health and diseases and is essential in pork quality. The molecular mechanisms controlling lipid metabolism and intramuscular fat accretion across tissues in pigs, and how these changes in response to pig breeds, remain largely unknown.ResultsWe surveyed the tissue-resident cell types of the porcine jejunum, colon, liver, and longissimus dorsi muscle between Lantang and Landrace breeds by single-cell RNA sequencing. Combining lipidomics and metagenomics approaches, we also characterized gene signatures and determined key discriminating markers of lipid digestibility, absorption, conversion, and deposition across tissues in two pig breeds. In Landrace, lean-meat swine mainly exhibited breed-specific advantages in lipid absorption and oxidation for energy supply in small and large intestinal epitheliums, nascent high-density lipoprotein synthesis for reverse cholesterol transport in enterocytes and hepatocytes, bile acid formation, and secretion for fat emulsification in hepatocytes, as well as intestinal-microbiota gene expression involved in lipid accumulation product. In Lantang, obese-meat swine showed a higher synthesis capacity of chylomicrons responsible for high serum triacylglycerol levels in small intestinal epitheliums, the predominant characteristics of lipid absorption in muscle tissue, and greater intramuscular adipcytogenesis potentials from muscular fibro-adipogenic progenitor subpopulation.ConclusionsThe findings enhanced our understanding of the cellular biology of lipid metabolism and opened new avenues to improve animal production and human diseases.D7xkEMpXE5aNHjWuhXhcDpVideo

A review of the reproductive biology of mormyroidfishes: An emerging model for biomedical research.

Mormyroidea is a superfamily of weakly electric African fishes with great potential as a model in a variety of biomedical research areas including systems neuroscience, muscle cell and craniofacial development, ion channel biophysics, and flagellar/ciliary biology. However, they are currently difficult to breed in the laboratory setting, which is essential for any tractable model organism. As such, there is a need to better understand the reproductive biology of mormyroids to breed them more reliably in the laboratory to effectively use them as a biomedical research model. This review seeks to (1)briefly highlight the biomedically relevant phenotypes of mormyroids and (2) compile information about mormyroid reproduction including sex differences, breeding season, sexual maturity, gonads, gametes, and courtship/spawning behaviors. We also highlight areas of mormyroid reproductive biology that are currently unexplored and/or have the potential for further investigation that may provide insights into more successful mormyroid laboratory breeding methods.

Importance of Zebrafish as a Non-Mammalian Vertebrate Model for Studying Neurodegenerative Disorders Using Ayurvedic Medicinal Plants: A Review

Alzheimer's disease and Parkinson's disease are debilitating neurodegenerative disorders that impose a significant burden on the affected individuals and the society as a whole. Despite extensive research efforts, effective treatments for these diseases remain elusive till date. Ayurveda, a traditional system of medicinal practice which originated in ancient India, has long touted the potential of various plants possessing neuroprotective properties. The effects of a few relevant Ayurvedic plants viz. Guduchi, Kapikachhu, Shankhapushpi, Turmeric, Mandukparni, Ashwagadha, Brahmi, Jatamansi etc. on several non-human primates and rodents have been reported. The therapeutic potential of those plants to mitigate the pathological hallmarks associated with Alzheimer's disease and Parkinson's disease was assessed. We have outlined the most recent research on Ayurveda's effects on neurodegenerative brain illnesses in this review article, with an emphasis on Alzheimer's disease and Parkinson's disease. As the zebrafish (Danio rerio Hamilton) has emerged as a useful, non-mammalian vertebrate model organism for studying a wide range of diseases, the effect of few other medicinal plants on zebrafish was also mentioned. Powerful live imaging and genetic tools which is currently available for zebrafish has transformed this fish to a top model in biomedical research and toxicity testing. However, further research is needed to elucidate the precise mechanisms of action and to translate these promising results into clinical applications. The exploration of traditional medicinal systems, in conjunction with modern scientific methodologies using novel model organisms, such as zebrafish offers a valuable avenue for the development of innovative treatments for neurodegenerative disorders.

Establishment of a Practical Sperm Cryopreservation Pathway for the Axolotl (Ambystoma mexicanum): A Community-Level Approach to Germplasm Repository Development.

The axolotl (Ambystoma mexicanum) draws great attention around the world for its importance as a biomedical research model, but housing and maintaining live animals is increasingly expensive and risky as new transgenic lines are developed. The goal of this work was to develop an initial practical pathway for sperm cryopreservation to support germplasm repository development. The present study assembled a pathway through the investigation of axolotl sperm collection by stripping, refrigerated storage in various osmotic pressures, cryopreservation in various cryoprotectants, and in vitro fertilization using thawed sperm. By the stripping of males, 25-800 µL of sperm fluid was collected at concentrations of 1.6 × 106 to 8.9 × 107 sperm/mL. Sperm remained motile for 5 d in Hanks' Balanced Salt Solution (HBSS) at osmolalities of 100-600 mOsm/kg. Sperm cryopreserved in 0.25 mL French straws at 20 °C/min in a final concentration of 5% DMFA plus 200 mM trehalose and thawed at 25 °C for 15 s resulted in 52 ± 12% total post-thaw motility. In six in vitro fertilization trials, 20% of eggs tested with thawed sperm continued to develop to stage 7-8 after 24 h, and a third of those embryos (58) hatched. This work is the first report of successful production of axolotl offspring with cryopreserved sperm, providing a general framework for pathway development to establish Ambystoma germplasm repositories for future research and applications.

Morphometric Analysis of Growth in Captive-bred Pig-tailed macaque (Macaca nemestrina Linnaeus 1766)

ABSTRACT&#x0D; The pig-tailed macaque has a high vulnerability to human infectious disease pathogens as well as nonhuman primate viruses, making it a good animal model for biomedical research. The goals of this research are to better understand the morphometric and growth rate variations between male and female pig-tailed macaques living in tropical captivity as their natural climate, which will be useful in developing research techniques as well as modifying and developing equipment and instruments.&#x0D; The research was carried out on captive pig-tailed macaques born and kept at the Research Animal Facility in Lodaya (RAF-L) Primate Research Center IPB University (PRC-IPB). The characteristics were separated into four categories: head size, torso, upper limb, and lower limb. During the study period, 70 animals were measured, 32 males and 38 females. The repetition of measurements at distinct timepoints according to body development varies for each individual depending on the animal's situation at that time.&#x0D; There was no visible difference in body and extremity sizes between male and female animals between the ages of 1 and 4 years. Males' head proportions appear to expand consistently in height and width after they are beyond 2 years old, in contrast to females. The growth trend of females tends to decrease from one year of age until sexual maturity, in contrast to males which show a growth spurt at the ages of 1 and 4 years. Differences in size and growth rate indicating sexual dimorphism are visible after the female reaches sexual maturity.&#x0D;

Study of tree shrew biology and models: A booming and prosperous field for biomedical research.

The tree shrew ( Tupaia belangeri) has long been proposed as a suitable alternative to non-human primates (NHPs) in biomedical and laboratory research due to its close evolutionary relationship with primates. In recent years, significant advances have facilitated tree shrew studies, including the determination of the tree shrew genome, genetic manipulation using spermatogonial stem cells, viral vector-mediated gene delivery, and mapping of the tree shrew brain atlas. However, the limited availability of tree shrews globally remains a substantial challenge in the field. Additionally, determining the key questions best answered using tree shrews constitutes another difficulty. Tree shrew models have historically been used to study hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, myopia, and psychosocial stress-induced depression, with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases. Despite these efforts, the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research. This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model. We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies. The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models, meeting the increasing demands of life science and biomedical research.

Identification of novel mammalian viruses in tree shrews ( Tupaia belangeri chinensis).

The Chinese tree shrew ( Tupaia belangeri chinensis), a member of the mammalian order Scandentia, exhibits considerable similarities with primates, including humans, in aspects of its nervous, immune, and metabolic systems. These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer, infectious diseases, metabolic disorders, and mental health conditions. Herein, we used meta-transcriptomic sequencing to analyze plasma, as well as oral and anal swab samples, from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses. In total, eight mammalian viruses with complete genomes were identified, belonging to six viral families, including Flaviviridae, Hepeviridae, Parvovirinae, Picornaviridae, Sedoreoviridae, and Spinareoviridae. Notably, the presence of rotavirus was recorded in tree shrews for the first time. Three viruses - hepacivirus 1, parvovirus, and picornavirus - exhibited low genetic similarity (<70%) with previously reported viruses at the whole-genome scale, indicating novelty. Conversely, three other viruses - hepacivirus 2, hepatovirus A and hepevirus - exhibited high similarity (>94%) to known viral strains. Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants. These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews, highlighting the necessity for further research into their potential for cross-species transmission.

Understanding zebrafish sleep and wakefulness physiology as an experimental model for biomedical research.

Sleep is a globally observable fact, or period of reversible distracted rest, that can be distinguished from arousal by various behavioral criteria. Although the function of sleep is an evolutionarily conserved behavior, its mechanism is not yet clear. The zebrafish (Danio rerio) has become a valuable model for neurobehavioral studies such as studying learning, memory, anxiety, and depression. It is characterized by a sleep-like state and circadian rhythm, making it comparable to mammals. Zebrafish are a good model for behavioral studies because they share genetic similarities with humans. A number of neurotransmitters are involved in sleep and wakefulness. There is a binding between melatonin and the hypocretin system present in zebrafish. The full understanding of sleep and wakefulness physiology in zebrafish is still unclear among researchers. Therefore, to make a clear understanding of the sleep/wake cycle in zebrafish, this article covers the mechanism involved behind it, and the role of the neuromodulator system followed by the mechanism of the HPA axis.