Characterizing the adult zebrafish model of Parkinson's disease: a systematic review of dynamic changes in behavior and physiology post-MPTP administration.

Introduction: Adult zebrafish are increasingly used in Parkinson's disease (PD) research due to their well-characterized dopaminergic system. Among the toxin-based models, the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is widely utilized to induce parkinsonism in adult zebrafish. Therefore, this review presents an overview of the procedures and the dynamic changes in behavior and physiology observed in the adult zebrafish PD model following a single intraperitoneal injection of MPTP. Methods: A systematic literature search in the PubMed and Google Scholar databases was conducted to identify relevant articles. Of the 165 articles identified, 9 were included in this review. These chosen articles are original works published before March 2024, all of which utilized adult zebrafish induced with MPTP as the model for PD. Other articles were excluded based on factors such as limited relevance, utilization of zebrafish embryos or larvae instead of adults, and variations in MPTP deliveries. Results: Studies indicated that the ideal model entails the utilization of mixed gender zebrafish aged between 4 and 6 months from the wild-type strain. The acceptable MPTP doses ranges between 20 µg/g (lowest) and 225 µg/g (highest) and doses above 292 µg/g are lethal. Furthermore, noticeable parkinsonian symptoms appear 1 day after administration and persist for more than 1 week. Discussion: Mitochondrial dysfunction precedes dopaminergic neurodegeneration within this experimental regime. A single administration of MPTP effectively induces PD in adult zebrafish. This study aids in crafting the adult zebrafish PD model, outlining the progressive behavioral and physiological changes ensuing from MPTP administration.

Bibliometric Analysis of Diagnostic Yield of CT Pulmonary Angiogram (CTPA) in the Diagnosis of Pulmonary Embolism (PE).

CT pulmonary angiography (CTPA) is the investigation of choice for diagnosing pulmonary embolism (PE). Due to the speed and ease of performing the CTPA scans, more clinicians are becoming overly reliant on them, even for patients without strong suspicion of PE. We conducted a bibliometric analysis on the PubMed database from 1990 to 2022 to investigate the literature on the diagnostic yield of CTPA in the diagnosis of PE. A total of 166 articles were published in 98 journals. The number of publications has steadily increased since 2010 and peaked in 2020. Authors from 24 countries contributed to these publications, with the overwhelming majority emanating from United States of America, totaling 66 articles. The authors' contributions were relatively well spread out, with the top four authors publishing the highest number of articles at six each. When we investigated the collaboration between the authors, we found limited multinational and multi-institutional collaborations on this topic. Therefore, more multinational and multi-institutional collaborations will be valuable in future studies. In conclusion, this bibliometric analysis summarizes the literature on diagnostic yield of CTPA in the diagnosis of PE and sheds light on the future pathway that researchers and institutions can focus on.

Mitophagy: A Bridge Linking HMGB1 and Parkinson's Disease Using Adult Zebrafish as a Model Organism.

High-mobility group box 1 (HMGB1) has been implicated as a key player in two critical factors of Parkinson's disease (PD): mitochondrial dysfunction and neuroinflammation. However, the specific role of HMGB1 in PD remains elusive. We investigated the effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration on mitochondrial dysfunction and HMGB1-associated inflammatory genes as well as locomotor activity in zebrafish, aiming to elucidate the role of HMGB1 in PD. Adult zebrafish received MPTP injections, and locomotor activity was measured at 24- and 48-h post-administration. Gene expression levels related to mitophagy (fis1, pink1, and park2) and HMGB1-mediated inflammation (hmgb1, tlr4, and nfkb) were quantified through RT-qPCR analysis. Following MPTP injection, the significant increase in transcript levels of fis1, pink1, and park2 indicated notable changes in PINK1/Parkin mitophagy, while the upregulation of hmgb1, tlr4, and nfkb genes pointed to the activation of the HMGB1/TLR4/NFκB inflammatory pathway. Furthermore, MPTP-injected zebrafish exhibited decreased locomotor activity, evident through reduced distance travelled, mean speed, and increased freezing durations. HMGB1 plays a major role in cellular processes as it is involved in both the mitophagy process and functions as a pro-inflammatory protein. MPTP administration in adult zebrafish activated mitophagy and inflammatory signaling, highlighting the significant role of HMGB1 as a mediator in both processes and further emphasizing its significant contribution to PD pathogenesis.

High-Mobility Group Box 1 (HMGB1) Protein in Parkinson's Disease Research: A 10-Year Bibliometric Analysis.

BACKGROUND: Parkinson's disease (PD), the most prevalent motoric neurodegenerative disease, has been intensively studied to better comprehend its complicated pathogenesis. Chronic neuroinflammation is a major factor contributing to the development of PD. Reportedly, high-mobility group box 1 (HMGB1) protein is capable of mediating neuroinflammatory response. In this regard, knowledge mapping of the research linking HMGB1 to PD is necessary. OBJECTIVE: Herein, we perform a dynamic and longitudinal bibliometric analysis to explore the hotspots and current trends of HMGB1-related PD publications during the past decade. METHODS: All PD publications focusing on HMGB1 protein were retrieved from the PubMed database using the search terms "Parkinson's disease" and "hmgb1". Using filters, only English articles published between 2011 and 2022 were selected. The Bibliometrix and Biblioshiny packages from R software were used to conduct the bibliometric analysis. RESULTS: The filtered search identified 47 articles (34 original articles and 13 review articles), published between 2011 and 2022. There was an increase trend in the number of articles published, with an annual growth rate of 19.35 percent. In terms of research and scientific collaboration in this field, the United States is in the lead, followed by China, Malaysia, and Australia. Compared to other countries, the United States and China had the highest level of collaboration in this research area. Neuroinflammation, microglia, and receptor for advanced glycation end-products (RAGE) represent the top three frontiers and hotspots for HMGB1-related PD research. According to the thematic evolution analysis, over the last decade, PD, HMGB1 and microglia were addressed individually, however, since 2017, these topics were frequently discussed within the same cluster: neuroinflammation. Furthermore, PD, HMGB1, and neuroinflammation domains co-occurred in majority of the research discussion. CONCLUSIONS: The link between HMGB1 and PD was realized a decade ago and becomes increasingly important over time. Our findings can aid scholars in comprehending the global context of HMGB1/PD relationship and provide significant insights for future PD research.

Characterization of neurobehavioral pattern in a zebrafish 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced model: A 96-hour behavioral study.

Parkinson's disease (PD) is the most common brain motor disorder, characterized by a substantial loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Motor impairments, such as dyskinesia, bradykinesia, and resting tremors, are the hallmarks of PD. Despite ongoing research, the exact PD pathogenesis remains elusive due to the disease intricacy and difficulty in conducting human studies. Zebrafish (Danio rerio) has emerged as an ideal model for researching PD pathophysiology. Even though 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been used to induce PD in zebrafish, behavioural findings are frequently limited to a single time point (24 hours post-injection). In this sense, we aim to demonstrate the effects of MPTP on zebrafish swimming behaviour at multiple time points. We administered a single dosage of MPTP (200µg/g bw) via intraperitoneal injection (i/p) and assessed the locomotor activity and swimming pattern at 0h, 24h, and 96h post-injection through an open field test. Analysis of the behaviour revealed significant reductions in swimming velocity (cm/s) and distance travelled (cm), concurrent with an increase in freezing maintenance (duration and bouts) in zebrafish injected with MPTP. In addition, the MPTP-injected zebrafish exhibited complex swimming patterns, as measured by the turn angle, meander, and angular velocity, and showed abnormal swimming phenotypes, including freezing, looping, and erratic movement. To conclude, MPTP administration into adult zebrafish induced hypolocomotion and elicited motor incoordination. Plus, the effects of MPTP were observable 24 hours after the injection and still detectable 96 hours later. These findings contribute to the understanding of MPTP effects on adult zebrafish, particularly in terms of swimming behaviours, and may pave the way for a better understanding of the establishment of PD animal models in the future.

Integrating nutriepigenomics in Parkinson's disease management: New promising strategy in the omics era.

Parkinson's disease (PD) is the most prevalent brain motor disorder and is frequently regarded as an idiopathic and sporadic disease due to its unclear etiology. Although the pathological mechanisms of PD have already been investigated at various omics levels, no disease-modifying drugs are currently available. At the moment, treatments can only provide symptomatic relief to control or improve motor symptoms. Parkinson's disease is a multifactorial disease, the development and progression of which are influenced by multiple factors, including the genetic markups and the environment. As an indispensable component of our daily life, nutrition is considered one of the most robust environmental factors affecting our health. Consequently, depending on our dietary habits, nutrition can either induce or reduce our susceptibility to PD. Epigenetic mechanisms regulate gene expression through DNA methylation, histone modifications, and non-coding RNAs (ncRNAs) activity. Accumulating evidence from nutriepigenomics studies has reported altered epigenetic mechanisms in clinical and pre-clinical PD models, and the potential role of nutrition in modifying the changes. In addition, through nutrigenetics and nutrigenomics studies, the diet-gene, and gene-diet interactions concerning PD development and progression have been investigated. Herein, current findings on the roles of nutrition in epigenetic mechanisms underpinning PD development and progression are discussed. Recent advancements in the multi-omics approach in PD nutrition research are also underlined. The ability of nutrients to influence epigenetic mechanisms and the availability of multi-omics applications compel the immediate use of personalized nutrition as adjuvant therapy for PD.

The Promise of the Zebrafish Model for Parkinson's Disease: Today's Science and Tomorrow's Treatment.

The second most prevalent neurodegenerative disorder in the elderly is Parkinson's disease (PD). Its etiology is unclear and there are no available disease-modifying medicines. Therefore, more evidence is required concerning its pathogenesis. The use of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the basis of most animal models of PD. MPTP is metabolized by monoamine oxidase B (MAO B) to MPP + and induces the loss of dopaminergic neurons in the substantia nigra in mammals. Zebrafish have been commonly used in developmental biology as a model organism, but owing to its perfect mix of properties, it is now emerging as a model for human diseases. Zebrafish (Danio rerio) are cheap and easy to sustain, evolve rapidly, breed transparent embryos in large amounts, and are readily manipulated by different methods, particularly genetic ones. Furthermore, zebrafish are vertebrate species and mammalian findings obtained from zebrafish may be more applicable than those derived from genetic models of invertebrates such as Drosophila melanogaster and Caenorhabditis elegans. The resemblance cannot be taken for granted, however. The goal of the present review article is to highlight the promise of zebrafish as a PD animal model. As its aminergic structures, MPTP mode of action, and PINK1 roles mimic those of mammalians, zebrafish seems to be a viable model for studying PD. The roles of zebrafish MAO, however, vary from those of the two types of MAO present in mammals. The benefits unique to zebrafish, such as the ability to perform large-scale genetic or drug screens, should be exploited in future experiments utilizing zebrafish PD models.