visualizing-gatekeeper-evan-s-blue-dye-based-assessment-blood-brain

Visualizing the Gatekeeper: Evan's Blue Dye-Based Assessment of Blood-Brain Barrier Permeability in Adult Zebrafish

The Blood-Brain Barrier (BBB) is a semi-permeable interface that maintains central nervous system (CNS) homeostasis by regulating the movement of ...

International Islamic University Malaysia (IIUM)

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 () 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  and . 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.

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

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.

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

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.

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

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.

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

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.

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

Article	Year
The Promise of the Zebrafish Model for Parkinson's Disease: Today's Science and Tomorrow's Treatment. Frontiers in genetics\| PubMed ID: 33936174	2021
Integrating nutriepigenomics in Parkinson's disease management: New promising strategy in the omics era. IBRO neuroscience reports\| PubMed ID: 36590101	2022
Mitophagy: A Bridge Linking HMGB1 and Parkinson's Disease Using Adult Zebrafish as a Model Organism. Brain sciences\| PubMed ID: 37509008	2023
High-Mobility Group Box 1 (HMGB1) Protein in Parkinson's Disease Research: A 10-Year Bibliometric Analysis. Journal of integrative neuroscience\| PubMed ID: 37519176	2023
Characterizing the adult zebrafish model of Parkinson's disease: a systematic review of dynamic changes in behavior and physiology post-MPTP administration. Frontiers in neuroscience\| PubMed ID: 39319314	2024

Khairiah Razali

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