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)

Menoufia University

The adolescent brain has a higher vulnerability to alcoholinduced neurotoxicity, compared to adult's brain. Most studies have investigated the effect of ethanol consumption on the body, however, methanol consumption, which peaked in the last years, is still poorly explored.

Light-Emitting Diode (LED) Therapy Attenuates Neurotoxicity of Methanol-Induced Memory Impairment and Apoptosis in The Hippocampus.

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.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) in which activated immune cells attack the CNS and cause inflammation and demyelination. While the etiology of MS is still largely unknown, the interaction between hormones and the immune system plays a role in disease progression, but the mechanisms by which this occurs are incompletely understood. Several  and  experimental, but also clinical studies, have addressed the possible role of the endocrine system in susceptibility and severity of autoimmune diseases. Although there are several demyelinating models, experimental autoimmune encephalomyelitis (EAE) is the oldest and most commonly used model for MS in laboratory animals which enables researchers to translate their findings from EAE into human. Evidences imply that there is great heterogeneity in the susceptibility to the induction, the method of induction, and the response to various immunological or pharmacological interventions, which led to conflicting results on the role of specific hormones in the EAE model. In this review, we address the role of endocrine system in EAE model to provide a comprehensive view and a better understanding of the interactions between the endocrine and the immune systems in various models of EAE, to open up a ground for further detailed studies in this field by considering and comparing the results and models used in previous studies.

Hormones in experimental autoimmune encephalomyelitis (EAE) animal models.

Schizophrenia remains one of the most chronic and highly disabling mental disorders. Lumateperone is a recent FDA-approved atypical antipsychotic drug for the treatment of schizophrenia. However, the internal FDA pathologist raised concerns regarding pigment deposition associated with degeneration in different tissue in animal studies with lumateperone treatment. The adrenal gland may be implicated in lumateperone side effects, and quercetin may have the ability to fulfill this treatment gap. To prove this hypothesis, 40 male guinea pigs were used and divided into four groups; control, quercetin-treated, lumateperone-treated, and quercetin/lumateperone cotreated orally for 28 consecutive days. Behavioral forced swim (FST) and open field (OF) tests were done at the end of treatment. Retro-orbital blood samples were taken to assess hormones: adrenocorticotropic hormone (ACTH), cortisol, dehydroepiandrosterone acetate (DHEA), and aldosterone, along with an assessment of oxidative stress parameters: malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD). Adrenal glands were extracted for histopathological assessment with H&E, Mallory trichome staining, immunostaining, and electron microscopy studies. Lumateperone-treated group showed a significant reduction in the activity in FST and OF with histopathological deterioration in adrenal secretory function and structure and increased expression of interleukin-6 (IL-6), CASPASE-3, collagen deposition, and decreased proliferating cell nuclear antigen (PCNA). Cytoplasmic vacuolation, pyknosis of the nuclei, increase in the lysosome, lipofuscin pigment, and cellular infiltration with diminishing in the number of secretory granules could all be observed in lumateperone-treated group. Coadministration of quercetin and lumateperone showed improvement of the previously deteriorated parameters. Quercetin had a prophylactic effect against lumateperone depressive-like effect on animal behavior and its possible adrenal damage. Graphical AbstractConceptual framework for the proposed mechanism of action of coadministration of quercetin and lumateperone.

Atypical Antipsychotic Lumateperone Effects on the Adrenal Gland With Possible Beneficial Effect of Quercetin Co-administration.

Cognitive enhancement is defined as the augmentation of the mind's core capabilities through the improvement of internal or external information processing systems. Recently, the focus has shifted to the potential therapeutic effects of natural products in improving cognitive function. Edible bird's nest (EBN) is a natural food substance derived from the saliva of swiftlets. Until today, EBN is regarded as a high-priced nutritious food with therapeutic effects. The effectiveness of dietary EBN supplementation to enhance brain development in mammals has been documented. Although the neuroprotection of EBN has been previously reported, however, the impact of EBN on learning and memory control and its potential as a cognitive enhancer drug remains unknown. Thus, this article aims to address the neuroprotective benefits of EBN and its potential effect as a cognitive enhancer. Notably, the current challenges and the future study direction in EBN have been demonstrated.

Edible Bird's Nest as a Potential Cognitive Enhancer.

The Glycoprotein GPNMB: A Secret Ingredient for Understanding Parkinson's Disease Etiology?

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.

Glia, which was formerly considered to exist just to connect neurons, now plays a key function in a wide range of physiological events, including formation of memory, learning, neuroplasticity, synaptic plasticity, energy consumption, and homeostasis of ions. Glial cells regulate the brain's immune responses and confers nutritional and structural aid to neurons, making them an important player in a broad range of neurological disorders. Alzheimer's, ALS, Parkinson's, frontotemporal dementia (FTD), and epilepsy are a few of the neurodegenerative diseases that have been linked to microglia and astroglia cells, in particular. Synapse growth is aided by glial cell activity, and this activity has an effect on neuronal signalling. Each glial malfunction in diverse neurodegenerative diseases is distinct, and we will discuss its significance in the progression of the illness, as well as its potential for future treatment.

Neurodegeneration and inflammation crosstalk: Therapeutic targets and perspectives.

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.

Neurodegenerative disorders (NDs) cause progressive neuronal loss and are a significant public health concern, with NDs projected to become the second leading global cause of death within two decades. Huntington's disease (HD) is a rare, progressive ND caused by an autosomal-dominant mutation in the huntingtin () gene, leading to severe neuronal loss in the brain and resulting in debilitating motor, cognitive, and psychiatric symptoms. Given the complex pathology of HD, biomarkers are essential for performing early diagnosis, monitoring disease progression, and evaluating treatment efficacy. However, the identification of consistent HD biomarkers is challenging due to the prolonged premanifest HD stage, HD's heterogeneous presentation, and its multiple underlying biological pathways. This study involves a 10-year bibliometric analysis of HD biomarker research, revealing key research trends and gaps. The study also features a comprehensive literature review of emerging HD biomarkers, concluding the need for better stratification of HD patients and well-designed longitudinal studies to validate HD biomarkers. Promising candidate wet HD biomarkers- including neurofilament light chain protein (NfL), microRNAs, the mutant HTT protein, and specific metabolic and inflammatory markers- are discussed, with emphasis on their potential utility in the premanifest HD stage. Additionally, biomarkers reflecting brain structural deficits and motor or behavioral impairments, such as neurophysiological (e.g., motor tapping, speech, EEG, and event-related potentials) and imaging (e.g., MRI, PET, and diffusion tensor imaging) biomarkers, are evaluated. The findings underscore that the discovery and validation of reliable HD biomarkers urgently require improved patient stratification and well-designed longitudinal studies. Reliable biomarkers, particularly in the premanifest HD stage, are crucial for optimizing HD clinical management strategies, enabling personalized treatment approaches, and advancing clinical trials of HD-modifying therapies.

Advances in Huntington's Disease Biomarkers: A 10-Year Bibliometric Analysis and a Comprehensive Review.

The genetic architecture of Parkinson's disease (PD) varies considerably across ancestries, yet most genetic studies have focused on individuals of European descent, limiting our insights into the genetic architecture of PD at a global scale.

The Global Landscape of Genetic Variation in Parkinson's disease: Multi-Ancestry Insights into Established Disease Genes and their Translational Relevance.

Article	Year
Light-Emitting Diode (LED) Therapy Attenuates Neurotoxicity of Methanol-Induced Memory Impairment and Apoptosis in The Hippocampus. CNS & neurological disorders drug targets\| PubMed ID: 29968547	2018
The Promise of the Zebrafish Model for Parkinson's Disease: Today's Science and Tomorrow's Treatment. Frontiers in genetics\| PubMed ID: 33936174	2021
Hormones in experimental autoimmune encephalomyelitis (EAE) animal models. Translational neuroscience\| PubMed ID: 34046214	2021
Atypical Antipsychotic Lumateperone Effects on the Adrenal Gland With Possible Beneficial Effect of Quercetin Co-administration. Frontiers in physiology\| PubMed ID: 34276400	2021
Edible Bird's Nest as a Potential Cognitive Enhancer. Frontiers in neurology\| PubMed ID: 35599726	2022
The Glycoprotein GPNMB: A Secret Ingredient for Understanding Parkinson's Disease Etiology? Movement disorders : official journal of the Movement Disorder Society\| PubMed ID: 36321268	2022
Integrating nutriepigenomics in Parkinson's disease management: New promising strategy in the omics era. IBRO neuroscience reports\| PubMed ID: 36590101	2022
Neurodegeneration and inflammation crosstalk: Therapeutic targets and perspectives. IBRO neuroscience reports\| PubMed ID: 37388502	2023
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
Advances in Huntington's Disease Biomarkers: A 10-Year Bibliometric Analysis and a Comprehensive Review. Biology\| PubMed ID: 40001897	2025
The Global Landscape of Genetic Variation in Parkinson's disease: Multi-Ancestry Insights into Established Disease Genes and their Translational Relevance. medRxiv : the preprint server for health sciences\| PubMed ID: 40672482	2025
Neuroscience in Asia-Pacific : Horizons and Innovations. IBRO neuroscience reports\| PubMed ID: 40934064	2025

Wael Mohamed

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