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The zebrafish (Danio rerio) is routinely used in biological studies as a vertebrate model system that provides unique strengths allowing applications in studies of neurodevelopmental and neurodegenerative diseases. One specific advantage is that the neurotransmitter systems are highly conserved throughout vertebrate evolution, including between zebrafish and humans. Disruption of the dopaminergic signaling pathway is linked to multiple neurological disorders. One of the most common is Parkinson’s disease, a neurodegenerative disease associated with the loss of dopaminergic neurons, among other neuropathological characteristics. In this review, the development of the zebrafish’s dopaminergic system, focusing on genetic control of the dopaminergic system, is detailed. Second, neurotoxicant models used to study dopaminergic neuronal loss, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the pesticides paraquat and rotenone, and 6-hydroxydopamine (6-OHDA), are described. Next, zebrafish genetic knockdown models of dj1, pink1, and prkn established for investigating mechanisms of Parkinson’s disease are discussed. Chemical modulators of the dopaminergic system are also highlighted to showcase the applicability of the zebrafish to identify mechanisms and treatments for neurodegenerative diseases such as Parkinson’s disease associated with the dopaminergic system.

Neurotransmission is the basis of neuronal communication and is critical for normal brain development, behavior, learning, and memory. Exposure to drugs and chemicals can alter neurotransmission, often through unknown pathways and mechanisms. The zebrafish (Danio rerio) model system is increasingly being used to study the brain and chemical neurotoxicity. In this review, the major neurotransmitter systems, including glutamate, GABA, dopamine, norepinephrine, serotonin, acetylcholine, histamine, and glutamate are surveyed and pathways of synthesis, transport, metabolism, and action are examined. Differences between human and zebrafish neurochemical pathways are highlighted. We also review techniques for evaluating neurological function, including the measurement of neurotransmitter levels, assessment of gene expression through transcriptomic analysis, and the recording of neurobehavior. Finally examples of chemical toxicity studies evaluating alterations in neurotransmitter systems in the zebrafish model are reviewed.

Atrazine is an herbicide commonly used on crops to prevent broadleaf weeds. Atrazine is an endocrine-disrupting chemical mainly targeting the neuroendocrine system and associated axes, especially as a reproductive toxicant through attenuation of the luteinizing hormone (LH). Current regulatory levels for chronic exposure are based on no observed adverse effect levels (NOAELs) of these LH alterations in rodent studies. Atrazine has also been studied for its effects on the central nervous system and neurotransmission. The European Union (EU) recognized the health risks of atrazine exposure as a public health concern with no way to contain contamination of drinking water. As such, the EU banned atrazine use in 2003. The United States recently reapproved atrazine’s use in the fall of 2020. Research has shown that there is a wide array of adverse health effects that are seen across multiple models, exposure times, and exposure periods leading to dysfunction in many different systems in the body with most pointing to a neuroendocrine target of toxicity. There is evidence of crosstalk between systems that can be affected by atrazine exposure, causing widespread dysfunction and leading to changes in behavior even with no direct link to the hypothalamus. The hypothetical mechanism of toxicity of atrazine endocrine disruption and neurotoxicity can therefore be described as a web of pathways that are influenced through changes occurring in each and their multiple feedback loops with further research needed to refine NOAELs for neurotoxic outcomes.

Antiretroviral therapy (ART) is a lifesaver for individual patients treated for Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS). Maintaining optimal adherence to antiretroviral drugs is essential for HIV infection management. This study aimed to understand the factors influencing adherence amongst ART-prescribed patients and care providers in Nepal. A cross-sectional mixed-methods study surveying 330 ART-prescribed patients and 34 in-depth interviews with three different types of stakeholders: patients, care providers, and key people at policy level. Adherence was assessed through survey self-reporting and during the interviews. A multivariate logistic regression model was used to identify factors associated with adherence, supplemented with a thematic analysis of the interview transcripts. A total of 282 (85.5%) respondents reported complete adherence, i.e. no missed doses in the four-weeks prior to interview. Major factors influencing adherence were: non-disclosure of HIV status (OR = 17.99, p = 0.014); alcohol use (OR = 12.89, p = <0.001), being female (OR = 6.91, p = 0.001), being illiterate (OR = 4.58, p = 0.015), side-effects (OR = 6.04, p = 0.025), ART started ≤24 months (OR = 3.18, p = 0.009), travel time to hospital >1 hour (OR = 2.84, p = 0.035). Similarly, lack of knowledge and negative perception towards ART medications also significantly affected non-adherence. Transport costs (for repeat prescription), followed by pills running out, not wanting others to notice, side-effects, and being busy were the most common reasons for non-adherence. The interviews also revealed religious or ritual obstacles, stigma and discrimination, ART-associated costs, transport problems, lack of support, and side-effects as contributing to non-adherence. Improving adherence requires a supportive environment; accessible treatment; clear instructions about regimens; and regimens tailored to individual patients' lifestyles. Healthcare workers should address some of the practical and cultural issues around ART medicine whilst policy-makers should develop appropriate social policy to promote adherence among ART-prescribed patients.

Iconic as a novelist and popular cultural figure, Zora Neale Hurston remains underappreciated as an anthropologist. Is it inevitable that Hurston's literary authority should eclipse her anthropological authority? If not, what socio-cultural and institutional values and processes shape the different ways we read her work? Jennifer L. Freeman Marshall considers the polar receptions to Hurston's two areas of achievement by examining the critical response to her work across both fields. Drawing on a wide range of readings, Freeman Marshall explores Hurston's popular appeal as iconography, her elevation into the literary canon, her concurrent marginalization in anthropology despite her significant contributions, and her place within constructions of Black feminist literary traditions. Perceptive and original, Ain't I an Anthropologist is an overdue reassessment of Zora Neale Hurston's place in American cultural and intellectual life.

Exposure to environmental neurotoxicants such as lead (Pb) during critical developmental periods and adulthood has been linked to persistent neurological deficits and pathological features resembling Alzheimer's disease (AD). Epidemiological studies have reported associations between Pb exposure and an increased risk of AD later in life, a link further supported by animal models. However, the molecular mechanisms underlying this association remain poorly understood. In this study, we utilized hiPSC-derived cortical neurons to investigate the impact of Pb exposure at different life stages on the onset of AD-like pathogenesis. We selected environmentally relevant Pb concentrations (0, 15, and 50 ppb) and assessed both immediate and persistent neurological effects using immunofluorescence, Western blotting, RNA sequencing, enzyme-linked immunosorbent assay (ELISA), microelectrode array (MEA) and a \"secondary hit\" model. Although neurite morphology remained largely intact, Pb-exposed neurons displayed significant hyperactivity and mitochondrial dysfunction. Transcriptomic profiling identified differentially expressed genes enriched in oxidative phosphorylation and AD-related pathways. Furthermore, Pb exposure led to an increase in phosphorylated Tau, Tau aggregates, and Aβ42/40 ratios-hallmarks of AD pathology. Notably, Pb-exposed neurons exhibited increased susceptibility to AD-relevant secondary stressors, including PHF-Tau and the mitochondrial toxin MPP+, with these vulnerabilities persisting even after Pb withdrawal. These findings provide mechanistic insight into how Pb exposure may contribute to AD pathogenesis, highlighting potential molecular pathways that could mediate the increased AD risk observed in Pb-exposed populations.

The growing pressure on food production has led to the widespread use of pesticides to ensure high crop yields. Herbicides are extensively applied in Brazil, with diquat-based herbicides (DBH) being one of the most commercialized. DBH has gained prominence as a substitute for paraquat and as a solution for glyphosate-resistant weeds. However, strict regulations govern the permissible levels of these substances in drinking water. In this context, we evaluated environmentally relevant concentrations of DBH in zebrafish ( Danio rerio ), a model organism in ecotoxicological studies. To evaluate the impact on behavior and early development, embryos were exposed to DBH at concentrations of 20, 50, or 250 µg L −1 during organogenesis (3–120 hpf). Developmental impacts were assessed through survival rates, spontaneous movement, and heart rate, while behavioral effects were analyzed using open-field and aversive stimulus tests. DBH exposure reduced survival, increased spontaneous movements and heart rate, and impaired larval behavior. Notably, all tested concentrations induced adverse effects in at least one endpoint, clearly demonstrating the detrimental impact of DBH on zebrafish embryos and larvae at environmentally relevant concentrations.

Falls are a significant issue in people with multiple sclerosis (MS), with research demonstrating fall rates of more than 50%. The purpose of this study was to evaluate the risk factors associated with falling in people with MS. Mixed search methods were used, including computer-based and manual searches. Additionally, hand searches of reference lists and conference abstracts were performed. All literature published from the source's earliest date to January 2012 was included; only full-text English-language sources (or those where a translation was available) were included. Eligibility criteria specified articles evaluating any aspect of fall risk in adults with a confirmed MS diagnosis, where the incidence of falling as determined by prospective or retrospective participant report was included. Data were extracted independently by 2 reviewers using a written protocol and standardized extraction documentation. Detailed assessment of each article was independently undertaken by both reviewers, including assessment of study quality using an adaptation of the Newcastle Ottawa Scale plus extraction of key data (participant characteristics, fall incidence, and outcomes). The final review comprised 8 articles with a total of 1,929 participants; 1,037 (53.75%) were classified as fallers. Eighteen different risk factors were assessed within the included studies. Meta-analysis demonstrated an increase in fall risk associated with impairments of balance and cognition, progressive MS, and use of a mobility aid. Narrative review of the qualitative articles and those factors where meta-analysis was not possible also was undertaken. Variation in assessment, analysis, and reporting methods allowed meta-analysis for only 4 factors. There is limited evidence of the factors associated with fall risk in people with MS. Further methodologically robust studies are needed.

Arsenic (As) and lead (Pb) are environmental pollutants found in common sites and linked to similar adverse health effects. Multiple studies have investigated the toxicity of each metal individually or in complex mixtures. Studies defining the joint interaction of a binary exposure to As and Pb, especially during the earliest stages of development, are limited and lack confirmation of the predicted mixture interaction. We hypothesized that a mixture of As (iAsIII) and Pb will have a concentration addition (CA) interaction informed by common pathways of toxicity of the two metals. To test this hypothesis, developing zebrafish (1–120 h post fertilization; hpf) were first exposed to a wide range of concentrations of As or Pb separately to determine 120 hpf lethal concentrations. These data were then used in the CA and independent action (IA) models to predict the type of mixture interaction from a co-exposure to As and Pb. Three titration mixture experiments were completed to test prediction of observed As and Pb mixture interaction by keeping the Pb concentration constant and varying As concentrations in each experiment. The prediction accuracy of the two models was then calculated using the prediction deviation ratio (PDR) and Chi-square test and regression modeling applied to determine type of interaction. Individual metal exposures determined As and Pb concentrations at which 25% (39.0 ppm Pb, 40.2 ppm As), 50% (73.8 ppm Pb, 55.4 ppm As), 75% (99.9 ppm Pb, 66.6 ppm As), and 100% (121.7 ppm Pb, 77.3 ppm As) lethality was observed at 120 hpf. These data were used to graph the predicted mixture interaction using the CA and IA models. The titration experiments provided experimental observational data to assess the prediction. PDR values showed the CA model approached 1, whereas all PDR values for the IA model had large deviations from predicted data. In addition, the Chi-square test showed most observed results were significantly different from the predictions, except in the first experiment (Pb LC25 held constant) with the CA model. Regression modeling for the IA model showed primarily a synergistic response among all exposure scenarios, whereas the CA model indicated additive response at lower exposure concentrations and synergism at higher exposure concentrations. The CA model was a better predictor of the Pb and As binary mixture interaction compared to the IA model and was able to delineate types of mixture interactions among different binary exposure scenarios.

Endocrine disrupting chemicals (EDC) are exogenous agents that alter endogenous hormone signaling pathways. These chemicals target the neuroendocrine system which is composed of organs throughout the body that work alongside the central nervous system to regulate biological processes. Of primary importance is the hypothalamic-pituitary-gonadal (HPG) axis which is vital for maintaining proper reproductive function. Atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) is a pre-emergent herbicide used to prevent the growth of weeds on various crops. This herbicide is reported to widely contaminate potable water supplies everywhere it is applied. As such, the European Union banned the use of atrazine in 2004. Currently the United States Environmental Protection Agency regulates atrazine at 3 parts per billion (ppb; μg/L) in drinking water, while the World Health Organization recently changed their drinking water guideline to 100 ppb. Atrazine is implicated to be an EDC that alters reproductive dysfunction by targeting the HPG axis. However, questions remain as to the human health risks associated with atrazine exposure with studies reporting mixed results on the ability of atrazine to alter the HPG axis. In this review, the current findings for atrazine’s effects on the HPG axis are examined in mammalian, anuran, and fish models and in epidemiological studies.