Effects of chronic exposure to bisphenol-S on social behaviors in adult zebrafish: Disruption of the neuropeptide signaling pathways in the brain

Lead and lead-derived compounds have been extensively utilized in industry, and their chronic toxicity towards aquatic animals has not been thoroughly addressed at a behavioral level. In this study, we assessed the risk of exposure to lead at a waterborne environmental concentration in adult zebrafish by behavioral and biochemical analyses. Nine tests, including three-dimension (3D) locomotion, novel tank exploration, mirror biting, predator avoidance, social interaction, shoaling, circadian rhythm locomotor activity, color preference, and a short-term memory test, were performed to assess the behavior of adult zebrafish after the exposure to 50 ppb PbCl2 for one month. The brain tissues were dissected and subjected to biochemical assays to measure the relative expression of stress biomarkers and neurotransmitters to elucidate the underlying mechanisms for behavioral alterations. The results of the behavioral tests showed that chronic exposure to lead could elevate the stress and anxiety levels characterized by elevated freezing and reduced exploratory behaviors. The chronic exposure to PbCl2 at a low concentration also induced a sharp reduction of aggressiveness and short-term memory. However, no significant change was found in predator avoidance, social interaction, shoaling, or color preference. The biochemical assays showed elevated cortisol and reduced serotonin and melatonin levels in the brain, thus, altering the behavior of the PbCl2-exposed zebrafish. In general, this study determined the potential ecotoxicity of long-term lead exposure in adult zebrafish through multiple behavioral assessments. The significant findings were that even at a low concentration, long-term exposure to lead could impair the memory and cause a decrease in the aggressiveness and exploratory activities of zebrafish, which may reduce their survival fitness.

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Peptides Derived from Growth Factors to Treat Alzheimer’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22116071 ◽

2021 ◽

Vol 22 (11) ◽

pp. 6071

Author(s):

Suzanne Gascon ◽

Jessica Jann ◽

Chloé Langlois-Blais ◽

Mélanie Plourde ◽

Christine Lavoie ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Growth Factors ◽

Signaling Pathways ◽

Brain Structures ◽

Therapeutic Strategies ◽

Native Proteins ◽

Receptor Sites ◽

The Brain

Alzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by progressive neuron losses in memory-related brain structures. The classical features of AD are a dysregulation of the cholinergic system, the accumulation of amyloid plaques, and neurofibrillary tangles. Unfortunately, current treatments are unable to cure or even delay the progression of the disease. Therefore, new therapeutic strategies have emerged, such as the exogenous administration of neurotrophic factors (e.g., NGF and BDNF) that are deficient or dysregulated in AD. However, their low capacity to cross the blood–brain barrier and their exorbitant cost currently limit their use. To overcome these limitations, short peptides mimicking the binding receptor sites of these growth factors have been developed. Such peptides can target selective signaling pathways involved in neuron survival, differentiation, and/or maintenance. This review focuses on growth factors and their derived peptides as potential treatment for AD. It describes (1) the physiological functions of growth factors in the brain, their neuronal signaling pathways, and alteration in AD; (2) the strategies to develop peptides derived from growth factor and their capacity to mimic the role of native proteins; and (3) new advancements and potential in using these molecules as therapeutic treatments for AD, as well as their limitations.

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Mice with Deficiency of G Protein γ3 Are Lean and Have Seizures

Molecular and Cellular Biology ◽

10.1128/mcb.24.17.7758-7768.2004 ◽

2004 ◽

Vol 24 (17) ◽

pp. 7758-7768 ◽

Cited By ~ 54

Author(s):

William F. Schwindinger ◽

Kathryn E. Giger ◽

Kelly S. Betz ◽

Anna M. Stauffer ◽

Elaine M. Sunderlin ◽

...

Keyword(s):

Signaling Pathways ◽

G Protein ◽

Gene Targeting ◽

Wild Type ◽

Phenotypic Changes ◽

Reduced Body ◽

Γ Subunit ◽

Body Weights ◽

The Brain ◽

Increased Susceptibility

ABSTRACT Emerging evidence suggests that the γ subunit composition of an individual G protein contributes to the specificity of the hundreds of known receptor signaling pathways. Among the twelve γ subtypes, γ3 is abundantly and widely expressed in the brain. To identify specific functions and associations for γ3, a gene-targeting approach was used to produce mice lacking the Gng3 gene (Gng3 −/−). Confirming the efficacy and specificity of gene targeting, Gng3 −/− mice show no detectable expression of the Gng3 gene, but expression of the divergently transcribed Bscl2 gene is not affected. Suggesting unique roles for γ3 in the brain, Gng3 −/− mice display increased susceptibility to seizures, reduced body weights, and decreased adiposity compared to their wild-type littermates. Predicting possible associations for γ3, these phenotypic changes are associated with significant reductions in β2 and αi3 subunit levels in certain regions of the brain. The finding that the Gng3 −/− mice and the previously reported Gng7 −/− mice display distinct phenotypes and different αβγ subunit associations supports the notion that even closely related γ subtypes, such as γ3 and γ7, perform unique functions in the context of the organism.

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Exposure to aluminium causes behavioural alterations and oxidative stress in the brain of adult zebrafish

Environmental Toxicology and Pharmacology ◽

10.1016/j.etap.2021.103636 ◽

2021 ◽

Vol 85 ◽

pp. 103636

Author(s):

Teresa Capriello ◽

Luis M. Félix ◽

Sandra M. Monteiro ◽

Dércia Santos ◽

Rita Cofone ◽

...

Keyword(s):

Oxidative Stress ◽

Adult Zebrafish ◽

The Brain ◽

And Oxidative Stress

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Microglia, Cytokines, and Neural Activity: Unexpected Interactions in Brain Development and Function

Frontiers in Immunology ◽

10.3389/fimmu.2021.703527 ◽

2021 ◽

Vol 12 ◽

Author(s):

Austin Ferro ◽

Yohan S. S. Auguste ◽

Lucas Cheadle

Keyword(s):

Brain Development ◽

Signaling Pathways ◽

Immune Cells ◽

Neural Activity ◽

Signaling Molecules ◽

Evolutionary Strategy ◽

Inflammatory Signaling ◽

Peripheral Tissues ◽

And Function ◽

The Brain

Intercellular signaling molecules such as cytokines and their receptors enable immune cells to communicate with one another and their surrounding microenvironments. Emerging evidence suggests that the same signaling pathways that regulate inflammatory responses to injury and disease outside of the brain also play powerful roles in brain development, plasticity, and function. These observations raise the question of how the same signaling molecules can play such distinct roles in peripheral tissues compared to the central nervous system, a system previously thought to be largely protected from inflammatory signaling. Here, we review evidence that the specialized roles of immune signaling molecules such as cytokines in the brain are to a large extent shaped by neural activity, a key feature of the brain that reflects active communication between neurons at synapses. We discuss the known mechanisms through which microglia, the resident immune cells of the brain, respond to increases and decreases in activity by engaging classical inflammatory signaling cascades to assemble, remodel, and eliminate synapses across the lifespan. We integrate evidence from (1) in vivo imaging studies of microglia-neuron interactions, (2) developmental studies across multiple neural circuits, and (3) molecular studies of activity-dependent gene expression in microglia and neurons to highlight the specific roles of activity in defining immune pathway function in the brain. Given that the repurposing of signaling pathways across different tissues may be an important evolutionary strategy to overcome the limited size of the genome, understanding how cytokine function is established and maintained in the brain could lead to key insights into neurological health and disease.

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Modeling Neuroimmune Interactions in Human Subjects and Animal Models to Predict Subtype-Specific Multidrug Treatments for Gulf War Illness

International Journal of Molecular Sciences ◽

10.3390/ijms22168546 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8546

Author(s):

Francisco J. Carrera Arias ◽

Kristina Aenlle ◽

Maria Abreu ◽

Mary A. Holschbach ◽

Lindsay T. Michalovicz ◽

...

Keyword(s):

Signaling Pathways ◽

Human Subjects ◽

Treatment Strategies ◽

Gulf War ◽

Clinical Samples ◽

Stable States ◽

Response Dynamics ◽

Gulf War Illness ◽

Bbb Permeability ◽

The Brain

Gulf War Illness (GWI) is a persistent chronic neuroinflammatory illness exacerbated by external stressors and characterized by fatigue, musculoskeletal pain, cognitive, and neurological problems linked to underlying immunological dysfunction for which there is no known treatment. As the immune system and the brain communicate through several signaling pathways, including the hypothalamic–pituitary–adrenal (HPA) axis, it underlies many of the behavioral and physiological responses to stressors via blood-borne mediators, such as cytokines, chemokines, and hormones. Signaling by these molecules is mediated by the semipermeable blood–brain barrier (BBB) made up of a monocellular layer forming an integral part of the neuroimmune axis. BBB permeability can be altered and even diminished by both external factors (e.g., chemical agents) and internal conditions (e.g., acute or chronic stress, or cross-signaling from the hypothalamic–pituitary–gonadal (HPG) axis). Such a complex network of regulatory interactions that possess feed-forward and feedback connections can have multiple response dynamics that may include several stable homeostatic states beyond normal health. Here we compare immune and hormone measures in the blood of human clinical samples and mouse models of Gulf War Illness (GWI) subtyped by exposure to traumatic stress for subtyping this complex illness. We do this via constructing a detailed logic model of HPA–HPG–Immune regulatory behavior that also considers signaling pathways across the BBB to neuronal–glial interactions within the brain. We apply conditional interactions to model the effects of changes in BBB permeability. Several stable states are identified in the system beyond typical health. Following alignment of the human and mouse blood profiles in the context of the model, mouse brain sample measures were used to infer the neuroinflammatory state in human GWI and perform treatment simulations using a genetic algorithm to optimize the Monte Carlo simulations of the putative treatment strategies aimed at returning the ill system back to health. We identify several ideal multi-intervention strategies and potential drug candidates that may be used to treat chronic neuroinflammation in GWI.

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Long-Term Exposure of Alcohol Induced Behavioral Impairments and Oxidative Stress in the Brain Mitochondria and Synaptosomes of Adult Zebrafish

Zebrafish ◽

10.1089/zeb.2020.1913 ◽

2021 ◽

Author(s):

Manisha Nahar ◽

Deepali Jat

Keyword(s):

Oxidative Stress ◽

Brain Mitochondria ◽

Adult Zebrafish ◽

Behavioral Impairments ◽

The Brain ◽

And Oxidative Stress

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Neutrophil affinity for PGP and HAIYPRH (T7) peptide dual-ligand functionalized nanoformulation enhances the brain delivery of tanshinone IIA and exerts neuroprotective effects against ischemic stroke by inhibiting proinflammatory signaling pathways

New Journal of Chemistry ◽

10.1039/c8nj04819c ◽

2018 ◽

Vol 42 (23) ◽

pp. 19043-19061

Author(s):

Yutao Li ◽

Chiying An ◽

Danan Han ◽

Yanxin Dang ◽

Xin Liu ◽

...

Keyword(s):

Ischemic Stroke ◽

Physicochemical Properties ◽

Signaling Pathways ◽

Blood Brain Barrier ◽

Tanshinone Iia ◽

Brain Barrier ◽

Brain Delivery ◽

Neuroprotective Effects ◽

The Poor ◽

The Brain

A great challenge to the therapy of ischemic stroke is the poor physicochemical properties and inability of the drug to cross the blood–brain barrier (BBB).

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