scholarly journals Calcium Hypothesis of Gulf War Illness: Role of Calcium Ions in Neurological Morbidities in a DFP-Based Rat Model for Gulf War Illness

2020 ◽  
Vol 15 ◽  
pp. 263310552097984
Author(s):  
Kristin F Phillips ◽  
Laxmikant S Deshpande
Keyword(s):  
Experimental Models ◽  
Gulf War ◽  
Signaling Cascades ◽  
Gulf War Illness ◽  
Downstream Signaling ◽  
Cholinergic Signaling ◽  
Glutamatergic Signaling ◽  
The Central Nervous System ◽  
System Disorder

Gulf War Illness (GWI) refers to a multi-system disorder that afflicts approximately 30% of First Gulf War (GW) veterans. Amongst the symptoms exhibited, mood and memory impairment are commonly reported by GW veterans. Exposure to organophosphate (OP) compounds which target the cholinergic system is considered a leading cause for GWI symptoms. It is hypothesized that chronic OP-based war-time stimulation of cholinergic signaling led to recruitment of excitatory glutamatergic signaling and other downstream signaling cascades leading to neuronal injury, neuroinflammation, generation of reactive oxygen species, oxidative stress, and mitochondrial damage within the central nervous system. These findings have been observed in both experimental models and GWI veterans. In this context the role of calcium (Ca2+) signaling in GWI has come to the forefront. Here we present our Ca2+ hypothesis of GWI that suggests sustained neuronal Ca2+ elevations serve as a molecular trigger for pathological synaptic plasticity that has allowed for the persistence of GWI symptoms. Subsequently we discuss that therapeutic targeting of Ca2+ homeostatic mechanisms provides novel targets for effective treatment of GWI-related neurological signs in our rodent model.

scholarly journals Adaptive Immune Responses Associated with the Central Nervous System Pathology of Gulf War Illness

2021 ◽  
Vol 16 ◽  
pp. 263310552110184
Author(s):  
Aurore Nkiliza ◽  
Utsav Joshi ◽  
James E Evans ◽  
Ghania Ait-Ghezala ◽  
Megan Parks ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Responses ◽  
Potential Role ◽  
Gulf War ◽  
Gulf War Illness ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
The Central Nervous System

Gulf War Illness is a multisymptomatic condition which affects 30% of veterans from the 1991 Gulf War. While there is evidence for a role of peripheral cellular and humoral adaptive immune responses in Gulf War Illness, a potential role of the adaptive immune system in the central nervous system pathology of this condition remains unknown. Furthermore, many of the clinical features of Gulf War Illness resembles those of autoimmune diseases, but the biological processes are likely different as the etiology of Gulf War Illness is linked to hazardous chemical exposures specific to the Gulf War theatre. This review discusses Gulf War chemical–induced maladaptive immune responses and a potential role of cellular and humoral immune responses that may be relevant to the central nervous system symptoms and pathology of Gulf War Illness. The discussion may stimulate investigations into adaptive immunity for developing novel therapies for Gulf War Illness.

scholarly journals Cholinergic Signaling, Neural Excitability, and Epilepsy

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2258
Author(s):  
Yu Wang ◽  
Bei Tan ◽  
Yi Wang ◽  
Zhong Chen
Keyword(s):  
Cholinergic Neurons ◽  
Epileptic Seizures ◽  
Brain Disorder ◽  
Neural Excitability ◽  
Cholinergic Signaling ◽  
The Central Nervous System ◽  
Muscarinic And Nicotinic Receptors ◽  
Cumulative Evidence ◽  
Precise Role

Epilepsy is a common brain disorder characterized by recurrent epileptic seizures with neuronal hyperexcitability. Apart from the classical imbalance between excitatory glutamatergic transmission and inhibitory γ-aminobutyric acidergic transmission, cumulative evidence suggest that cholinergic signaling is crucially involved in the modulation of neural excitability and epilepsy. In this review, we briefly describe the distribution of cholinergic neurons, muscarinic, and nicotinic receptors in the central nervous system and their relationship with neural excitability. Then, we summarize the findings from experimental and clinical research on the role of cholinergic signaling in epilepsy. Furthermore, we provide some perspectives on future investigation to reveal the precise role of the cholinergic system in epilepsy.

scholarly journals Social Isolation: How Can the Effects on the Cholinergic System Be Isolated?

2021 ◽  
Vol 12 ◽  
Author(s):  
Jaromir Myslivecek
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Social Isolation ◽  
Cholinergic System ◽  
System Response ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Cholinergic Signaling ◽  
The Central Nervous System

Social species form organizations that support individuals because the consequent social behaviors help these organisms survive. The isolation of these individuals may be a stressor. We reviewed the potential mechanisms of the effects of social isolation on cholinergic signaling and vice versa how changes in cholinergic signaling affect changes due to social isolation.There are two important problems regarding this topic. First, isolation schemes differ in their duration (1–165 days) and initiation (immediately after birth to adulthood). Second, there is an important problem that is generally not considered when studying the role of the cholinergic system in neurobehavioral correlates: muscarinic and nicotinic receptor subtypes do not differ sufficiently in their affinity for orthosteric site agonists and antagonists. Some potential cholinesterase inhibitors also affect other targets, such as receptors or other neurotransmitter systems. Therefore, the role of the cholinergic system in social isolation should be carefully considered, and multiple receptor systems may be involved in the central nervous system response, although some subtypes are involved in specific functions. To determine the role of a specific receptor subtype, the presence of a specific subtype in the central nervous system should be determined using search in knockout studies with the careful application of specific agonists/antagonists.

scholarly journals Exploring the Role of Chemokine Receptor 6 (Ccr6) in the BXD Mouse Model of Gulf War Illness

2020 ◽  
Vol 14 ◽  
Author(s):  
Jun Gao ◽  
Fuyi Xu ◽  
Athena Starlard-Davenport ◽  
Diane B. Miller ◽  
James P. O’Callaghan ◽  
...  
Keyword(s):  
Mouse Model ◽  
Chemokine Receptor ◽  
Gulf War ◽  
Gulf War Illness

scholarly journals Novel Toolboxes for the Investigation of Activity-Dependent Myelination in the Central Nervous System

2021 ◽  
Vol 15 ◽  
Author(s):  
Jack Kent Heflin ◽  
Wenjing Sun
Keyword(s):  
Cell Interaction ◽  
Precursor Cells ◽  
Signaling Cascades ◽  
Initial Contact ◽  
Downstream Signaling ◽  
Cellular Processes ◽  
Proliferation And Differentiation ◽  
The Central Nervous System ◽  
Underlying Mechanisms ◽  
Activity Dependent

Myelination is essential for signal processing within neural networks. Emerging data suggest that neuronal activity positively instructs myelin development and myelin adaptation during adulthood. However, the underlying mechanisms controlling activity-dependent myelination have not been fully elucidated. Myelination is a multi-step process that involves the proliferation and differentiation of oligodendrocyte precursor cells followed by the initial contact and ensheathment of axons by mature oligodendrocytes. Conventional end-point studies rarely capture the dynamic interaction between neurons and oligodendrocyte lineage cells spanning such a long temporal window. Given that such interactions and downstream signaling cascades are likely to occur within fine cellular processes of oligodendrocytes and their precursor cells, overcoming spatial resolution limitations represents another technical hurdle in the field. In this mini-review, we discuss how advanced genetic, cutting-edge imaging, and electrophysiological approaches enable us to investigate neuron-oligodendrocyte lineage cell interaction and myelination with both temporal and spatial precision.

scholarly journals Role of mitochondrial DNA damage and dysfunction in veterans with Gulf War Illness

PLoS ONE ◽  
2017 ◽  
Vol 12 (9) ◽  
pp. e0184832 ◽  
Author(s):  
Yang Chen ◽  
Joel N. Meyer ◽  
Helene Z. Hill ◽  
Gudrun Lange ◽  
Michael R. Condon ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mitochondrial Dna ◽  
Gulf War ◽  
Gulf War Illness ◽  
Mitochondrial Dna Damage

scholarly journals Reprogramming cells from Gulf War veterans into neurons to study Gulf War illness

Neurology ◽  
2017 ◽  
Vol 88 (20) ◽  
pp. 1968-1975 ◽  
Author(s):  
Liang Qiang ◽  
Anand N. Rao ◽  
Gustavo Mostoslavsky ◽  
Marianne F. James ◽  
Nicole Comfort ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cell Types ◽  
Experimental Models ◽  
Gulf War ◽  
Gulf War Illness ◽  
War Veterans ◽  
Gulf War Veterans ◽  
Chronic Headaches ◽  
The Persian Gulf ◽  
Impaired Sleep

Gulf War illness (GWI), which afflicts at least 25% of veterans who served in the 1990–1991 war in the Persian Gulf, is thought to be caused by deployment exposures to various neurotoxicants, including pesticides, anti–nerve gas pills, and low-level nerve agents including sarin/cyclosarin. GWI is a multisymptom disorder characterized by fatigue, joint pain, cognitive problems, and gastrointestinal complaints. The most prominent symptoms of GWI (memory problems, poor attention/concentration, chronic headaches, mood alterations, and impaired sleep) suggest that the disease primarily affects the CNS. Development of urgently needed treatments depends on experimental models appropriate for testing mechanistic hypotheses and for screening therapeutic compounds. Rodent models have been useful thus far, but are limited by their inability to assess the contribution of genetic or epigenetic background to the disease, and because disease-vulnerable proteins and pathways may be different in humans relative to rodents. As of yet, no postmortem tissue from the veterans has become available for research. We are moving forward with a paradigm shift in the study of GWI, which utilizes contemporary stem cell technology to convert somatic cells from Gulf War veterans into pluripotent cell lines that can be differentiated into various cell types, including neurons, glia, muscle, or other relevant cell types. Such cell lines are immortal and will be a resource for GWI researchers to pursue mechanistic hypotheses and therapeutics.

scholarly journals Peripheral Mechanisms of Symptom Generation in Irritable Bowel Syndrome

2001 ◽  
Vol 15 (suppl b) ◽  
pp. 14B-16B ◽  
Author(s):  
Stephen M Collins
Keyword(s):  
Nervous System ◽  
Irritable Bowel Syndrome ◽  
Experimental Models ◽  
Low Grade ◽  
Sensory Physiology ◽  
Somatic Pain ◽  
Inflammatory Stimuli ◽  
The Central Nervous System ◽  
Irritable Bowel

There is considerable interest in the mechanisms that underlie symptom generation in irritable bowel syndrome (IBS) and particularly those mechanisms peripheral to higher centres in the nervous system. While the central nervous system is important in IBS, it is restricted largely to the role of behaviour in stress perception and symptom reporting. The gut and the autonomic nervous system are principal areas of research in identifying mechanisms underlying symptom generation and in the identification of new targets for drug development. While motility changes occur in IBS, they are neither specific nor predictable, and this is one reason why drugs aimed at influencing motility patterns have enjoyed limited success to date. This success has prompted interest in sensory physiology to explain pain and other discomforts expressed by patients with IBS. Patients with IBS exhibit intolerance to rectal distension and other manoeuvres of the gut, while exhibiting normal or raised thresholds for somatic pain. The mechanisms underlying the development of hyperalgesia or allodynia in the gut remain to be determined. In other systems and experimental models, low grade inflammation is a predicable inducer of these states, and recent evidence suggests that a subpopulation of patients with IBS develop chronic symptoms after acute gastroenteritis. This and other inflammatory stimuli may induce a hyperalgesic state and alter motor function in patients with IBS. Substances that mediate these changes are not fully understood, but there is growing recognition of the role of serotonin as a sensitizing agent.

scholarly journals Impact of estrogens and estrogen receptor-α in brain lipid metabolism

2018 ◽  
Vol 315 (1) ◽  
pp. E7-E14 ◽  
Author(s):  
Eugenia Morselli ◽  
Roberta de Souza Santos ◽  
Su Gao ◽  
Yenniffer Ávalos ◽  
Alfredo Criollo ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Intracellular Signaling ◽  
Fatty Acid Content ◽  
Estrogen Receptor Α ◽  
Signaling Cascades ◽  
Brain Lipid ◽  
Adipose Tissues ◽  
The Central Nervous System ◽  
The Brain

Estrogens and their receptors play key roles in regulating body weight, energy expenditure, and metabolic homeostasis. It is known that lack of estrogens promotes increased food intake and induces the expansion of adipose tissues, for which much is known. An area of estrogenic research that has received less attention is the role of estrogens and their receptors in influencing intermediary lipid metabolism in organs such as the brain. In this review, we highlight the actions of estrogens and their receptors in regulating their impact on modulating fatty acid content, utilization, and oxidation through their direct impact on intracellular signaling cascades within the central nervous system.

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