Ozone (O3) is a component of photochemical smog, which is a major air pollutant and demonstrates properties that are harmful to health because of the toxic properties that are inherent to its powerful oxidizing capabilities. Environmental O3 exposure is associated with many symptoms related to respiratory disorders, which include loss of lung function, exacerbation of asthma, airway damage, and lung inflammation. The effects of O3 are not restricted to the respiratory system or function - adverse effects within the central nervous system (CNS) such as decreased cognitive response, decrease in motor activity, headaches, disturbances in the sleep-wake cycle, neuronal dysfunctions, cell degeneration, and neurochemical alterations have also been described; furthermore, it has also been proposed that O3 could have epigenetic effects. O3 exposure induces the reactive chemical species in the lungs, but the short half-life of these chemical species has led some authors to attribute the injurious mechanisms observed within the lungs to inflammatory processes. However, the damage to the CNS induced by O3 exposure is not well understood. In this review, the basic mechanisms of inflammation and activation of the immune system by O3 exposure are described and the potential mechanisms of damage, which include neuroinflammation and oxidative stress, and the signs and symptoms of disturbances within the CNS caused by environmental O3 exposure are discussed.
Huntington's disease is an autosomal‐dominant, neurodegenerative disorder caused by a CAG repeat expansion in exon‐1 of the huntingtin gene. Alterations in cholesterol metabolism and distribution have been reported in Huntington's disease, including abnormal interactions between mutant huntingtin and sterol regulatory element‐binding proteins, decreased levels of apolipoprotein E/cholesterol/low‐density lipoprotein receptor complexes, and alterations in the synthesis of ATP‐binding cassette transporter A1. Plasma levels of 24S‐hydroxycholestrol, a key intermediary in cholesterol metabolism and a possible marker in neurodegenerative diseases, decreased proportionally to the degree of caudate nucleus atrophy. The interaction of mutant huntingtin with sterol regulatory element‐binding proteins is of particular interest given that sterol regulatory element‐binding proteins play a dual role: They take part in lipid and cholesterol metabolism, but also in the inflammatory response that induces immune cell migration as well as toxic effects, particularly in astrocytes. This work summarizes current evidence on the metabolic and immune implications of sterol regulatory element‐binding protein dysregulation in Huntington's disease, highlighting the potential use of drugs that modulate these alterations. © 2020 International Parkinson and Movement Disorder Society
The World Health Organization identified urban outdoor air pollution as the eighth highest mortality risk factor in high-income countries. Exposure to ambient pollutants such as ozone (O3) increases the number of hospital admissions. O3 is a highly reactive gas that reacts with cells lining the airways, producing the formation of reactive oxygen species and inflammation. Beyond the respiratory system, O3 exposure also produces fatigue, lethargy, headaches, and significant decrease in rapid-eye-movement sleep related to an increase in slow-wave sleep. Interestingly, these sleep changes can be significantly mitigated by treatment with indomethacin, which suggests that an inflammatory mechanism may be responsible for these neurological symptoms. To characterize the inflammatory mechanisms by which O3 affects tissues outside the pulmonary system, we evaluated inflammatory factors in both lung and brain. Rats exposed to 1 part per million O3 for 1, 3 or 6 h, as well as rats exposed daily for 1 or 3 h over five consecutive days, showed increases in TNF-α and IL-6 levels within the lungs as well as increases in TNF-α, IL-6, NF-κB p50 and GFAP levels in the cerebral cortex. These results support the hypothesis that the neuroinflammatory response may be responsible for the central nervous system effects of O3 exposure.
Essential fatty acids have an important effect on oxidative stress-related diseases. The Huntington's disease (HD) is a hereditary neurologic disorder in which oxidative stress caused by free radicals is an important damage mechanism. The HD experimental model induced by quinolinic acid (QUIN) has been widely used to evaluate therapeutic effects of antioxidant compounds. The aim of this study was to test whether the fatty acid content in olive- or fish-oil-rich diet prevents against QUIN-related oxidative damage in rats. Rats were fed during 20 days with an olive- or a fish-oil-rich diet (15% w/w). Posterior to diet period, rats were striatally microinjected with QUIN (240 nmol/µl) or saline solution. Then, we evaluated the neurological damage, oxidative status, and gamma isoform of the peroxisome proliferator-activated receptor (PPARγ) expression. Results showed that fatty acid-rich diet, mainly by fish oil, reduced circling behavior, prevented the fall in GABA levels, increased PPARγ expression, and prevented oxidative damage in striatal tissue. In addition none of the enriched diets exerted changes neither on triglycerides or cholesterol blood levels, nor or hepatic function. This study suggests that olive- and fish-oil-rich diets exert neuroprotective effects.
Nitric oxide (NO) is an essential messenger molecule in brain, where it is produced in neurons mostly by the activity of the neuronal isoform of nitric oxide synthase (nNOS). To understand the participation of the different isoforms of NOS in physiological functioning and in pathological processes, mice with null mutations for each of the NOS isoforms have been generated. In the present paper, we report that there is a selective protection from oxidative damage in the brain of mice with a targeted disruption of the nNOS gene. The cerebellum of these mice shows reduced levels of lipid peroxidation (LP) at the different ages tested, compared with wild-type mice, and also a reduction in the formation of reactive oxygen species (ROS). We observed a decrease of LP in cortex, and no effect on either LP or ROS formation was observed in striatum of knockout mice compared with wild type. We also report increased spontaneous motor activity of knockout mice. The expression and activity of nNOS are crucial to maintain redox status in brain, and we consider that the alteration in oxidative damage may help us to explain the phenotypical characteristics of nNOS knockout mice and their differential susceptibility to brain insults.
In the past two years, the world has faced the pandemic caused by the severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2), which by August of 2022 has infected around 619 million people and caused the death of 6.55 million individuals globally. Although SARS-CoV-2 mainly affects the respiratory tract level, there are several reports, indicating that other organs such as the heart, kidney, pancreas, and brain can also be damaged. A characteristic observed in blood serum samples of patients suffering COVID-19 disease in moderate and severe stages, is a significant increase in proinflammatory cytokines such as interferon-α (IFN-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6) and interleukin-18 (IL-18), as well as the presence of autoantibodies against interferon-α (IFN-α), interferon-λ (IFN-λ), C-C motif chemokine ligand 26 (CCL26), CXC motif chemokine ligand 12 (CXCL12), family with sequence similarity 19 (chemokine (C-C motif)-like) member A4 (FAM19A4), and C-C motif chemokine ligand 1 (CCL1). Interestingly, it has been described that the chronic cytokinemia is related to alterations of blood-brain barrier (BBB) permeability and induction of neurotoxicity. Furthermore, the generation of autoantibodies affects processes such as neurogenesis, neuronal repair, chemotaxis and the optimal microglia function. These observations support the notion that COVID-19 patients who survived the disease present neurological sequelae and neuropsychiatric disorders. The goal of this review is to explore the relationship between inflammatory and humoral immune markers and the major neurological damage manifested in post-COVID-19 patients.
We concluded that there is a higher activity of the Wnt/β-Catenin pathway associated with increased number of stimuli may be related with the presence of apoptosis in the cerebellum treated with amygdala kindling. In this way, we suggest this pathway as one of the mechanisms by which cerebellar neurons death in generalized seizures.
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