Immunoassay standardization for the detection of immunoglobulin A (IgA) against Porphyromonas gingivalis antigens in saliva of individuals with and without leprosy

Leprosy reactions are immune processes that cause neural damage in individuals with leprosy. As periodontitis is an infectious disease related to its development, specific antibodies to periodontal pathogens must be evaluated to better understand the humoral mechanisms underlying this relationship. Therefore, the objective of this study was to standardize an immunoassay to measure IgA specific to P. gingivalis antigens in the saliva of individuals with leprosy. An ELISA checkerboard titration was performed. A validation test involving 53 individuals with leprosy, 24 with and 19 without periodontitis, was conducted and a ROC curve constructed to calculate sensitivity and specificity. The coefficient of the optical densities was 2.21 and 2.66 for P. gingivalis crude extract and the recombinant protein HmuY, respectively. Sensitivity and specificity for the P. gingivalis crude extract were 66.7% and 73.7%, respectively, and for HmuY, were 62.5% and 52.6%, respectively. Specific recognition of P. gingivalis occurred predominantly in individuals with periodontitis, which validates the use of this test for studying periodontitis in individuals with leprosy.Trial registration CAEE 64476117.3.0000.0049, 21/07/2017, retrospectively registered

Particulate Air Pollution and Risk of Neuropsychiatric Outcomes. What We Breathe, Swallow, and Put on Our Skin Matters

We appraise newly accumulated evidence of the impact of particle pollution on the brain, the portals of entry, the neural damage mechanisms, and ultimately the neurological and psychiatric outcomes statistically associated with exposures. PM pollution comes from natural and anthropogenic sources such as fossil fuel combustion, engineered nanoparticles (NP ≤ 100 nm), wildfires, and wood burning. We are all constantly exposed during normal daily activities to some level of particle pollution of various sizes—PM2.5 (≤2.5 µm), ultrafine PM (UFP ≤ 100 nm), or NPs. Inhalation, ingestion, and dermal absorption are key portals of entry. Selected literature provides context for the US Environmental Protection Agency (US EPA) ambient air quality standards, the conclusions of an Independent Particulate Matter Review Panel, the importance of internal combustion emissions, and evidence suggesting UFPs/NPs cross biological barriers and reach the brain. NPs produce oxidative stress and neuroinflammation, neurovascular unit, mitochondrial, endoplasmic reticulum and DNA damage, protein aggregation and misfolding, and other effects. Exposure to ambient PM2.5 concentrations at or below current US standards can increase the risk for TIAs, ischemic and hemorrhagic stroke, cognitive deficits, dementia, and Alzheimer’s and Parkinson’s diseases. Residing in a highly polluted megacity is associated with Alzheimer neuropathology hallmarks in 99.5% of residents between 11 months and ≤40 y. PD risk and aggravation are linked to air pollution and exposure to diesel exhaust increases ALS risk. Overall, the literature supports that particle pollution contributes to targeted neurological and psychiatric outcomes and highlights the complexity of the pathophysiologic mechanisms and the marked differences in pollution profiles inducing neural damage. Factors such as emission source intensity, genetics, nutrition, comorbidities, and others also play a role. PM2.5 is a threat for neurological and psychiatric diseases. Thus, future research should address specifically the potential role of UFPs/NPs in inducing neural damage.

Using electrocochleography to detect sensory and neural damages in a gerbil model

Hearing is one of the five sensory organs that allows us to interact with society and our environment. However, one in eight Americans suffers from sensorineural hearing loss that is great enough to adversely impact their daily life. There is an urgent need to identify what part/degree of the auditory pathway (sensory or neural) is compromised so that appropriate treatment/intervention can be implemented. Single- or two-tone evoked potentials, the electrocochleography (eCochG), were measured along the auditory pathway, i.e., at the round window and remotely at the vertex, with simultaneous recordings of ear canal distortion product otoacoustic emissions. Sensory (cochlear) and neural components in the (remote-) eCochG responses showed distinct level- and frequency-dependent features allowing to be differentiated from each other. Specifically, the distortion products in the (remote-)eCochGs can precisely localize the sensory damage showing that they are effective to determine the sensory or neural damage along the auditory pathway.

Diosgenin Prevents Microglial Activation and Protects Dopaminergic Neurons from Lipopolysaccharide-Induced Neural Damage In Vitro and In Vivo

Background: The prevention of age-related neurodegenerative disorders is an important issue in an aging society. Microglia-mediated neuroinflammation resulting in dopaminergic neuron loss may lead to the pathogenesis of Parkinson’s disease (PD). Lipopolysaccharide (LPS), an endotoxin, induces neuroinflammatory microglial activation, contributing to dopaminergic neuron damage. Diosgenin is a phytosteroid sapogenin with a wide spectrum of pharmacological activities, e.g., anti-inflammatory activity. However, the preventive effect of diosgenin on neuroinflammation is not clear. Thus, in this study, we further investigated the neuroprotective effect of diosgenin on LPS-induced neural damage in vitro and in vivo. Methods: For in vitro experiments, primary mesencephalic neuron-glia cultures and primary microglia cultures isolated from Sprague–Dawley rats were used. Cells were pretreated with diosgenin and then stimulated with LPS. The expression of proinflammatory cytokines or tyrosine hydroxylase (TH) in the cells was analyzed. In vivo, rats were fed a diet containing 0.1% (w/w) diosgenin for 4 weeks before being administered a unilateral substantia nigra (SN) injection of LPS. Four weeks after the LPS injection, the rats were assessed for lesion severity using the amphetamine-induced rotation test and TH immunohistochemistry. Results: Diosgenin pretreatment prevented LPS-induced neurite shortening in TH-positive neurons in mesencephalic neuron-glia cultures. In addition, pretreatment of primary microglia with diosgenin significantly reduced tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) expression. Moreover, diosgenin pretreatment significantly suppressed LPS-induced extracellular signal-regulated kinase (ERK) activation. In vivo, the intranigral injection of LPS in rats fed a diosgenin-containing diet significantly improved motor dysfunction and reduced TH expression in SN. Conclusion: These results support the effectiveness of diosgenin in protecting dopaminergic neurons from LPS-induced neuroinflammation.

Blockage of IL-17 Ameliorates Aβ-Induced Neurotoxicity and Cognitive Decline

BackgroundNeuroinflammation plays a critical role in the pathophysiology of Alzheimer’s disease (AD), particularly in amyloid-β (Aβ) production. But the impact of the cytokine, interleukin-17A (IL-17) on the course of AD has not been well defined. The goal was to determine the effect of IL-17 on neural damage and whether IL-17 inhibitor (Y-320) could ameliorate Aβ-induced neurotoxicity and cognitive decline.MethodsThe expression level of IL-17 was analyzed in APP/PS1 mice. Then IL-17 was injected into the lateral ventricle of C57BL WT mice and roles on synaptic dysfunction and cognitive impairments were examined. Aβ42 was injected into the lateral ventricle of to mimic Aβ42 model mice. The effects of IL-17 inhibitor by oral gavage on Aβ42-induced neurotoxicity and cognitive decline were examined. ResultsWe found that IL-17 was increased in the hippocampus of APP/PS1 transgenic mouse, which has a fundamental role in mediating brain damage in neuroinflammatory processes. Furthermore, we reported that IL-17 was administrated in primary hippocampal neurons, leading to neural damage and synaptic dysfunction. At the same time, IL-17 caused synaptic dysfunction and cognitive impairments accompanying with increased of Aβ levels in mice. In addition, we found that Y-320 could rescue Aβ42–induced neural damage in primary hippocampal neurons, and ameliorate neuronal damage and cognitive impairments in Aβ42 model mice. Interestingly, we observed that IL-17 upregulated the production of soluble amyloid precursor protein β (sAPPβ) and phosphorylation of APP at T668 (pT668), moreover, Y-320 inhibited the Aβ production by down-regulation the sAPPβ and pT668. Conclusions Blockage of IL-17 might ameliorate Aβ-induced neurotoxicity and cognitive decline. These results strongly demonstrate a potential therapeutic role for IL-17 inhibitor in AD.

Exogenous microRNA 322-5p Reduced Neuronal Inflammation via the TRAF6/IRF5/NF-kB Axis and Restored GAD1/GABA Expression in a Pilocarpine-induced Epileptic Rat Model

Objective: MicroRNAs (miRNAs) are small noncoding RNAs that control gene expression at the posttranscriptional level. Some dysregulated miRNAs have been shown to play essential roles in epileptic development. This study aimed to determine if microRNA-322-5p regulates seizure and seizure damage by targeting the NFκB-TLR4 associated inflammatory signaling pathway.Methods: Pilocarpine-induced epileptic rat model was established. Immunohistochemical staining demonstrated the pathology of epilepsy. The expression of microRNA-322-5p, inflammatory markers, NF-kB, TLR4, IL-1β and IL-6, and synaptic inhibitory molecules, GAD1 and GABA, were assessed by a quantitative polymerase chain reaction, and western blotting, respectively.Results: The expression of microRNA-322-5p was significantly decreased in the SE (status epilepticus) rats compared with the normal counterparts. The reduction of miR-322-5p was accompanied by an increased level of pro‑inflammatory cytokines such as IL-6 and TNF-α via increased NF-kB expression and reduced GAD1 and GABA expression. The exogenously increased miR-322-5p level by mimic molecules significantly reduced the inflammatory profiles and increased GAD1 and GABA expressions in the S.E. rat brain compared to nontreated counterparts. Conclusions: Our findings suggest that the restoration of miR-322-5p resulted in a significantly reduced TRL4/IRF1/NF-kb associated inflammatory circuit and increased GAD1 and GABA expression. These findings suggest that miR-322-5p induction may be of therapeutic potential for neural damage as a result of repeated epileptic episodes.

Enhanced IL-6 and IL-12B Gene Expression After SARS-CoV-2 Infection in Leprosy Patients May Increase the Risk of Neural Damage

Experts have called attention to the possible negative impact of the coronavirus disease 2019 (COVID-19)–related cytokine storm syndrome on the progression of leprosy-related disabilities. We assessed the frequency of reactional states in patients co-infected with Mycobacterium leprae and severe acute respiratory syndrome (SARS) coronavirus (CoV) 2 (SARS-CoV-2). We consecutively included patients during the first peak of the COVID-19 epidemic in Brazil and analyzed the expressions of genes encoding interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12A, IL-12B, and tumor necrosis factor-α in peripheral blood mononuclear cells. We included 64 leprosy patients and 50 controls. Twelve of the leprosy patients and 14 of the controls had been diagnosed with COVID-19. Co-infection was associated with increased IL-6 (P = 0.043) and IL-12B (P = 0.017) expression. The median disability grades were higher for leprosy/COVID-19 patients; however, the difference was not significant (P = 0.194). Patients co-infected with M. leprae and SARS-CoV-2 may experience a higher-grade proinflammatory state.