Search in the Periphery for Potential Inflammatory Biomarkers of Dementia with Lewy Bodies and Alzheimer's Disease.

Background: Neuroinflammation, with altered peripheral proinflammatory cytokine production, plays a major role in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), while the role of inflammation in dementia with Lewy bodies (DLB) is less known and the results of different studies are often in disagreement. Objective: The present study aimed to investigate the levels of TNFα and IL-6 in serum and supernatants, and the related DNA methylation in patients affected by DLB and AD compared to healthy controls (HCs), to clarify the role of epigenetic mechanisms of DNA promoter methylation on of pro-inflammatory cytokines overproduction. Methods: Twenty-one patients with DLB and fourteen with AD were frequency-matched for age and sex with eleven HCs. Clinical evaluation, TNFα and IL-6 gene methylation status, cytokine gene expression levels and production in serum and peripheral blood mononuclear cell (PBMC) supernatants were performed. Results: In AD and DLB patients, higher serum levels of IL-6 and TNFα were detected than in HCs. Differences in LPS-stimulated versus spontaneous PBMCs were observed between DLB, AD, and HC in the levels of TNFα (p = 0.027) and IL-6 (p < 0.001). Higher levels were also revealed for sIL-6R in DLB (p < 0.001) and AD (p < 0.001) in comparison with HC.DNA hypomethylation in IL-6 and TNFα CpG promoter sites was detected for DLB and AD patients compared to the corresponding site in HCs. Conclusions: Our preliminary study documented increased levels of IL-6 and TNFα in DLB and AD patients to HCs. This overproduction can be due to epigenetic mechanisms regarding the hypomethylation of DNA promoters.

Pulsed Radiofrequency Electromagnetic Fields as Modulators of Inflammation and Wound Healing in Primary Dermal Fibroblasts of Ulcers.

Venous leg ulcers are one of the most common nonhealing conditions and represent an important clinical problem. The application of pulsed radiofrequency electromagnetic fields (PRF-EMFs), already applied for pain, inflammation, and new tissue formation, can represent a promising approach for venous leg ulcer amelioration. This study aims to evaluate the effect of PRF-EMF exposure on the inflammatory, antioxidant, cell proliferation, and wound healing characteristics of human primary dermal fibroblasts collected from venous leg ulcer patients. The cells' proliferative and migratory abilities were evaluated by means of a BrdU assay and scratch assay, respectively. The inflammatory response was investigated through TNFα, TGFß, COX2, IL6, and IL1ß gene expression analysis and PGE2 and IL1ß production, while the antioxidant activity was tested by measuring GSH, GSSG, tGSH, and GR levels. This study emphasizes the ability of PRF-EMFs to modulate the TGFß, COX2, IL6, IL1ß, and TNFα gene expression in exposed ulcers. Moreover, it confirms the improvement of the proliferative index and wound healing ability presented by PRF-EMFs. In conclusion, exposure to PRF-EMFs can represent a strategy to help tissue repair, regulating mediators involved in the wound healing process.

Anti-Obesity and Anti-Inflammatory Effects of Novel Carvacrol Derivatives on 3T3-L1 and WJ-MSCs Cells.

(1) Background: Obesity, a complex metabolic disease resulting from an imbalance between food consumption and energy expenditure, leads to an increase in adipocytes and chronic inflammatory conditions. The aim of this paper was to synthesize a small series of carvacrol derivatives (CD1-3) that are able to reduce both adipogenesis and the inflammatory status often associated with the progression of the obesity disease. (2) Methods: The synthesis of CD1-3 was performed using classical procedures in a solution phase. Biological studies were performed on three cell lines: 3T3-L1, WJ-MSCs, and THP-1. The anti-adipogenic properties of CD1-3 were evaluated using western blotting and densitometric analysis by assessing the expression of obesity-related proteins, such as ChREBP. The anti-inflammatory effect was estimated by measuring the reduction in TNF-α expression in CD1-3-treated THP-1 cells. (3) Results: CD1-3-obtained through a direct linkage between the carboxylic moiety of anti-inflammatory drugs (Ibuprofen, Flurbiprofen, and Naproxen) and the hydroxyl group of carvacrol-have an inhibitory effect on the accumulation of lipids in both 3T3-L1 and WJ-MSCs cell cultures and an anti-inflammatory effect by reducing TNF- α levels in THP-1 cells. (4) Conclusions: Considering the physicochemical properties, stability, and biological data, the CD3 derivative-obtained by a direct linkage between carvacrol and naproxen-resulted in the best candidate, displaying anti-obesity and anti-inflammatory effects in vitro.

TNFα, IL-6, miR-103a-3p, miR-423-5p, miR-23a-3p, miR-15a-5p and miR-223-3p in the crevicular fluid of periodontopathic patients correlate with each other and at different stages of the disease.

Periodontitis is one of the main frequent intraoral diseases. Pathogenesis triggers are the immune responses with pro-inflammatory cytokines production and non-coding RNAs expression. The purpose of the present study was to evaluate the involvement of selected miRNAs in various stages of periodontitis and their relationship with the levels of inflammatory mediators in gingival crevicular fluid (GCF). For this study, 36 subjects (21 with periodontal disease, 15 healthy controls) were selected with an age mean of 59.1 ± 3.7 years. Clinical parameters included plaque index, gingival index, sulcus bleeding index, pocket depth, and clinical attachment level. The GCF samples were taken using capillary paper. The levels of miRNAs in GCF were estimated using a Real-Time PCR and TNFα and IL-6 levels were assessed by enzyme-linked immunosorbent assay (ELISA). The results indicated that the miRNA-103a-3p, miRNA-23a-3p, miRNA-15a-5p, and miRNA-223-3p were significantly upregulated with respect to healthy controls. Significant differences were observed for miRNA-23a-3p, miRNA-103a-3p and miRNA-423-5p levels in accord with the disease stages. Inflammatory mediators evaluated in GCF correlate well with the clinical parameters and the severity of the periodontal disease. miRNAs can represent biomarkers of disease stage and can be investigated as a possible therapeutic target, as well as levels of TNFα and IL-6 may drive the disease progression by acting as prognostic markers.

Neuroprotective Potential of Bacopa monnieri: Modulation of Inflammatory Signals.

BACKGROUND: To date, much evidence has shown the increased interest in natural molecules and traditional herbal medicine as alternative bioactive compounds to fight many inflammatory conditions, both in relation to immunomodulation and in terms of their wound healing potential. Bacopa monnieri is a herb that is used in the Ayurvedic medicine tradition for its anti-inflammatory activity. OBJECTIVE: In this study, we evaluate the anti-inflammatory and regenerative properties of the Bacopa monnieri extract (BME) in vitro model of neuroinflammation. METHODS: Neuronal SH-SY5Y cells were stimulated with TNFα and IFNγ and used to evaluate the effect of BME on cell viability, cytotoxicity, cytokine gene expression, and healing rate. RESULTS: Our results showed that BME protects against the Okadaic acid-induced cytotoxicity in SH-SY5Y cells. Moreover, in TNFα and IFNγ primed cells, BME reduces IL-1ß, IL-6, COX-2, and iNOS, mitigates the mechanical trauma injury-induced damage, and accelerates the healing of wounds. CONCLUSION: This study indicates that BME might become a promising candidate for the treatment of neuroinflammation.

Proteomic Signature and mRNA Expression in Hippocampus of SAMP8 and SAMR1 Mice during Aging.

Aging is a complex process often accompanied by cognitive decline that represents a risk factor for many neurodegenerative disorders including Alzheimer's and Parkinson's disease. The molecular mechanisms involved in age-related cognitive decline are not yet fully understood, although increased neuroinflammation is considered to play a significant role. In this study, we characterized a proteomic view of the hippocampus of the senescence-accelerated mouse prone-8 (SAMP8), a model of enhanced senescence, in comparison with the senescence-accelerated-resistant mouse (SAMR1), a model of normal aging. We additionally investigated inflammatory cytokines and cholinergic components gene expression during aging in the mouse brain tissues. Proteomic data defined the expression of key proteins involved in metabolic and cellular processes in neuronal and glial cells of the hippocampus. Gene Ontology revealed that most of the differentially expressed proteins are involved in the cytoskeleton and cell motility regulation. Molecular analysis results showed that both inflammatory cytokines and cholinergic components are differentially expressed during aging, with a downward trend of cholinergic receptors and esterase enzymes expression, in contrast to an upward trend of inflammatory cytokines in the hippocampus of SAMP8. Together, our results support the important role of the cholinergic and cytokine systems in the aging of the murine brain.

Effects of Curcumin and Lactoferrin to Inhibit the Growth and Migration of Prostatic Cancer Cells.

Prostate cancer remains one of the main causes of death for men worldwide. Despite recent advances in cancer treatment, patients develop resistance after an initial period of optimal efficacy. Nowadays, it is accepted that natural compounds can result in health benefits with a preventive or adjuvant effect. The purpose of this study was to evaluate the effects of curcumin (CU), a bioactive compound in the spice turmeric, and lactoferrin (LF), a natural glycoprotein with immunomodulatory properties, on DU145 and PC3. Prostate cancer cells were cultured with and without LF (175 µM) and CU (2.5 µg/mL and 5 µg/mL), alone and in combination. Cell viability, migration ability, death receptors (DRs), and integrins (α3, ß1) gene expression were evaluated, as well as human annexin V quantification and Akt phosphorylation. Differences among cells group, defined according to the treatment used, were assessed with ANOVA. The results showed that the effects of CU and LF are different between the two prostatic cell lines analyzed. In DU145, a reduction in cell proliferation and migration is reported both in the presence of single and combined treatments. In PC3 cells, there is a significant reduction in proliferation in the presence of CU alone, while the inhibition of migration is mainly related to the LF treatment and its combination with CU, compared to untreated cells. Moreover, the reduction in gene expression of integrins and Akt pathway activation were observed mostly in the presence of the CU and LF combination, including the upregulation of DR and annexin V levels, with greater significance for the DU145 cells. In conclusion, our results suggest that CU and LF may have a potentially beneficial effect, mainly when administered in combination, leading to a reduction in cancer cells' aggressiveness.

Medicinal herbs and multiple sclerosis: Overview on the hard balance between new therapeutic strategy and occupational health risk.

Multiple sclerosis (MS) is an autoimmune disease characterized by demyelination and axonal loss of the central nervous system (CNS). Despite its spread throughout the world, the mechanisms that determine its onset are still to be defined. Immunological, genetic, viral, and environmental factors and exposure to chemicals may trigger MS. Many studies have highlighted the anti-inflammatory and anti-oxidant effects of medicinal herbs, which make them a natural and complementary treatment for neurodegenerative diseases. A severe reduction of several MS symptoms occurs with herbal therapy. Thus, the request for medicinal plants with potential beneficial effects, for MS patients, is constantly increasing. Consequently, a production increase needs. Unfortunately, many medicinal herbs were untested and their action mechanism, possible adverse effects, contraindications, or interactions with other drugs, are poorly or not investigated. Keeping in mind the pathological mechanisms of MS and the oxidative damages and mitochondrial dysfunctions induced by pesticides, it is important to understand if pesticides used to increase agricultural productivity and their residues in medicinal plants, may increase the risk of developing MS in both workers and consumers. Studies providing some indication about the relationship between environmental exposure to pesticides and MS disease incidence are few, fragmentary, and discordant. The aim of this article is to provide a glance at the therapeutic potential of medicinal plants and at the risk for MS onset of pesticides used by medicinal plant growers and present in medicinal herbs.

Wound-Healing Promotion and Anti-Inflammatory Properties of Carvacrol Prodrugs/Hyaluronic Acid Formulations.

BACKGROUND: Wound healing (WH) is a complex process involving several stages, such as hemostasis, inflammation, re-epithelialization, and remodeling. Many factors can impair WH, and different pharmacological approaches were studied to date, but the increase in antibiotic resistance, invasiveness, treatment duration, and high cost, have often hampered the resolution of the wound. In this study, we investigated the possible application of water-soluble carvacrol prodrugs (WSCPs) and hyaluronic acid (HA) and their formulations (WSCPs/HA) to improve WH and regulate the inflammatory response. MATERIALS AND METHODS: Firstly, the cytotoxicity of 0.1, 1 and 10 µg/mL of HA, WSCPs and WSCPs/HA formulations were evaluated on HaCaT cells and THP-1 cell lines. The ability of WSCPs/HA formulations to modulate wound repair was evaluated in an in vitro model of WH, using HaCaT cells at 6, 18, and 24 h. The expression of WH mediators, after wound closure was determined by qRT-PCR. Following, we polarized THP-1 cells in M1/M2-like macrophages and tested the anti-inflammatory properties of WSCPs/HA formulations. After, we tested the in vitro WH model for the effects of conditioned medium (CM) from M1/M2-like cells cultured in the presence of WSCPs/HA. RESULTS: Results showed that WSCPs/HA formulations were able to significantly raise the wound closure rate, compared to the single constituents, promoting a complete wound closure after 18 h for WSCP1/HA (10 µg/mL) and after 24 h for WSCP2/HA (10 µg/mL), modulating the MMPs, TGFß, and COX-2 gene expression. The effects of CM derived from M1/M2 polarized cells cultured in the presence of WSCPs/HA determined WH regulation, with a better ability of the WSCP2/HA formulation to modulate the time-dependent expression of reparative and inflammatory mediators. CONCLUSION: Our data underline the possible application of WSCPs/HA formulations as bioactive agents for the regulation of the wound repair process by the modulation of inflammatory and remodeling phases, affecting the activity of immune cells.

Improved osteogenic differentiation by extremely low electromagnetic field exposure: possible application for bone engineering.

Human periodontal ligament mesenchymal stem cells (hPDLSCs) are a promising cell type model for regenerative medicine applications due to their anti-inflammatory, immunomodulatory and non-tumorigenic potentials. Extremely low-frequency electromagnetic fields (ELF-EMF) are reported to affect biological properties such as cell proliferation and differentiation and modulate gene expression profile. In this study, we investigated the effects of an intermittent ELF-EMF exposure (6 h/day) for the standard differentiation period (28 days) and for 10 days in hPDLSCs in the presence or not of osteogenic differentiation medium (OM). We evaluated cell proliferation, de novo calcium deposition and osteogenic differentiation marker expression in sham and ELF-EMF-exposed cells. After ELF-EMF exposure, compared with sham-exposed, an increase in cell proliferation rate (p < 0.001) and de novo calcium deposition (p < 0.001) was observed after 10 days of exposure. Real-time PCR and Western blot results showed that COL1A1 and RUNX-2 gene expression and COL1A1, RUNX-2 and OPN protein expression were upregulated respectively in the cells exposed to ELF-EMF exposure along with or without OM for 10 days. Altogether, these results suggested that the promotion of osteogenic differentiation is more efficient in ELF-EMF-exposed hPDLSCs. Moreover, our analyses indicated that there is an early induction of hPDLSC differentiation after ELF-EMF application.

Evaluation of Cell Migration and Cytokines Expression Changes under the Radiofrequency Electromagnetic Field on Wound Healing In Vitro Model.

Wound healing (WH) proceeds through four distinct phases: hemostasis, inflammation, proliferation, and remodeling. Impaired WH may be the consequence of the alteration of one of these phases and represents a significant health and economic burden to millions of individuals. Thus, new therapeutic strategies are the topics of intense research worldwide. Although radiofrequency electromagnetic field (RF-EMF) has many medical applications in rehabilitation, pain associated with musculoskeletal disorders, and degenerative joint disorders, its impact on WH is not fully understood. The process of WH begins just after injury and continues during the inflammatory and proliferative phases. A thorough understanding of the mechanisms by which RF-EMF can improve WH is required before it can be used as a non-invasive, inexpensive, and easily self-applicable therapeutic strategy. Thus, the aim of this study is to explore the therapeutic potential of different exposure setups of RF-EMF to drive faster healing, evaluating the keratinocytes migration, cytokines, and matrix metalloproteinases (MMPs) expression. The results showed that RF-EMF treatment promotes keratinocytes' migration and regulates the expression of genes involved in healing, such as MMPs, tissue inhibitors of metalloproteinases, and pro/anti-inflammatory cytokines, to improve WH.

"Titer of anti-HBs in health professions trainees: prevalence of antibody coverage in a University of Central Italy".

OBJECTIVE: This observational retrospective study aims at verifying hepatitis-B-virus (HBV) vaccination coverage in students vaccinated before and after 1992, in order to optimize health surveillance and vaccination recall. METHODS: Vaccination status was evaluated using the anti-HBs antibody titer (anti-HBs). Student t-test and the chi-square test were performed to identify the average age and the difference in antibody coverage between the two genders and in the two populations analyzed. RESULTS: Our study outlined a prevalence of 21.83% uncovered trainees among those vaccinated at age 12 and 45.03% among those vaccinated in neonatal age. CONCLUSION: In conclusion, our data showed persistent protection against HBV infection in healthcare students.

Muscarinic Receptors Expression in the Peripheral Blood Cells Differentiate Dementia with Lewy Bodies from Alzheimer's Disease.

BACKGROUND: Central nervous system disruption of cholinergic (ACh) signaling, which plays a major role in cognitive processes, is well documented in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). The expression of muscarinic ACh receptors type 1 and 4 (CHRM1 and CHRM4) has been reported to be altered in the brain of DLB patients. OBJECTIVE: We aim to assess the peripheral gene expression of CHRM1 and 4 in DLB as a possible marker as compared to AD and healthy control (HC) subjects. METHODS: Peripheral blood mononuclear cells were collected from 21 DLB, 13 AD, and 8 HC matched subjects. RT-PCR was performed to estimate gene expression of CHRM1 and CHRM4. RESULTS: Peripheral CHRM1 expression was higher and CHRM4 was lower in DLB and AD compared to HC, whereas both CHRM1 and CHRM4 levels were higher in AD compared to DLB patients. Receiver operating characteristics curves, with logistic regression analysis, showed that combining peripheral CHRM1 and CHRM4 levels, DLB and AD subjects were classified with an accuracy of 76.0%. CONCLUSION: Alterations of peripheral CHRM1 and CHRM4 was found in both AD and DLB patients as compared to HC. CHRM1 and CHRM4 gene expression resulted to be lower in DLB patients compared to AD. In the future, peripheral CHRM expression could be studied as a possible marker of neurodegenerative conditions associated with cholinergic deficit and a possible marker of response to acetylcholinesterase inhibitors.

Effects of Probiotic Mixture Supplementation on the Immune Response to the 13-Valent Pneumococcal Conjugate Vaccine in People Living with HIV.

BACKGROUND: In people living with HIV, combination antiretroviral therapy (cART) reduces the risk of death, but the persistent immune-deficient state predisposes them to pneumococcal infections. Current guidelines encourage administering pneumococcal vaccine Prevenar 13 to patients living with HIV. Since probiotic supplementation could act as adjuvants and improve vaccine immunogenicity by modulating gut microbiota, the present study aimed to assess whether the effect of a formulation containing a combination of specific probiotics (Vivomixx®) could improve the immune response to 13-valent pneumococcal conjugate vaccine (PCV13) in adult people living with HIV. METHODS: Thirty patients who were clinically stable and virologically suppressed, without opportunistic infections during this time and no ART changes in the 12 months before the study started were enrolled. Patients were divided into two groups: (1) received a placebo dose and (2) received Vivomixx® (1800 billion CFU) for four weeks before and after the vaccination with a single dose of PCV13. RESULTS: Vivomixx® supplementation induced a better response to PCV13 immunization, as shown by greater change in anti-Pn CPS13 IgG and increase in salivary IgA, IL-10 and IL-8. CONCLUSIONS: Additional investigations will help to clearly and fully elucidate the optimal strains, doses, and timing of administration of probiotics to improve protection upon vaccination in immunocompromised individuals and the elderly.

In Vitro Wound-Healing Properties of Water-Soluble Terpenoids Loaded on Halloysite Clay.

Recently, mineral healing clays have gained much attention for wound-dressing applications. Here, we selected halloysite (HAL) clay as a biocompatible, non-toxic material that is useful as a drug delivery system to enhance the healing properties of water-soluble terpenoids 1-3 (T1-3). Terpenoids-loaded HAL clay (TH1-3) was prepared and characterized by adsorption equilibrium studies, X-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, and release studies. The results reveal that T1-3 were adsorbed at the HAL surface with good efficiency. The prevalent mechanism of drug retention is due to the adsorption via electrostatic interactions between the cationic groups of the T1-3 and the HAL's external surface. Release studies demonstrated that T3 was released in a higher percentage (>60%) compared to T1-2 (≈50%). Additionally, TH1-3 were assessed for their antimicrobial activity and capability to promote the re-epithelialization of scratched HaCat monolayers, through the time-kill test and the wound-healing assays, respectively. The results reveal that all the tested formulations were able to reduce the microbial growth after 1 h of incubation and that they ensured complete wound closure after 48 h. Furthermore, at the concentration of 1 µg/mL, TH3 exhibited 45% wound closure at 24 h, compared to TH1 (27%) and TH2 (30%), proving to be the best candidate in making the tissue-repair process easier and faster.

Wound Repair and Extremely Low Frequency-Electromagnetic Field: Insight from In Vitro Study and Potential Clinical Application.

Wound healing is a complex, staged process. It involves extensive communication between the different cellular constituents of various compartments of the skin and its extracellular matrix (ECM). Different signaling pathways are determined by a mutual influence on each other, resulting in a dynamic and complex crosstalk. It consists of various dynamic processes including a series of overlapping phases: hemostasis, inflammation response, new tissue formation, and tissue remodeling. Interruption or deregulation of one or more of these phases may lead to non-healing (chronic) wounds. The most important factor among local and systemic exogenous factors leading to a chronic wound is infection with a biofilm presence. In the last few years, an increasing number of reports have evaluated the effects of extremely low frequency (ELF) electromagnetic fields (EMFs) on tissue repair. Each experimental result comes from a single element of this complex process. An interaction between ELF-EMFs and healing has shown to effectively modulate inflammation, protease matrix rearrangement, neo-angiogenesis, senescence, stem-cell proliferation, and epithelialization. These effects are strictly related to the time of exposure, waveform, frequency, and amplitude. In this review, we focus on the effect of ELF-EMFs on different wound healing phases.

Assessment of the Vanillin Anti-Inflammatory and Regenerative Potentials in Inflamed Primary Human Gingival Fibroblast.

BACKGROUND: Inflammatory responses have been associated with delayed oral mucosal wound healing and the pathogenesis of the periodontal disease. The invasion of microbes into the tissues and the establishment of a chronic infection may be due to impaired healing. The protracted inflammatory phase may delay wound healing and probably support tissue fibrosis and reduce tissue regeneration. Vanillin is a well-known natural compound with potential anti-inflammatory capacity. Hence, we hypothesized that Vanillin could accelerate wound healing reducing inflammation and especially cytokine production making the oral tissue repair process easier. METHODS: Our hypothesis was tested using primary human gingival fibroblast (HGF) cell pretreated with Vanillin and primed with IL-1ß, as inductor of proinflammatory environment. After 24 hours of treatments, the gene expression and production of IL-6, TNF-α, IL-8, COX-2, iNOS, and nitric oxide (NO) generation and the wound healing rate were determined. RESULTS: In IL-1ß-primed cells, preincubation with Vanillin reduced IL-6, IL-8, COX-2, and iNOS expression and NO release, compared to IL-1ß-primed cells. Moreover, Vanillin determines the increased gene expression of nAChRα7, leading us to hypothesize a role of Vanillin in the activation of the cholinergic anti-inflammatory pathway. Furthermore, in presence of mechanical injury, the Vanillin preincubation, wound closure may be reducing the expression and release of IL-6 and TNF-α and upregulation of COX-2 and IL-8. CONCLUSION: Together, the results of this study highlight the anti-inflammatory and tissue repair ability of Vanillin in IL-1ß-primed HGF. Therefore, Vanillin shows a potential therapeutic interest as an inflammatory modulator molecule with novel application in periodontal regeneration and oral health.

nAChRs gene expression and neuroinflammation in APPswe/PS1dE9 transgenic mouse.

An evaluation of the APPswe/PS1dE9 transgenic AD mouse, presenting with the toxic Aß1-42 deposition found in human AD, allowed us to characterize time-dependent changes in inflammatory and cholinergic markers present in AD. Astrogliosis was observed in cortex and hippocampus, with cellular loss occurring in the same areas in which Aß plaques were present. In this setting, we found early significantly elevated levels of IL-1ß and TNFα gene expression; with the hippocampus showing the highest IL-1ß expression. To investigate the cholinergic anti-inflammatory pathway, the expression of nicotinic receptors (nAChRs) and cholinesterase enzymes also was evaluated. The anti-inflammatory nAChRα7, α4, and ß2 were particularly increased at 6 months of age in the hippocampus, potentially as a strategy to counteract Aß deposition and the ensuing inflammatory state. A time-dependent subunit switch to the α3ß4 type occurred. Whether α3, ß4 subunits have a pro-inflammatory or an inhibitory effect on ACh stimulation remains speculative. Aß1-42 deposition, neuronal loss and increased astrocytes were detected, and a time-dependent change in components of the cholinergic anti-inflammatory pathway were observed. A greater understanding of time-dependent Aß/nAChRs interactions may aid in defining new therapeutic strategies and novel molecular targets.

Cholinergic Modulation of the Immune System in Neuroinflammatory Diseases.

Frequent diseases of the CNS, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and psychiatric disorders (e.g., schizophrenia), elicit a neuroinflammatory response that contributes to the neurodegenerative disease process itself. The immune and nervous systems use the same mediators, receptors, and cells to regulate the immune and nervous systems as well as neuro-immune interactions. In various neurodegenerative diseases, peripheral inflammatory mediators and infiltrating immune cells from the periphery cause exacerbation to current injury in the brain. Acetylcholine (ACh) plays a crucial role in the peripheral and central nervous systems, in fact, other than cells of the CNS, the peripheral immune cells also possess a cholinergic system. The findings on peripheral cholinergic signaling, and the activation of the "cholinergic anti-inflammatory pathway" mediated by ACh binding to α7 nAChR as one of the possible mechanisms for controlling inflammation, have restarted interest in cholinergic-mediated pathological processes and in the new potential therapeutic target for neuro-inflammatory-degenerative diseases. Herein, we focus on recent progress in the modulatory mechanisms of the cholinergic anti-inflammatory pathway in neuroinflammatory diseases.