An Inflammation-Centric View of Neurological Disease: Beyond the Neuron

Inflammation is a complex biological response fundamental to how the body deals with injury and infection to eliminate the initial cause of cell injury and effect repair. Unlike a normally beneficial acute inflammatory response, chronic inflammation can lead to tissue damage and ultimately its destruction, and often results from an inappropriate immune response. Inflammation in the nervous system ("neuroinflammation"), especially when prolonged, can be particularly injurious. While inflammation per se may not cause disease, it contributes importantly to disease pathogenesis across both the peripheral (neuropathic pain, fibromyalgia) and central [e.g., Alzheimer disease, Parkinson disease, multiple sclerosis, motor neuron disease, ischemia and traumatic brain injury, depression, and autism spectrum disorder] nervous systems. The existence of extensive lines of communication between the nervous system and immune system represents a fundamental principle underlying neuroinflammation. Immune cell-derived inflammatory molecules are critical for regulation of host responses to inflammation. Although these mediators can originate from various non-neuronal cells, important sources in the above neuropathologies appear to be microglia and mast cells, together with astrocytes and possibly also oligodendrocytes. Understanding neuroinflammation also requires an appreciation that non-neuronal cell-cell interactions, between both glia and mast cells and glia themselves, are an integral part of the inflammation process. Within this context the mast cell occupies a key niche in orchestrating the inflammatory process, from initiation to prolongation. This review will describe the current state of knowledge concerning the biology of neuroinflammation, emphasizing mast cell-glia and glia-glia interactions, then conclude with a consideration of how a cell's endogenousmechanisms might be leveraged to provide a therapeutic strategy to target neuroinflammation

Nanoscale mechanical properties of lipid bilayers and their relevance in biomembrane organization and function

The mechanical properties of biological systems are emerging as fundamental in determining their functional activity. For example, cells continuously probe their environment by applying forces and, at the same time, are exposed to forces produced by the same environment. Also in biological membranes, the activity of membrane related proteins are affected by the overall mechanical properties of the hosting environment. Traditionally, the mesoscopic mechanical properties of lipid bilayers have been studied by micropipette aspiration techniques. In recent years, the possibility of probing mechanical properties of lipid bilayers at the nanoscale has been promoted by the force spectroscopy potentiality of Atomic Force Microscopes (AFM). By acquiring force-curves on supported lipid bilayers (SLBs) it is possible to probe the mechanical properties on a scale relevant to the interaction between membrane proteins and lipid bilayers and to monitor changes of these properties as a result of a changing environment. Here, we review a series of force spectroscopy experiments performed on SLBs with an emphasis on the functional consequences the measured mechanical properties can have on membrane proteins. We also discuss the force spectroscopy experiments on SLBs in the context of theories developed for dynamic force spectroscopy experiments with the aim to extract the kinetic and energetic description of the process of membrane rupture

Choir transhumance in the Filipino Catholic community in Rome

The article is part of a research project (2014-2018) among Christian immigrants in Rome and focuses particularly on the Filipino community. Serena Facci presents the general context of the migrant church experience of Rome, a city historically considered as central to the wider transnational community of Catholic Christians, where, thanks to the hosting politics of the Vicariate, there are several ‘national’ and ‘multinational’ churches, characterised by liturgies in different languages and by repertoires of chants in different geocultural styles. The migrants’ position in the holy city is juxtaposed with the multicentricity of the diaspora and the mediation between the motherland and the new places of residence. Grazia Tuzi shows how the Filipinos in Rome represent this multicentricity through the liturgical services of musical groups and choirs from the peripheral churches surrounding Rome. On Sundays, the Filipino micro-communities proceed in a kind of “transhumant” movement according to a predetermined schedule, from their parishes to the Chaplaincy located in the Basilica of Santa Pudenziana, which is the gathering place of all Filipinos living in Rome. Here they accompany the Sunday liturgy and religious Festivals in performances that bear witness to a remarkable musical variety. The analysis of these musical practices and the complex organization of the choir’s "transhumance" from the periphery to the centre can facilitate the understanding of the processes used by this migrant community in the re-articulation and maintenance of their own identity in the new socio-cultural spheres.  The article is part of a research project (2014-2018) among Christian immigrants in Rome and focuses particularly on the Filipino community. Serena Facci presents the general context of the migrant church experience of Rome, a city historically considered as central to the wider transnational community of Catholic Christians, where, thanks to the hosting politics of the Vicariate, there are several ‘national’ and ‘multinational’ churches, characterised by liturgies in different languages and by repertoires of chants in different geocultural styles. The migrants’ position in the holy city is juxtaposed with the multicentricity of the diaspora and the mediation between the motherland and the new places of residence. Grazia Tuzi shows how the Filipinos in Rome represent this multicentricity through the liturgical services of musical groups and choirs from the peripheral churches surrounding Rome. On Sundays, the Filipino micro-communities proceed in a kind of “transhumant” movement according to a predetermined schedule, from their parishes to the Chaplaincy located in the Basilica of Santa Pudenziana, which is the gathering place of all Filipinos living in Rome. Here they accompany the Sunday liturgy and religious Festivals in performances that bear witness to a remarkable musical variety. The analysis of these musical practices and the complex organization of the choir’s "transhumance" from the periphery to the centre can facilitate the understanding of the processes used by this migrant community in the re-articulation and maintenance of their own identity in the new socio-cultural spheres.

A co-ultramicronized palmitoylethanolamide/luteolin composite mitigates clinical score and disease-relevant molecular markers in a mouse model of experimental autoimmune encephalomyelitis

Background: Persistent and/or recurrent inflammatory processes are the main factor leading to multiple sclerosis (MS) lesions. The composite ultramicronized palmitoylethanolamide, an endogenous N-acylethanolamine, combined with the flavonoid luteolin, PEALut, have been found to exert neuroprotective activities in experimental models of spinal and brain injury and Alzheimer disease, as well as a clinical improvement in human stroke patients. Furthermore, PEALut enhances the expression of different myelin proteins in oligodendrocyte progenitor cells suggesting that this composite might have protective effects in MS experimental models. Methods: The mouse model of experimental autoimmune encephalomyelitis (EAE) based on active immunization with a fragment of myelin oligodendrocyte glycoprotein (MOG35-55) was used. The daily assessment of clinical score and the expression of serum amyloid A (SAA1), proinflammatory cytokines TNF-\u3b1, IL-1\u3b2, IFN-\u3b3, and NLRP3 inflammasome, as well as TLR2, Fpr2, CD137, CD3-\u3b3, and TCR-\u3b6 chain, heterodimers that form T cell surface glycoprotein (TCR), and cannabinoid receptors CB1, CB2, and MBP, were evaluated in the brainstem and cerebellum at different postimmunization days (PIDs). Results: Vehicle-MOG35-55-immunized (MOG35-55) mice developed ascending paralysis which peaked several days later and persisted until the end of the experiment. PEALut, given intraperitoneally daily starting on day 11 post-immunization, dose-dependently improved clinical score over the range 0.1-5 mg/kg. The mRNA expression of SAA1, TNF-\u3b1, IL-1\u3b2, IFN-\u3b3, and NLRP3 were significantly increased in MOG35-55 mice at 14 PID. In MOG35-55 mice treated with 5 mg /kg PEALut, the increase of SAA1, TNF- \u3b1, IL-1\u3b2, and IFN-\u3b3transcripts at 14 PID was statistically downregulated as compared to vehicle-MOG35-55 mice (p < 0.05). The expression of TLR2, Fpr2, CD137, CD3-\u3b3, TCR-\u3b6 chain, and CB2 receptors showed a significant upregulation in vehicle-MOG35-55 mice at 14 PID. Instead, CB1 and MBP transcripts have not changed in expression at any time. In MOG/PEALut-treated mice, TLR2, Fpr2, CD137, CD3-\u3b3, TCR-\u3b6 chain, and CB2 mRNAs were significantly downregulated as compared to vehicle MOG35-55 mice. Conclusions: The present results demonstrate that the intraperitoneal administration of the composite PEALut significantly reduces the development of clinical signs in the MOG35-55 model of EAE. The dose-dependent improvement of clinical score induced by PEALut was associated with a reduction in transcript expression of the acute-phase protein SAA1, TNF-\u3b1, IL-1\u3b2, IFN-\u3b3, and NLRP3 proinflammatory proteins and TLR2, Fpr2, CD137, CD3-\u3b3, TCR-\u3b6 chain, and CB2 receptors