The hippocampus is a plastic brain area that shows functional segregation along its longitudinal axis, reflected by a higher level of long-term potentiation (LTP) in the CA1 region of the dorsal ...hippocampus (DH) compared to the ventral hippocampus (VH), but the mechanisms underlying this difference remain elusive. Numerous studies have highlighted the importance of microglia-neuronal communication in modulating synaptic transmission and hippocampal plasticity, although its role in physiological contexts is still largely unknown. We characterized in depth the features of microglia in the two hippocampal poles and investigated their contribution to CA1 plasticity under physiological conditions. We unveiled the influence of microglia in differentially modulating the amplitude of LTP in the DH and VH, showing that minocycline or PLX5622 treatment reduced LTP amplitude in the DH, while increasing it in the VH. This was recapitulated in Cx3cr1 knockout mice, indicating that microglia have a key role in setting the conditions for plasticity processes in a region-specific manner, and that the CX3CL1-CX3CR1 pathway is a key element in determining the basal level of CA1 LTP in the two regions. The observed LTP differences at the two poles were associated with transcriptional changes in the expression of genes encoding for Il-1, Tnf-α, Il-6, and Bdnf, essential players of neuronal plasticity. Furthermore, microglia in the CA1 SR region showed an increase in soma and a more extensive arborization, an increased prevalence of immature lysosomes accompanied by an elevation in mRNA expression of phagocytic markers Mertk and Cd68 and a surge in the expression of microglial outward K
currents in the VH compared to DH, suggesting a distinct basal phenotypic state of microglia across the two hippocampal poles. Overall, we characterized the molecular, morphological, ultrastructural, and functional profile of microglia at the two poles, suggesting that modifications in hippocampal subregions related to different microglial statuses can contribute to dissect the phenotypical aspects of many diseases in which microglia are known to be involved.
Introduction
Obsessive Compulsive Disorder (OCD) and Tic Disorder (TD) are two highly disabling, comorbid and difficult-to-treat conditions. DSM-5 acknowledged a new “tic-related” specifier for OCD, ...i.e., Obsessive-Compulsive Tic-related Disorder (OCTD), which may show poor treatment response.
Objectives
The aim of the present study was to evaluate rates and clinical correlates of response, remission and resistance to treatment in a large multicentre sample of OCD patients with versus without tics.
Methods
398 patients with a DSM-5 diagnosis of OCD with and without comorbid TD was assessed from ten psychiatric departments across Italy. Treatment response profiles in the whole sample were analysed comparing the rates of response, remission and treatment-resistance as well as related clinical features. Multivariate logistic regressions were performed to highlight possible treatment response related factors.
Results
Later ages of onset of TD and OCD were found in the remission group. Moreover, significantly higher rates of psychiatric comorbidities, TD, and lifetime suicidal ideation and attempts were associated to the treatment-resistant group, with larger degrees of perceived worsened quality of life and family involvement.
Conclusions
While remission was related to later ages of OCD and TD onset, specific clinical factors, such as early onset and presence of psychiatric comorbidities and concomitant TD, predicted a worse treatment response, with a significant impairment in quality of life for both patients and their caregivers. These findings suggest a worse profile of treatment response for patients with OCTD.
Disclosure
No significant relationships.
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a hyperinflammatory state and lymphocytopenia, a hallmark that appears as both signature and ...prognosis of disease severity outcome. Although cytokine storm and a sustained inflammatory state are commonly associated with immune cell depletion, it is still unclear whether direct SARS-CoV-2 infection of immune cells could also play a role in this scenario by harboring viral replication. We found that monocytes, as well as both B and T lymphocytes, were susceptible to SARS-CoV-2 infection in vitro, accumulating double-stranded RNA consistent with viral RNA replication and ultimately leading to expressive T cell apoptosis. In addition, flow cytometry and immunofluorescence analysis revealed that SARS-CoV-2 was frequently detected in monocytes and B lymphocytes from coronavirus disease 2019 (COVID-19) patients. The rates of SARS-CoV-2-infected monocytes in peripheral blood mononuclear cells from COVID-19 patients increased over time from symptom onset, with SARS-CoV-2-positive monocytes, B cells, and CD4+ T lymphocytes also detected in postmortem lung tissue. These results indicated that SARS-CoV-2 infection of blood-circulating leukocytes in COVID-19 patients might have important implications for disease pathogenesis and progression, immune dysfunction, and virus spread within the host.
•Acute Escape Deficit model unveils vulnerable and resilient phenotypes in rats.•Bdnf exon IV mRNA increases in the hippocampus of resilient animals 3 h post test.•Npas4 and Arc respond in a time- ...and region-specific manner in stress-exposed rats.
Understanding resilience is a major challenge to improve current pharmacological therapies aimed at complementing psychological-based approaches of stress-related disorders. In particular, resilience is a multi-factorial construct where the complex network of molecular events that drive the process still needs to be resolved. Here, we exploit the acute escape deficit model, an animal model based on exposure to acute unavoidable stress followed by an escape test, to define vulnerable and resilient phenotypes in rats. Hippocampus and prefrontal cortex (PFC), two of the brain areas most involved in the stress response, were analysed for gene expression at two different time points (3 and 24 h) after the escape test. Total Brain-Derived Neurotrophic Factor (BDNF) was highly responsive in the PFC at 24-h after the escape test, while expression of BDNF transcript IV increased in the hippocampus of resistant animals 3 h post-test. Expression of memory enhancers like Neuronal PAS Domain Protein 4 (Npas4) and Activity-regulated cytoskeleton-associated protein (Arc) decreased in a time- and region-dependent fashion in both behavioural phenotypes. Also, the memory inhibitor Protein Phosphatase 1 (Ppp1ca) was increased in the hippocampus of resilient rats at 3 h post-test. Given the importance of neurotrophic factors and synaptic plasticity-related genes for the development of appropriate coping strategies, our data contribute to an additional step forward in the comprehension of the psychobiology of stress and resiliency.
pHEMA hydrogels Passos, M. F.; Dias, D. R. C.; Bastos, G. N. T. ...
Journal of thermal analysis and calorimetry,
07/2016, Volume:
125, Issue:
1
Journal Article
Peer reviewed
Hydrogels of poly (2-hydroxyethyl methacrylate) (pHEMA) are suitable materials for medical applications. Synthesis, structural characterization, kinetic, physical properties and cell viability of ...these materials are reported in this article. The system was conducted via free radical polymerization in the absence of solvents or cross-linking agents. Hydrogels were obtained with excellent dimensional stability and high thermal stability (738 K), glass transition temperature of approximately 375 K and a degree of swelling of 66 ± 4 % in ethanol. The conversion of C=C double bond of the monomer 2-hydroxyethyl methacrylate was confirmed by Fourier transform infrared spectroscopy. Results showed dense and rough morphologies in the pHEMA, presence of high molecular interactions and good resistance to various organic solvents. In vitro tests showed excellent cell viability. The materials did not display cytotoxicity, and cells proliferated and adhered at a satisfactory rate on the hydrogel. These materials have great potential for biomedical application.
Graphical Abstract
pHEMA hydrogels are materials receiving great attention among researchers due to their ease of synthesis and biomedical application. This article demonstrates a new method of obtaining pHEMA hydrogels by bulk polymerization, in a single processing step and without the use of cross-linking agents. A kinetic study was evaluated, and the results of in vitro tests showed good cell proliferation.
Introduction
During the COVID-19 pandemic, health workers represented a group particularly vulnerable to work-related stress, but prevention and management of psychiatric symptoms are still under ...evaluation. Neurofeedback is a safe and non-invasive neuromodulation technique with the target of training participants in the self-regulation of neural substrates underlying specific psychiatric disorders. Protocols based on the increase of alpha frequencies, associated with the process of relaxation, are used for the treatment of stress, anxiety and sleep disturbances.
Objectives
The aim of the present study was to assess the effectiveness of an alpha-increase NF protocol for the treatment of stress in healthcare workers exposed to the COVID-19 pandemic.
Methods
Eighteen medical doctors belonging to the Sacco Hospital were recruited during the COVID-19 health emergency and underwent a 10 sessions NF alpha-increase protocol during two consecutive weeks. The level of stress was assessed at the beginning (T0) and at the end (T1) of the protocol through the following questionnaires: Severity of Acute Symptoms Stress (SASS), Copenhagen Burnout Inventory (CBI), Pittsburgh Sleep Quality Index (PSQI), Brief-COPE. Statistical analyses were performed with Paired Samples t-Test for continuous variables, setting significance at p < 0.05.
Results
A significant increase in alpha waves mean values between T0 and T1 was observed. In addition, a significant reduction in the PSQI test score between T0 and T1 was observed.
Conclusions
Alpha-increase protocol showed promising results in terms of stress modulation, sleep quality improvement and safety profile in a pilot sample of health-care workers. Larger controlled studies are warranted to confirm present results.
Vortioxetine is a novel multimodal antidepressant that modulates a wide range of neurotransmitters throughout the brain. Preclinical and clinical studies have shown that vortioxetine exerts positive ...effects on different cognitive domains and neuroprotective effects. Considering the key role of microglial cells in brain plasticity and cognition, we aimed at investigating the effects of pretreatment with vortioxetine in modulating behavioral and molecular effects induced by an immune challenge: peripheral injection of lipopolysaccharide (LPS). To this purpose, C57BL/6J male mice were first exposed to a 28-day standard diet or vortioxetine-enriched diet, which was followed by an acute immune challenge with LPS. Sickness symptoms and depressive-like behaviors (anhedonia and memory impairment) were tested 6 and 24 h after exposure to LPS, respectively. Moreover, the expressions of markers of immune activation and M1/M2 markers of microglia polarization were measured in the dorsal and ventral parts of the hippocampus. The pretreatment with vortioxetine did not affect both LPS-induced sickness behavior and anhedonia but prevented the deficit in the recognition memory induced by the immune challenge. At the transcriptional level, chronic exposure to vortioxetine did not prevent LPS-induced upregulation of proinflammatory cytokines 6 h after the immune challenge but rather seemed to potentiate the immune response to the challenge also by affecting the levels of expression of markers of microglia M1 phenotype, like cluster of differentiation (CD)14 and CD86, in an area-dependent manner. However, at the same time point, LPS injection significantly increased the expression of the M2 polarization inducer, interleukin 4, only in the hippocampus of animals chronically exposed to vortioxetine. These results demonstrate that a chronic administration of vortioxetine specifically prevents LPS-induced memory impairment, without affecting acute sickness behavior and anhedonia, and suggest that hippocampal microglia may represent a cellular target of this novel antidepressant medication. Moreover, we provide a useful model to further explore the molecular mechanisms specifically underlying cognitive impairments following an immune challenge.
Context. Stellar activity is currently challenging the detection of young planets via the radial velocity (RV) technique. Aims. We attempt to definitively discriminate the nature of the RV variations ...for the young active K5 star BD+20 1790, for which visible (VIS) RV measurements show divergent results on the existence of a substellar companion. Methods. We compare VIS data with high precision RVs in the near-infrared (NIR) range by using the GIANO–B and IGRINS spectrographs. In addition, we present for the first time simultaneous VIS-NIR observations obtained with GIARPS (GIANO–B and HARPS–N) at Telescopio Nazionale Galileo (TNG). Orbital RVs are achromatic, so the RV amplitude does not change at different wavelengths, while stellar activity induces wavelength-dependent RV variations, which are significantly reduced in the NIR range with respect to the VIS. Results. The NIR radial velocity measurements from GIANO–B and IGRINS show an average amplitude of about one quarter with respect to previously published VIS data, as expected when the RV jitter is due to stellar activity. Coeval multi-band photometry surprisingly shows larger amplitudes in the NIR range, explainable with a mixture of cool and hot spots in the same active region. Conclusions. In this work, the claimed massive planet around BD+20 1790 is ruled out by our data. We exploited the crucial role of multi-wavelength spectroscopy when observing young active stars: thanks to facilities like GIARPS that provide simultaneous observations, this method can reach its maximum potential.
Severe cases of COVID-19 are characterized by a strong inflammatory process that may ultimately lead to organ failure and patient death. The NLRP3 inflammasome is a molecular platform that promotes ...inflammation via cleavage and activation of key inflammatory molecules including active caspase-1 (Casp1p20), IL-1β, and IL-18. Although participation of the inflammasome in COVID-19 has been highly speculated, the inflammasome activation and participation in the outcome of the disease are unknown. Here we demonstrate that the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection and is active in COVID-19 patients. Studying moderate and severe COVID-19 patients, we found active NLRP3 inflammasome in PBMCs and tissues of postmortem patients upon autopsy. Inflammasome-derived products such as Casp1p20 and IL-18 in the sera correlated with the markers of COVID-19 severity, including IL-6 and LDH. Moreover, higher levels of IL-18 and Casp1p20 are associated with disease severity and poor clinical outcome. Our results suggest that inflammasomes participate in the pathophysiology of the disease, indicating that these platforms might be a marker of disease severity and a potential therapeutic target for COVID-19.
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