16 research outputs found
JAB1 deletion in oligodendrocytes causes senescence-induced inflammation and neurodegeneration in mice
Oligodendrocytes are the primary target of demyelinating disorders, and progressive neurodegenerative changes may evolve in the CNS. DNA damage and oxidative stress are considered key pathogenic events, but the underlying molecular mechanisms remain unclear. Moreover, animal models do not fully recapitulate human diseases, complicating the path to effective treatments. Here we report that mice with cell-autonomous deletion of the nuclear COP9 signalosome component CSN5 (JAB1) in oligodendrocytes develop DNA damage and defective DNA repair in myelinating glial cells. Interestingly, oligodendrocytes lacking JAB1 expression underwent a senescence-like phenotype that fostered chronic inflammation and oxidative stress. These mutants developed progressive CNS demyelination, microglia inflammation, and neurodegeneration, with severe motor deficits and premature death. Notably, blocking microglia inflammation did not prevent neurodegeneration, whereas the deletion of p21CIP1 but not p16INK4a pathway ameliorated the disease. We suggest that senescence is key to sustaining neurodegeneration in demyelinating disorders and may be considered a potential therapeutic target
JAB1 deletion in oligodendrocytes causes senescence-induced inflammation and neurodegeneration in mice
Oligodendrocytes are the primary target of demyelinating disorders and progressive neurodegenerative changes may evolve in the CNS. DNA damage and oxidative stress are considered key pathogenic events, but the underlying molecular mechanisms remain unclear. Moreover, animal models do not fully recapitulate human diseases, complicating the path to effective treatments. Here we report that mice with cell autonomous deletion of the nuclear COP9 signalosome component CSN5 (JAB1) in oligodendrocytes develop DNA damage and defective DNA repair in myelinating glial cells. Interestingly, oligodendrocytes lacking JAB1 expression underwent a senescence-like phenotype that fostered chronic inflammation and oxidative stress. These mutants developed progressive CNS demyelination, microglia inflammation and neurodegeneration, with severe motor deficits and premature death. Notably, blocking microglia inflammation did not prevent neurodegeneration, whereas the deletion of p21CIP1 but not p16INK4a pathway ameliorated the disease. We suggest that senescence is key to sustaining neurodegeneration in demyelinating disorders and may be considered a potential therapeutic target
Effects of Mountain Ultra-Marathon Running on ROS Production and Oxidative Damage by Micro-Invasive Analytic Techniques
Multicenter study report: electrophysiological monitoring procedures for subthalamic deep brain stimulation surgery in Parkinson’s disease
A Semantic-Enabled Smart Home for AAL and Continuity of Care
The rise of Internet of Things (IoT) technologies provided the means to enable the smart home (SH), a residence aimed at anticipating and responding to its dwellers\u2019 needs and one of the most promising Ambient Assisted Living (AAL) solutions. However, the massive adoption of monitoring techniques and some shortcomings in the field of security can hinder the adoption of IoT-based SH solutions. In this work, we describe how we have addressed the challenges arising from the fields of AAL and continuity of care, by creating the Smart Human-Centred Living Environment Lab, an innovative prototype of a SH that can address the specificities of each inhabitant. The system on which the SH relies is a knowledge-based system that leverages the semantic representations of relevant concepts and data, thus allowing for the customization of services according to each inhabitant\u2019s needs and preferences, without the need of continuous monitoring. A semantic middleware ensures the semantic interoperability of the information and thus the realization of an IoT-based architecture optimizing the provision of each service. Finally, digital applications and virtual reality-based systems are integrated in the SH to provide support to the activities of daily living and the execution of rehabilitative exercises, in the perspective of continuity of care. The system tries to address the issues of other SHs, in which privacy concerns, stigma, and ageism may hinder the use of innovative technologies in daily life. However, a few issues still remain: among these, the validation of the whole system in terms of users\u2019 acceptance and the possibility of providing such a service on a large scale
A High Precision Method for Quantitative Measurements of Reactive Oxygen Species in Frozen Biopsies
Objective: An electron paramagnetic resonance (EPR) technique using the spin probe cyclic hydroxylamine 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH) was introduced as a versatile method for high precision quantification of reactive oxygen species, including the superoxide radical in frozen biological samples such as cell suspensions, blood or biopsies. Materials and Methods: Loss of measurement precision and accuracy due to variations in sample size and shape were minimized by assembling the sample in a well-defined volume. Measurement was carried out at low temperature (150 K) using a nitrogen flow Dewar. The signal intensity was measured from the EPR 1st derivative amplitude, and related to a sample, 3-carboxy-proxyl (CPN) with known spin concentration. Results: The absolute spin concentration could be quantified with a precision and accuracy better than +/- 10 mu M (k = 1). The spin concentration of samples stored at -80 degrees C could be reproduced after 6 months of storage well within the same error estimate. Conclusion: The absolute spin concentration in wet biological samples such as biopsies, water solutions and cell cultures could be quantified with higher precision and accuracy than normally achievable using common techniques such as flat cells, tissue cells and various capillary tubes. In addition; biological samples could be collected and stored for future incubation with spin probe, and also further stored up to at least six months before EPR analysis, without loss of signal intensity. This opens for the possibility to store and transport incubated biological samples with known accuracy of the spin concentration over time