Hippocampal Proliferation Is Increased in Presymptomatic Parkinson’s Disease and due to Microglia

Besides dopamine-deficiency related motor symptoms, nonmotor symptoms, including cognitive changes occur in Parkinson's disease (PD) patients, that may relate to accumulation of α-synuclein in the hippocampus (HC). This brain region also contains stem cells that can proliferate. This is a well-regulated process that can, for example, be altered by neurodegenerative conditions. In contrast to proliferation in the substantia nigra and subventricular zone, little is known about the HC in PD. In addition, glial cells contribute to neurodegenerative processes and may proliferate in response to PD pathology. In the present study, we questioned whether microglial cells proliferate in the HC of established PD patients versus control subjects or incidental Lewy body disease (iLBD) cases as a prodromal state of PD. To this end, proliferation was assessed using the immunocytochemical marker minichromosome maintenance protein 2 (MCM2). Colocalization with Iba1 was performed to determine microglial proliferation. MCM2-positive cells were present in the HC of controls and were significantly increased in the presymptomatic iLBD cases, but not in established PD patients. Microglia represented the majority of the proliferating cells in the HC. This suggests an early microglial response to developing PD pathology in the HC and further indicates that neuroinflammatory processes play an important role in the development of PD pathology

H2020 COVR FSTP LIAISON – D2.5 LIAISON Lessons learned and evaluation report.

Horizon 2020(H2020)779966Effective Protection of Fundamental Rights in a pluralist worl

H2020 COVR FSTP LIAISON – D2.4 Policy brief for standard and policymakers (EU & NEN)

Horizon 2020(H2020)779966Effective Protection of Fundamental Rights in a pluralist worl

H2020 COVR FSTP LIAISON – D2.6 MS2 COVR presentation describing MS2 results and achievements.

Horizon 2020(H2020)779966Effective Protection of Fundamental Rights in a pluralist worl

H2020 COVR FSTP LIAISON – D2.2 Lecture on the ‘future of law’

Horizon 2020(H2020)779966Effective Protection of Fundamental Rights in a pluralist worl

H2020 COVR FSTP LIAISON – D2.1 Recommendations for the COVR Toolkit update

Horizon 2020(H2020)779966Effective Protection of Fundamental Rights in a pluralist worl

H2020 COVR FSTP LIAISON – D2.3 Academic publication featuring the future of robot governance.

Horizon 2020(H2020)779966Effective Protection of Fundamental Rights in a pluralist worl

Thinking about the action potential: the nerve signal as a window to the physical principles guiding neuronal excitability

Ever since the work of Edgar Adrian, the neuronal action potential has been considered as an electric signal, modeled and interpreted using concepts and theories lent from electronic engineering. Accordingly, the electric action potential, as the prime manifestation of neuronal excitability, serving processing and reliable “long distance” communication of the information contained in the signal, was defined as a non-linear, self-propagating, regenerative, wave of electrical activity that travels along the surface of nerve cells. Thus, in the ground-breaking theory and mathematical model of Hodgkin and Huxley (HH), linking Nernst’s treatment of the electrochemistry of semi-permeable membranes to the physical laws of electricity and Kelvin’s cable theory, the electrical characteristics of the action potential are presented as the result of the depolarization-induced, voltage- and time-dependent opening and closure of ion channels in the membrane allowing the passive flow of charge, particularly in the form of Na+ and K+ -ions, into and out of the neuronal cytoplasm along the respective electrochemical ion gradient. In the model, which treats the membrane as a capacitor and ion channels as resistors, these changes in ionic conductance across the membrane cause a sudden and transient alteration of the transmembrane potential, i.e., the action potential, which is then carried forward and spreads over long(er) distances by means of both active and passive conduction dependent on local current flow by diffusion of Na+ ion in the neuronal cytoplasm. However, although highly successful in predicting and explaining many of the electric characteristics of the action potential, the HH model, nevertheless cannot accommodate the various non-electrical physical manifestations (mechanical, thermal and optical changes) that accompany action potential propagation, and for which there is ample experimental evidence. As such, the electrical conception of neuronal excitability appears to be incomplete and alternatives, aiming to improve, extend or even replace it, have been sought for. Commonly misunderstood as to their basic premises and the physical principles they are built on, and mistakenly perceived as a threat to the generally acknowledged explanatory power of the “classical” HH framework, these attempts to present a more complete picture of neuronal physiology, have met with fierce opposition from mainstream neuroscience and, as a consequence, currently remain underdeveloped and insufficiently tested. Here we present our perspective that this may be an unfortunate state of affairs as these different biophysics-informed approaches to incorporate also non-electrical signs of the action potential into the modeling and explanation of the nerve signal, in our view, are well suited to foster a new, more complete and better integrated understanding of the (multi)physical nature of neuronal excitability and signal transport and, hence, of neuronal function. In doing so, we will emphasize attempts to derive the different physical manifestations of the action potential from one common, macroscopic thermodynamics-based, framework treating the multiphysics of the nerve signal as the inevitable result of the collective material, i.e., physico-chemical, properties of the lipid bilayer neuronal membrane (in particular, the axolemma) and/or the so-called ectoplasm or membrane skeleton consisting of cytoskeletal protein polymers, in particular, actin fibrils. Potential consequences for our view of action potential physiology and role in neuronal function are identified and discussed

Harnessing robot experimentation to optimize the regulatory framing of emerging robot technologies

Horizon 2020(H2020)779963Effective Protection of Fundamental Rights in a pluralist worl

An iterative regulatory process for robot governance

There is an increasing gap between the policy cycle’s speed and that of technological and social change. This gap is becoming broader and more prominent in robotics, that is, movable machines that perform tasks either automatically or with a degree of autonomy. This is because current legislation was unprepared for machine learning and autonomous agents. As a result, the law often lags behind and does not adequately frame robot technologies. This state of affairs inevitably increases legal uncertainty. It is unclear what regulatory frameworks developers have to follow to comply, often resulting in technology that does not perform well in the wild, is unsafe, and can exacerbate biases and lead to discrimination. This paper explores these issues and considers the background, key findings, and lessons learned of the LIAISON project, which stands for “Liaising robot development and policymaking,” and aims to ideate an alignment model for robots’ legal appraisal channeling robot policy development from a hybrid top-down/bottom-up perspective to solve this mismatch. As such, LIAISON seeks to uncover to what extent compliance tools could be used as data generators for robot policy purposes to unravel an optimal regulatory framing for existing and emerging robot technologies