Impairment and Restoration of Homeostatic Plasticity in Cultured Cortical Neurons From a Mouse Model of Huntington Disease

Huntington disease (HD) is an inherited neurodegenerative disorder caused by a mutation in the huntingtin gene. The onset of symptoms is preceded by synaptic dysfunction. Homeostatic synaptic plasticity (HSP) refers to processes that maintain the stability of networks of neurons, thought to be required to enable new learning and cognitive flexibility. One type of HSP is synaptic scaling, in which the strength of all of the synapses onto a cell increases or decreases following changes in the cell’s level of activity. Several pathways implicated in synaptic scaling are dysregulated in HD, including brain-derived neurotrophic factor (BDNF) and calcium signaling. Here, we investigated whether HSP is disrupted in cortical neurons from an HD mouse model. We treated cultured cortical neurons from wild-type (WT) FVB/N or YAC128 HD mice with tetrodotoxin (TTX) for 48 h to silence action potentials and then recorded miniature excitatory postsynaptic currents. In WT cultures, these increased in both amplitude and frequency after TTX treatment, and further experiments showed that this was a result of insertion of AMPA receptors and formation of new synapses, respectively. Manipulation of BDNF concentration in the culture medium revealed that BDNF signaling contributed to these changes. In contrast to WT cortical neurons, YAC128 cultures showed no response to action potential silencing. Strikingly, we were able to restore the TTX-induced changes in YAC128 cultures by treating them with pridopidine, a drug which enhances BDNF signaling through stimulation of the sigma-1 receptor (S1R), and with the S1R agonist 3-PPP. These data provide evidence for disruption of HSP in cortical neurons from an HD mouse model that is restored by stimulation of S1R. Our results suggest a potential new direction for developing therapy to mitigate cognitive deficits in HD

Proceedings of the Fourth Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies

This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson’s disease, essential tremor, Alzheimer’s disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year’s international Think Tank, with a view toward current and near future advancement of the field

Intrusive Traumatic Re-Experiencing Domain (ITRED) – Functional Connectivity Feature Classification by the ENIGMA PTSD Consortium

Background Intrusive Traumatic Re-Experiencing Domain (ITRED) was recently introduced as a novel perspective on posttraumatic psychopathology, proposing to focus research of posttraumatic stress disorder (PTSD) on the unique symptoms of intrusive and involuntary re-experiencing of the trauma, namely, intrusive memories, nightmares, and flashbacks. The aim of the present study was to explore ITRED from a neural network connectivity perspective. Methods Data was collected from nine sites taking part in the ENIGMA-PTSD Consortium (n=584) and included itemized PTSD symptoms scores and resting-state functional connectivity (rsFC) data. We assessed the utility of rsFC in classifying PTSD, ITRED-only (no PTSD diagnosis), and Trauma-exposed (TE)-only (no PTSD or ITRED) groups using a machine learning approach, examining well-known networks implicated in PTSD. Random forest classification model was built on a training set using cross-validation (CV), and the averaged CV model performance for classification was evaluated using area-under-the-curve (AUC). The model was tested using a fully independent portion of the data (test dataset), and the test AUC was evaluated. Results RsFC signatures differentiated TE-only participants from PTSD and from ITRED-only participants at about 60% accuracy. Conversely, rsFC signatures did not differentiate PTSD from ITRED-only individuals (45% accuracy). Common features differentiating TE-only participants from PTSD and from ITRED-only participants mainly involved default mode network-related pathways. Some unique features, such as connectivity within the frontal-parietal network, differentiated TE-only participants from one group (PTSD or ITRED-only), but to a lesser extent from the other. Conclusion Neural network connectivity supports ITRED as a novel neurobiologically-based approach to classifying post-trauma psychopathology

Specific ion channels contribute to key elements of pathology during secondary degeneration following neurotrauma

Background: Following partial injury to the central nervous system, cells beyond the initial injury site undergo secondary degeneration, exacerbating loss of neurons, compact myelin and function. Changes in Ca 2+ flux are associated with metabolic and structural changes, but it is not yet clear how flux through specific ion channels contributes to the various pathologies. Here, partial optic nerve transection in adult female rats was used to model secondary degeneration. Treatment with combinations of three ion channel inhibitors was used as a tool to investigate which elements of oxidative and structural damage related to long term functional outcomes. The inhibitors employed were the voltage gated Ca 2+ channel inhibitor Lomerizine (Lom), the Ca 2+ permeable AMPA receptor inhibitor YM872 and the P2X 7 receptor inhibitor oxATP. Results: Following partial optic nerve transection, hyper-phosphorylation of Tau and acetylated tubulin immunoreactivity were increased, and Nogo-A immunoreactivity was decreased, indicating that axonal changes occurred acutely. All combinations of ion channel inhibitors reduced hyper-phosphorylation of Tau and increased Nogo-A immunoreactivity at day 3 after injury. However, only Lom/oxATP or all three inhibitors in combination significantly reduced acetylated tubulin immunoreactivity. Most combinations of ion channel inhibitors were effective in restoring the lengths of the paranode and the paranodal gap, indicative of the length of the node of Ranvier, following injury. However, only all three inhibitors in combination restored to normal Ankyrin G length at the node of Ranvier. Similarly, HNE immunoreactivity and loss of oligodendrocyte precursor cells were only limited by treatment with all three ion channel inhibitors in combination. Conclusions: Data indicate that inhibiting any of a range of ion channels preserves certain elements of axon and node structure and limits some oxidative damage following injury, whereas ionic flux through all three channels must be inhibited to prevent lipid peroxidation and preserve Ankyrin G distribution and OPCs

Bearing capacity of closed and open ended pipe piles installed in loose sand with emphasis on soil plug

703-724Present study investigates the behaviour of plug on pile load capacity and effect of plug removal. Different parameters are considered such as pile diameter to length ratio, type of installation in loose sand, removal of plug in three stages (50%, 75% and 100%) with respect to length of plug. Kerbala sand from Iraq, which is used as a foundation soil is poorly graded clean sand. It was concluded that the percentage of reduction in pile load capacity for open–ended pile increases with increase of the length of removal of the soil plug. Open-ended pipe pile behaves as a closed-ended if the soil plug formed inside piles is in state of partial plug or full plug. The failure of a pile to plug during driving does not necessarily mean that it will not plug during static loading, since inertia effects, which are present during driving are absent during static loading. This can be observed from the load-settlement curves where the open-ended piles exhibit large resistance to penetration due to mobilization of internal friction during static loading

Intravenous iron therapy for anemic cancer patients: A review of recently published clinical studies

Based on available literature and on the present review, IV iron administration to anemic cancer patients can increase significantly the level of Hb, probably independently from the precise mechanism of anemia itself. However, in future studies, the benefit should be evaluated taking into account whether the anemia is due to absolute or functional iron deficiency; therapeutic modalities might be different for these two conditions. Along the same lines, it appears important to further evaluate the respective roles of PO and IV iron therapies and the modalities of their use in clinical practice. Until the results of such studies are available, it appears reasonable to propose IV iron therapy to anemic cancer patients as the resulting rise of Hb level may increase their quality of life and performance status and reduce the need for erythropoietin-stimulating agents and/or blood transfusions.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Transition Metal Carbides Filler-Reinforced Composite Polymer Electrolyte for Solid-State Lithium-Sulfur Batteries at Room Temperature: Breakthrough

All solid-state room-temperature lithium-sulfur (Li-S) batteries have gained increasing attention due to their ability to eliminate the polysulfides shuttle effects and the safety dangers associated with the liquid electrolytes. Herein, a novel composite solid-state electrolyte, which is nickel-tungsten carbides (NiWC) over mesoporous silica (SBA-15) filled polyethylene oxide (PEO), was developed and investigated for Li-S batteries. The filler minimizes the crystallinity of the PEO and increases the ionic conductivity of the electrolyte, resulting in lowering the AC impedance of electrolyte composite from 26,256 ohm to 2416 ohm and to 5734 ohm after adding the electrolyte material with Ni/W ratios of 1:1 and 9:1, respectively. A high initial specific capacity of 1305 mAh g−1 and a capacity retention of 66.7% after 8 cycles at C/10 was obtained at room temperature after adding NiWC/SBA-15 with a Ni/W ratio of 1:1. This novel composite solid-state electrolyte shows a remarkable long-term performance at high current rates (1, 2, 4, and 5C) and rate capabilities at 0.1, 0.2, 0.5, 1, 2, 4 and back to 0.1C. The battery was able to recover 77% of the initial specific capacity at 0.1C. The materials were characterized by XRD and SEM-EDX to study the crystallinity and elemental distributions, respectively

Transition Metal Carbides Filler-Reinforced Composite Polymer Electrolyte for Solid-State Lithium-Sulfur Batteries at Room Temperature: Breakthrough

All solid-state room-temperature lithium-sulfur (Li-S) batteries have gained increasing attention due to their ability to eliminate the polysulfides shuttle effects and the safety dangers associated with the liquid electrolytes. Herein, a novel composite solid-state electrolyte, which is nickel-tungsten carbides (NiWC) over mesoporous silica (SBA-15) filled polyethylene oxide (PEO), was developed and investigated for Li-S batteries. The filler minimizes the crystallinity of the PEO and increases the ionic conductivity of the electrolyte, resulting in lowering the AC impedance of electrolyte composite from 26,256 ohm to 2416 ohm and to 5734 ohm after adding the electrolyte material with Ni/W ratios of 1:1 and 9:1, respectively. A high initial specific capacity of 1305 mAh g−1 and a capacity retention of 66.7% after 8 cycles at C/10 was obtained at room temperature after adding NiWC/SBA-15 with a Ni/W ratio of 1:1. This novel composite solid-state electrolyte shows a remarkable long-term performance at high current rates (1, 2, 4, and 5C) and rate capabilities at 0.1, 0.2, 0.5, 1, 2, 4 and back to 0.1C. The battery was able to recover 77% of the initial specific capacity at 0.1C. The materials were characterized by XRD and SEM-EDX to study the crystallinity and elemental distributions, respectively