Rett syndrome (RTT) is a rare neurodevelopmental disorder caused by mutation in the X-linked gene methyl-CpG-binding protein 2 (Mecp2), a ubiquitously expressed transcriptional regulator. RTT results in mental retardation and developmental regression that affects approximately 1 in 10,000 females. Currently, there is no curative treatment for RTT.
View Article and Find Full Text PDFWireless powered optogenetic cell-based implant provides a strategy to deliver subcutaneously therapeutic proteins. Immortalize Human Mesenchymal Stem Cells (hMSC-TERT) expressing the bacteriophytochrome diguanylate cyclase (DGCL) were validated for optogenetic controlled interferon-β delivery (Optoferon cells) in a bioelectronic cell-based implant. Optoferon cells transcriptomic profiling was used to elaborate an in-silico model of the recombinant interferon-β production.
View Article and Find Full Text PDFWe report for the first time to our knowledge on top-down percussion drilling of high-quality deep holes in different glasses with femtosecond laser pulses in GHz-burst mode. We reveal the dynamics of the percussion drilling process by pump-probe shadowgraphy and thermal camera imaging demonstrating that the drilling process in GHz-burst mode is fundamentally different from single-pulse processing and confirming the presence of thermal accumulation. Moreover, we show a comparison to drilling by femtosecond single-pulses containing an equal laser fluence in sodalime, alkali-free alumina-borosilicate, fused silica, and sapphire.
View Article and Find Full Text PDF: The delta opioid receptor (DOR) contributes to pain control, and a major challenge is the identification of DOR populations that control pain, analgesia, and tolerance. Astrocytes are known as important cells in the pathophysiology of chronic pain, and many studies report an increased prevalence of pain in women. However, the implication of astrocytic DOR in neuropathic pain and analgesia, as well as the influence of sex in this receptor activity, remains unknown.
View Article and Find Full Text PDFImproving a drug delivery system is critical to treat central nervous system disorders. Here we studied an innovative approach based on implantation of a wireless-powered cell-based device in mice. This device, coupling biologic material and electronics, is the first of its kind.
View Article and Find Full Text PDFMetachromatic leukodystrophy (MLD) is a lysosomal storage disorder characterized by accumulation of sulfatides in both glial cells and neurons. MLD results from an inherited deficiency of arylsulfatase A (ARSA) and myelin degeneration in the central and peripheral nervous systems. Currently, no effective treatment is available for the most frequent late infantile (LI) form of MLD after symptom onset.
View Article and Find Full Text PDFFor more than 10 years, gene therapy for neurological diseases has experienced intensive research growth and more recently therapeutic interventions for multiple indications. Beneficial results in several phase 1/2 clinical studies, together with improved vector technology have advanced gene therapy for the central nervous system (CNS) in a new era of development. Although most initial strategies have focused on orphan genetic diseases, such as lysosomal storage diseases, more complex and widespread conditions like Alzheimer's disease, Parkinson's disease, epilepsy, or chronic pain are increasingly targeted for gene therapy.
View Article and Find Full Text PDFWe report on crater formation, line scribing and cavity milling experiments on Silicon, Copper, Aluminum and stainless steel with GHz bursts of femtosecond pulses. The intra-burst repetition rate has been varied between 0.88 and 3.
View Article and Find Full Text PDFMicromachining with high repetition rate femtosecond lasers and galvo scanners shows some limitations in the pulses positioning accuracy due to the galvo mirrors acceleration. This is particularly evident during scan speed or direction changes, resulting in a poor quality and overtreatment e.g.
View Article and Find Full Text PDFA major challenge in medicine is developing potent pain therapies without the adverse effects of opiates. Neuroinflammation and in particular microglial activation have been shown to contribute to these effects. However, the implication of the microglial mu opioid receptor (MOR) is not known.
View Article and Find Full Text PDFWe report on silicon ablation with a 20 W GHz amplified femtosecond laser source. This novel laser delivers burst energies up to 400 μJ, providing flexible intra-pulse repetition rates of 0.88 or 3.
View Article and Find Full Text PDFMicroglia activation contributes to chronic pain and to the adverse effects of opiate use such as analgesic tolerance and opioid-induced hyperalgesia. Both mu opioid receptor (MOR) encoded by gene and toll like receptor 4 (TLR4) have been reported to mediate these morphine effects and a current question is whether microglia express the Oprm1 transcript and MOR protein. The aim of this study was to characterize -MOR expression in naive murine and human microglia, combining transcriptomics datasets previously published by other groups with our own imaging study using the Cx3cr1-eGFP-MOR-mCherry reporter mouse line.
View Article and Find Full Text PDFOpiates are potent analgesics but their clinical use is limited by side effects including analgesic tolerance and opioid-induced hyperalgesia (OIH). The Opiates produce analgesia and other adverse effects through activation of the mu opioid receptor (MOR) encoded by the Oprm1 gene. However, MOR and morphine metabolism involvement in OIH have been little explored.
View Article and Find Full Text PDFIn Alzheimer disease, the development of tau pathology follows neuroanatomically connected pathways, suggesting that abnormal tau species might recruit normal tau by passage from cell to cell. Herein, we analyzed the effect of stereotaxic brain injection of human Alzheimer high-molecular-weight paired helical filaments (PHFs) in the dentate gyrus of wild-type and mutant tau THY-Tau22 mice. After 3 months of incubation, wild-type and THY-Tau22 mice developed an atrophy of the dentate gyrus and a tau pathology characterized by Gallyas and tau-positive grain-like inclusions into granule cells that extended in the hippocampal hilus and eventually away into the alveus, and the fimbria.
View Article and Find Full Text PDFBesides its crucial role in the pathogenesis of Alzheimer's disease, the knowledge of amyloid precursor protein (APP) physiologic functions remains surprisingly scarce. Here, we show that APP regulates the transcription of the glial cell line-derived neurotrophic factor (GDNF). APP-dependent regulation of GDNF expression affects muscle strength, muscular trophy, and both neuronal and muscular differentiation fundamental for neuromuscular junction (NMJ) maturation in vivo In a nerve-muscle coculture model set up to modelize NMJ formation in vitro, silencing of muscular APP induces a 30% decrease in secreted GDNF levels and a 40% decrease in the total number of NMJs together with a significant reduction in the density of acetylcholine vesicles at the presynaptic site and in neuronal maturation.
View Article and Find Full Text PDFSeveral neurodegenerative diseases are characterized by both cognitive and motor deficits associated with accumulation of tau aggregates in brain, brainstem, and spinal cord. The Tg30 murine tauopathy model expresses a human tau protein bearing two frontotemporal dementia with Parkinsonism linked to chromosome 17 pathogenic mutations and develops a severe motor deficit and tau aggregates in brain and spinal cord. To investigate the origin of this motor deficit, we analyzed the age-dependent innervation status of the neuromuscular junctions and mutant tau expression in Tg30 mice.
View Article and Find Full Text PDFWe hypothesized that vascular endothelial growth factor (VEGF)-containing hydrogels that gelify in situ after injection into a traumatized spinal cord, could stimulate spinal cord regeneration. Injectable hydrogels composed of 0.5% Pronova UPMVG MVG alginate, supplemented or not with fibrinogen, were used.
View Article and Find Full Text PDFThe Onecut (OC) family of transcription factors comprises three members in mammals, namely HNF-6 (or OC-1), OC-2 and OC-3. During embryonic development, these transcriptional activators control cell differentiation in pancreas, in liver and in the nervous system. Adult Hnf6 mutant mice exhibit locomotion defects characterized by hindlimb muscle weakness, abnormal gait and defective balance and coordination.
View Article and Find Full Text PDFWe have investigated femtosecond (fs) laser (130 fs, 800 nm, 5 kHz) ablation of polypropylene (PP). The following laser process conditions were varied: power density and number of pulses. The morphological parameters' response (depth, ablation diameter, ablation volume) to the laser process conditions, measured by an optical profiler, was investigated by the statistical analysis technique to determine the relationship between them.
View Article and Find Full Text PDFPrecise weight measurements of stainless steel, PZT and PMMA samples were performed after groove machining with femtosecond laser pulses (150 fs, 800 nm, 5 kHz) to determine volume ablation rates and ablation threshold with good accuracy. Weighing clearly enables faster determination of such phenomenological parameters without any methodological issue compared to other methods. Comparisons of the three types of materials reveal similar monotonous trends depending on peak fluences from 0.
View Article and Find Full Text PDFThe neuromuscular junctions are the specialized synapses whereby spinal motor neurons control the contraction of skeletal muscles. The formation of the neuromuscular junctions is controlled by a complex interplay of multiple mechanisms coordinately activated in motor nerve terminals and in their target myotubes. However, the transcriptional regulators that control in motor neurons the genetic programs involved in neuromuscular junction development remain unknown.
View Article and Find Full Text PDFThe femtosecond laser processing enabled the structuring of six types of surfaces on titanium-6aluminium-4vanadium (Ti-6Al-4V) plates. The obtained hierarchical features consisted of a combination of microgrooves and oriented nanostructures. By adjusting beam properties such as laser polarization, the width of the microgrooves (20 or 60 μm) and the orientation of the nanostructures (parallel or perpendicular to the microgrooves) can be precisely controlled.
View Article and Find Full Text PDFEmploying a method of in-situ control we propose an approach for the optimization of self-arranged nanogratings in bulk fused silica under the action of ultrashort laser pulses with programmable time envelopes. A parametric study of the influence of the pulse duration and temporal form asymmetries is given. Using the diffraction properties of the laser-triggered subwavelength patterns we monitor and regulate the period and the quality of the periodic nanoscale arrangement via the effective nonlinear excitation dose.
View Article and Find Full Text PDFPlanar electrochemical microcells were micromachined in a microcrystalline boron-doped diamond (BDD) thin layer using a femtosecond laser. The electrochemical performances of the new laser-machined BDD microcell were assessed by differential pulse anodic stripping voltammetry (DPASV) determinations, at the nanomolar level, of the four heavy metal ions of the European Water Framework Directive (WFD): Cd(II), Ni(II), Pb(II), Hg(II). The results are compared with those of previously published BDD electrodes.
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