Search results for "NEUROSCIENCE"

The search for novel targets in Alzheimer's disease—The 90s redux

2021

Alzheimer's disease (AD) is a complex disease of the brain. Despite over 100 years of basic and clinical research, significantly intensified in the last three decades, the exact cause of this neurodegeneration is still an enigma. Based on neuroanatomical, experimental, and clinical findings, a series of hypotheses on AD pathogenesis have evolved. Among them, the "amyloid cascade hypothesis" has been most prominent. Clinical efforts targeting the biochemistry of amyloid β-protein (Aβ) as causal therapy have all failed so far, which may mean that the pathogenic mechanism of AD is less straightforward than initially thought. While there was good scientific reason to support this hypothesis bef…

Studying the blood-brain barrier will provide new insights into neurodegeneration - Commentary.

2018

Supplementary medication in multiple sclerosis: Real-world experience and potential interference with neurofilament light chain measurement

2020

Background As vitamins and dietary supplements are obtainable without prescription, treating physicians often ignore their intake by patients with multiple sclerosis (MS) and may therefore miss potential adverse effects and interactions. Objective We aimed to assess the spectrum and intake frequency of supplementary medication in a cohort of MS patients and to analyse the effect of biotin intake on measurement of serum neurofilament light chain (sNfL), an emerging marker of disease activity. Methods MS patients visiting our neurology outpatient clinic completed a questionnaire on their past or present use of vitamins or dietary supplements. In addition, the impact of two different doses of …

Extrinsic and intrinsic mechanisms of axon regeneration: the need for spinal cord injury treatment strategies to address both

2016

Spinal cord injury (SCI) causes disturbances in motor and sensory functions leading to paralysis, the severity of which depends on the spinal level of the injury. Traumatic lesions of spinal cord axon projection tracts are untreatable in human patients, although numerous research groups worldwide are studying putative treatment strategies. Both extrinsic factors in the environment of the axons as well as intrinsic factors in the neurons themselves play important roles in the regeneration process (Chew et al., 2012). The peripheral nervous system (PNS) provides a good example where the extrinsic and intrinsic factors play optimally together to allow regeneration. Schwann cells dedifferentiat…

Alexander Disease Mutations Produce Cells with Coexpression of Glial Fibrillary Acidic Protein and NG2 in Neurosphere Cultures and Inhibit Differenti…

2017

Background Alexander disease (AxD) is a rare disease caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP). The disease is characterized by presence of GFAP aggregates in the cytoplasm of astrocytes and loss of myelin. Objectives Determine the effect of AxD-related mutations on adult neurogenesis. Methods We transfected different types of mutant GFAP into neurospheres using the nucleofection technique. Results We find that mutations may cause coexpression of GFAP and NG2 in neurosphere cultures, which would inhibit the differentiation of precursors into oligodendrocytes and thus explain the myelin loss occurring in the disease. Transfection produces cells that diff…

2017

AbstractThe E2F transcription factor 1 is subtly regulated along the cell cycle progression and in response to DNA damage by post-translational modifications. Here, we demonstrated that the E3-ubiquitin ligase cellular inhibitor of apoptosis 1 (cIAP1) increases E2F1 K63-poly-ubiquitination on the lysine residue 161/164 cluster, which is associated with the transcriptional factor stability and activity. Mutation of these lysine residues completely abrogates the binding of E2F1 to CCNE, TP73 and APAF1 promoters, thus inhibiting transcriptional activation of these genes and E2F1-mediated cell proliferation control. Importantly, E2F1 stabilization in response to etoposide-induced DNA damage or …

2017

The biogenic amines octopamine (OA) and tyramine (TA) modulate insect motor behavior in an antagonistic manner. OA generally enhances locomotor behaviors such as Drosophila larval crawling and flight, whereas TA decreases locomotor activity. However, the mechanisms and cellular targets of TA modulation of locomotor activity are incompletely understood. This study combines immunocytochemistry, genetics and flight behavioral assays in the Drosophila model system to test the role of a candidate enzyme for TA catabolism, named Nazgul (Naz), in flight motor behavioral control. We hypothesize that the dehydrogenase/reductase Naz represents a critical step in TA catabolism. Immunocytochemistry rev…

Dynamic compartmentalization of calcium channel signalling in neurons.

2020

Calcium fluxes through the neuronal membrane are strictly limited in time due to biophysical properties of voltage-gated and ligand-activated ion channels and receptors. Being embedded into the crowded dynamic environment of biological membranes, Ca2+-permeable receptors and channels undergo perpetual spatial rearrangement, which enables their temporary association and formation of transient signalling complexes. Thus, efficient calcium-mediated signal transduction requires mechanisms to support very precise spatiotemporal alignment of the calcium source and Ca2+-binding lipids and proteins in a highly dynamic environment. The mobility of calcium channels and calcium-sensing proteins themse…

Pre-imaginal conditioning alters adult sex pheromone response in Drosophila

2018

https://peerj.com/articles/5585/#supplemental-information; International audience; Pheromones are chemical signals that induce innate responses in individuals of the same species that may vary with physiological and developmental state. In Drosophila melanogaster, the most intensively studied pheromone is 11-cis-vaccenyl acetate (cVA), which is synthezised in the male ejaculatory bulb and is transferred to the female during copulation. Among other effects, cVA inhibits male courtship of mated females. We found that male courtship inhibition depends on the amount of cVA and this effect is reduced in male flies derived from eggs covered with low to zero levels of cVA. This effect is not obser…

Disruption of otoferlin alters the mode of exocytosis at the mouse inner hair cell ribbon synapse

2019

Sound encoding relies on Ca2+-mediated exocytosis at the ribbon synapse between cochlear inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs). Otoferlin, a multi-C-2 domain protein, is proposed to regulate Ca2+-triggered exocytosis at this synapse, but the precise mechanisms of otoferlin function remain to be elucidated. Here, performing whole-cell voltage-clamp recordings of excitatory postsynaptic currents (EPSCs) from SGNs in otoferlin mutant mice, we investigated the impact of Otof disruption at individual synapses with single release event resolution. Otof deletion decreased the spontaneous release rate and abolished the stimulus-secretion coupling. This was evident from f…