Search results for " Neuroscience"

Crosstalk between receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCR) in the brain: Focus on heteroreceptor complexes and related…

2019

Neuronal events are regulated by the integration of several complex signaling networks in which G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) are considered key players of an intense bidirectional cross-communication in the cell, generating signaling mechanisms that, at the same time, connect and diversify the traditional signal transduction pathways activated by the single receptor. For this receptor-receptor crosstalk, the two classes of receptors form heteroreceptor complexes resulting in RTKs transactivation and in growth-promoting signals. In this review, we describe heteroreceptor complexes between GPCR and RTKs in the central nervous system (CNS) and their …

Taurine as an Essential Neuromodulator during Perinatal Cortical Development

2017

A variety of experimental studies demonstrated that neurotransmitters are an important factor for the development of the central nervous system, affecting neurodevelopmental events like neurogenesis, neuronal migration, programmed cell death, and differentiation. While the role of the classical neurotransmitters glutamate and gamma-aminobutyric acid (GABA) on neuronal development is well established, the aminosulfonic acid taurine has also been considered as possible neuromodulator during early neuronal development. The purpose of the present review article is to summarize the properties of taurine as neuromodulator in detail, focusing on the direct involvement of taurine on various neurode…

2016

We determine knotting probabilities and typical sizes of knots in double-stranded DNA for chains of up to half a million base pairs with computer simulations of a coarse-grained bead-stick model: Single trefoil knots and composite knots which include at least one trefoil as a prime factor are shown to be common in DNA chains exceeding 250,000 base pairs, assuming physiologically relevant salt conditions. The analysis is motivated by the emergence of DNA nanopore sequencing technology, as knots are a potential cause of erroneous nucleotide reads in nanopore sequencing devices and may severely limit read lengths in the foreseeable future. Even though our coarse-grained model is only based on …

Optical Cross-Sectional Muscle Area Determination of <em>Drosophila Melanogaster</em> Adult Indirect Flight Muscles

2018

Muscle mass wasting, known as muscle atrophy, is a common phenotype in Drosophila models of neuromuscular diseases. We have used the indirect flight muscles (IFMs) of flies, specifically the dorso-longitudinal muscles (DLM), as the experimental subject to measure the atrophic phenotype brought about by different genetic causes. In this protocol, we describe how to embed fly thorax muscles for semi thin sectioning, how to obtain a good contrast between muscle and the surrounding tissue, and how to process optical microscope images for semiautomatic acquisition of quantifiable data and analysis. We describe three specific applications of the methodological pipeline. First, we show how the met…

2020

Communication with the hematopoietic system is a vital component of regulating brain function in health and disease. Traditionally, the major routes considered for this neuroimmune communication are by individual molecules such as cytokines carried by blood, by neural transmission, or, in more severe pathologies, by the entry of peripheral immune cells into the brain. In addition, functional mRNA from peripheral blood can be directly transferred to neurons via extracellular vesicles (EVs), but the parameters that determine their uptake are unknown. Using varied animal models that stimulate neuronal activity by peripheral inflammation, optogenetics, and selective proteasome inhibition of dop…

2020

Phytochrome proteins control the growth, reproduction, and photosynthesis of plants, fungi, and bacteria. Light is detected by a bilin cofactor, but it remains elusive how this leads to activation of the protein through structural changes. We present serial femtosecond X-ray crystallographic data of the chromophore-binding domains of a bacterial phytochrome at delay times of 1 ps and 10 ps after photoexcitation. The data reveal a twist of the D-ring, which leads to partial detachment of the chromophore from the protein. Unexpectedly, the conserved so-called pyrrole water is photodissociated from the chromophore, concomitant with movement of the A-ring and a key signaling aspartate. The chan…

2018

We use the myotendinous junction of Drosophila flight muscles to explore why many integrin associated proteins (IAPs) are needed and how their function is coordinated. These muscles revealed new functions for IAPs not required for viability: Focal Adhesion Kinase (FAK), RSU1, tensin and vinculin. Genetic interactions demonstrated a balance between positive and negative activities, with vinculin and tensin positively regulating adhesion, while FAK inhibits elevation of integrin activity by tensin, and RSU1 keeps PINCH activity in check. The molecular composition of myofibril termini resolves into 4 distinct layers, one of which is built by a mechanotransduction cascade: vinculin facilitates …

Sensory neuropathy in progressive motor neuronopathy(pmn)mice is associated with defects in microtubule polymerization and axonal transport

2016

Motor neuron diseases such as amyotrophic lateral sclerosis (ALS) are now recognized as multi-system disorders also involving various non-motor neuronal cell types. The precise extent and mechanistic basis of non-motor neuron damage in human ALS and ALS animal models remain however unclear. To address this, we here studied progressive motor neuronopathy (pmn) mice carrying a missense loss-of-function mutation in tubulin binding cofactor E (TBCE). These mice manifest a particularly aggressive form of motor axon dying back and display a microtubule loss, similar to that induced by human ALS-linked TUBA4A mutations. Using whole nerve confocal imaging of pmn × thy1.2-YFP16 fluorescent reporter …

Treatment strategies for lysosomal storage disorders.

2017

Over the past several years the number of treatments available for patients with lysosomal storage disorders has rapidly increased. Haematopoietic stem cell transplantation, enzyme replacement therapy, substrate reduction, and chaperone therapies are currently available, and gene therapies and other treatments are rapidly advancing. Despite remarkable advances, the efficacy of most of these therapies is limited, particularly because the treatments are usually initiated when organ damage has already occurred. To circumvent this limitation, screening in newborn infants for lysosomal storage disorders has been introduced in many countries. However, this screening is complicated by the broad cl…

Expression of endogenous mouse APP modulates β-amyloid deposition in hAPP-transgenic mice

2017

Amyloid-β (Aβ) deposition is one of the hallmarks of the amyloid hypothesis in Alzheimer’s disease (AD). Mouse models using APP-transgene overexpression to generate amyloid plaques have shown to model only certain parts of the disease. The extent to which the data from mice can be transferred to man remains controversial. Several studies have shown convincing treatment results in reducing Aβ and enhancing cognition in mice but failed totally in human. One model-dependent factor has so far been almost completely neglected: the endogenous expression of mouse APP and its effects on the transgenic models and the readout for therapeutic approaches. Here, we report that hAPP-transgenic models of …