Astrocytes as a Source for Extracellular Matrix Molecules and Cytokines

Research of the past 25 years has shown that astrocytes do more than participating and building up the blood-brain barrier and detoxify the active synapse by reuptake of neurotransmitters and ions. Indeed, astrocytes express neurotransmitter receptors and, as a consequence, respond to stimuli. Within the tripartite synapse, the astrocytes owe more and more importance. Besides the functional aspects the differentiation of astrocytes has gained a more intensive focus. Deeper knowledge of the differentiation processes during development of the central nervous system might help explaining and even help treating neurological diseases like Alzheimer’s disease, Amyotrophic lateral sclerosis, Parkinsons disease, and psychiatric disorders in which astrocytes have been shown to play a role. Specific differentiation of neural stem cells toward the astroglial lineage is performed as a multi-step process. Astrocytes and oligodendrocytes develop from a multipotent stem cell that prior to this has produced primarily neuronal precursor cells. This switch toward the more astroglial differentiation is regulated by a change in receptor composition on the cell surface and responsiveness to Fibroblast growth factor and Epidermal growth factor (EGF). The glial precursor cell is driven into the astroglial direction by signaling molecules like Ciliary neurotrophic factor, Bone Morphogenetic Proteins, and EGF. However, the early astrocytes influence their environment not only by releasing and responding to diverse soluble factors but also express a wide range of extracellular matrix (ECM) molecules, in particular proteoglycans of the lectican family and tenascins. Lately these ECM molecules have been shown to participate in glial development. In this regard, especially the matrix protein Tenascin C (Tnc) proved to be an important regulator of astrocyte precursor cell proliferation and migration during spinal cord development. Nevertheless, ECM molecules expressed by reactive astrocytes are also known to act mostly in an inhibitory fashion under pathophysiological conditions. Thus, we further summarize resent data concerning the role of chondroitin sulfate proteoglycans and Tnc under pathological conditions

Characterization of Hamamatsu 64-channel TSV SiPMs

The Hamamatsu UV-light enhanced 64-channel SiPM array of the newest generation (S13361-3050AS-08) has been examined for the purpose of being used for the Silicon Elementary Cell Add-on (SiECA) of the EUSO-SPB balloon experiment. Characterization measurements have been performed with the newly installed Single Photon Calibration Stand at KIT (SPOCK). The results of the characterization measurements including the breakdown voltage, the gain, the PDE, the dark-count rate and the crosstalk probability of all 64 SiPM channels are presented. Additional measurements of the SiPM sensitivity to photons with wavelengths lower than 400nm show an improved PDE for small wavelengths compared to the SiPM array S12642-0808PA-50, which was also investigated for comparison. The response dynamics have been investigated for low numbers of incoming photons. Temperature dependent measurements of the gain, the PDE, the dark-count rate and the crosstalk probability have been performed for one channel of the SiPM array.Comment: Accepted for publication in Nuclear Instruments and Methods

Disease burden and direct medical costs of incident adult ADHD:A retrospective longitudinal analysis based on German statutory health insurance claims data

Background. Adult attention-deficit/hyperactivity disorder (aADHD) is still a largely unrecognized psychiatric condition despite its strong impact on individuals' well-being. Here, we describe the healthcare situation of individuals with incident aADHD over 4 years before and 4 years after initial administrative diagnosis. Methods. A retrospective, longitudinal cohort analysis was conducted using German claims data. The InGef database contained approximately 5 million member-records from over 60 nationwide statutory health insurances (SHI). Individuals were indexed upon initial diagnosis of aADHD. Results. Average age at diagnosis of aADHD was 35 years, and 60% of individuals were male. Comorbidities, resource use, and healthcare costs were substantial before initial diagnosis and decreased within the 4 years thereafter. Only 32% of individuals received initial ADHD medication and adherence was low. The majority received psychotherapy. Individuals with initial ADHD medication showed the highest share in comorbidities, physician visits, medication use for comorbidities, psychotherapy, and costs. Overall, healthcare costs were at over euro4,000 per individual within the year of aADHD diagnosis. Conclusions. We conclude that earlier recognition of aADHD could prevent the development and aggravation of comorbid mental illnesses. At the same time, comorbid conditions may have masked ("over-shadowed") aADHD and delayed diagnosis. The burden of disease in aADHD is high, which was noticeable especially among individuals who received initial ADHD-medication, suggesting that psychopharmacological treatment was mainly considered for the most severely ill. We conclude that measures to facilitate access of aADHD patients to clinical experts are required to improve reality of care in the outpatient setting

Regulatory functions of the neural extracellular matrix for the maturation of the spinal cord radial glia and its progeny

Teilung u. Differenzierung neuraler Vorläuferzellen müssen präzise reguliert werden. Extrinsische Faktoren der neuralen Extrazellulär Matrix (EZM) spielen bei der Regulierung dieser Prozesse eine wichtige Rolle. Das Ziel dieser Dissertation war neue Faktoren zu identifizieren, die das zellbiologische Verhalten neuraler Vorläuferzellen während der Rückenmarksentwicklung der Maus beeinflussen. Die funktionelle Analyse einer für das Glycoprotein Tenascin C (TnC) defizienten Maus ergab, dass dieses Protein eine wichtige Rolle für die Teilung u. Wanderung unreifer Astrozyten in vivo spielt. Neben TnC erwiesen sich Chondroitin Sulfat Proteoglykane (CSPGs), eine weitere Klasse von EZM Molekülen, als wichtig für die Reifung von Oligodendrozyten. Insbesondere der enzymatische Verdau von CSPG Zuckerseitenketten führte zu einer verstärkten Bildung von membran-bildenden Oligodendrozyten. Insgesamt stellt diese Arbeit die Wichtigkeit der neuralen EZM während der Rückenmarksentwicklung unter Beweis.Neural precursor cell behaviour must be tightly regulated with respect to proliferation or differentiation. Extrinsic cues coming from the extracellular matrix (ECM) are thought to play important roles in regulating these cell biological processes. The aim of this thesis was to identify new extracellular players which regulate the cell biological behaviour during embryonic spinal cord development. The functional analysis of a mouse mutant lacking the glycoprotein Tenascin C (TnC) revealed important functions of this protein for the proliferation and migration of immature astrocytes. Besides TnC chondroitin sulphate proteoglycans (CSPGs), yet another class of ECM molecules, proved to be particularly important for oligodendrocyte lineage progression. The enzymatic removal of CSPG sugar side chains strongly enhanced myelin membrane formation from spinal cord NPC derived oligodendrocytes. In summary, this thesis highlights the importance of the neural ECM during spinal cord development