Neurocan Contributes to Perineuronal Net Development
NEUROSCIENCE
Authors: Schmidt, Sophie; Arendt, Thomas; Morawski, Markus; Sonntag, Mandy
Abstract
Perineuronal nets (PNs) are matrix molecule assemblies surrounding neuronal somata, dendrites and axon initial segments in a lattice-like appearance. PN molecules are involved in many structural and physiological processes during development and in adulthood, suggesting a crucial role in normal brain function. Neurocan, as one of the main PN proteoglycans, is suggested to control important developmental processes of neuronal tissue. This statement relies on thorough and excellent experimental work mainly conducted in reduced systems, such as cell cultures. However, previous data collected in neurocan-deficient mice do not seem to support neurocan's role in development since brain development in general and the formation of PNs especially in the hippocampus were reported to be undisturbed in neurocan-deficient mice. Here, we aim to re-address the role of neurocan in developmental processes by investigating the influence of neurocan on PN formation in the medial nucleus of the trapezoid body, a PN-enriched nucleus in the auditory brainstem, using neurocan-deficient mice. Immunohis-tochemical and biochemical analyses demonstrate that neurocan controls the regulation of PN development by influencing mRNA and protein quantity of various PN molecules. Resulting alterations in PN fine structure are crit-ical for PN function as estimated by reduced amount of GAD65/67 and prolongation of synaptic transmission delay of calyx of Held synapses. Thus, neurocan contributes to proper PN formation and synapse physiology in the MNTB. (c) 2020 IBRO. Published by Elsevier Ltd. All rights reserved.
THE NEURONAL EXTRACELLULAR MATRIX RESTRICTS DISTRIBUTION AND INTERNALIZATION OF AGGREGATED TAU-PROTEIN
NEUROSCIENCE
Authors: Suttkus, A.; Holzer, M.; Morawski, M.; Arendt, T.
Abstract
Alzheimer's disease (AD) is a chronic degenerative disorder characterized by fibrillary aggregates of A beta and Tau-protein. Formation and progression of these pathological hallmarks throughout the brain follow a specific spatio-temporal pattern which provides the basis for neuropathological staging. Previously, we could demonstrate that cortical and subcortical neurons are less frequently affected by neurofibrillary degeneration if they are enwrapped by a specialized form of the hyaluronan-based extracellular matrix (ECM), the so called 'perineuronal net' (PN). PNs are composed of large aggregating chondroitin sulfate proteoglycans connected to a hyaluronan backbone, stabilized by link proteins and cross-linked via tenascin-R. Recently, PN-associated neurons were shown to be better protected against iron-induced neurodegeneration compared to neurons without PN, indicating a neuroprotective function. Here, we investigated the role of PNs in distribution and internalization of exogenous Tau-protein by using organotypic slice cultures of wildtype mice as well as mice lacking the ECM-components aggrecan, HAPLN1 or tenascin-R. We could demonstrate that PNs restrict both distribution and internalization of Tau. Accordingly, PN-ensheathed neurons were less frequently affected by Tau-internalization, than neurons without PN. Finally, the PNs as well as their three investigated components were shown to modulate the processes of distribution as well as internalization of Tau. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.