Extracellular matrix

…cell morphology, adhesion, the local extracellular matrix and secreted vesicles. Inspired by mutations associated with neurodevelopmental disorders, we focus on understanding the role of extracellular mechanisms essential for the proper development of the human brain. Therefore, we combine 2D and 3D in vitro human models to better understand the molecular and cellular mechanisms involved in progenitor proliferation and fate, migration and maturation of excitatory and inhibitory

The brain’s Extracellular Matrix (ECM) is a unique 3-dimensional macromolecular network implicated in homeostasis, neuronal plasticity, and aging-related cognitive alterations. Based on previous animal studies we hypothesized that neural ECM molecules like the proteoglycan brevican (BCAN) affect cognitive flexibility (CFL) also in humans. We addressed this hypothesis in young and older healthy human subjects by assessing flexibility performance and gray matter volumes (GMV) in dorsal anterior cingulate cortex (dACC), a key structure for cognitive control, together with serum concentrations of

…The extracellular matrix, a lesser understood region of the brain, potentially provides mechanisms for change in mood states. Mood disorders associate with change in plasticity; specifically, perineuronal nets (PNNs) associate with synaptic plasticity. PNNs mostly surround Parvalbumin neurons (PV) thereby altering inhibitory signalling.The aim of this study was to induce a positive or negative affective state in rats through housing conditions, validate this with behav

…the interactions between the brain extracellular matrix (ECM) and glial cells1 critically contribute to post-stroke neuroplasticity and can help promote stroke recovery.We investigated the role of perineuronal nets (PNNs), facet-like ECM layers surrounding fast-spiking interneurons, in neurological recovery following focal cerebral ischemia in mice. Using superresolution stimulated emission depletion (STED), stru

…The brain's perineuronal extracellular matrix (ECM), composed mainly of chondroitin sulfate proteoglycans from the lectican family, suppresses structural plasticity in the mature brain. Several members of this family, such as aggrecan and brevican, undergo proteolytic cleavage by proteases from the ADAMTS family, which may loosen the ECM structure. Therefore, we hypothesize that activity-dependent extracellular proteolysis weakens the ECM, supporting neuronal plasticity

Dendritic branching mechanisms are precisely controlled during brain development, as dendritic architecture provides the specificity and capacity of the synaptic input. Integrin receptors on the neuronal membrane are critical regulators of when and where the dendritic arborization will take place during neuronal differentiation. Integrin activity is not solely dictated by external ligand binding – the receptor's shape and function are also fine-tuned by intracellular binding proteins, including actin-binding protein Filamin A (FlnA). By combining in vitro mouse neuronal cultures with genetic a

Although diverse stimulation patterns induce excitatory plasticity, they concurrently trigger long-term potentiation (iLTP) or depression (iLTD) at inhibitory synapses. Nevertheless, the precise plasticity rules and molecular mechanisms governing the interaction between excitatory and GABAergic plasticity remain unclear. Here, we aimed to elucidate these mechanisms in slices by simultaneously recording excitatory and distinct optogenetically evoked inhibitory postsynaptic currents in hippocampal CA1 pyramidal cells (CA1PCs). Long-term plasticity was induced by NMDA treatment.Our experiments re

Axonal growth cones mediate axonal guidance and growth regulation and their activities are crucial for neuronal circuit development. However, the function of growth-cone-like structure at the tip of leading process of migrating neurons is largely unknown. Here, using live imaging analyses, we show that migrating neurons in mice possess a growth cone at the tip of their leading process, similar to that of axons, in terms of the cytoskeletal dynamics and functional responsivity through protein tyrosine phosphatase receptor type sigma (PTPσ). Migrating-neuron growth cones respond to chondroitin s

Microglia continuously remodel synapses, which are embedded in the extracellular matrix (ECM). However, the mechanisms which govern this process remain elusive. To investigate the influence of the neural ECM in synaptic remodeling by microglia, we disrupted ECM integrity by injection of chondroitinase ABC (ChABC) into the retrosplenial cortex of healthy adult mice. Using in vivo two-photon microscopy we found that ChABC treatment increased microglial branching and ECM phagocytic capacity and decreased spine elimination rate under basal conditions. Moreover, ECM attenuation largely prevented sy

Integrins are biomechanical receptors that connect both physically and functionally the extracellular matrix (ECM) to the intracellular cytoskeleton, regulating synaptic connectivity and plasticity in response to extracellular cues. In particular, in the brain, β3 integrin interacts with the αV subunit to form the αVβ3 integrin heterodimer, which mediates adhesion strengthening of excitatory synapses in cortical pyramidal neurons.Alteration in integrin structure, expression or signalling is involved in the aetiology of various brain pathologies, including autism spectrum disorder (ASD) and epi

Background: Adult stem cell niches are specialized forms of extracellular matrix suitable for maintaining the development of newborn neurons. The process is regulated by internal and external factors, such as enriched environment (EE). The subgranular zone (SGZ) in the hippocampus is enriched with molecules such as tenascin C (TnC). It is a regulatory glycoprotein involved in the proliferation and migration of different cell types. The aim of this study was to examine how TnC affects the distribution of different biomolecules and the number of developing cells in the adult SGZ.Methods: To dire

…nets (PNNs), condensed forms of extracellular matrix (ECM) that enwrap mainly parvalbumin expressing (PV+) inhibitory interneurons. Glycoprotein tenascin-C (TnC) is one of the ECM molecules that interacts with components of PNNs and that modulates the synaptic plasticity in the hippocampus. The aim of this study was to investigate whether TnC deficiency

Glioblastoma (GBM) is a frequent, treatment resistant adult brain tumour which is classified as a grade IV glioma (Louis et al., 2016). To date treatment options for glioblastoma brain tumours are limited and no reliable markers are available to distinguish migratory active from resting glioblastoma cells. Here, we investigated the rat glioblastoma cell line C6 and their invasive behaviour on living brain tissue, represented by rat hippocampal slice cultures. We established a model system where brain tissue (represented by organotypic slice cultures) is overlayed with fluorescently labelled gl

Spinal cord injury (SCI) is a trauma that results in loss of function below the site of injury. Additionally, SCI induces systemic inflammation, which is in part responsible of brain dysfunction. Currently, many therapeutic approaches have been carried out. In particular, transplantation of bulbar olfactory ensheathing cells (bOECs) has shown therapeutic effects in mice and, to a lesser extent, in humans. Given these observations, we wondered about the effect of the lesion on the quality of the transplanted therapeutic material when cells are harvested after SCI. First, the effects of SCI on b

Perineuronal nets (PNNs), a specialized form of the extracellular matrix, enwrap subtypes of neurons and have many proposed functions including regulating adult brain plasticity. Removal of PNNs in adult mice by the bacterial enzyme chondroitinase ABC restores brain plasticity levels to that of juveniles. However, chondroitinase ABC indiscriminately degrades all chondroitin sulfate proteoglycans in the extracellular matrix, its effect is not restricted to PNNs. In contrast, several endogenous metalloproteinases specifically target PNN components. Some of these are selectively expressed in PNN-

…mechanosensitive ion channels and the extracellular matrix mediated by protein tethers. In sensory neurons cultured on a laminin matrix and imaged either with TEM or FIB/SEM, these tethers

…nets (PNNs), specialized forms of extracellular matrix which form around neurons during postnatal development in many brain areas. These nets are preferentially established around Parvalbumin-positive GABAergic interneurons (PVIs), and their presence reduces brain plasticity. PNN and PVI expression is altered in various neuropsychiatric disorders and in some cases their manipulation

…their adhesion molecules, the local extracellular matrix and the secreted vesicles. Inspired by mutations associated with neurodevelopmental disorders, we focus on understanding the role of extracellular mechanisms essential for the correct development of the human brain. Hence, we combine the in vivo mouse model and the in vitro human-derived neurons, cerebral organoids, and dorso-ventral assembloids in order to better comprehend the molecular an

…guided us to microglia enabled extracellular matrix remodeling and reinstatment of juvenile-l

In the adult brain, synapses are tightly enwrapped by lattices of extracellular matrix that consist of extremely long-lived molecules. These lattices are deemed to stabilize synapses, restrict the reorganization of their transmission machinery, and prevent them from undergoing structural or morphological changes. At the same time, they are expected to retain some degree of flexibility to permit occasional events of synaptic plasticity. The recent understanding that structural changes to synapses are significantly more frequent than previously assumed (occurring even on a timescale of minutes)

Microglia are the immune cells of the brain, and play increasingly appreciated roles in synapse formation, brain plasticity, and cognition. A growing appreciation that the immune system involved in diseases like schizophrenia, epilepsy, and neurodegenerative diseases has led to renewed interest in how microglia regulate synaptic connectivity. Our group previously identified the IL-1 family cytokine Interleukin-33 (IL-33) as a novel regulator of microglial activation and function. I will discuss a mechanism by which microglia regulate synaptic plasticity and long-term memories by engulfing brai

Corticospinal neurons (CSN) are the cortical projection neurons that innervate the spinal cord and some brainstem targets with segmental precision to control voluntary movement of specific functional motor groups, limb sections, or individual digits, yet molecular regulation over CSN segmental target specificity is essentially unknown. CSN subpopulations exhibit striking axon targeting specificity from development into maturity: Evolutionarily newer rostrolateral CSN exclusively innervate bulbar-cervical targets (CSNBC-lat), while evolutionarily older caudomedial CSN (CSNmed) are more heteroge