Publications

The extracellular matrix (ECM) is a dynamic and complex network of proteins and molecules that surrounds cells and tissues in the nervous system and orchestrates a myriad of biological functions. This review carefully examines the diverse interactions between cells and the ECM, as well as the transformative chemical and physical changes that the ECM undergoes during neural development, aging, and disease. These transformations play a pivotal role in shaping tissue morphogenesis and neural activity, thereby influencing the functionality of the central nervous system (CNS). In our comprehensive review, we describe the diverse behaviors of the CNS ECM in different physiological and pathological scenarios and explore the unique properties that make ECM-based strategies attractive for CNS repair and regeneration. Addressing the challenges of scalability, variability, and integration with host tissues, we review how advanced natural, synthetic, and combinatorial matrix approaches enhance biocompatibility, mechanical properties, and functional recovery. Overall, this review highlights the potential of decellularized ECM as a powerful tool for CNS modeling and regenerative purposes and sets the stage for future research in this exciting field. This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Implantable Materials and Surgical Technologies > Nanomaterials and Implants

JTD Keywords: Amyotrophic-lateral-sclerosis, Biologic scaffold, Central nervous system, Central-nervous-system, Chondroitin sulfate proteoglycans, Decellularization, Extracellular matrix, Motor-neurons, Neural disorders, Neural regeneratio, Perineuronal nets, Self-healing hydrogel, Spinal-cord-injury, Stem-cell, Vascular basement-membrane

Neurotrophic factors are essential not only for guiding the organization of the developing nervous system but also for supporting the survival and growth of neurons after traumatic injury. In the central nervous system (CNS), inhibitory factors and the formation of a glial scar after injury hinder the functional recovery of neurons, requiring exogenous therapies to promote regeneration. Netrin-1, a neurotrophic factor, can initiate axon guidance, outgrowth, and branching, as well as synaptogenesis, through activation of deleted in colorectal cancer (DCC) receptors. We report here the development of a nanofiber-shaped supramolecular mimetic of netrin-1 with monomers that incorporate a cyclic peptide sequence as the bioactive component. The mimetic structure was found to activate the DCC receptor in primary cortical neurons using low molar ratios of the bioactive comonomer. The supramolecular nanofibers enhanced neurite outgrowth and upregulated maturation as well as pre- and postsynaptic markers over time, resulting in differences in electrical activity similar to neurons treated with the recombinant netrin-1 protein. The results suggest the possibility of using the supramolecular structure as a therapeutic to promote regenerative bioactivity in CNS injuries.

JTD Keywords: axon growth, axon guidance, cell-migration, colorectal-cancer, dcc, dopaminergic-neurons, force-field, functional recovery, netrin-1, neurite outgrowth, neuronal maturation, neurotrophic factor, neurotrophicfactor mimetic, synapsis, Axon growth, Axons, Cells, cultured, Central nervous system, Coarse-grained model, Nanofibers, Netrin-1, Neurogenesis, Neuronal maturation, Neurons, Neurotrophic factor mimetic, Peptide amphiphile, Synapsis

During development, organs reach precise shapes and sizes. Organ morphology is not always obtained through growth; a classic counterexample is the condensation of the nervous system during Drosophila embryogenesis. The mechanics underlying such condensation remain poorly understood. Here, we characterize the condensation of the embryonic ventral nerve cord (VNC) at both subcellular and tissue scales. This analysis reveals that condensation is not a unidirectional continuous process but instead occurs through oscillatory contractions. The VNC mechanical properties spatially and temporally vary, and forces along its longitudinal axis are spatially heterogeneous. We demonstrate that the process of VNC condensation is dependent on the coordinated mechanical activities of neurons and glia. These outcomes are consistent with a viscoelastic model of condensation, which incorporates time delays and effective frictional interactions. In summary, we have defined the progressive mechanics driving VNC condensation, providing insights into how a highly viscous tissue can autonomously change shape and size.

JTD Keywords: actomyosin, central nervous system, drosophila, glia, mechanics, morphogenesis, neuron, ventral nerve cord, Actomyosin, Animals, Central nervous system, Collagen-iv, Contraction, Drosophila, Embryonic development, Forces, Gene, Glia, Glial-cells, Mechanics, Migration, Morphogenesis, Neuroglia, Neuron, Neurons, Quantification, System, Tissue, Ventral nerve cord, Viscolelastic model

Animals in their ecological context behave not only in response to external events, such as opportunities and threats but also according to their internal needs. As a result, the survival of the organism is achieved through regulatory behaviour. Although homeostatic and allostatic principles play an important role in such behaviour, how an animal's brain implements these principles is not fully understood yet. In this paper, we propose a new model of regulatory behaviour inspired by the functioning of the medial Reticular Formation (mRF). This structure is spread throughout the brainstem and has shown generalized Central Nervous System (CNS) arousal control and fundamental action-selection properties. We propose that a model based on the mRF allows the flexibility needed to be implemented in diverse domains, while it would allow integration of other components such as place cells to enrich the agent's performance. Such a model will be implemented in a mobile robot that will navigate replicating the behaviour of the sand-diving lizard, a benchmark for regulatory behaviour. © 2020 Elsevier B.V.. All rights reserved.

JTD Keywords: Action selection, Allostasi, Allostasis, Animal brain, Animals, Behavior-based, Brainstem, Central nervous systems, Cognitive architecture, Cognitive architectures, Elsevier, Homeostasis, Homoeostasis, Magnetorheological fluids, Regulatory behavior, Regulatory behaviour, Reticular formation, Robots