We describe a compartmentalized circular microfluidic platform that enables directed cell placement within defined microenvironments for the study of axon-glia interactions. The multi-compartment platform consists of independent units of radial microchannel arrays that fluidically isolate somal from axonal compartments. Fluidic access ports punched near the microchannels allow for direct pipetting of cells into the device. Adjacent somal or axonal compartments can be readily merged so that independent groups of neurons or axons can be maintained in either separate or uniform microenvironments. We demonstrate three distinct modes of directed cell placement in this device, to suit varying experimental needs for the study of axon-glia interactions: (1) centrifugation of the circular platform can result in a two-fold increase in axonal throughput in microchannels and provides a new technique to establish axon-glia interactions; (2) microstencils can be utilized to directly place glial cells within areas of interest; and (3) intimate axon-glia co-culture can be attained via standard pipetting techniques. We take advantage of this microfluidic platform to demonstrate a two-fold preferential accumulation of microglia specifically near injured CNS axons, an event implicated in the maintenance and progression of a number of chronic neuroinflammatory and neurodegenerative diseases.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1039/b918640a | DOI Listing |
Glia
January 2025
Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
The molecules that constitute myelin are critical for the integrity of axon/myelin-units and thus speed and precision of impulse propagation. In the CNS, the protein composition of oligodendrocyte-derived myelin has evolutionarily diverged and differs from that in the PNS. Here, we hypothesized that the CNS myelin proteome also displays variations within the same species.
View Article and Find Full Text PDFNeurosci Lett
October 2024
Max-Planck-Institute for Multidisciplinary Sciences, 37075 Göttingen, Germany.
Understanding the sequence of cellular responses and their contributions to pathomorphogical changes in spinal white matter injuries is a prerequisite for developing efficient therapeutic strategies for spinal cord injury (SCI) as well as neurodegenerative and inflammatory diseases of the spinal cord such as amyotrophic lateral sclerosis and multiple sclerosis. We have developed several types of surgical procedures suitable for acute one-time and chronic recurrent in vivo multiphoton microscopy of spinal white matter [1]. Sophisticated surgical procedures were combined with transgenic mouse technology to image spinal tissue labeled with up to four fluorescent proteins (FPs) in axons, astrocytes, microglia, and blood vessels.
View Article and Find Full Text PDFGlia
September 2024
Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
The velocity of axonal impulse propagation is facilitated by myelination and axonal diameters. Both parameters are frequently impaired in peripheral nerve disorders, but it is not known if the diameters of myelinated axons affect the liability to injury or the efficiency of functional recovery. Mice lacking the adaxonal myelin protein chemokine-like factor-like MARVEL-transmembrane domain-containing family member-6 (CMTM6) specifically from Schwann cells (SCs) display appropriate myelination but increased diameters of peripheral axons.
View Article and Find Full Text PDFGlia
May 2024
Department of Anesthesiology, University of California San Diego, La Jolla, California, USA.
Schwann cells (SCs) undergo phenotypic transformation and then orchestrate nerve repair following PNS injury. The ligands and receptors that activate and sustain SC transformation remain incompletely understood. Proteins released by injured axons represent important candidates for activating the SC Repair Program.
View Article and Find Full Text PDFNat Commun
October 2023
Department of Neurology, Section of Developmental Neurobiology, University Hospital Würzburg, Würzburg, Germany.
Axon degeneration and functional decline in myelin diseases are often attributed to loss of myelin but their relation is not fully understood. Perturbed myelinating glia can instigate chronic neuroinflammation and contribute to demyelination and axonal damage. Here we study mice with distinct defects in the proteolipid protein 1 gene that develop axonal damage which is driven by cytotoxic T cells targeting myelinating oligodendrocytes.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!