Connexin Signaling Is Involved in the Reactivation of a Latent Stem Cell Niche after Spinal Cord Injury
| Autor: | Gabriela Fabbiani, Raúl E. Russo, María Victoria Falco, Cecilia Reali, Jimena Fagetti, María Inés Rehermann, Adrián Valentin-Kahan |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Cell Membrane Permeability Patch-Clamp Techniques Ependymal Cell Connexin Nerve Tissue Proteins Poloxamer In Vitro Techniques Biology Connexins Connexon Glial scar Mice Random Allocation 03 medical and health sciences 0302 clinical medicine Ependyma medicine Animals Amino Acid Sequence Stem Cell Niche Progenitor cell Spinal cord injury Spinal Cord Injuries Research Articles Fluorescent Dyes General Neuroscience Cell Membrane Age Factors Gap Junctions Hydrogels medicine.disease Spinal cord Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Animals Newborn Female Peptides 030217 neurology & neurosurgery |
| Zdroj: | J Neurosci |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.2056-19.2020 |
| Popis: | The ependyma of the adult spinal cord is a latent stem cell niche that is reactivated by spinal cord injury contributing new cells to the glial scar. The cellular events taking place in the early stages of the reaction of the ependyma to injury remain little understood. Ependymal cells are functionally heterogeneous with a mitotically active subpopulation lining the lateral domains of the central canal (CC) that are coupled via gap junctions. Gap junctions and connexin hemichannels are key regulators of the biology of neural progenitors during development and in adult neurogenic niches. Thus, we hypothesized that communication via connexins in the CC is developmentally regulated and may play a part in the reactivation of this latent stem cell niche after injury. To test these possibilities, we combined patch-clamp recordings of ependymal cells with immunohistochemistry for various connexins in the neonatal and the adult (P > 90) normal and injured spinal cord of male and female mice. We find that coupling among ependymal cells is downregulated as postnatal development proceeds but increases after injury, resembling the immature CC. The increase in gap junction coupling in the adult CC was paralleled by upregulation of connexin 26, which correlated with the resumption of proliferation and a reduction of connexin hemichannel activity. Connexin blockade reduced the injury-induced proliferation of ependymal cells. Our findings suggest that connexins are involved in the early reaction of ependymal cells to injury, representing a potential target to improve the contribution of the CC stem cell niche to repair.SIGNIFICANCE STATEMENTEpendymal cells in the adult spinal cord are latent progenitors that react to injury to support some degree of endogenous repair. Understanding the mechanisms by which these progenitor-like cells are regulated in the aftermath of spinal cord injury is critical to design future manipulations aimed at improving healing and functional recovery. Gap junctions and connexin hemichannels are key regulators of the biology of neural progenitors during development and in adult neurogenic niches. We find here that connexin signaling in the ependyma changes after injury of the adult spinal cord, functionally resembling the immature active-stem cell niche of neonatal animals. Our findings suggest that connexins in ependymal cells are potential targets to improve self-repair of the spinal cord. |
| Databáze: | OpenAIRE |
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