Enigmatic Central Canal Contacting Cells: Immature Neurons in “Standby Mode”?

Abstract

The region that surrounds the central canal of the spinal cord derives from the neural tube and retains a substantial degree of plasticity. In turtles, this region is a neurogenic niche where newborn neurons coexist with precursors, a fact that may be related with the endogenous repair capabilities of low vertebrates. Immunohistochemical evidence suggests that the ependyma of the mammalian spinal cord may contain cells with similar properties, but their actual nature remains unsolved. Here, we combined immunohistochemistry for cell-specific markers with patch-clamp recordings to test the hypothesis that the ependyma of neonatal rats contains immature neurons similar to those in low vertebrates. We found that a subclass of cells expressed HuC/D neuronal proteins, doublecortin, and PSA-NCAM (polysialylated neural cell adhesion molecule) but did not express NeuN (anti-neuronal nuclei). These immature neurons displayed electrophysiological properties ranging from slow Ca 2ϩ -mediated responses to fast repetitive Na ϩ spikes, suggesting different stages of maturation. These cells originated in the embryo, because we found colocalization of neuronal markers with 5-bromo-2Ј-deoxyuridine when injected during embryonic day 7-17 but not in postnatal day 0 -5. Our findings represent the first evidence that the ependyma of the rat spinal cord contains cells with molecular and functional features similar to immature neurons in adult neurogenic niches. The fact that these cells retain the expression of molecules that participate in migration and neuronal differentiation raises the possibility that the ependyma of the rat spinal cord is a reservoir of immature neurons in "standby mode," which under some circumstances (e.g., injury) may complete their maturation to integrate spinal circuits.

The late and dual origin of cerebrospinal fluid-contacting neurons in the mouse spinal cord

“…However, despite this evolutionary conservation, their function has not yet been fully elucidated. Gata2 + neurons of the central canal in newborn and young mice exhibit molecular and physiological characteristics of immature neurons, in agreement with previous observations (Stoeckel et al, 2003;Marichal et al, 2009;Sabourin et al, 2009;Orts-Del'Immagine et al, 2014Kútna et al, 2014).…”

“…S1J-N). Whole-cell GFP labeling identified these cells as the cerebrospinal fluidcontacting neurons of the central canal (CSF-cNs) VighTeichmann, 1971, 1998;Vigh et al, 1977;Stoeckel et al, 2003;Marichal et al, 2009) (Fig. 1J-M).…”

“…Those settled in the lateral wall account for 73±6% of CSF-cNs at P0 (Fig. 1J,K Although spinal CSF-cNs have been described in a wide number of vertebrate species (Vigh and Vigh-Teichmann, 1971;Vigh et al, 1977Vigh et al, , 1983Stoeckel et al, 2003;Marichal et al, 2009;Huang et al, 2006;Djenoune et al, 2014;Jalalvand et al, 2014), their characteristics remain to be fully clarified. We evaluated the expression of distinct cellular markers and found that CSF-cNs express high levels of Nkx6-1 and Sox2 ( Fig.…”

Regional differences of proliferation activity in the spinal cord ependyma of adult rats

“…Recently, Marichal [34] brought immunohistochemical evidence that a subpopulation of ependymal cells exhibits features of immature neurons which are in "stand by mode". The functional role of such persistent proliferation activity in the spinal cord is not fully understood but anyway could contribute to the plasticity of the central nervous system.…”

The Cannabinoid 1 Receptor and Progenitor Cells in the Adult Central Nervous System

“…Also there are instances of indirect injury to the adult spinal cord, such as dorsal rhizotomy (cutting of the dorsal root at the cervical spinal level) in which neurogenesis is observed in the dorsal horn at the corresponding spinal level (Vessal, Aycock et al 2007). Recent papers showed that in non-injured, intact adult spinal cords, immature neurons can be found in the area surrounding the central canal (Shechter, Ziv et al 2007;Marichal, Garcia et al 2009), but also throughout the spinal cord, with a preferential dorsal gray matter localization and exclusive GABAergic phenotype (Shechter, Ziv et al 2007;Shechter, Baruch et al 2011). The exact roles of these immature neurons in the healthy spinal cord have not been determined, but may indicate physiological roles for new GABAergic neurons in nociception (Shechter, Baruch et al 2011), and also for movement.…”