The Ryk Receptor Is Expressed in Glial and Fibronectin-Expressing Cells after Spinal Cord Injury

Abstract

Wnt proteins play a critical role in central nervous system development and have been implicated in several neuropathologies, including spinal cord injury (SCI). Ryk, an unconventional Wnt receptor, regulates axonal regeneration after SCI, although its expression pattern in this neuropathology remains unclear. Therefore, we sought to define the spatiotemporal and cellular pattern of Ryk expression after a contusive SCI in adult rats using quantitative reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunohistochemical analysis. Under physiological conditions, Ryk is expressed in neurons, astrocytes, and blood vessels, but not in oligodendrocytes, microglia, NG2+ glial precursor cells, or axonal projections. Following SCI, we observed an increase in Ryk mRNA expression from 24 h post-injury until 7 days post-injury, whereas its protein levels were significantly augmented at 7 and 14 days post-injury. Moreover, the spatial and cellular Ryk expression pattern was altered in the damaged tissue, where this receptor was observed in reactive astrocytes and microglia/macrophages, NG2+ glial precursors, fibronectin + cells, oligodendrocytes, and axons. In conclusion, we demonstrate that Ryk is expressed in the unlesioned spinal cord and that, after SCI, its spatiotemporal and cellular expression pattern changed dramatically, being expressed in cells involved in the spinal cord response to damage.

Wnt Signaling Alterations in the Human Spinal Cord of Amyotrophic Lateral Sclerosis Cases: Spotlight on Fz2 and Wnt5a

“…Interestingly, recent studies carried out in animal models have shown that the Wnt family of proteins, a well-known regulator of crucial processes in the developing [16][17][18] and adult [18][19][20] central nervous system (CNS) under physiological conditions, is also clearly involved in many of the cellular and molecular processes that characterize the progression and outcome of different CNS pathologies [21][22][23][24][25][26][27][28]. Notably, recent studies have described a dysregulation in the expression of several members of this family of proteins in the spinal cord of a mouse model of ALS and also in an in vitro model of the disease [29][30][31][32][33][34][35][36][37].…”

Altered expression of atypical PKC and Ryk in the spinal cord of a mouse model of amyotrophic lateral sclerosis

“…However, recently it was shown to have proapoptotic function in ovarian cancer (Nazarenko et al, ). Ryk is a Wnt binding receptor that mediates axon repulsion in development and inhibition of axon plasticity in adulthood after traumatic injury (Liu et al, ; Keeble and Cooper, ; Keeble et al, ; Schmitt et al, ; Liu et al, ; Miyashita et al, ; Fradkin et al, ; Hollis and Zou, ,; Gonzalez et al, ). Therefore, we elected to characterize these two key regulators of axon growth and plasticity in an animal model of ALS.…”

Effects of Wnt5a overexpression in spinal cord injury

“…33,34 Given that the effects of Wnt5a in axonal growth are largely dictated by the available receptors in the axonal membrane, 53 axonal level, but also in neuronal somas, reactive astrocytes and microglia/macrophages, NG2+ glial precursors and oligodendrocytes. 3,4,7 These observations indicate that these cell types are able to respond to Wnt5a and, thus, that this Wnt ligand might be influencing their critical responses to SCI. For instance, both Fz5 and Ryk are not only expressed in neurons in the healthy spinal cord but also in adjacent areas to the lesion epicentre after SCI, 3,4 which are thought to be affected by the secondary progression of the injury.…”

“…In this sense, we have pression of these Wnt5a receptors can be observed in this cell type after SCI, mainly in those NG2+ cells that are located in the lesion epicenter. 4,7 Finally, since the presence of oligodendroglial and astroglial cells was unaltered in the same time post-injury and rostro-caudal levels, it is plausible that the reduction observed in the accumulation of this cell type in the lesion epicentre might be due to a Wnt5a-mediated decrease in its proliferation and/or survival, rather than an increase in their differentiation rate.…”