Abstract
BackgroundSpinal cord injury is a major cause of disability that has no clinically accepted treatment. Functional decline following spinal cord injury is caused by mechanical damage, secondary cell death, reactive gliosis and a poor regenerative capacity of damaged axons. Wnt proteins are a family of secreted glycoproteins that play key roles in different developmental processes although little is known of the expression patterns and functions of Wnts in the adult central nervous system in normal or diseased states.FindingsUsing qRT-PCR analysis, we demonstrate that mRNA encoding most Wnt ligands and soluble inhibitors are constitutively expressed in the healthy adult spinal cord. Strikingly, contusion spinal cord injury induced a time-dependent increase in Wnt mRNA expression from 6 hours until 28 days post-injury, and a narrow peak in the expression of soluble Wnt inhibitors between 1 and 3 days post-injury. These results are consistent with the increase in the migration shift, from day 1 to 7, of the intracellular Wnt signalling component, Dishevelled-3. Moreover, after an initial decrease by 1 day, we also found an increase in phosphorylation of the Wnt co-receptor, low-density lipoprotein receptor-related protein 6, and an increase in active β-catenin protein, both of which suffer a dramatic change, from a homogeneous expression pattern in the grey matter to a disorganized injury-induced pattern.ConclusionsOur results suggest a role for Wnts in spinal cord homeostasis and injury. We demonstrate that after injury Wnt signalling is activated via the Wnt/β-catenin and possibly other pathways. These findings provide an important foundation to further address the function of individual Wnt proteins in vivo and the pathophysiology of spinal cord injury.
Highlights
Spinal cord injury (SCI) is a major cause of disability with no clinically accepted treatment [1]
We demonstrate that after injury Wnt signalling is activated via the Wnt/b-catenin and possibly other pathways. These findings provide an important foundation to further address the function of individual Wnt proteins in vivo and the pathophysiology of spinal cord injury
The epicentre of the SCI is characterized by necrotic neural death, while secondary tissue damage is evident in the penumbra zone, where processes such as ischemia, hypoxia, excitotoxicity, free radical formation, protease release and inflammation contribute to the expansion of segmental loss of function
Summary
Spinal cord injury (SCI) is a major cause of disability with no clinically accepted treatment [1]. The epicentre of the SCI is characterized by necrotic neural death, while secondary tissue damage is evident in the penumbra zone, where processes such as ischemia, hypoxia, excitotoxicity, free radical formation, protease release and inflammation contribute to the expansion of segmental loss of function. The Wnt family of proteins plays key roles during the development of the nervous system, influencing cell proliferation and patterning, cell polarity and motility, axonal guidance, neuronal survival and connectivity, and cell-cell adhesion [5,6] This wide range of effects is possible because the specific responses elicited in target cells are dependent on the spatiotemporal distribution of Wnt ligands, modulators and receptors [7,8,9,10,11]. Wnt proteins are a family of secreted glycoproteins that play key roles in different developmental processes little is known of the expression patterns and functions of Wnts in the adult central nervous system in normal or diseased states
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
