Abstract
A common characteristic of axonopathy is the abnormal accumulation of cytoskeletal proteins. We recently reported that streptozotocin (STZ)-induced type 1 diabetes produced a change in the morphology of sympathetic nerve fibers supplying rat plantar metatarsal arteries (PMAs). Here we investigated whether these morphological changes are associated with axonal accumulation of the type III intermediate filament peripherin and the microtubule protein β-tubulin III, as both are implicated in axonal remodeling. PMAs from hyperglycemic STZ-treated rats receiving a low dose of insulin (STZ-LI) were compared with those from normoglycemic STZ-treated rats receiving a high dose of insulin (STZ-HI) and vehicle-treated controls. Western blotting revealed an increase in protein expression level for peripherin in PMAs from STZ-LI rats but no change in that for β-tubulin III. In addition, there was an increase in the number of peripherin immunoreactive nerve fibers in the perivascular nerve plexus of PMAs from STZ-LI rats. Co-labeling for peripherin and neuropeptide Y (a marker for sympathetic axons) revealed that peripherin immunoreactivity increased in sympathetic axons. None of these changes were detected in PMAs from STZ-HI rats, indicating that increased peripherin in sympathetic axons of STZ-LI rats is likely due to hyperglycemia and provides a marker of diabetes-induced nerve damage.
Highlights
We demonstrated impaired sympathetic neurovascular transmission in plantar metatarsal arteries (PMAs) from rats with streptozotocin (STZ)-induced diabetes, a well-studied model of type I diabetes (Johansen et al, 2013)
This study shows that STZ-induced type I diabetes increased both the thickness of perivascular nerve fibers and the expression of peripherin in the perivascular nerve plexus of PMAs
As the increase in peripherin immunolabeling occurred in nerve fibers that were neuropeptide Y (NPY)-IR, they are sympathetic nerve terminals
Summary
We demonstrated impaired sympathetic neurovascular transmission in plantar metatarsal arteries (PMAs) from rats with streptozotocin (STZ)-induced diabetes, a well-studied model of type I diabetes (Johansen et al, 2013). In PMAs from hyperglycemic STZ-treated rats that received a low dose of insulin (i.e., a dose insufficient to affect systemic glycemia), neither neurovascular transmission nor perivascular nerve fiber density were changed. In both groups of hyperglycemic STZ-treated rats, the PMA perivascular nerve fibers were thickened and had increased tyrosine hydroxylase (TH) immunoreactivity. It is possible that diabetes produces changes to the sympathetic innervation of PMAs before functional changes can be detected For this reason it is important to identify diabetesinduced changes to the perivascular sympathetic nerves that precede disruption of neurovascular function
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