BACKGROUND: Diabetic neuropathy is a debilitating disorder whose causation is poorly understood. Recent studies have shown significant reduction in the activity of nerve growth factor (NGF) and in the amount of talin cytoskeleton protein immunoreactivity in the perineurium in patients with diabetic neuropathy. OBJECTIVE: Since talin is involved in transmembrane connections between extracellular matrix and cytoskeleton, this study investigates the subcellular pattern of talin immunoreactivity and the effect of NGF treatment of diabetic rats on the distribution of talin in the sciatic nerve. MATERIALS AND METHODS: Post-embedding immunogold electron microscopy using monoclonal antibody against talin in combination with quantitative procedures was employed to localize talin-like immunoreactivity in the sciatic nerve of normal, diabetic and NGF treated diabetic rats. RESULTS: We found the highest densities of gold particles in the Schwann cells (139.6+/-5.6 particles/microm2) and in the fibroblasts (127.4+/-4.1 particles/microm2). A moderate amount of immunoreactivity was also present in the endothelial cells of vasa nervosa (32.3+/-9.1 particles/microm2). The myelinated and unmyelinated nerve fibers and the extracellular matrix profiles were not labeled (8.7+/-2.1 particles/microm2, 4.2+/-2.2 particles/microm2, 6.1+/-3.2 particles/microm2, 9.5+/-5.3 particles/microm2, respectively). The immunogold localization of talin in diabetic rats was significantly (p<0.001) reduced in Schwann cells (66.3+/-6.5 particles/microm2) and perineurial and epineurial fibroblasts (56.8+/-3.9 particles/microm2). Diabetic rats treated with NGF for 12 weeks showed significant (p<0.005) increase in talin-like immunogold density in Schwann cells and fibroblasts. Talin immunogold density in Schwann cells and fibroblasts increased approximately 68% and 58%, respectively, after NGF treatment. The endothelial cells of endoneurial and epineurial vessel walls showed no significant change in the talin-like immunogold particle density among control, diabetic and NGF treated diabetic animals. CONCLUSIONS: These results have shown that the administration of exogenous NGF may be essential for inducing functionally significant regenerative mechanisms in diabetic neuropathy through maintaining the permeability of the barrier properties of the peripheral nerve.
BACKGROUND:Diabetic neuropathy is a debilitating disorder whose causation is poorly understood. Recent studies have shown significant reduction in the activity of nerve growth factor (NGF) and in the amount of talin cytoskeleton protein immunoreactivity in the perineurium in patients with diabetic neuropathy. OBJECTIVE: Since talin is involved in transmembrane connections between extracellular matrix and cytoskeleton, this study investigates the subcellular pattern of talin immunoreactivity and the effect of NGF treatment of diabeticrats on the distribution of talin in the sciatic nerve. MATERIALS AND METHODS: Post-embedding immunogold electron microscopy using monoclonal antibody against talin in combination with quantitative procedures was employed to localize talin-like immunoreactivity in the sciatic nerve of normal, diabetic and NGF treated diabeticrats. RESULTS: We found the highest densities of gold particles in the Schwann cells (139.6+/-5.6 particles/microm2) and in the fibroblasts (127.4+/-4.1 particles/microm2). A moderate amount of immunoreactivity was also present in the endothelial cells of vasa nervosa (32.3+/-9.1 particles/microm2). The myelinated and unmyelinated nerve fibers and the extracellular matrix profiles were not labeled (8.7+/-2.1 particles/microm2, 4.2+/-2.2 particles/microm2, 6.1+/-3.2 particles/microm2, 9.5+/-5.3 particles/microm2, respectively). The immunogold localization of talin in diabeticrats was significantly (p<0.001) reduced in Schwann cells (66.3+/-6.5 particles/microm2) and perineurial and epineurial fibroblasts (56.8+/-3.9 particles/microm2). Diabeticrats treated with NGF for 12 weeks showed significant (p<0.005) increase in talin-like immunogold density in Schwann cells and fibroblasts. Talin immunogold density in Schwann cells and fibroblasts increased approximately 68% and 58%, respectively, after NGF treatment. The endothelial cells of endoneurial and epineurial vessel walls showed no significant change in the talin-like immunogold particle density among control, diabetic and NGF treated diabetic animals. CONCLUSIONS: These results have shown that the administration of exogenous NGF may be essential for inducing functionally significant regenerative mechanisms in diabetic neuropathy through maintaining the permeability of the barrier properties of the peripheral nerve.