NF-κB subunits are differentially distributed in cells of lumbar dorsal root ganglia in naïve and diabetic rats

Previous studies demonstrated that nuclear factor κB (NF-κB) activation is decreased in dorsal root ganglia (DRG) of rats having streptozotocin (STZ)-induced diabetes. DRG contain cell bodies of neurons that convey sensory signals from the periphery. To determine the relationship between diabetes-induced neuropathy and NF-κB expression in DRG, behavioral, immunohistochemical, and biochemical studies were performed on naïve and 3-month diabetic rats. Behavioral studies confirmed that many diabetic rats develop tactile allodynia, or increased sensitivity to light touch, in the hind paws. Immunohistochemical studies on lumbar DRG that receive input from the affected regions revealed that p50 and p65, frequent NF-κB subunit partners, are differentially localized. Intense p65 immunostaining was detected in the cytoplasm of small- and medium-sized neurons as well as in satellite cells. In contrast, p50 was localized in the cytoplasm of virtually all neurons. In many cases, prominent staining was also present in nuclei, a location consistent with transcription factor activation. Immunohistochemical and biochemical studies found that the nuclear to cytoplasmic ratio of p50 expression was significantly reduced in diabetic rats compared to that in naïve animals. Our findings raise the possibility that changes in NF-κB activation in a subset of DRG neurons participates in mediating diabetes-induced sensory neuropathy.

Research highlights▶ NFkB p50 and p65 subunits are differentially distributed in DRG neurons. ▶ p50 is found in many neuronal nuclei; the nuclear/cytoplasmic ratio of p50 decreases in diabetes. ▶ p65 is expressed mainly in the cytoplasm of small/medium-sized neurons. ▶ p65 is also present in satellite cells surrounding large neurons. ▶ p50 and p65 are found in medium/small DRG neurons expressing CGRP or IB4.