Expressions of phosphorylated cAMP response element‐binding protein and neuronal nitric oxide synthase in the dorsal medulla of Zucker Diabetic Fatty rats

Abstract

The purpose of this study was to examine the expressions of phosphorylated cyclic‐AMP response element binding protein (pCREB) and neuronal NO synthase (nNOS) in the brainstem of Zucker Diabetic Fatty (ZDF) rats compared to age‐matched lean rats. Sections of rat medulla were examined by immunolabeling with a polyclonal antibody directed against nNOS and NADPH diaphorase histochemistry, a marker of nNOS activity. The brainstem nuclei were also visualized through double labeling the neurons by immunohistochemistry with anti‐pCREB antibody combined with NAPDH diaphorase reactivity. The number of nNOS immunostaining neurons and NAPDH diaphorase positive neurons were significantly decreased in the gracile nucleus and the medial nucleus tractus solitarius (mNTS), but not altered in other brainstem regions of ZDF rats compared to lean rats. pCREB positive cells containing NAPDH diaphorase reactivity were significantly decreased in the mNTS and gracile nucleus of ZDF rats compared to lean rats. The results show that pCREB neurons endowed with nNOS are decreased in the gracile nucleus and mNTS of ZDF rats. We conclude that reduced pCREB causes decreased nNOS‐NO level in the dorsal medulla, which modifies somatosensory functions in Type II diabetic rats. Supported by ADA 7–07–RA–100 and NIH RO1 AT 002478 to S. Ma.