title: Streptozotocin-induced diabetes and the neurochemistry of vagal afferent neurons.
abstract: To assess whether diabetes alters the content and/or expression of neuroactive agents and protooncogenes in afferent neurons of the vagus nerve, the nodose ganglia of streptozotocin (STZ)-induced diabetic rats were studied at 8, 16, and 24 weeks after induction of diabetes. Neuronal nitric oxide synthase (nNOS), tyrosine hydroxylase (TH), the immediate early gene c-Jun, vasoactive intestinal peptide (VIP) and calcitonin gene related peptide (CGRP) content and expression were measured in nodose ganglia of control, diabetic, and diabetic+insulin-treated rats using immunocytochemistry and reverse transcription-polymerase chain reaction (RT-PCR). The numbers of nNOS-immunoreactive (ir) neurons were increased in the nodose ganglion of diabetic compared to control rats at the 8- and 16-week time points. However, no change was noted in the nNOS mRNA content of the diabetic nodose ganglion at either time point. Moreover, no alterations in the numbers of vagal efferent NOS-containing neurons (labeled with NADPH-diaphorase histochemistry) were noted in the dorsal motor nucleus of the vagus (DMV) or the nucleus ambiguous (NA) of control, diabetic, and diabetic+insulin-treated rats at any time point. Neither the numbers of TH-ir neurons nor the content of TH mRNA was altered in the diabetic rats at the 8- and 16-week time points. However, 24 weeks of diabetes resulted in a reduction in the numbers of TH-ir neurons in the diabetic nodose ganglia when compared to control, an effect not seen in diabetic rats receiving insulin. The number of nodose ganglion neurons labeled for the protooncogene, c-Jun, was small yet slightly increased in the diabetic nodose ganglia at the 8-week time point and was reversed with insulin treatment. The increase in c-Jun-ir neurons was not found at 16 or 24 weeks of diabetes. VIP-ir and CGRP-ir were unchanged at any of the time points. These data show that diabetes affects the content of some, but not all, neuroactive agents in the nodose ganglion and may reflect a modest level of diabetes-induced damage and/or alterations in axonal transport in the vagus nerve.
authors.affiliation: Department of Pharmacology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
authors.forename: Jen
authors.initials: J
authors.lastname: Regalia
authors.forename: Fang
authors.initials: F
authors.lastname: Cai
authors.forename: Cinda
authors.initials: C
authors.lastname: Helke
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D016758:Genes, jun / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D009252:NADPH Dehydrogenase / Q000032:analysis*; D019001:Nitric Oxide Synthase / Q000032:analysis*; D052248:Nitric Oxide Synthase Type I; D009620:Nodose Ganglion / Q000737:chemistry* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013311:Streptozocin; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis*; D014630:Vagus Nerve / Q000737:chemistry; D014660:Vasoactive Intestinal Peptide / Q000032:analysis*
chemical_list: D014660:Vasoactive Intestinal Peptide; D013311:Streptozocin; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D014446:Tyrosine 3-Monooxygenase; D009252:NADPH Dehydrogenase; D015740:Calcitonin Gene-Related Peptide