Streptozotocin-induced diabetes reduces retrograde axonal transport in the afferent and efferent vagus nerve.
Diabetes-induced alterations in nerve function include reductions in the retrograde axonal transport of neurotrophins. A decreased axonal accumulation of endogenous nerve growth factor (NGF) and neurotrophin-3 (NT-3) in the vagus nerve of streptozotocin (STZ)-induced diabetic rats was previously shown. In the current study, no changes in the NGF and NT-3 protein or mRNA levels in the stomach or atrium, two vagally innervated organs, were noted after 16 or 24 weeks of diabetes. Moreover, the amounts of neurotrophin receptor (p75, TrkA, TrkC) mRNAs in the vagus nerve and vagal afferent nodose ganglion were not reduced in diabetic rats. These data suggest that neither diminished access to target-derived neurotrophins nor the loss of relevant neurotrophin receptors accounts for the diabetes-induced alteration in the retrograde axonal transport of neurotrophins. To assess whether diabetes causes a defect in axonal transport that may not be specific to neurotrophin transport, we studied the ability of a neuronal tracer (FluoroGold, FG) to be retrogradely transported by vagal neurons of control and diabetic rats. After vagal target tissue (stomach) injections of FG, the numbers of FG-labeled afferent and efferent vagal neurons were counted in the nodose ganglion and in the dorsal motor nucleus of the vagus, respectively. After 24 weeks of diabetes, FG was retrogradely transported to more than 50% fewer afferent and efferent vagal neurons in the STZ-diabetic compared to control rats. The diabetes-induced deficit in retrograde axonal transport of FG is likely to reflect alterations in basic axonal transport mechanisms in both the afferent and efferent vagus nerve that contribute to the previously observed reductions in neurotrophin transport.
Lee
Paek Gyu
PG
Department of Pharmacology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
Cai
Fang
F
Helke
Cinda J
CJ
D000344:Afferent Pathways / Q000378:metabolism; D000818:Animals; D001370:Axonal Transport; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D004525:Efferent Pathways / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D006325:Heart Atria / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism; D009620:Nodose Ganglion / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014630:Vagus Nerve / Q000378:metabolism*
D009414:Nerve Growth Factors; D017475:Receptors, Nerve Growth Factor