Effects of long-term diabetes and treatment with gangliosides on cardiac sympathetic innervation: a biochemical and functional study in mice.
The effect of long-term diabetes on cardiac sympathetic innervation was investigated in genetically obese diabetic mice (db/db). Previous studies have shown the presence of a peripheral neuropathy starting a few months after birth, and we recently reported a significant reduction of myocardial norepinephrine (NE) levels in the hearts of diabetic mice at the age of 6 months. In the present study, histofluorescence analysis of comparable sections of cardiac tissue of both control and diabetic animals confirmed the picture of a sympathetic denervated heart in this experimental model. Furthermore, functional studies in isolated atria revealed a difference between the two groups of animals: in fact heart rate increases induced by transmural stimulation were significantly lower in diabetic mice. Since a bovine brain ganglioside mixture (Cronassial) has been extensively studied for its effect on peripheral diabetic neuropathy, a group of diabetic mice was treated throughout the sixth month with this drug (10 mg/kg/day i.p.). The ganglioside treated animals showed a marked recovery of atrial function and cardiac NE concentration. The above results clearly indicate sympathetic neural damage in db/db animals, likely related to an autonomic diabetic neuropathy and a possible protection by ganglioside of adrenergic nerves from this alteration.
Tessari
F
F
Fidia Research Laboratories, Abano Terme, Italy.
Travagli
R A
RA
Zanoni
R
R
Prosdocimi
M
M
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D005732:Gangliosides / Q000627:therapeutic use*; D006321:Heart / Q000294:innervation*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008820:Mice, Obese; D009206:Myocardium / Q000032:analysis*; D009638:Norepinephrine / Q000032:analysis*; D013564:Sympathetic Nervous System / Q000032:analysis* / Q000187:drug effects
D005732:Gangliosides; C037470:cronassial; D009638:Norepinephrine