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.