Ultrastructrual effects of chemical sympathectomy on brown adipose tissue

Adult rats maintained at 20-22 degrees C, were exposed to 4 degrees C for 30-60 min and injected with 50 or 100 mg/kg 6-hydroxydopamine (6-OHDA) in an attempt to achieve a similar degree of chemical sympathectomy of nerves terminating among the adipocytes and the smooth muscle cells of the blood vessels in the interscapular brown adipose tissue (BAT). After 1, 4 or 10 days the pads of BAT were removed and small sections from each pad prepared for electron microscopy; the remaining tissue was used for noradrenaline (NA) analysis for fluorescence histochemistry. Ultrastructural observations showed that 24 h after the 6-OHDA injection virtually all noradrenergic nerve terminals were distorted and contained aggregates of degenerated cell organelles. The destruction could be correlated with a disappearance of fluorescent varicosities and a reduction of measurable NA to 8-12% of the control value. There was no differential toxic effect of 6-OHDA on the terminals among the adipocytes compared to those associated with blood vessels. Thus, treatment with 6-OHDA is more effective than previous attempts using immunological or surgical methods to produce sympathectomy, because both of the latter methods only eliminate the innervation of the blood vessels and spare the nerve terminals of the adipocytes. 4 days after 6-OHDA injection there was no improvement in the morphology of the terminals but after 10 days there was an increase in the number of terminals and axons with a normal appearance and this was paralleled by an increase in extractable NA to 50% of the control value. Because of the relatively rapid recovery of NA content and reappearance of terminals of normal appearance within 10 days after 6-OHDA injection, these animals should be injected weekly when a more permanent sympathectomy of adipocytes and blood vessels is desired.