Acrylamide-induced sympathetic autonomic neuropathy resulting in pineal denervation.

The effect of acrylamide on the sympathetic innervation of the rat pineal gland was examined by using ultrastructural, immunohistological, biochemical, and physiological methods. Separation of sympathetic terminals from perivascular pineocyte processes was facilitated by administration of the false neurotransmitter 5-hydroxydopamine, which preferentially labeled sympathetic terminals, shortly before sacrifice. Administration of acrylamide (50 mg/kg/day, intraperitoneally) for 1 to 2 weeks resulted in the near-total loss of pineal parenchymal perivascular axons and axons intercalated between individual pineocytes. More proximal portions of these sympathetic axons located within the capsule of the pineal gland developed markedly enlarged swellings containing neurofilaments and tubulovesicular elements. The ultrastructural appearance of axons swollen by tubulovesicular elements resembled that of regenerating axons and axons whose regenerative progress had been frustrated. The activity of pineal dopamine-beta-hydroxylase, a noradrenergic marker enzyme confined to sympathetic axons and their terminals and absent in pineocytes, was determined in an attempt to develop a quantitative measure of the extent of sympathetic denervation. The loss of 50% of pineal dopamine-beta-hydroxylase activity underestimated the extent of parenchymal denervation due to the marked engorgement of remaining capsular sympathetic axons by immunoreactive dopamine-beta-hydroxylase. The daily rhythm of pineal serotonin N-acetyltransferase (NATase) activity, which is dependent on the circadian variation in the activity of pineal sympathetic axons, was decreased 90% by chronic acrylamide administration. Pineal NATase activity increased 25- to 50-fold in acrylamide intoxicated rats in which isoproterenol was used to stimulate pineocyte beta-adrenergic receptors directly, which is evidence against a nonspecific toxic effect of acrylamide on pineocytes. Administration of N,N'methylene-bis-acrylamide, a non-neurotoxic analog of acrylamide, was without effect on pineal ultrastructure or NATase activity.