Recovery of function following unilateral denervation, but not unilateral decentralization, of the pineal gland as indicated by measurements of pineal melatonin content and urinary melatonin metabolites

Abstract

The rat pineal gland is an attractive system for studies on the capacity of neural systems to recover following partial injury, allowing both for the creation of precise subtotal lesions and for the measurement of recovery of function at the cellular level. The pineal gland receives overlapping sympathetic innervation from the right and left internal carotid nerves from neurons whose cell bodies are located in the two superior cervical ganglia. This innervation regulates several aspects of pineal metabolism in a circadian fashion, with the most dramatic being a marked increase in the night-time activity of N-acetyltransferase, a key enzyme regulating the rate of melatonin synthesis. We have previously shown that a highly divergent pattern takes place in the night-time activity of this enzyme following two different unilateral lesions of the sympathetic innervation to the gland. Thus, following a unilateral lesion of the internal carotid nerve (unilateral denervation), there is an initial decline in N-acetyltransferase activity; however, normal activity is again seen during the second and subsequent nights. In contrast, a unilateral lesion of the cervical sympathetic trunk, the nerve that innervates the superior cervical ganglion (unilateral decentralization), results in “permanent” impairment of N-acetyltransferase activity. In the present study, we report that the functional capacity of the entire pathway for melatonin synthesis is similarly affected following these lesions, as reflected by the levels of melatonin and of its precursor N-acetylserotonin in the pineal gland, as well as the levels of the main melatonin metabolite 6-hydroxy-melatonin in the urine. N-Acetyltransferase activity was determined 1.5, 14 and 21 days after unilateral denervation and was found to be 97%, 122% and 98% of the night-time activity in sham-operated animals. At all three points, the pineal contents of N-acetylserotonin (84%, 129% and 105%) and of melatonin (90%, 110% and 115%) were also similar to the levels obtained in sham-operated animals. In contrast, after unilateral decentralization the activity of N-acetyltransferase (18%, 32% and 21%) and the content of both N-acetylserotonin (12%, 43% and 41%) and melatonin (35%, 55% and 47%) were lower than in sham-operated animals. Urinary measurements of 6-hydroxymelatonin, the main melatonin metabolite, showed a robust diurnal rhythm in control animals, with increased excretion at night. Measurements of this metabolite in the urine allowed assessment of pineal function in individual animals, before and after specific lesions. Following unilateral denervation, there was a return of normal 6-hydroxymelatonin levels by the second night after surgery. However, following unilateral decentralization, night-time 6-hydroxymelatonin measurements remained lower than prelesion values for at least 13 nights after the lesion. This study provides additional evidence for our hypothesis that, after certain lesions, intact, but electrophysiologically silent, nerve terminals of decentralized nerve cells may adversely affect the function of terminals from unoperated neurons and, thereby, prevent functional recovery.