FUNCTIONAL RECOVERY AND COLLATERAL NEURONAL SPROUTING EXAMINED IN YOUNG AND AGED RATS FOLLOWING A PARTIAL NEURAL LESION

The rat pineal gland was chosen as a model system to study how aging affects the capacity of surviving neurons to compensate for partial destruction of a neural pathway. The pineal gland receives bilateral overlapping sympathetic innervation from the two internal carotid nerves, whose activity regulates several aspects of pineal metabolism in a circadian fashion. The most dramatic of these is the marked nighttime increase in the activity of N-acetyltransferase, the rate-limiting enzyme in melatonin synthesis. These features allow for the pineal gland to be used as a model system for studies on neuronal plasticity, since it is possible to create specific partial neural lesions and to evaluate functional recovery subsequently at the cellular level. We examined the activity of N-acetyltransferase and the content of melatonin in the pineal gland as indices of pineal function at various time points after unilateral surgical denervation (lesion of one of the two internal carotid nerves) in 4-month-(young) and 25-month-old (aged) rats. At both ages, the nighttime levels of the two parameters were significantly lower 8 h after this lesion than in sham-operated animals of the same age, indicating impaired function. When examined at later time points (i.e., 1.5 and 10 days after this lesion), both young and aged animals exhibited full recovery in these two parameters. Measurement of specific neuronal uptake of [H-3]norepinephrine was utilized as an index of the number of sympathetic varicosities innervating the pineal gland. One and a half days after unilateral denervation, [H-3]norepinephrine uptake in 4-, 10-, 16- and 25-month-old animals was approximately 50% of that obtained in sham-operated animals of the same age, as expected if half of the innervation of the gland was lesioned. Ten days after surgery, [H-3]norepinephrine uptake in 4- and 10-month-old animals was 78% of the value found in sham-operated animals of the same age, suggesting collateral sprouting of the remaining sympathetic nerve fibers. However, in 16- and 25-month-old animals, uptake remained at 50%. These data indicate that recovery of pineal function after unilateral denervation occurs to a similar extent and with a similar time course in young and aged animals. In contrast, the data suggest that collateral sprouting is impaired in aged animals. The fact that functional recovery occurs in young animals sooner after the lesions than does collateral sprouting and that recovery occurs in the aged animals in the apparent absence of collateral sprouting suggests that the relationship between this anatomical form of plasticity and functional recovery may be complex. Among other possibilities, collateral sprouting may play a role in the maintenance of recovered function rather than in the initial recovery process or sprouting may be functionally important after nerve losses greater than those represented by a 50% lesion.