Growth-associated protein-43 immunohistochemical and ultrastructural changes in jaw muscle spindles of the rat following loss of occlusion

Abstract

The effects of complete loss of occlusion on the structural and functional status of these muscle spindles were investigated by immunohistochemistry either for protein gene product 9.5 (PGP 9.5) or growth-associated protein-43 (GAP-43) by light and electron microscopy. All the upper molars of 4-week-old Wistar rats were extracted and the erupted portions of the upper and lower incisors of the sarne animals were cut-off at the level of the interdental papilla every other day. In a control group, iminunoreactivity for GAP-43 was positive in the developing annulospiral endings of 2-week-old rats, but was not detected in any of the muscle spindles after 3 weeks of age. At 4 weeks of age, the PGP 9.5 immunostained spindles had well-differentiated annulospiral endings. Ultrastructurally, these afferent endings showed lenticular or circular profiles in cross-sections, and were differentially indented into the intrafusal-fibres. The inner surfaces of the terminals formed rather smooth myoneural junctions, while the outer surfaces were covered only by basal lamina continuous with that of the underlying intrafusal muscle fibres. After the experimental elimination of occlusal contact, GAP-43 immunoreactivity reappeared in some nerve endings of muscle spindles by 3 days, and persisted for at least 28 days. During this period, the afferent-terminals exhibited various fine structural abnormalities such as irregular outlines and invaginated neuromuscular interfaces. Some sensory-terminal (ST) profiles were completely engulfed by intrafusal-fibres. However, GAP-43 expression and ultrastructural alterations became undetectable within a week of the end of incisal cutting and the recovery of incisal-contact. These data indicate that remodelling of nerve terminals in muscle spindles, as assessed by GAP-43 expression and ultrastructural changes, occurs soon after a loss of occlusion, and ceases if incisal-contact is restored. It is concluded that possible changes in jaw muscle function, as well as a sudden loss of proprioceptive sensory input from the periodontal mechanoreceptors of molars and incisors, induce the structural reorganisation of nerve terminations in jaw muscle spindles that is associated with the appearance and disappearance of GAP-43 immunoreactivity.