MANDIBLE AUTONOMIC INNERVATION AND BONE MASS WITH AGING

Abstract

Advanced age is a critical risk factor for many chronic, debilitating conditions including osteoporosis and periodontitis. The mechanisms that maintain maxilla and mandible during aging remain largely unknown. It has been recognized that autonomic nervous system (ANS) affects bone homeostasis. The ANS is composed of sympathetic and parasympathetic nerves, which mediate their actions via neurotransmitters norepinephrine (NE) and acetylcholine (Ach), respectively. This study explored the ANS innervation in tooth-bone microenvironment associated with aging. Fifty wild type C57BL/6J mice, each group consisted of 10 mice (5 females and 5 males), were from five ages - 4 weeks, 12 weeks, 24 weeks, 48 weeks, and 72 weeks, respectively. The right mandibles were collected for NE/Ach quantification by high-performance liquid chromatography (HPLC). The left mandibles were used for bone density and architecture measurement by micro-computed tomography (µCT). Immunohistochemistry (IHC) identified the presence and distribution of sympathetic nerve marker tyrosine hydroxylase (TH) and parasympathetic nerve marker choline acetyltransferase (ChAT) in the left hemisphere of the brain and the mandibles. Ach level peaked at 4 weeks, after which it declined. The NE level, stayed stable from 4 weeks to 72 weeks. The mandible trabecular v bone reached a peak bone mass at 12 weeks, similar to that of other trabecular bones. However, from 12 weeks to 72 weeks, the trabecular bone mass in the mandible was stable, in contrast to trabecular bone in other bones. An inverse relationship exists between the mandible Ach content and the mandible trabecular bone volume and bone mineral density (γ = -0.5243, 95% CI: -0.7004, -0.2879, p< 0.001; γ = -0.536, 95% CI: -0.7086, -0.3029, p <0.0001, respectively). IHC confirmed that the sympathetic nerve activity stays unchanged with aging (from 4 weeks to 72 weeks) in both the brain and mandible while IHC did not replicate the change in the parasympathetic nerve activity with aging observed in HPLC. Our results suggest that the Ach released from the parasympathetic nerves may influence the aging mandible.