Strukturelle und funktionelle Veränderungen der Glandula submandibularis der Wistar-Ratte nach intraglandlärer Applikation von Botulinumtoxin

Background and purpose: Intraglandular injection of botulinum toxin (BoNT) leads to a transient denervation of the submandibular gland, associated with reduced salivary secretion. The purpose of the present study is to explore the morphological and functional changes in submandibular tissue after chemical denervation of the glands by botulinumtoxin application. Experimental approach: Tissue specimens of the right submandibular gland from 18 Wistar rats were examined after intraglandular injection of BoNT A, BoNT B, or a combination of both. As a sham control, an equivalent volume of saline was injected into the left submandibular gland. Morphometric measurements, immunohistochemistry, electron microscopy and western blot analysis were used to analyse the morphological and functional changes of the denervated glands. Key results: Morphological and ultrastructural analyses of the cell organelles and secretory granula showed clear atrophy of the acini, which was more prominent in glands treated with the combination of BoNT/A and B. Morphometric measurements of the glandular acini revealed a significantly reduced cell area of acinar cells after injection of BoNT (P=0.031). Furthermore, the expression of amylase was significantly reduced in BoNT treated glands. Conclusions and implications: Intraglandular application of BoNT induces major structural and functional changes in the salivary glands, indicated by glandular atrophy and reduced production of amylase. These effects may be due to glandular denervation by the inhibition of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors (SNAREs) involved in acetylcholine release at the neuroglandular junction. Moreover, the effects may also be due to the inhibition of SNAREs which are involved in exocytosis of the granula in acinar cells. The combination of BoNT/A and BoNT/B showed the most promising results in this study, indicating that the subtypes have different effectivities in the inhibition of SNAREs at neuroglangular junctions or in acinar cells.