Human liver afferent and efferent nerves revealed by 3D/Airyscan super-resolution imaging

Am J Physiol Endocrinol Metab. 2024 Jan 3. doi: 10.1152/ajpendo.00205.2023. Online ahead of print.ABSTRACTNeural regulation of hepatic metabolism has long been recognized. However, the detailed afferent and efferent innervation of the human liver has not been systematically characterized. This is largely due to the liver's high lipid and pigment contents, causing false negative (light scattering and absorption) and false positive (autofluorescence) results in in-depth fluorescence imaging. Here, to avoid the artifacts in 3D liver neurohistology, we embed the bleached human liver in the high-refractive-index polymer for tissue clearing and antifade 3D/Airyscan super-resolution imaging. Importantly, using the paired substance P (SP, sensory marker) and PGP9.5 (pan-neuronal marker) labeling, we detect the sensory nerves in the portal space, featuring the SP+ varicosities in the PGP9.5+ nerve bundles/fibers, confirming the afferent liver innervation. Also, using the tyrosine hydroxylase (TH, sympathetic marker) labeling, we identify: (1) condensed TH+ sympathetic nerves in the portal space, (2) extension of sympathetic nerves from the portal to the intralobular space, in which the TH+ nerve density is 2.6±0.7-fold higher than that of the intralobular space in the human pancreas, and (3) the TH+ nerve fibers and varicosities contacting the ballooning cells, implicating potential sympathetic influence on hepatocytes with macrovesicular fatty change. Finally, using the vesicular ac...
Source: Am J Physiol Endocri... - Category: Endocrinology Authors: Source Type: research