Neurochemical phenotypes of huntingtin-associated protein 1 in reference to secretomotor and vasodilator neurons in the submucosal plexuses of rodent small intestine

Abstract

Huntingtin-associated protein 1(HAP1) is an immunohistochemical marker of the stigmoid body (STB). Brain and spinal cord regions with lack of STB/HAP1 immunoreactivity are always neurodegenerative targets, whereas STB/HAP1 abundant regions are usually spared from neurodegeneration. In addition to the brain and spinal cord, HAP1 is abundantly expressed in the excitatory and inhibitory motor neurons in myenteric plexuses of the enteric nervous system (ENS). However, the detailed expression of HAP1 and its neurochemical characterization in submucosal plexuses of ENS are still unknown. In this study, we aimed to clarify the expression and neurochemical characterization of HAP1 in the submucosal plexuses of the small intestine in adult mice and rats. HAP1 was highly expressed in the submucosal plexuses of both rodents. The percentage of HAP1-immunoreactive submucosal neurons was not significantly varied between the intestinal segments of these rodents. Double immunofluorescence results revealed that almost all the cholinergic secretomotor neurons containing ChAT/ CGRP/ somatostatin/ calretinin, non-cholinergic secretomotor neurons containing VIP/NOS/TH/calretinin, and vasodilator neurons containing VIP/calretinin expressed HAP1. Our current study is the first to clarify that STB/HAP1 is expressed in secretomotor and vasodilator neurons of submucosal plexuses, suggesting that STB/HAP1 might modulate or protect the secretomotor and vasodilator functions of submucosal neurons in ENS.