Immunohistochemical expression and neurochemical phenotypes of huntingtin-associated protein 1 in the myenteric plexus of mouse gastrointestinal tract

• Published in: Cell and tissue research 2021-12, Vol.386 (3), p.533-558
• Main Authors: Tarif, Abu Md Mamun, Islam, Md Nabiul, Jahan, Mir Rubayet, Yanai, Akie, Nozaki, Kanako, Masumoto, Koh-hei, Shinoda, Koh
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Calbindin; Calcitonin gene-related peptide; Calretinin; Cytoplasm; DNA-Binding Proteins - metabolism; Enteric nervous system; Fluorescence microscopy; Gastrointestinal system; Gastrointestinal tract; Gastrointestinal Tract - physiology; Genetic aspects; Hap1 protein; Human Genetics; Huntingtin; Immunohistochemistry - methods; Immunoreactivity; Interneurons; Male; Mice; Molecular Medicine; Motor neurons; Myenteric plexus; Myenteric Plexus - metabolism; Nervous system diseases; Neurodegeneration; Neurodegenerative diseases; Neurons; Neurophysiology; Phenotype; Phenotypes; Proteomics; Regular Article; Sensory neurons; Somatostatin; Spinal cord; Western blotting
• ISSN: 0302-766X; 1432-0878
• DOI: 10.1007/s00441-021-03542-4

Huntingtin-associated protein 1 (HAP1) is a neural huntingtin interactor and being considered as a core molecule of stigmoid body (STB). Brain/spinal cord regions with abundant STB/HAP1 expression are usually spared from neurodegeneration in stress/disease conditions, whereas the regions with little STB/HAP1 expression are always neurodegenerative targets. The enteric nervous system (ENS) can act as a potential portal for pathogenesis of neurodegenerative disorders. However, ENS is also a neurodegenerative target in these disorders. To date, the expression of HAP1 and its neurochemical characterization have never been examined there. In the current study, we determined the expression of HAP1 in the ENS of adult mice and characterized the morphological relationships of HAP1-immunoreactive (ir) cells with the markers of motor neurons, sensory neurons, and interneurons in the myenteric plexus using Western blotting and light/fluorescence microscopy. HAP1-immunoreaction was present in both myenteric and submucosal plexuses of ENS. Most of the HAP1-ir neurons exhibited STB in their cytoplasm. In myenteric plexus, a large number of calretinin, calbindin, NOS, VIP, ChAT, SP, somatostatin, and TH-ir neurons showed HAP1-immunoreactivity. In contrast, most of the CGRP-ir neurons were devoid of HAP1-immunoreactivity. Our current study is the first to clarify that HAP1 is highly expressed in excitatory motor neurons, inhibitory motor neurons, and interneurons but almost absent in sensory neurons in myenteric plexus. These suggest that STB/HAP1-ir neurons are mostly Dogiel type I neurons. Due to lack of putative STB/HAP1 protectivity, the sensory neurons (Dogiel type II) might be more vulnerable to neurodegeneration than STB/HAP1-expressing motoneurons/interneurons (Dogiel type I) in myenteric plexus.