Abstract
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.
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Acknowledgements
We would like to extend our gratitude to Ms. Takahashi, Mr. Chikahisa Matsuo, and Mr. Jun Oba for their administrative assistance.
Funding
This work was supported by Grants-in-Aid for Scientific Research of the Japan Society for the Promotion of Science (KAKENHI Grant Numbers 18K15006, 20K16108 to MNI, and 19K02318 to AY) and Grants-in-Aid for Basic Research of Fujii Setsuro Memorial Foundation (to KS).
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Experimental protocols used in the present study were approved by the Committee on the Ethics of Animal Experimentation at Yamaguchi University School of Medicine. The experiments were performed following the guidelines for Animal Research of Japanese Government’s Law (No. 105) and Notification (No. 6).
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Tarif, A.M.M., Islam, M., Jahan, M.R. et al. Immunohistochemical expression and neurochemical phenotypes of huntingtin-associated protein 1 in the myenteric plexus of mouse gastrointestinal tract. Cell Tissue Res 386, 533–558 (2021). https://doi.org/10.1007/s00441-021-03542-4
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DOI: https://doi.org/10.1007/s00441-021-03542-4