• IslamMd NabiulMNDivision of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan., Emi Miyasato, Mir Rubayet Jahan, TarifAbu Md MamunAMMDivision of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan., Kanako Nozaki, Koh-Hei Masumoto, Akie Yanai, and Koh Shinoda.
• Division of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan.
• Neuroscience. 2022 Sep 1; 499: 40-63.

AbstractHuntingtin-associated protein 1 (HAP1) is a core component of stigmoid body (STB) and is known as a neuroprotective interactor with causal agents for various neurodegenerative diseases. Brain regions rich in STB/HAP1 immunoreactivity are usually spared from cell death, whereas brain regions with negligible STB/HAP1 immunoreactivity are the major neurodegenerative targets. Recently, we have shown that STB/HAP1 is abundantly expressed in the spinal preganglionic sympathetic/parasympathetic neurons but absent in the motoneurons of spinal cord, indicating that spinal motoneurons are more vulnerable to neurodegenerative diseases. In light of STB/HAP1 neuroprotective effects, it is also essential to clarify the distribution of STB/HAP1 in another major neurodegenerative target, the brainstem. Here, we examined the expression and detailed immunohistochemical distribution of STB/HAP1 and its relationships with choline acetyltransferase (ChAT) in the midbrain, pons, and medulla oblongata of adult mice. Abundant STB/HAP1 immunoreactive neurons were disseminated in the periaqueductal gray, Edinger-Westphal nucleus, raphe nuclei, locus coeruleus, pedunculopontine tegmental nucleus, superior/inferior salivatory nucleus, and dorsal motor nucleus of vagus. Double-label immunohistochemistry of HAP1 with ChAT (or with urocortin-1 for Edinger-Westphal nucleus centrally projecting population) confirmed that STB/HAP1 was highly present in parasympathetic preganglionic neurons but utterly absent in cranial nerve motor nuclei throughout the brainstem. These results suggest that due to deficient putative STB/HAP1-protectivity, cranial nerve motor nuclei might be more vulnerable to certain neurodegenerative stresses than STB/HAP1-expressing brainstem nuclei, including preganglionic parasympathetic nuclei. Our current results also lay a basic foundation for future studies that seek to clarify the physiological/pathological roles of STB/HAP1 in the brainstem.Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.

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