title: Immunohistochemical analysis of huntingtin-associated protein 1 in adult rat spinal cord and its regional relationship with androgen receptor.
abstract: Huntingtin-associated protein 1 (HAP1) is a neuronal interactor with causatively polyglutamine (polyQ)-expanded huntingtin in Huntington's disease and also associated with pathologically polyQ-expanded androgen receptor (AR) in spinobulbar muscular atrophy (SBMA), being considered as a protective factor against neurodegenerative apoptosis. In normal brains, it is abundantly expressed particularly in the limbic-hypothalamic regions that tend to be spared from neurodegeneration, whereas the areas with little HAP1 expression, including the striatum, thalamus, cerebral neocortex and cerebellum, are targets in several neurodegenerative diseases. While the spinal cord is another major neurodegenerative target, HAP1-immunoreactive (ir) structures have yet to be determined there. In the current study, HAP1 expression was immunohistochemically evaluated in light and electron microscopy through the cervical, thoracic, lumbar, and sacral spinal cords of the adult male rat. Our results showed that HAP1 is specifically expressed in neurons through the spinal segments and that more than 90% of neurons expressed HAP1 in lamina I-II, lamina X, and autonomic preganglionic regions. Double-immunostaining for HAP1 and AR demonstrated that more than 80% of neurons expressed both in laminae I-II and X. In contrast, HAP1 was specifically lacking in the lamina IX motoneurons with or without AR expression. The present study first demonstrated that HAP1 is abundantly expressed in spinal neurons of the somatosensory, viscerosensory, and autonomic regions but absent in somatomotor neurons, suggesting that the spinal motoneurons are, due to lack of putative HAP1 protectivity, more vulnerable to stresses in neurodegenerative diseases than other HAP1-expressing neurons probably involved in spinal sensory and autonomic functions.
authors.affiliation: Division of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Md Nabiul
authors.initials: MN
authors.lastname: Islam
authors.affiliation: Division of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Takeshita
authors.affiliation: Division of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Akie
authors.initials: A
authors.lastname: Yanai
authors.affiliation: Division of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Amami
authors.initials: A
authors.lastname: Imagawa
authors.affiliation: Division of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Mir Rubayet
authors.initials: MR
authors.lastname: Jahan
authors.affiliation: Division of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Greggory
authors.initials: G
authors.lastname: Wroblewski
authors.affiliation: Division of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Joe
authors.initials: J
authors.lastname: Nemoto
authors.affiliation: Division of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Fujinaga
authors.affiliation: Division of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan. Electronic address: shinoda@yamaguchi-u.ac.jp.
authors.forename: Koh
authors.initials: K
authors.lastname: Shinoda
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010784:Photomicrography; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism*
chemical_list: C490757:Hap1 protein, rat; D009419:Nerve Tissue Proteins; D011944:Receptors, Androgen
keywords: huntingtin-associated protein 1; immunohistochemistry; motoneurons; neurodegenerative diseases; neuroprotection; stigmoid body