Expression of huntingtin-associated protein 1 in adult mouse dorsal root ganglia and its neurochemical characterization in reference to sensory neuron subpopulations

Md Nabiul Islam; Naoki Maeda; Emi Miyasato; Mir Rubayet Jahan; Abu Md Mamun Tarif; Taiga Ishino; Kanako Nozaki; Koh-Hei Masumoto; Akie Yanai; Koh Shinoda

doi:10.1016/j.ibror.2020.10.001

Expression of huntingtin-associated protein 1 in adult mouse dorsal root ganglia and its neurochemical characterization in reference to sensory neuron subpopulations

IBRO Rep. 2020 Oct 6:9:258-269. doi: 10.1016/j.ibror.2020.10.001. eCollection 2020 Dec.

Authors

Affiliations

¹ Division of Neuroanatomy, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, 755-8505, Japan.
² Department of Anatomy and Histology, Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh, 2202, Bangladesh.
³ Department of Basic Laboratory Sciences, Faculty of Medicine and Health Sciences, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, 755-8505, Japan.

Abstract

Huntingtin-associated protein 1 (HAP1) is a polyglutamine (polyQ) length-dependent interactor with causal agents in several neurodegenerative diseases and has been regarded as a protective factor against neurodegeneration. In normal rodent brain and spinal cord, HAP1 is abundantly expressed in the areas that are spared from neurodegeneration while those areas with little HAP1 are frequent targets of neurodegeneration. We have recently showed that HAP1 is highly expressed in the spinal dorsal horn and may participate in modification/protection of certain sensory functions. Neurons in the dorsal root ganglia (DRG) transmits sensory stimuli from periphery to spinal cord/brain stem. Nevertheless, to date HAP1 expression in DRG remains unreported. In this study, the expression of HAP1 in cervical, thoracic, lumbar and sacral DRG in adult male mice and its relationships with different chemical markers for sensory neurons were examined using Western blot and immunohistochemistry. HAP1-immunoreactivity was detected in the cytoplasm of DRG neurons, and the percentage of HAP1-immunoreactive (ir) DRG neurons was ranged between 28-31 %. HAP1-immunoreactivity was comparatively more in the small cells (47-58 %) and medium cells (40-44 %) than that in the large cells (9-11 %). Double-immunostaining for HAP1 and markers for nociceptive or mechanoreceptive neurons showed that about 70-80 % of CGRP-, SP-, CB-, NOS-, TRPV1-, CR- and PV-ir neurons expressed HAP1. In contrast, HAP1 was completely lacking in TH-ir neurons. Our current study is the first to clarify that HAP1 is highly expressed in nociceptive/proprioceptive neurons but absent in light-touch-sensitive TH neurons, suggesting the potential importance of HAP1 in pain transduction and proprioception.

Keywords: CB, calbindin; CGRP, calcitonin gene-related peptide; CR, calretinin; DAB, diaminobenzidine; DRG, dorsal root ganglia; HAP1, Huntingtin-associated protein 1; Huntingtin-associated protein 1; Iba1, ionized calcium-binding adapter molecule 1; Immunohistochemistry; LTMRs, low-threshold mechanoreceptors; MRGPR, Mas-related G-protein-coupled receptor; NDS, normal donkey serum; NOS, nitric oxide synthetase; NeuN, neuronal nuclei; Neurodegeneration; Neuroprotection; PB, phosphate buffer; PV, parvalbumin; Peripheral nervous system; SBMA, spinal and bulbar muscular atrophy; SP, substance P; STB, stigmoid body; Sensory neurons; TBST, Tris-buffered saline with 0.1 % Tween; TH, tyrosine hydroxylase; TRPV1, transient receptor potential vanilloid 1; VGLUT, vesicular glutamate transporter; htt, huntingtin; polyQ, polyglutamine.