Motoneuron degeneration in the trigeminal motor nucleus innervating the masseter muscle in Dystonia musculorum mice. (October 2018)

• Record Type: Journal Article
• Authors: Hossain, M. Ibrahim; Horie, Masao; Yoshioka, Nozomu; Kurose, Masayuki; Yamamura, Kensuke; Takebayashi, Hirohide
• Is Part Of: Neurochemistry international. Volume 119(2018)
• Page Start: 159
• Page End: 170
• Publication Date: 2018-10
• Subjects: Dystonia musculorum -- Trigeminal motor nucleus (Mo5) -- Motor neuron -- Neurodegeneration -- Mandibular nerve -- Masseter muscle; ATF3 activating transcription factor 3 -- AUC area under the curve -- BP230 the 230 kDa bullous pemphigoid antigen -- BPAG1 bullous pemphigoid antigen 1 -- CNS central nervous system -- ChAT choline acetyltransferase -- CHOP C/EBP homologous protein -- CTB cholera toxin B subunit -- DAPI 4′, 6-diamidino-2-phenylindole -- DRG dorsal root ganglia -- Dst Dystonin -- EMG electromyography -- GFAP glial fibrillary acidic protein -- HE hematoxylin and eosin -- HSAN6 hereditary sensory autonomic neuropathy type VI -- IHC immunohistochemistry -- ISH in situ hybridization -- KO knockout -- Lcn2 lipocalin 2 -- MBP myelin basic protein -- Mo5 trigeminal motor nucleus -- NF neurofilament -- PFA paraformaldehyde -- P postnatal days -- PNS peripheral nervous system -- V3 mandibular nerve; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2017.10.009
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: Dystonia musculorum ( dt ) mice, which have a mutation in the Dystonin ( Dst ) gene, are used as animal models to investigate the human disease known as hereditary sensory and autonomic neuropathy type VI. Massive neuronal cell death is observed, mainly in the peripheral nervous system (PNS) of dt mice. We and others have recently reported a histopathological feature of these mice that neurofilament (NF) accumulates in various areas of the central nervous system (CNS), including motor pathways. Although dt mice show motor disorder and growth retardation, the causes for these are still unknown. Here we performed histopathological analyses on motor units of the trigeminal motor nucleus (Mo5 nucleus), because they are a good system to understand neuronal responses in the mutant CNS, and abnormalities in this system may lead to problems in mastication, with subsequent growth retardation. We report that motoneurons with NF accumulation in the Mo5 nuclei of Dst Gt homozygous mice express the stress-induced genes CHOP, ATF3, and lipocalin 2 (Lcn2) . We also show a reduced number of Mo5 motoneurons and a reduced size of Mo5 nuclei in Dst Gt homozygous mice, possibly due to apoptosis, given the presence of cleaved caspase 3-positive Mo5 motoneurons. In the mandibular (V3) branches of the trigeminal nerve, which contains axons of Mo5 motoneurons and trigeminal sensory neurons, there was infiltration of Iba1-positive macrophages. Finally, we report atrophy of the masseter muscles in Dst Gt homozygous mice, which showed abnormal nuclear localization of myofibrils and increased expression of atrogin-1 mRNA, a muscle atrophy-related gene and weaker masseter muscle strength with uncontrolled muscle activity by electromyography (EMG). Taken together, our findings strongly suggest that mastication in dt mice is affected due to abnormalities of Mo5 motoneurons and masseter muscles, leading to growth retardation at the post-weaning stages. Highlights: Mo5 Motoneurons degenerate in the brainstem of Dst Gt homozygous mice. Stress-induced genes are expressed in the motoneurons with abnormal NF accumulations. Iba1-positive macrophages infiltrate into the mandibular (V3) nerve. Atrophy and weak activity of masseter, target muscle of Mo5 motoneurons, is observed. Growth retardation of dt mice after weaning may due to affected mastication.