Research Report The number of nociceptors in the trigeminal ganglion but not proprioceptors in the mesencephalic trigeminal tract nucleus is reduced in dystonin deficient dystonia musculorum mice H. Ichikawa a, ⁎ , R. Terayama a , T. Yamaai a , Y. De Repentigny b , R. Kothary b , T. Sugimoto a a Department of Oral Function and Anatomy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8525, Japan b Ottawa Health Research Institute, Ottawa, Ontario, Canada ARTICLE INFO ABSTRACT Article history: Accepted 27 May 2008 Available online 3 June 2008 The trigeminal ganglion (TG) and mesencephalic trigeminal tract nucleus (Mes5) were investigated in wild type and dystonia musculorum (dt) mice to study the effect of dystonin deficiency on primary sensory neurons in the trigeminal nervous system. At postnatal day 14, the number of TG neurons was markedly decreased in dt mice when compared to wild type mice (43.1% reduction). In addition, dystonin disruption decreased the number of sensory neurons which bound to isolectin B4, and contained calcitonin gene-related peptide or high-affinity nerve growth factor receptor TrkA. Immunohistochemistry for caspase-3 demonstrated that dystonin deficiency induced excess cell death of TG neurons during the early postnatal period. In contrast, Mes5 neurons were barely affected in dt mice. These data together suggest that dystonin is necessary for survival of nociceptors but not proprioceptors in the trigeminal nervous system. © 2008 Elsevier B.V. All rights reserved. Keywords: Immunohistochemistry Mesencephalic trigeminal tract nucleus Mutant mouse Neurochemical substance Sensory neuron Trigeminal ganglion Plakins Dystonin [also known as Bullous Pemphigoid Antigen 1 (Bpag1)] is a member of the plakin family of high molecular weight cytoskeletal linker proteins (Young and Kothary, 2007). The Dst gene is expressed by the developing cranial and spinal sensory ganglia (Bernier et al., 1995) and neural isoforms of dystonin/Bpag1 are predicted to link actin filaments to microtubules. Thus, the dystonin isoforms are considered to play a role in cytoskeleton organization during axonogenesis (Dalpé et al., 1998; Leung et al., 1999). Targeted and sponta- neous mutation of the dystonin locus in mice [dystonia muscu- lorum (dt) mice] results in dystonic movement and severe ataxia after birth (Bernier et al., 1995). In these mice, the motor system has not yet been shown to have neuronal degenera- tion. However, sensory nerve fibers are reduced and numerous axonal swellings are detected in the remaining fibers (Bernier et al., 1995). In the spinal nervous system, proprioceptors are located in the dorsal root ganglia (DRG). These neurons have large cell bodies and innervate the musculature. In the trigeminal ganglion, however, muscular proprioceptors are very rare. Trigeminal proprioceptors are primarily located in the mesencephalic trigeminal tract nucleus (Mes5). Mes5 neu- rons innervate masticatory muscles and periodontal liga- ments. Primary proprioceptors in the spinal and trigeminal BRAIN RESEARCH 1226 (2008) 33 – 38 ⁎ Corresponding author. Fax: +81 86 235 6639. E-mail address: hiroichi@md.okayama-u.ac.jp (H. Ichikawa). 0006-8993/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2008.05.063 available at www.sciencedirect.com www.elsevier.com/locate/brainres