Shingo Kakimoto

Distribution of nociceptin/orphanin FQ precursor protein and receptor in brain and spinal cord: A study using in situ hybridization and X-gal histochemistry in receptor-deficient mice

Nociceptin/orphanin FQ (N/OFQ) is an opioid‐like heptadecapeptide agonist for the opioid receptor homolog, N/OFQ receptor. To explore the precise distribution of the peptide‐receptor system, the authors examined the brain and spinal cord from receptor‐deficient mice bearing the targeted mutation (morcm1), a lacZ insertional mutation in the N/OFQ receptor gene. Precursor protein N/OFQ (preproN/OFQ) mRNA was detected by using in situ hybridization, and the N/OFQ receptor was detected by using X‐gal histochemistry. The N/OFQ receptor reflected by lacZ expression was observed at high levels in the dentate gyrus, lateral septum, subparafascicular thalamic nucleus, medial preoptic area, median preoptic nucleus, ventromedial preoptic nucleus, anterior hypothalamic area, paraventricular hypothalamic nucleus, ventromedial hypothalamic nucleus, auditory brainstem nuclei, pontine dorsal tegmentum, and nucleus of the solitary tract. In situ detection of the N/OFQ receptor mRNA by digoxigenin‐labeled riboprobes coupled with tyramide signal amplification in normal and wild‐type mice resulted in the regional distribution paralleling the lacZ expression in these regions. PreproN/OFQ mRNA was expressed at high levels in the subparafascicular thalamic nucleus, central gray, central tegmental field, auditory brainstem nuclei, caudal spinal trigeminal nucleus, and spinal dorsal horn. Furthermore, variable levels of expression of the peptide and receptor were seen in distinct sites of the brain and spinal cord. These data indicate a correspondence of the peptide and the receptor in local distribution at limbic, hypothalamic, and brainstem sites. Together with concurrent physiologic and behavioral studies in mutant mice, the results suggest functional roles for the N/OFQ system, including the central regulation of learning and memory, hearing ability, water balance, food intake, and blood pressure. J. Comp. Neurol. 424:489–508, 2000.

Distribution of neurons expressing α1G subunit mRNA of T-type voltage-dependent calcium channel in adult rat central nervous system

T-type voltage-dependent calcium channel has central roles in neuronal burst firing. The alpha1G subunit of T-type channel has been recently cloned and we here reported a cellular distribution of the alpha1G by in situ hybridization in adult rat brain and spinal cord. The cells expressing alpha1G were widely distributed in the central nervous system. The distribution seemed to be restricted to neurons, and exhibited a specific pattern in the cerebellum, thalamus, hippocampus and cerebral cortex.

Comparative distribution of GABAergic and peptide-containing neurons in the lateral lemniscal nuclei of the rat.

By immunostaining, neurons expressing peptides (dynorphin and corticotropin-releasing factor, CRF) and glutamate decarboxylase (GAD), a GABA-synthesizing enzyme, were precisely mapped in the rat lateral lemniscal nuclei. While GAD neurons were numerous and preferably localized in the dorsal (DLL) and ventral (VLL) nuclei, neurons expressing these peptides were less numerous and localized primarily in the intermediate (ILL) nucleus of the lateral lemniscus. The ILL nucleus was shown to project to the inferior colliculus and to express Fos rapidly in response to peripheral acoustic stimulation, suggesting that the ILL nucleus may take part in non-GABAergic relay of acoustic information in the lateral lemniscus.

Brainstem auditory regions in mice: expression of nociceptin/orphanin FQ precursor mRNA in select neurons.

Nociceptin peptide-receptor system is known to be essential for the regulation of hearing ability. The mRNA for nociceptin precursor protein is highly expressed in the brainstem. We explored a detailed hybridohistochemical expression pattern of the nociceptin precursor mRNA in the mouse brainstem, and identified positive cells in several auditory brainstem nuclei. Positive cells were seen in the dorsal and ventral nuclei of the lateral lemniscus, the rostral periolivary region, the lateroventral and medioventral periolivary nuclei, the dorsal periolivary region, the superior paraolivary nucleus, and the external cortex and dorsal cortex of the inferior colliculus. Of these, the medioventral and lateroventral periolivary nuclei, the major sites of origin of olivocochlear bundle, were most populated by positive cells.

A subset of nociceptin/orphanin FQ receptor-expressing neurons in the anterior hypothalamic area, as revealed in mice with lacZ reporter gene.

Nociceptin/orphanin FQ (N/OFQ) is an endogenous peptide agonist for the opioid receptor homolog, N/OFQ receptor, and serves for the central control of autonomic functions. Morphological details including the cell types that may account for such N/OFQ functions, however, remain unclear. By using X-gal histochemistry for the detection of receptor-expressing cells at both light and electron microscopic levels, we examined the hypothalamus from the receptor-deficient mice bearing a lacZ insertional mutation in the N/OFQ receptor gene. The N/OFQ receptor reflected by lacZ expression was seen at high levels in the anterior hypothalamic area. With electron microscopy, lacZ expression was observed in a subset of neurons showing large cell size and indented nucleus.

Perilymph Fistula Caused By Paracentesis: A Case Report

A 39-year-old female was diagnosed with left acute otitis media and had paracentesis. Because she had continuous vertigo immediately after the paracentesis, she was sent to our hospital. At first she was treated with conservative therapy, but the severe hearing loss, dizziness and tinnitus worsened, so she underwent surgical exploration of the tympanic cavity 10 days after the onset. During the surgery, there was no dislocation of the ossicle, but perilymphatic leakage from the oval window was observed. The window membrane was repaired with temporal fascia and fat. Although her dizziness disappeared completely, her tinnitus persisted. However, the tinnitus disappeared with time and the hearing loss gradually recovered. This case was possibly a medical accident, but it is important to recognize that perilymph fistula is one of the complications of paracentesis, and when it occurs, it must be diagnosed accurately.

The Efficacy of Cryosurgery Combined with Laser Surgery in the Treatment of Perennial Allergic Rhinitis

A combined treatment of laser surgery to the inferior turbinate and transnasal cryodegeneration of the vidian nerve using endoscopy were evaluated. The study consisted of 79 patients with perennial allergic rhinitis caused by house dust. All were refractory to conservative treatment, including allergic desensitization. The CO2 laser surgery was repeated once a week for 3 weeks. After the third laser surgery, the area that was endoscopically estimated to be the sphenopalatine foramen was frozen over the mucous membrane by an extrafine pointed cryoprobe. The subjective results 6 months after the operation are promising, and no major complications were noted. The combined treatment of laser and cryosurgery using endoscopy is a minor surgical procedure with high efficacy and minimal postoperative morbidity. More cases and a longer follow-up are necessary to provide long-term results.

Effective Treatment at Early Stage for Anaplastic Carcinoma of the Thyroid : A Case Report

Generally, the prognosis of thyroid anaplastic carcinoma is extremely unsatisfactory. We report here excellent results due to early treatment in a patient with anaplastic carcinoma. The patient was a 74-year-old female, who presented with an enlarged frontal neck tumor, together with cervix and throat pain, and undifferentiated carcinoma was strongly suspected based on aspiration biopsy cytology. The patient was admitted and six days after the first examination, total thyroidectomy was performed, and a diagnosis of anaplastic thyroid carcinoma was made based on the permanent pathological specimen. Postoperatively, EAP (Etoposide, Adriamycin, and Cisplatin) treatment and radiotherapy (56 Gy) were performed, with a subsequent second chemotherapy course. At two years no recurrence or metastasis has been noted and the patient has returned to her normal daily life. In conclusion, if radical dissection of the tumor is possible in the early stages, we consider that in patients with anaplastic thyroid carcinoma immediate operation and radiation and chemotherapy treatment should result in a positive prognosis.

Differential distribution of two forms of glutamic acid decarboxylase in brainstem auditory regions

We studied fiber connections of the sonic motor nucleus (SMN) in Sebusriscus matmorufus, by means of tracers methods using biocytin, HRP, and carbocyanine dye (Dir). The SMN is located in the caudal medulla and rostra1 spinal cord. After tracer injection into the SMN, retrogradely labeled neurons were found in the medial nucleus of the lateral line system and the reticular formation (RF) of the medulla. The labeled neurons of the RF are bipolar. One dendrite extends laterally to the descending octaval nucleus and the other dendrite extends medioventrally to an area around the tractus tectobulbaris. After biocytin injections into the medial nucleus, orthogradely labeled fibers terminate on the premotor neurons of the RF and the SMN. In cases of DiI applied to the medioventral dendritic field of the premotor neuron of the RF, neurons of the tectum opticum (TO) and torus semicircularis (TS) were retrogradely labeled. The results show that the premotor neurons of the RF receive projections from the medial nucleus in the lateral line system, TO, and TS. The premotor neurons might also receive input from the octaval nerve directly.

Nociceptin peptide-receptor system in the brainstem auditory regions

Nociceptin (orphanin FQ) is an opioid-like hexadecapeptide agonist for the opioid receptor homolog nociceptin receptor. We have reported that the mRNA of nociceptin precursor protein is highly expressed in the brainstem auditory regions and also that the nociceptin peptide-receptor system is essential for the regulation of hearing ability (Houtani et al., Biochem. Biophys. Res. Commun. 219, 714-719, 1996; Nishi et al., EMBO J., 16, 1858-1864, 1997). We here report a detailed distribution of the nociceptin peptidereceptor system in the mouse brainstem auditory regions. Nociceptin precursor protein was expressed in the dorsal and ventral nuclei of the lateral lemniscus, the rostra1 periolivary region, the lateral ventral and medioventral periolivary nuclei, and the external cortex of the inferior colliculus. Nociceptin receptor was expressed in these regions and also in the nucleus of the brachium of the inferior colliculus. In the brainstem auditory regions, nociceptin peptide-receptor system was shown to have a unique distribution pattern which differs from those of major opioid systems.