Biomedical subjects

N Mizuno

Publications and source records attributed to N Mizuno.

At least 91 records · Page 5Linked to original sources

PubMed1998

Islet cell tumor in von Hippel-Lindau disease.

We describe a 42-year-old man with von Hippel-Lindau disease and islet cell tumor of the pancreas. He had retinal and cerebellar hemangioblastomas. His sister had pheochromocytoma. A pancreatic tumor was detected by ultrasonography at his periodical medical checkup. Contrast enhanced computed tomography and abdominal angiography revealed a hypervascular tumor in the pancreatic head. Histological examination of the resected tumor revealed characteristics of islet cell tumor of the pancreas, which was positive for chromogranin-A, S-100 protein, and pancreatic polypeptide, but was negative for insulin, gastrin, glucagon, somatostatin, vasoactive intestinal peptide, serotonin, and adrenocorticotropic hormone.

Adenoma, Islet Cell↗

PubMed1998

[Analysis of neuronal connections in the basal ganglia].

Morphological features indicating occurrence of two types of extrasynaptic chemical transmission were observed within rat basal ganglia. (1) Striatonigral neurons containing substance P (SP) sent many axon collaterals equipped with axonal varicosities to the striatum: the varicosities displayed synaptophysin-like immunoreactivity (-LI). However, only 15% of the varicosities appeared to be in close contact with structures showing SP receptor (SPR)-LI. Many of axon terminals of striatonigral neurons were confirmed electron microscopically not to be in synaptic contact with SPR-like immunoreactive structures within the striatum. SP released from the varicosities might, at least partly, diffuse to reach SPR at distance from the release sites. (2) Immunoreactivities for metabotropic glutamate receptors (mGluRs) 4 a, 7 a, 7 b and 8 were in axon terminals within the globus pallidus (external segment of the globus pallidus in primates). The immunoreactivities disappeared after destruction of the striatum, but not after destruction of the subthalamic nucleus. The immunoreactivity for mGluR 7 a was confirmed electron microscopically to be within axon terminals showing glutamic acid decarboxylase-LI. Glutamate released from glutamatergic subthalamopallidal neurons might partly spilled over from the synaptic sites to reach mGluRs on "nearby" axon terminals of GABAergic striatopallidal neurons. Functional significance of thalamostriatal and corticosubthalamic fibers was also discussed.

Animals↗

PubMed1997

Collateral projections from striatonigral neurons to substance P receptor-expressing intrinsic neurons in the striatum of the rat.

It is well known that striatonigral neurons produce substance P (SP); however, no SP receptor (SPR) has so far been found in the substantia nigra. On the other hand, a previous study in the rat striatum indicated that SPR was expressed only in cholinergic or somatostatinergic intrinsic neurons (Kaneko et al. [1993] Brain Res. 631:297-303). Thus, it was assumed that SP produced by striatonigral neurons might be released through their intrastriatal axon collaterals to act upon intrinsic neurons in the striatum. To confirm this assumption, the distribution of axon collaterals of striatonigral neurons was examined in the striatum of the rat. The experiments were performed on brain slices by combining retrograde labeling with tetramethylrhodamine-dextran amine, electrophysiological recording, intracellular staining with biocytin, and immunocytochemistry for SPR. The distribution of axons of cholinergic striatal neurons (a group of SP-negative intrinsic striatal neurons) was also examined. It was observed that 16% of varicosities of intrastriatal axon collaterals of striatonigral neurons, as well as 6% of axonal varicosities of cholinergic neurons, were in close apposition to dendrites and cell bodies of SPR-immunoreactive striatal neurons. Since SPR-immunoreactive striatal neurons constituted only 2.7% of the total population of striatal neurons (Kaneko et al. [1993] Brain Res. 631:297-303), it appeared that axonal varicosities of striatonigral neurons were preferentially apposed to SPR-immunoreactive striatal neurons and that the varicosities in close apposition to SPR-immunoreactive neurons were derived more frequently from striatonigral neurons than from cholinergic interneurons. Confocal laser scanning microscopy indicated that axonal varicosities in close apposition to SPR-immunoreactive cells showed synaptophysin immunoreactivity, a marker of synaptic vesicles. In intrastriatal axons of striatonigral neurons, it was further revealed from electron microscopy that axonal varicosities in close apposition to SPR-immunoreactive dendrites, at least a part of them, made synapses of the symmetric type. Striatonigral neurons might release SP preferentially around cholinergic or somatostatinergic intrinsic neurons to regulate them through SP-SPR interactions.

Action Potentials↗

PubMed1997

Direct projections from nucleus X to the external cortex of the inferior colliculus in the rat.

Direct projections from nucleus X to the external cortex of the inferior colliculus (ICe) were found in the rat by the retrograde single- and double-labeling methods. The projections are bilateral with a clear contralateral dominance. Some of these projections are made by axon collaterals of projection fibers from nucleus X to the ventrobasal thalamus. On the other hand, projection fibers from nucleus X to the cerebellum send no axon collaterals to ICe.

Animals↗

PubMed1997

Expression of messenger RNA for the prostaglandin D receptor in the leptomeninges of the mouse brain.

The localization of prostaglandin D receptor in the mouse brain was examined by in situ hybridization histochemistry. The autoradiography showed significant hybridization signals of mRNA for prostaglandin D receptor in the leptomeninges covering the surface of the brain, but not in neurons or glia in the brain parenchyma. This finding was confirmed by Northern blot analysis using mRNA prepared from either the whole brain with the leptomeninges, brain parenchyma without the leptomeninges or the leptomeninges alone. A weak signal corresponding to the major 3.5-kbp transcript was detected in the whole brain. This band was significantly enriched in the leptomeninges, but was not detected in the brain parenchyma. These results suggest that prostaglandin D receptor is most highly, if not exclusively, expressed in the leptomeninges of the mouse brain.

Animals↗

PubMed1997

Auditory projections from the IC to the SCN by way of the LG in the mole, Mogera.

To study morphological substrates for sensory specialization in subterranean mammals, we investigated both auditory and visual pathways in the mole. The inferior colliculus (IC), an auditory relay, projects not only to the medial geniculate, the major gateway to the auditory cortex, but also to the lateral geniculate (LG), the major gateway to visual cortex. Further evidence is that the LG does not send many fibers to the cortex in the mole. Instead, the auditory inputs to the LG are likely to be conveyed to the suprachiasmatic hypothalamic nucleus (SCN), which plays a role in photoperiodic functions in common mammals. Auditory inputs to the SCN may subserve periodic reproductive behaviors in the exclusively separated territorial domains of subterranean mammals.

Animals↗

PubMed1997

Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus.

Neurotransmission in the hippocampus is modulated variously through presynaptic metabotropic glutamate receptors (mGluRs). To establish the precise localization of presynaptic mGluRs in the rat hippocampus, we used subtype-specific antibodies for eight mGluRs (mGluR1-mGluR8) for immunohistochemistry combined with lesioning of the three major hippocampal pathways: the perforant path, mossy fiber, and Schaffer collateral. Immunoreactivity for group II (mGluR2) and group III (mGluR4a, mGluR7a, mGluR7b, and mGluR8) mGluRs was predominantly localized to presynaptic elements, whereas that for group I mGluRs (mGluR1 and mGluR5) was localized to postsynaptic elements. The medial perforant path was strongly immunoreactive for mGluR2 and mGluR7a throughout the hippocampus, and the lateral perforant path was prominently immunoreactive for mGluR8 in the dentate gyrus and CA3 area. The mossy fiber was labeled for mGluR2, mGluR7a, and mGluR7b, whereas the Schaffer collateral was labeled only for mGluR7a. Electron microscopy further revealed the spatial segregation of group II and group III mGluRs within presynaptic elements. Immunolabeling for the group III receptors was predominantly observed in presynaptic active zones of asymmetrical and symmetrical synapses, whereas that for the group II receptor (mGluR2) was found in preterminal rather than terminal portions of axons. Target cell-specific segregation of receptors, first reported for mGluR7a (Shigemoto et al,., 1996), was also apparent for the other group III mGluRs, suggesting that transmitter release is differentially regulated by 2-amino-4-phosphonobutyrate-sensitive mGluRs in individual synapses on single axons according to the identity of postsynaptic neurons.

Animals↗

PubMed1997

Preprodynorphin-, preproenkephalin-, and preprotachykinin-expressing neurons in the rat neostriatum: an analysis by immunocytochemistry and retrograde tracing.

Specific antibodies were produced against C-terminal portions of rat preprodynorphin (PPD), preproenkephalin (PPE), and preprotachykinin A (PPT). PPD, PPE, and PPT C-terminal immunoreactivity was observed in many cell bodies of medium-sized neurons in the rat neostriatum (caudate-putamen). Intense PPE immunoreactivity was found in neuropil of the globus pallidus, whereas intense to moderate PPD and PPT immunoreactivity was distributed in neuropil of the substantia nigra and the entopeduncular nucleus. A double-immunofluorescence analysis revealed that PPE-immunoreactive neostriatal neurons rarely showed immunoreactivity for PPD (<1%) or PPT (<2%). In contrast, more than 95% of PPD-immunoreactive neostriatal neurons showed PPT immunoreactivity, and vice versa. No PPD-, PPE-, or PPT-immunoreactive neostriatal neurons showed immunoreactivity for the markers of neostriatal intrinsic neurons, such as calretinin, choline acetyltransferase, parvalbumin, or somatostatin. When tetramethylrhodamine-dextran amine (TMR-DA) was injected into the substantia nigra, almost all neurons that were labeled retrogradely with TMR-DA showed immunoreactivity for PPD (98%) or PPT (99%), but very few of them exhibited PPE immunoreactivity (1%). After injection of TMR-DA into the globus pallidus, 86%, 17%, and 10% of the retrogradely labeled neurons showed immunoreactivity for PPE, PPD, and PPT, respectively. These results support the notion that the neostriatal projection neurons are divided into at least two groups: The projection neurons of one group contain enkephalins and send projection fibers almost exclusively to the globus pallidus, and the others contain tachykinins and dynorphins/Leu-enkephalin and send projection fibers mainly to the substantia nigra.

Amino Acid Sequence↗

PubMed1997

Association of serotonin-like immunoreactive axons with nociceptive projection neurons in the caudal spinal trigeminal nucleus of the rat.

Serotoninergic projections to the spinal dorsal horn are implicated in the modulation of nociceptive transmission. However, morphological evidence indicating that serotoninergic projection fibers make synapses on nociceptive neurons in the medullary dorsal horn is still meager. Thus, we examined whether axonal varicosities with serotonin (5-HT)-like immunoreactivity (5-HT-LI) might make synapses on nociceptive projection neurons in the caudal spinal trigeminal nucleus (Vc) of the rat. Projection neurons were retrogradely labeled with tetramethylrhodamine-dextran amine (TMR-DA) or wheat germ agglutinin-horseradish peroxidase (WGA-HRP) that was injected into the parabrachial or thalamic region. Vc neurons in which c-fos protein-like immunoreactivity (Fos-LI) was induced by subcutaneous injection of formalin into the lip were considered nociceptive. Vc neurons in direct contact with axonal varicosities that bind isolectin I-B4 were also considered nociceptive. Triple labeling for 5-HT, TMR-DA, and Fos as well as that for 5-HT, TMR-DA, and I-B4 were done by using the immunofluorescence and fluorescence histochemical techniques. Confocal laser-scanning microscopy revealed that axonal varicosities with 5-HT-LI were in close apposition to TMR-DA-labeled neurons showing Fos-LI in lamina I and the outer part of lamina II (lamina IIo), and that both axonal varicosities with 5-HT-LI and those binding I-B4 were in close apposition to single neuronal profiles labeled with TMR-DA. The presumed nociceptive neuronal profiles in close apposition to axon terminals with 5-HT-LI were mainly those of laminae I and II neurons as well as dendrites of lamina III neurons. Electron microscopy confirmed that axon terminals with 5-HT-LI and those with I-B4 binding activity in laminae I and II made synapses on somatic and dendritic profiles that were labeled with WGA-HRP. The results indicate that serotoninergic neurons project directly on nociceptive projection neurons in the Vc.

Animals↗

PubMed1997

Collateral projections of single neurons in the posterior thalamic region to both the temporal cortex and the amygdala: a fluorescent retrograde double-labeling study in the rat.

It has been reported that the acoustic thalamus of the rat sends projection fibers to both the temporal cortical areas and the lateral amygdaloid nucleus to mediate conditioned emotional responses to an acoustic stimulus. In the present study, fluorescent retrograde double labeling with Fast Blue and Diamidino Yellow has been used in the rat to examine whether single neurons in the posterior thalamic region send axon collaterals to both the temporal cortical areas and lateral amygdaloid nucleus. One of the tracers was injected into the lateral amygdaloid nucleus and the other into the temporal cortical areas close to the rhinal sulcus. Neurons double-labeled with both tracers were found mainly in the posterior intralaminar nucleus and suprageniculate nucleus, and to a lesser extent in the subparafascicular nucleus and medial division of the medial geniculate nucleus. No double-labeled neurons were seen in either the dorsal or ventral division of the medial geniculate nucleus. When one of the tracers was injected into the lateral amygdaloid nucleus and the other into either the dorsal portion of the temporal cortex, the dorsal portion of the entorhinal cortex, or the posterior agranular insular cortex, no double-labeled neurons were found in the posterior thalamic region. The present results indicate that a substantial number of single neurons in the acoustic thalamus project to both the limbic cortical areas and lateral amygdaloid nucleus by way of axon collaterals. These neurons may be implicated in affective and autonomic components of responses to multi-sensory stimuli, including acoustic ones.

Amygdala↗

PubMed1997

Relationship of NK3 receptor-immunoreactivity to subpopulations of neurons in rat spinal cord.

The distribution of immunoreactivity to the neurokinin3 receptor (NK3R) was examined in segments C7, T11-12, L1-2, and L4-6 of the rat spinal cord. NK3R immunoreactivity was visualized by using two antisera generated against sequences of amino acids contained in the C-terminal region of the NK3R. NK3R-immunoreactive cells were numerous in the substantia gelatinosa of all spinal segments examined as well as the dorsal commissural nucleus of spinal segments L1-2. Isolated, immunoreactive cells were scattered throughout other regions of the spinal cord. The relationship of NK3R-immunoreactivity with neurons was demonstrated by colocalization with microtubule associated protein 2-immunoreactivity in individual cells. Within neurons, NK3R-immunoreactivity was associated predominately with the plasma membrane of cell bodies and dendrites. Within the substantia gelatinosa, 86% of nitric oxide synthase (NOS)-immunoreactive neurons were also NK3R-immunoreactive. Although NOS-immunoreactive neurons were found throughout all other regions of the spinal cord in the segments examined, these were not NK3R-immunoreactive. When preganglionic sympathetic neurons in spinal segments T11-12 and L1-2 were visualized by intraperitoneal injection of Fluorogold, less than 1% of the Fluorogold-labeled neurons were also immunoreactive for NK3R. The large number of NK3R-immunoreactive neurons in the substantia gelatinosa suggests that some effects of tachykinins on somatosensation may be mediated by NK3R.

Animals↗

PubMed1997

GABAergic synapses on mu-opioid receptor-expressing neurons in the superficial dorsal horn: an electron microscope study in the cat spinal cord.

A double-immunocytochemical electron microscope study was performed in the cat to examine whether GABAergic axons might be in synaptic contact with spinal neurons expressing mu-opioid receptor (MOR) in laminae I and II of the spinal dorsal horn at the lumbar cord segments. Structures showing MOR-like immunoreactivity (-LI) and those showing GABA-LI were labeled, respectively, with diaminobenzidine/peroxidase-reaction products and immunogold particles. Approximately one-third of dendritic profiles with MOR-LI in laminae I and II were postsynaptic to axon terminals with GABA-LI; about one-fourth of somatic profiles with MOR-LI were also postsynaptic to axon terminals with GABA-LI. The results suggest that activation of MOR on postsynaptic neurons may modulate effects which are induced by GABA released from presynaptic neurons.

Animals↗

PubMed1997

The locus coeruleus of the Japanese monkey (Macaca fuscata) does not express mu-opioid receptor-like immunoreactivity.

It is well known that locus coeruleus (LC) of the rat shows intense mu-opioid receptor-like immunoreactivity (MOR-LI). In the course of our study on the distribution of MOR-LI in the brain of the Japanese monkey (Macaca fuscata), however, no MOR-LI was found in the LC although the distribution pattern of MOR-LI in other regions of the lower brainstem of the monkey was essentially the same as that observed in the rat. It was also found that immunoreactivity for Met-enkephalin, the most potent endogenous ligand for MOR, was intense in the rat LC, but very weak, if any, in the monkey LC. MOR may not be expressed in the monkey LC.

Amino Acid Sequence↗

PubMed1997

Collateral projections from single neurons in the dorsal column nuclei to the inferior colliculus and the ventrobasal thalamus: a retrograde double-labeling study in the rat.

A number of single neurons in the dorsal column nuclei (DCN) and the sensory trigeminal nuclear complex were found to project to the thalamus and the inferior colliculus (IC). In the rats which were injected unilaterally with tetramethylrhodamine-dextran amine (TMR-DA) and Fluoro-Gold (FG) respectively into the posterolateral ventral thalamic nucleus and the external nucleus of IC, a number of neuronal cell bodies labeled retrogradely with both TMR-DA and FG were found throughout DCN contralateral to the injections. A few double-labeled neurons were also seen in the caudomedial part of the gracile nucleus ipsilateral to the injections. The double-labeled DCN neurons had relatively small cell bodies which are oval or fusiform in shape. When the injection sites in the thalamus extend into the posteromedial ventral thalamic nucleus, a few double-labeled neuronal cell bodies were seen contralaterally in the trigeminal sensory nuclear complex, mainly in the caudal part of the interpolar spinal trigeminal nucleus.

Animals↗

PubMed1997

Localization of a metabotropic glutamate receptor, mGluR7, in axon terminals of presumed nociceptive, primary afferent fibers in the superficial layers of the spinal dorsal horn: an electron microscope study in the rat.

It was examined electron microscopically in the rat if a metabotropic glutamate receptor, mGluR7, might be localized in axon terminals of nociceptive, primary afferent fibers in laminae I and II of the spinal dorsal horn. Nociceptive nature of axon terminals showing mGluR7-like immunoreactivity (mGluR7-LI) was indicated by binding to the isolectin I-B4 from Griffonia simplicifolia (I-B4), or by substance P-like immunoreactivity (SP-LI). Axon terminals labeled with immunogold particles indicating mGluR7-LI were usually filled with round synaptic vesicles and were in asymmetric synaptic contact with dendritic or somatic profiles; occasionally they contained pleomorphic vesicles and were in symmetric synaptic contact with somatic profiles in lamina II. The double-labeling studies revealed that most of axon terminals with I-B4 labeling as well as a small population of axon terminals with SP-LI, showed mGluR7-LI. About one-third or much smaller population of axon terminals with mGluR7-LI in laminae I and II were labeled, respectively, with I-B4 or SP-LI; these were in asymmetric synaptic contact with dendritic profiles.

Animals↗

PubMed1997

Distribution of trigeminohypothalamic and spinohypothalamic tract neurons displaying substance P receptor-like immunoreactivity in the rat.

Primary afferent neurons containing substance P (SP) are apparently implicated in the transmission of noxious information from the periphery to the central nervous system, and SP released from primary afferent neurons acts on second-order neurons with the SP receptor (SPR). In the rat, nociceptive information reached the hypothalamus not only through indirect pathways but also directly through trigeminohypothalamic and spinohypothalamic pathways. Thus, in the present study, the distribution pattern of trigeminohypothalamic and spinohypothalamic tract neurons showing SPR-like immunoreactivity (SPR-LI) was examined in the rat by a retrograde tract-tracing method combined with immunofluorescence histochemistry for SPR. A substantial number of trigeminal and spinal neurons with SPR-LI were retrogradely labeled with Fluoro-Gold (FG) injected into the hypothalamic regions. These neurons were distributed mainly in lamina I of the medullary and spinal dorsal horns, lateral spinal nucleus, regions around the central canal of the spinal cord, and the lateral aspect of the deep part of the spinal dorsal horn. A number of SPR-LI neurons in the spinal parasympathetic nucleus were labeled with FG injected into the area around the paraventricular hypothalamic nucleus. Some SPR-LI neurons in the lateral spinal nucleus and the lateral aspect of the deep part of the spinal dorsal horn were also labeled with FG injected into the septal region. On the basis of the distribution areas of SPR-LI trigeminal and spinal neurons projecting to the hypothalamic and septal regions, it is likely that these neurons are involved in the transmission of somatic and/or visceral noxious information.

Animals↗

PubMed1997

Distribution of GABAergic and glycinergic premotor neurons projecting to the facial and hypoglossal nuclei in the rat.

The distribution of inhibitory premotor neurons for the facial and hypoglossal nuclei was examined in the lower brainstem of the rat. A retrograde axonal tracing method with the fluorescent tracer, tetramethylrhodamine dextran amine (TMR-DA), was combined with immunofluorescence histochemistry for glutamic acid decarboxylase (GAD), i.e., the enzyme involved in gamma-aminobutyric acid synthesis, or glycine. In the rats injected with TMR-DA unilaterally into the facial or hypoglossal nucleus, the distribution of TMR-DA-labeled neurons showing GAD-like immunoreactivity (GAD/TMR-DA neurons) was essentially the same as that of TMR-DA-labeled neurons displaying glycine-like immunoreactivity (Gly/TMR-DA neurons). The distributions of GAD/TMR-DA and Gly/TMR-DA neurons in the rats injected with TMR-DA into the facial nucleus were also similar to those in the rats injected with TMR-DA into the hypoglossal nucleus. These neurons were seen most frequently in the lateral aspect of the pontine reticular formation, the supratrigeminal region, the dorsal aspect of the lateral reticular formation of the medulla oblongata, and the reticular regions around the raphe magnus nucleus and the gigantocellular reticular nucleus pars alpha, bilaterally with a slight dominance on the side ipsilateral to the injection site. A number of GAD/TMR-DA and Gly/TMR-DA neurons were also seen in the oral and interpolar subnuclei of the spinal trigeminal nucleus, bilaterally with a slight ipsilateral dominance. In the rats injected with TMR-DA into the facial nucleus, GAD/TMR-DA and Gly/TMR-DA neurons were also encountered in the paralemniscal zone of the midbrain tegmentum bilaterally with an apparent dominance on the side contralateral to the injection site. A large part of these inhibitory premotor neurons for the facial and hypoglossal nuclei and the excitatory ones may constitute premotor neuron pools common to the orofacial motor nuclei implicated in the control of integrated orofacial movements.

Animals↗

PubMed1997

Collateral projections from single neurons in the dorsal column nucleus to both the cochlear nucleus and the ventrobasal thalamus: a retrograde double-labeling study in the rat.

In the rats which were injected with Fluoro-Gold into the cochlear nucleus and simultaneously with tetramethylrhodamine-dextran amine into the ventrobasal thalamus, a number of neurons in the gracile and the cuneate nuclei of the dorsal column nucleus (DCN) and in the interpolar and caudal subnuclei of the spinal trigeminal nucleus (STN) were double-labeled retrogradely with the both tracers. The results indicated the existence of single DCN/STN-neurons which provided axons to the cochlear nucleus, mainly ipsilaterally, and to the contralateral ventrobasal thalamus.

Animals↗