Biomedical subjects

Takeshi Kaneko

Publications and source records attributed to Takeshi Kaneko.

At least 19 recordsLinked to original sources

PubMed2007

Metabotropic glutamate receptor 4-immunopositive terminals of medium-sized spiny neurons selectively form synapses with cholinergic interneurons in the rat neostriatum.

Metabotropic glutamate receptor 4 (mGluR4) is localized mainly to presynaptic membranes in the brain. Rat neostriatum has been reported to contain two types of mGluR4-immunoreactive axon varicosities: small, weakly immunoreactive varicosities that were distributed randomly (type 1) and large, intensely immunoreactive ones that were often aligned linearly (type 2). In the present study, most type 1 terminals formed asymmetric synapses on dendritic spines, whereas type 2 terminals made symmetric synapses on dendritic shafts, showing immunoreactivity for GABAergic markers. After depletion of neostriatal neurons, type 2 but not type 1 varicosities were largely decreased in the damaged region. When medium-sized spiny neurons (MSNs) were labeled with Sindbis virus expressing membrane-targeted green fluorescent protein, mGluR4 immunoreactivity was observed on some varicosities of their axon collaterals in immunofluorescence and immunoelectron microscopies. Furthermore, type 2 varicosities were often positive for substance P but mostly negative for striatal interneuron markers and preproenkephalin. Thus, striatonigral/striato-entopeduncular MSNs are likely to be the largest source of type 2 mGluR4-immunopositive axon terminals in the neostriatum. Next, in the double-immunofluorescence study, almost all choline acetyltransferase (ChAT)-immunopositive and 41% of NK1 receptor-positive dendrites were heavily associated with type 2 mGluR4-immunoreactive varicosities. Neuronal nitric oxide synthase (nNOS)-positive dendrites, in contrast, seemed associated with only a few type 2 varicosities. Conversely, almost all type 2 varicosities were closely apposed to NK1 receptor-positive dendrites that were known to be derived from cholinergic and nNOS-producing interneurons. These findings indicate that the mGluR4-positive terminals of MSN axon collaterals selectively form synapses with neostriatal cholinergic interneurons.

Animals↗

PubMed2006

Extensive overlap of mu-opioid and nicotinic sensitivity in cortical interneurons.

We studied mu-opioid transmission in acute slices of rat neocortex using whole-cell recordings and single-cell reverse transcription-polymerase chain reaction. The mu-opioid receptor (MOR) was found in gamma-aminobutyric acidergic (GABAergic) interneurons that were either layer I cells frequently expressing neuropeptide Y or layers II-V cells expressing vasoactive intestinal peptide and enkephalin (Enk). We found that mu-opioid agonists inhibit these interneurons that are selectively excited by nicotinic agonists. The extensive overlap of mu-opioid and nicotinic responsiveness allowed mu-opioid agonists to inhibit nicotinic excitation of responsive interneurons and of their GABAergic output onto pyramidal cells. Finally, nicotinic stimulation resulted in a dynamic sequence where GABAergic transmission was first enhanced and then depressed below its baseline. This latter disinhibitory effect was prevented by a mu-opioid antagonist, indicating that excitation of nicotinic-responsive interneurons induced the release of endogenous Enk, which in turn led to MOR activation. Our results suggest that neocortical mu-opioid transmission acts as an inhibitory feedback onto nicotinic-responsive interneurons, which may change network excitability and inhibition patterns during cholinergic excitation.

Animals↗

PubMed2006

Medullary dorsal horn neurons providing axons to both the parabrachial nucleus and thalamus.

It has often been suggested that the trigemino- and spino-thalamic pathways are highly implicated in sensory-discriminative aspects of pain, whereas the trigemino- and spino-parabrachial pathways are strongly implicated in affective/emotional aspects of pain. On the other hand, the superficial laminae of the spinal dorsal horn, where many nociceptive neurons are distributed, have been reported to contain projection neurons innervating both the parabrachial nucleus (PBN) and thalamus by way of axon collaterals (Hylden et al., 1989). For the medullary dorsal horn (caudal subnucleus of spinal trigeminal nucleus: Vc), however, the existence of such neurons has not been reported. Thus, in the present study, we examined whether the Vc might contain projection neurons sending their axons to both the thalamus and PBN. Dual retrograde labeling with fluorescence dyes was attempted. In each rat, tetramethylrhodamine-dextran amine and Fluoro-gold were stereotaxically injected into the PBN and thalamic regions, respectively. The proportion of the dually labeled Vc cells in the total population of all labeled Vc cells was about 20%. More than 90% of the dually labeled neurons were distributed in lamina I (marginal zone), less than 10% of them were located in lamina II (substantia gelatinosa), and only a few (about 1%) were found in lamina III (magnocellular zone). The results indicate that some Vc neurons in the superficial laminae mediate nociceptive information directly to the PBN and thalamus by way of axon collaterals and that the vast majority of them project to the ipsilateral PBN and contralateral thalamus.

Animals↗

PubMed2006

Prodynorphin storage and processing in axon terminals and dendrites.

The classical view postulates that neuropeptide precursors in neurons are processed into mature neuropeptides in the somatic trans-Golgi network (TGN) and in secretory vesicles during axonal transport. Here we show that prodynorphin (PDYN), precursor to dynorphin opioid peptides, is predominantly located in axon terminals and dendrites in hippocampal and striatal neurons. The molar content of unprocessed PDYN was much greater than that of dynorphin peptides in axon terminals of PDYN-containing neurons projecting to the CA3 region of the hippocampus and in the striatal projections to the ventral tegmental area. Electron microscopy showed coexistence of PDYN and dynorphins in the same axon terminals with occasional codistribution in individual dense core vesicles. Thus, the precursor protein is apparently stored at presynaptic sites. In comparison with the hippocampus and striatum, PDYN and dynorphins were more equally distributed between neuronal somata and processes in the amygdala and cerebral cortex, suggesting regional differences in the regulation of trafficking and processing of the precursor protein. Potassium-induced depolarization activated PDYN processing and secretion of opioid peptides in neuronal cultures and in a model cell line. Regulation of PDYN storage and processing at synapses by neuronal activity or extracellular stimuli may provide a local mechanism for regulation of synaptic transmission.

Animals↗

PubMed2006

Expression of vesicular glutamate transporter 1 immunoreactivity in peripheral and central endings of trigeminal mesencephalic nucleus neurons in the rat.

The major neuronal components of the trigeminal mesencephalic nucleus (Vmes) are primary afferent neurons that convey proprioceptive information from the cranioorofacial regions. In the present study, we examined expression of vesicular glutamate transporters (VGLUTs), VGLUT1 and VGLUT2, in the primary afferent neurons of the Vmes (Vmes neurons) in neonatal and adult rats. VGLUT1 immunoreactivity was detected in the cell bodies of Vmes neurons in neonatal rats younger than 11 days old, but not in older rats. However, in situ hybridization signals for VGLUT1 mRNA were detected in both neonatal and adult rats. No VGLUT2 immunoreactivity was detected in Vmes neurons of neonatal or adult rats. VGLUT1 immunoreactivity was also seen in the peripheral sensory endings on the equatorial regions of intrafusal fibers of muscle spindles in the masseter muscles in both neonatal and adult rats. In adult rats injected with cholera toxin B subunit (CTb) into the masseter nerve, central axon terminals of Vmes neurons were identified on masseter motoneurons within the trigeminal motor nucleus (Vm) by transganglionically and retrogradely transported CTb. VGLUT1-immunopositive axon terminals in close apposition to CTb-labeled Vm motoneurons were also detected by dual-immunofluorescence histochemistry for VGLUT1/CTb. Electron microscopy after dual immunolabeling for VGLUT1/CTb by the VGLUT1/immunoperoxidase and CTb/immunogold-silver methods further revealed synaptic contact of VGLUT1- and CTb-immunopositive axon terminals upon CTb-labeled neuronal profiles within the Vm. These data indicate that VGLUT1 is expressed in both the central axon terminals and the peripheral sensory endings of Vmes neurons, although no VGLUT1 immunoreactivity was detectable in the cell bodies of Vmes neurons in adult rats.

Aging↗

PubMed2006

Heme oxygenase-1, a potential biomarker of chronic silicosis, attenuates silica-induced lung injury.

RATIONALE: Heme oxygenase-1 (HO-1), a rate-limiting enzyme in heme catabolism, has antioxidative, antiapoptotic, and antiinflammatory activities. We examined whether HO-1 might be involved in silicosis. OBJECTIVES: To investigate whether HO-1 can reduce silicosis in mice and humans. METHODS AND MEASUREMENTS: Silicosis was studied using a murine model, and in 46 male patients. Serum HO-1 and 8-hydroxydeoxyguanosine (a marker of oxidative stress) were measured by enzyme-linked immunosorbent assay. Levels of HO-1 were measured by immunohistochemistry and immunoblotting. MAIN RESULTS: Serum HO-1 levels were significantly elevated in patients with silicosis compared with age-matched control subjects or patients with chronic obstructive pulmonary disease. Serum HO-1 levels also correlated inversely with serum 8-hydroxydeoxyguanosine levels and positively with vital capacity and forced expiratory volume in one second in patients with silicosis. HO-1 was present in the lungs of humans and mice with silicosis, especially at sites of silica particle deposition. In mice, silica exposure was associated with acute leukocyte infiltration, leading to development of silicotic lung lesions. The inflammation was suppressed by treatment with hemin, an inducer of HO-1, and enhanced by zinc protoporphyrin, an inhibitor of HO-1. CONCLUSIONS: Pulmonary HO-1 expression is increased in silicosis. HO-1 suppresses reactive oxygen species activity, and subsequent pathologic changes, thereby attenuating disease progression.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2006

Fos-enkephalin signaling in the rat medial vestibular nucleus facilitates vestibular compensation.

In the present study, we first observed up-regulation in preproenkephalin (PPE)-like immunoreactivity (-LIR), a precursor of Met- and Leu-enkephalin, in the rat ipsilateral medial vestibular nucleus (ipsi-MVN) after unilateral labyrinthectomy (UL). By means of double-staining immunohistochemistry with PPE and Fos, a putative regulator of PPE gene expression, we revealed that some of these PPE-LIR neurons were also Fos immunopositive. The time course of decay of these double-stained neurons was quite parallel to that of UL-induced behavioral deficits. This suggests that these double-labeled neurons could have something to do with development of vestibular compensation. We next examined correlation between Fos and PPE expression in the ipsi-MVN by means of a 15-min pre-UL application of antisense oligonucleotide probes against c-fos mRNA into the ipsi-MVN. Gel shift assay and Western blotting revealed that elimination of Fos expression significantly reduced both AP-1 DNA binding activity and PPE expression in the ipsi-MVN after UL. C-fos antisense study also revealed that depression of Fos-PPE signaling in the ipsi-MVN caused significantly more severe behavioral deficits during vestibular compensation. Furthermore, studies with PPE antisense and naloxone, an opioid receptor antagonist, demonstrated that specific depression of enkephalinergic effects in the ipsi-MVN significantly delayed vestibular compensation. All these findings suggest that, immediately after UL, Fos induced in some of the ipsi-MVN neurons could regulate consequent PPE expression via the AP-1 activation and facilitate the restoration of balance between bilateral MVN activities via the opioid receptor activation, resulting in progress of vestibular compensation.

Adaptation, Physiological↗

PubMed2006

Spatial arrangement of metal nanoparticles supported by porous polymer substrates studied by transmission electron microtomography.

Fine metal particles (nanoparticles) stabilized on porous (polymeric) substrates can be considered as a model system of a high-performance catalyst. In the present study, the substrate was made using the periodic microphase-separated structure of a block copolymer as the template, and the Pd nanoparticles were formed inside the porous material by reduction of the Pd2+ ions with 1-propanol as the reductant. The three-dimensional morphology of such a polymer-Pd hybrid material was studied by transmission electron microtomography. The characteristic structural parameters of the hybrid, e.g., the penetration of the Pd nanoparticles into the polymer substrate, number density of the Pd nanoparticles, and size distribution of the Pd nanoparticles, were measured for the first time.

Metal Nanoparticles↗

PubMed2006

Vesicular glutamate transporter 3 (VGLUT3) identifies spatially segregated excitatory terminals in the rat substantia nigra.

The excitability of dopaminergic (DA) neurons in the substantia nigra is controlled by the convergent activity of multiple glutamatergic afferents. Here, we show that vesicular glutamate transporter 3 (VGLUT3)-immunoreactive (ir) terminals segregate to the perisomatic region of DA neurons in the substantia nigra pars compacta, and VGLUT3 decorates a synapse population distinct from those marked by vesicular glutamate transporters 1 and 2. VGLUT3-ir nerve endings form asymmetric terminals on DA neurons. Retrograde tracing suggests the superior colliculus as an origin of excitatory VGLUT3-ir afferents. Collectively, our data indicate that VGLUT3 identifies a novel excitatory terminal subset that contributes to the tuning of DA cell excitability in the substantia nigra.

Animals↗

PubMed2006

Difference in organization of corticostriatal and thalamostriatal synapses between patch and matrix compartments of rat neostriatum.

The neostriatum, which possesses a mosaic organization consisting of patch and matrix compartments, receives glutamatergic excitatory afferents from the cerebral cortex and thalamus. Differences in the synaptic organization of these striatopetal afferents between the patch and matrix compartments were examined in the rat using confocal laser scanning and electron microscopes. Thalamostriatal terminals immunopositive for vesicular glutamate transporter (VGluT) 2 were less dense in the patch than in the matrix compartment, although the density of VGluT1-immunopositive corticostriatal terminals was almost evenly distributed in both the compartments. Quantitative analysis of ultrastructural images revealed that 84% of VGluT2-positive synapses in the patch compartment were formed with dendritic spines, whereas 70% in the matrix compartment were made with dendritic shafts. By contrast, VGluT1-positive terminals display a similar preference for specific synaptic targets in both compartments: about 80% made synapses with dendritic spines. In addition, VGluT2-positive axospinous synapses in the patch compartment were larger than the VGluT1-positive axospinous synapses in both compartments. As axospinous synapses are generally found in neuronal connections showing high synaptic plasticity, the present findings suggest that the thalamostriatal connection requires higher synaptic plasticity in the patch compartment than in the matrix compartment.

Animals↗

PubMed2006

[A case of large cell carcinoma of the lung with rhabdoid phenotype].

A 37-year-old man was admitted to our hospital because of suspicion of the lung cancer in November 2003. Transbronchial tumor biopsy revealed a small number of tumor cells with rhabdoid features, which had eosinophilic cytoplasmic globules. However, a definitive histological diagnosis was not obtained. We considered that a diagnosis of lung malignant tumor was likely according to the findings of chest CT scan and pathology. Although radiotherapy reduced the tumor size, he started to have abdominal pain and tarry stool one month after radio therapy. Multiple small intestine metastases were detected by gastroenterological endoscopy. The patient died due to bleeding from these metastatic lesions in May 2004. Immunohistologic staining of the cervical lymph node showed that rhabdoid cells were positive for epithelial membrane antigen (EMA), vimentin, and anticytokeratin antibody (CAM5.2), but not for thyroid transcription factor-1 (TTF-1). From the autopsy findings and clinical course, he was finally diagnosed with large cell carcinoma of the lung with rhabdoid phenotype. Because of its aggressive clinical course, early diagnosis and decision on therapy would be very important for this disease.

Adult↗

PubMed2005

Postnatal changes of vesicular glutamate transporter (VGluT)1 and VGluT2 immunoreactivities and their colocalization in the mouse forebrain.

Vesicular glutamate transporter 1 (VGluT1) and VGluT2 accumulate neurotransmitter glutamate into synaptic vesicles at presynaptic terminals, and their antibodies are thus considered to be a good marker for glutamatergic axon terminals. In the present study, we investigated the postnatal development and maturation of glutamatergic neuronal systems by single- and double-immunolabelings for VGluT1 and VGluT2 in mouse forebrain including the telencephalon and diencephalon. VGluT2 immunoreactivity was widely distributed in the forebrain, particularly in the diencephalon, from postnatal day 0 (P0) to adulthood, suggesting relatively early maturation of VGluT2-loaded glutamatergic axons. In contrast, VGluT1 immunoreactivity was intense only in the limbic regions at P0, and drastically increased in the other telencephalic and diencephalic regions during three postnatal weeks. Interestingly, VGluT1 immunoreactivity was frequently colocalized with VGluT2 immunoreactivity at single axon terminal-like profiles in layer IV of the primary somatosensory area from P5 to P10 and in the ventral posteromedial thalamic nucleus from P0 to P14. This was in sharp contrast to the finding that almost no colocalization was found in glomeruli of the olfactory bulb, patchy regions of the caudate-putamen, and the ventral posterolateral thalamic nucleus, where moderate to intense immunoreactivities for VGluT1 and VGluT2 were intermingled with each other in neuropil during postnatal development. The present results indicate that VGluT2-loaded glutamatergic axons maturate earlier than VGluT1-laden axons in the mouse telencephalic and diencephalic regions, and suggest that VGluT1 plays a transient developmental role in some glutamatergic systems that mainly use VGluT2 in the adulthood.

Animals↗

PubMed2005

In vivo function of Rnd2 in the development of neocortical pyramidal neurons.

The present study examined the in vivo role of Rnd2, a Rho family small GTPase, in brain development. Rnd2 was expressed by radially migrating cells, which primarily develop to pyramidal neurons, during their stay in the subventricular zone of embryonic cerebral cortex and hippocampus. Exogenous expression of wild-type and a constitutively active Rnd2, but not a negative mutant of Rnd2, in radially migrating cells by in utero electroporation disturbed their morphology and migration to upper layers. These results indicate that Rnd2 functions in vivo as a regulator of the migration and morphological changes associated with the development of pyramidal neurons.

Amino Acid Sequence↗

PubMed2005

Third pathway in the cortico-basal ganglia loop: Neurokinin B-producing striatal neurons modulate cortical activity via striato-innominato-cortical projection.

In the cortico-basal ganglia loop, striatal regions serve as 'entrances' to the basal ganglia, receiving massive inputs from the cerebral cortex and sending 'direct' and 'indirect' pathways to the output nuclei of the basal ganglia. However, we have recently identified a new striatofugal subgroup which produces neurokinin B (NKB). Although NKB-producing neurons constitute a minority of striatal neurons, this subgroup is distinguished by the unique distribution and chemical characteristics. NKB-producing striatal neurons are distributed in association with mu-opioid receptor localization, and rarely express DARPP32, which is produced by the major striatofugal neurons and coupled with dopaminergic signaling. Further interestingly NKB-producing striatal neurons send axons to basal forebrain regions, but not to the main target regions of striatal outflow, pallidal or mesencephalic regions. In the basal forebrain, some GABAergic inhibitory neurons express NK3 receptor, selective receptor for NKB, and directly send axons to the cerebral cortex. The NK3-expressing neurons show different electrical properties from cholinergic basal forebrain neurons, and display facilitatory responses to stimulation of NK3 receptor. These findings strongly suggest that NKB-producing striatal neurons and NK3-expressing basal forebrain neurons constitute a third pathway which bypasses the common output nuclei of the basal ganglia, and more directly control or modulate cortical activity.

Animals↗

PubMed2005

Pyramidal neurons of upper cortical layers generated by NEX-positive progenitor cells in the subventricular zone.

The generation of pyramidal neurons in the mammalian neocortex has been attributed to proliferating progenitor cells within the ventricular zone (VZ). Recently, the subventricular zone (SVZ) has been recognized as a possible source of migratory neurons in brain slice preparations, but the relevance of these observations for the developing neocortex in vivo remains to be defined. Here, we demonstrate that a subset of progenitor cells within the SVZ of the mouse neocortex can be molecularly defined by Cre recombinase expression under control of the NEX/Math2 locus, a neuronal basic helix-loop-helix gene that by itself is dispensable for cortical development. NEX-positive progenitors are generated by VZ cells, move into the SVZ, and undergo multiple asymmetrical and symmetrical cell divisions that produce a fraction of the neurons in the upper cortical layers. Our data suggest that NEX-positive progenitors within the SVZ are committed to a glutamatergic neuronal fate and have evolved to expand the number of cortical output neurons that is characteristic for the mammalian forebrain.

Animals↗

PubMed2005

Reduction of anisotropic image resolution in transmission electron microtomography by use of quadrangular prism-shaped section.

A quadrangular prism specimen (a 'prism-shaped' section) was observed in three-dimension (3-D) by transmission electron microtomography (TEMT) over as wide a tilt range as possible. Two types of specimens were prepared for the TEMT experiments: (i) a prism-shaped section of a block copolymer nanostructure, whose cross section was 200 nm on each side and (ii) a conventional ultrathin section having the same thickness (approximately 200 nm) as the prism-shaped section. Image quality of the projections taken at high tilt angles, e.g. 60 degrees, of the prism-shaped section was considerably better than that of the ultrathin section. This was because the path length of electron beam of the prism-shaped section was shorter (and hence the transmission was higher) than that of the ultrathin section at the same tilt angle. Thus, although the projections of the ultrathin section at the tilt angle larger than approximately 40 degrees did not effectively contribute to the 3-D reconstruction, those of the prism-shaped section at very high tilt angles, e.g. +/-75 degrees, can still be used for the 3-D reconstruction. Three orthogonal cross-sectional views of the 3-D reconstruction were extensively compared between the two sections. It was found that (i) the image contrast of the 3-D reconstruction was significantly enhanced and (ii) an elongation of structural object due to limitation of the angular range in the electron tomography was considerably reduced using the prism-shaped section.

Journal Article↗

PubMed2005

Complementary roles of cholecystokinin- and parvalbumin-expressing GABAergic neurons in hippocampal network oscillations.

In the hippocampal CA1 area, a relatively homogenous population of pyramidal cells is accompanied by a diversity of GABAergic interneurons. Previously, we found that parvalbumin-expressing basket, axo-axonic, bistratified, and oriens-lacunosum moleculare cells, innervating different domains of pyramidal cells, have distinct firing patterns during network oscillations in vivo. A second family of interneurons, expressing cholecystokinin but not parvalbumin, is known to target the same domains of pyramidal cells as do the parvalbumin cells. To test the temporal activity of these independent and parallel GABAergic inputs, we recorded the precise spike timing of identified cholecystokinin interneurons during hippocampal network oscillations in anesthetized rats and determined their molecular expression profiles and synaptic targets. The cells were cannabinoid receptor type 1 immunopositive. Contrary to the stereotyped firing of parvalbumin interneurons, cholecystokinin-expressing basket and dendrite-innervating cells discharge, on average, with 1.7 +/- 2.0 Hz during high-frequency ripple oscillations in an episode-dependent manner. During theta oscillations, cholecystokinin-expressing interneurons fire with 8.8 +/- 3.3 Hz at a characteristic time on the ascending phase of theta waves (155 +/- 81 degrees), when place cells start firing in freely moving animals. The firing patterns of some interneurons recorded in drug-free behaving rats were similar to cholecystokinin cells in anesthetized animals. Our results demonstrate that cholecystokinin- and parvalbumin-expressing interneurons make different contributions to network oscillations and play distinct roles in different brain states. We suggest that the specific spike timing of cholecystokinin interneurons and their sensitivity to endocannabinoids might contribute to differentiate subgroups of pyramidal cells forming neuronal assemblies, whereas parvalbumin interneurons contribute to synchronizing the entire network.

Action Potentials↗

PubMed2005

Sympathetic premotor neurons mediating thermoregulatory functions.

The sympathetic nervous system controls various homeostatic conditions, such as blood circulation, body temperature, and energy expenditure, through the regulation of diverse peripheral effector organs. In this system, sympathetic premotor neurons play a crucial role by mediating efferent signals from higher autonomic centers directly to sympathetic preganglionic neurons in the intermediolateral cell column of the spinal cord. The medulla oblongata is thought to subsume many sympathetic premotor neurons, and the rostral ventrolateral medulla (RVLM) has been established to contain the sympathetic premotor neurons responsible for cardiovascular control. Although premotor neurons controlling other effector organs than the cardiovascular system have been largely unknown, recent accumulating findings have suggested that medullary raphe regions including the raphe pallidus and raphe magnus nuclei are candidates for the pools of excitatory sympathetic premotor neurons involved in thermoregulation. Further recently, excitatory premotor neurons controlling the thermoregulatory effector organs, brown adipose tissue and tail, have been identified with expression of vesicular glutamate transporter (VGLUT)3, whereas those for cardiovascular control were characterized with VGLUT2 expression. The VGLUT3-expressing premotor neurons would mediate thermoregulation including fever induction, and could be also involved in the control of energy metabolism.

Amino Acid Transport Systems, Acidic↗