TBR2-immunopsitive unipolar brush cells are associated with ectopic zebrin II-immunoreactive Purkinje cell clusters in the cerebellum of scrambler mice / 대한해부학회지

Unipolar brush cells (UBCs) are excitatory interneurons with their somata located in the granular layer. Recently, T-brain factor 2 (Tbr2) was shown to be expressed in a subset of UBCs in mouse cerebellum. Scrambler mice exhibit severe cerebellum abnormalities, including the failure of embryonic Purkinje cell dispersal and a complete absence of foliation due to a mutation in the disabled-1 adaptor protein. Since most UBC markers are expressed postnatally, it has proven difficult to identify the relationship between developing Purkinje cell clusters and migrating UBCs. Because scrambler mice closely mimic normal embryonic day 18 cerebellum, we examined whether Tbr2-positive UBCs are associated with Purkinje cell cluster markers such as zebrin II, which is the most studied compartmentation marker in the cerebellum. We investigated the distribution of Tbr2-positive UBCs in this mutant by using anti-Tbr2 immunocytochemistry. The data revealed that Tbr2 immunoreactivity was exclusively present in the nucleus of UBCs in scrambler cerebellum. Based on expression data, a Tbr2-positive UBC map was constructed. In addition, Tbr2-positive UBCs are found associated with ectopic zebrin II-immunoreactive Purkinje cell clusters in scrambler cerebellum. These data suggest that UBCs use Purkinje cell compartmentation to migrate into their final position through interactions with the embryonic array of specific Purkinje cell subtypes.

Early cerebellar granule cell migration in the mouse embryonic development / 대한해부학회지

Pax6, a paired homeobox DNA binding protein, has been found to be expressed in the cerebellum in both granule cells and their precursors in the external granular layer (EGL). In this study we have traced Pax6 expression through embryonic development in mice by using a polyclonal antibody against Pax6 and used it to study the cellular dispersal pattern of the EGL. During dispersal the EGL was thicker and Pax6 expression was more intense on the rostral side of the lateral corners of the cerebellum. Pax6 immunoreactive cells were found to be migrating from the EGL during the early stage of EGL dispersal, which suggested the early inward migration of granule cells. Double staining with various markers confirmed that the early-migrating cells are not Purkinje cells, interneurons or glia. Although the Pax6 immunoreactive cells within the cerebellum were not apparently proliferating, NeuN, a marker for postmitotic granule cells, was not expressed in these cells until E16. Furthermore, granule cells were observed migrating inwards from the EGL both during and after EGL dispersal. These early migrating granule cells populated the whole cerebellum. These findings offer novel views on specific stages of granule cell dispersal and migration.

Absence Expression of Heat Shock Protein 25 in the Cerebellum of Ataxic Mutant Pogo Mouse / 대한해부학회지

Heat shock proteins (Hsps) are generally known to be induced in response to a range of stressful stimuli such as hyperthermia, immobilization, UV radiation, arsenite, various chemicals, and drugs. In addition, these proteins have been suggested to have roles in protecting cells against apoptotic cell death. The ataxic mutant Pogo (pogo/pogo) mouse is a novel neurological ataxic mutant, which is derived from Korean wild type mouse (KJR/Mskist) strain. Pogo mutation is considered as an alleles of alpha subunit of P/Q-type calcium channel mutants such as rolling mouse Nagoya (RMN), tottering, and leaner. We investigated the topographical Hsp25 expression using immunohistochemistry and western blot analysis in several ataxic mutant mice: RMN, tottering, leaner, Pogo and Korean wild mouse. In the cerebellum of the RMN, tottering, leaner, and normal mouse including Balb/C, C57BL/6 and ICR mouse, Hsp25 was expressed in a subset of Purkinje cells that form parasagittal stripes. The Hsp25 expression is largely restricted to specific cerebellar lobules: VI /VII (the central zone: CZ), and IX/X (the nodular zone: NZ). Surprisingly, no Hsp25-immunoreactive Purkinje cells were seen in CZ and NZ of the cerebellum of Pogo (pogo/pogo), heterozygotes Pogo (pogo/+), and Korean wild mouse. Moreover, in western blot analysis, there was no cerebellar Hsp25 expression in ataxic Pogo mouse including Korean wild mouse. These data suggest that cerebellar Hsp25 expression was irrelevant with the development of ataxia in Pogo mouse.

Decreased Calbindin-immunoreactive Renshaw Cells (RCs) in the Lumbar Spinal Cord of the Ataxic Pogo Mice / 대한해부학회지

Calbindin D-28K (CALB) is one of the calcium-binding proteins which is assumed to be buffering, transport of Ca2+, and regulation of various enzyme systems. In the spinal cord, a subpopulation of calbindin-immunoreactive neurons located in the ventral portion of lamina VII, medial to the motoneuron column, has recently been proposed to be Renshaw cells (RCs), that mediate recurrent inhibition of spinal alpha-motoneurons, based on the anatomical location. In this study, we have performed to investigate the correlation between RCs containing high levels of CALB and motoneurons in the ventral horn of lumbar spinal cord of the ataxic pogo mice, that characterized by a failures of interlimb coordination, and prolonged excessive tone of hindlimb extensor muscles. We have shown that CALB immunoreactive RCs was significantly decreased in the ventral horn of lumbar spinal cord of the ataxic pogo mice (p.0.05), when compared with the control mice. Whereas, CALB immunoreactivity expression levels were no difference in the dorsal horn. Furthermore, CALB protein was significantly decreased in the lumbar spinal cord of the ataxic pogo mice (p.0.01). However, there were no difference in the cervical and thoracic spinal cord of the between control and pogo mice. These results suggest that motoneurons of ventral horn of the lumbar spinal cord might be more excited state, results in the decreased CALB immunoreactive RCs have not mediated a motoneuron excitability, in the atxic mice, pogo.

Voltage-dependent Calcium Channel (VDCC) alpha(1A) Subunit Expression in the Ataxic Mutant, Pogo Mice Cerebellum / 대한해부학회지

The pogo mouse is a new ataxic mutant derived from a Korean wild mouse. The pogo mutation is inherited as an autosomal recessive trait on chromosome 8. Mutations in gene coding for the alpha(1A)subunit of voltagegated P/Q-type Ca(2+) channel have been shown to cause phenotypes in humans and mice, i.e., tottering, leaner, rolling mouse mouse Nagoya. Using immunohistochemistry, the expression of the alpha(1A)subunit of voltage-gated P/Q-type Ca(2+) channel was examined in pogo mice cerebellum including deep cerebellar nuclei (DCN). We observed alpha(1A)immunoreactivity in the cerebellar cortex (Purkinje cell and granule cell) and DCN of ataxic pogo mice and heterozygote control mice. There was no difference in cerebellar cortical alpha(1A)immunoreactivity between ataxic pogo mice and heterozygous littermate controls (pogo/+). However, we observed alpha(1A)immunoreactivity in the Purkinje cells of control and ataxic pogo mice cerebellum and DCN. We found a significant difference between pogo and heterozygous controls in terms of alpha(1A)immunoreactivities in the DCN. alpha(1A)immunoreactivity in this nucleus in pogo was much higher than in heterozygous littermate controls. No significant differences were observed in the interposed nucleus between pogo and heterozygous controls, but we found that the alpha(1A)subunits were clearer and more abundant in the lateral and medial regions of pogo than in control mice in these regions, where only weak immunoreactivity was observed. This elevated expression of the alpha(1A)subunit in deep cerebellar neurons of pogo might be a compensation for the altered function of P/Q type calcium channel and be related with the induction of the ataxic phenotype in pogo mice.

Distribution of Calretinin-immunoreactive Unipolar Brush Cells in Ataxic Mutant Pogo Mice Cerebellum / 대한해부학회지

Unipolar brush cells (UBCs) are a class of putative interneurons found in the granular layer of mammalian cerebellum and dorsal cochlear nucleus. The unipolar brush cells (UBCs), as with granular cells, which receives afferent synaptic input from extrinsic mossy fiber and whose axons branch in the granular layer and establish a system of cortex-intrinsic mossy fibers, which synapse with granule cells and other UBCs. In general, UBCs have been identified most readily by their expression of the calcium-binding protein, calretinin. The purpose of this study was to provide information about UBCs distributions of the new ataxic animal model, pogo mouse cerebellum using anti-calretinin immunohistochemistry, immunofluorescence and its effect on calcium homeostasis. Through the examination of calretinin immunohistochemistry and immunofluorescence, we observed that many calretinin immunoreactive UBCs were distributed widely throughout the lobules IX and X of the granular layer of both group. But, we found the number of calretinin immunoreactive UBCs of ataxic pogo (pogo/pogo) mouse was decreased and distribution pattern was altered, compared to control mouse. This result also suggest that reduced calretinin expression may effect on cerebellar Ca2+/-homeostasis, and it may in turn, explain the impaired motor coordination found in the ataxic pogo mice.

Elevated Serotonin-immunoreactive Neurons in the Raphe Nucleus of the Ataxic Mutant Mouse, Pogo / 대한해부학회지

This study was carried out to investigate the distribution of serotonin-immunoreactive neruons in the raphe nucleus of the ataxic pogo (pogo/pogo) mice derived from a Korean wild mice. Using by immunohistochemistry, we undertook to elucidate any correlation between the serotonin expression and behavior ataxia including abnormal hindlimb extension in the ataxic pogo mice. The present study has two important findings. First, serotonin immunoreactivity was increased in the raphe nucleus of the ataxic pogo mice. Second, serotonin immunoreactivity was different with the region of raphe nucleus. In the dorsal part of dorsal raphe nucleus (DRD), ventrolateral part of dorsal raphe nucleus (DRVL) and median raphe nucleus (MR), serotonin immunoreactivity was increased, whereas the ventral part of dorsal raphe nucleus (DRV) and interfascicular part of dorsal raphe nucleus (DRI) was similar with the control mice. Therefore, elevated expression of the serotonin in the raphe nucleus of ataxic pogo mice might be a source of behavior ataxia and may be related with the induction of the ataxic phenotype including abnormal hindlimb movements.

Abnormal Expression of Neuropeptide Y in the Cerebellar Purkinje Cells of the Ataxic Mutant Mice, Pogo / 체질인류학회지

The pogo mouse is an autosomal recessive ataxic mutant that arose spontaneously in the inbred KJR/MsKist strain derived originally from Korean wild mice. The ataxic phenotype is characterized by difficulty in maintaining posture and the consequent inability to walk straight. In our previous study about pogo mice cerebellum, we reported the Purkinje cell abnormalities and ectopic expression of tyrosine hydroxylase (TH) in Purkinje cell. In this study, we have provided an abnormal expression of NPY in ataxic mutant pogo mice for the first time. There was increased immunoreactivity for NPY in Purkinje cell of ataxic pogo (pogo/pogo) mice compared to those of heterozygote non-ataxic pogo mice (pogo/+, control group). In our previous study, TH is also expressed abnormally in Purkinje cells of ataxic mutant pogo (pogo/pogo) mouse cerebellum. To compare the expression patterns of TH and NPY within some Purkinje cell using double immunofluorescence, most of NPY-immunoreactive Purkinje cells in the ataxic pogo mice are TH-immunoreactive Purkinje cells. However, all of TH-immunoreactive Purkinje cells are not express the NPY. These data reveal that abnormal NPY-immunoreactivity in the ataxic pogo (pogo/pogo) cerebellum is restricted to a subset of cells within the ectopic TH-immunoreactive Purkinje cell subset. These results further suggest that Purkinje cell abnormalities contribute to motor ataxia in the ataxic pogo mouse.

Differences of Zebrin II Expression Pattern Between Normal Balb/C and Ataxic Pogo Mouse Cerebellum / 대한해부학회지

The purpose of this study is to identify the differences of zebrin II expression between ataxic pogo and normal Balb/C mouse cerebellum. Zebrin II is expressed by subsets of Purkinje cells that form an array of parasagittal bands that extend rostrocaudally throughout the cerebellar cortex, separated by similar bands of Purkinje cells that do not express zebrin II. Zebrin II immunoreactivity was localized in the perikarya of Purkinje cells, and the dendrites. Distribution of zebrin II-immunoreactive Purkinje cells were very similar pattern in pogo and Balb/C mouse cerebellum. But, in the lobule III, distribution of zebrin II expression was different between pogo and Balb/C mouse cerebellum. In lobule III of Balb/c mouse cerebellum, 10~15 zebrin II-immunoreactive Purkinje cells were observed and clustered to form a parasagittal bands. On the other hand, zebrin II expressions of lobule III in pogo mouse cerebellum showed a little different patterns. In lobule III of pogo mouse cerebellum, three bilateral zebrin II immunoreactive parasagittal band were observed. P1 band was almost same with lobule III of Balb/C mouse cerebellum. But, P2 bands were composed of 50~60 Purkinje cells which were immunoreactive with zebrin II. These kind of thickening in zebrin II expression of pogo mouse cerebellum may be due to the genetical difference. Furthermore, these results may provide useful information with further ataxic pogo mice cerebellum studies.

Glutamate and GABA concentrations in the cerebellum of novel ataxic mutant Pogo mice

The Pogo mouse is an autosomal recessive ataxic mutant that arose spontaneously in the inbred KJR/MsKist strain derived originally from Korean wild mice. The ataxic phenotype is characterized by difficulty in maintaining posture and side to side stability, faulty coordination between limbs and trunk, and the consequent inability to walk straight. In the present study, the cerebellar concentrations of glutamate and GABA were analyzed, since glutamate is a most prevalent excitatory neurotransmitter whereas gammar-aminobutyric acid (GABA) is one of the most abundant inhibitory neurotransmitters, which may be the main neurotransmitters related with the ataxia and epilepsy. The concentration of glutamate of cerebellum decreased significantly in ataxic mutant Pogo mouse compared to those of control mouse. However, GABA concentration was not decrease. These results suggested that the decrease in glutamate concentration may contribute to ataxia in mutant Pogo mouse.

Two Cases of Gastritis Cystica Superficialis without Previous Gastric Surgery / 대한소화기내시경학회지

Gastritis cystica superficialis (GCS) is a rare lesion which is characterized by glandular hyperplasia with regeneration and degeneration in the mucosa and muscularis mucosa. Recently, GCS is revealed as precancerous lesion, but most report has been associated with those found at the site of a gastroenterostomy. So, we report two cases with GCS who had not previous gastric surgery. A 45-year-old woman visited for epigastric discomfort and another 4Q-year-old woman for epigastric pain. They had not undergone any gastric surgery. The gastroscopy discovered one polyp on anterior wall of greater curvature, upper body and another polyp in the center of the fold of greater curvature, lower body. We removed it by snare polypectomy and the histologic finding showed the character of GCS.

Immunohistochemistry of Voltage-Gated Calcium Channel alpha1B Subunit in Mouse Cerebellum

Secretion of neurotransmitters is initiated by voltagegated calcium influx through presynaptic, voltage- gated N-type calcium channels. However, little is known about their cellular distribution in the mouse cerebellum. In the cerebellum, alpha1B immunoreactivity is found mainly on the cell bodies of all Purkinje cells. In addition, the immunoreactivity was detected on a subset of Purkinje cell dendrites, clustered to form a parasagittal array of bands. In the anterior lobe vermis, immunoreactive Purkinje cell dendrites form narrow stripes separated by broad bands of unstained dendrites. Moving caudally through the vermis, these stripes become thicker as a larger fraction of the Purkinje cell dendrites become immunoreactive. This localization study of the alpha1B pore-forming subunits in mouse cerebellum may guide future investigations of the role of calcium channels in neurological pathways.