Young Suk Suh

Morphologic investigation of rolling mouse Nagoya (tgrol/tgrol) cerebellar Purkinje cells: an ataxic mutant, revisited

Rolling mouse Nagoya (rolling: tg(rol)) is a neurologic mutant mouse exhibiting severe ataxia. Two alleles of the rolling mutation, tottering (tg) and leaner(tg(la)), have been identified as mutations in the voltage-dependent calcium channel alpha1A subunit. No specific light and electron microscopic findings have been reported for the rolling mouse cerebellum except a decreased number of granule cells, while altered Purkinje cell/parallel fiber synapses have been observed in tottering and leaner cerebella. Rolling mouse cerebella were analyzed using anti-calbindin-D immunohistochemistry and transmission electron microscopy to investigate Purkinje cell morphology and synaptic contacts between Purkinje cell dendritic spines and parallel fiber varicosities. Multiple Purkinje cell dendritic spines synapsing with single parallel fiber varicosities were frequently observed in rolling cerebella. The correlation between the presence of altered Purkinje cell synapses and ataxia in rolling mice warrants further investigation.

Magnetic resonance image-based cerebellar volumetry in healthy Korean adults.

The effects of age and gender on cerebellar size have not been established yet. To understand these effects, the area of cerebellar vermis and the volume of cerebellum were measured using serial magnetic resonance images of 124 Korean adults free of neurologic symptoms and signs. Cerebellar volume of male was significantly larger than that of female, although the size of vermis did not show significant gender difference. Correlation analysis revealed that cerebellar volume was not affected by aging. Regressional analysis demonstrated that female vermis had a tendency to shrink after age of 50, whereas male vermis and total cerebellar volume in both sexes were not altered with aging. The different response of vermis with aging and maintenance of cerebellum volume need to be more explored.

Apoptotic cell death of cerebellar granule cells in rolling mouse Nagoya.

Rolling mouse Nagoya is a voltage dependent calcium channel alpha1A subunit mutant showing moderate ataxia. Granule cell loss was previously reported in the cerebellar vermis of homozygous rolling. Apoptotic cerebellar granule cell death was reported in homozygous leaner mice, an allele of rolling. Cerebella of 21-day-old rolling and wild type mice were used for terminal dUTP nick-end-labeling (TUNEL) assay and electron microscopic observation to understand the mechanism of granule cell loss in rolling mice. The number of TUNEL-positive cells was significantly increased in rolling. More TUNEL-positive cells were observed in the anterior cerebellar vermis compared with posterior. Condensation and fragmentation of granule cell nuclei in rolling mouse were observed frequently. These results suggest that apoptosis is one of the mechanisms of granule cell loss in the rolling cerebellum.

Altered neuronal nitric oxide synthase expression in the cerebellum of calcium channel mutant mice.

Tottering, rolling Nagoya, and leaner mutant mice all exhibit cerebellar ataxia to varying degrees, from mild (tottering mice) to severe (leaner mice). Collectively, these mice are regarded as tottering locus mutants because each of these mutant mice expresses a different autosomal recessive mutation in the gene coding for the alpha(1A) calcium ion channel protein, which is the pore forming subunit for P/Q-type high voltage activated calcium ion channels. These mutant mice all exhibit varying degrees of cerebellar dysfunction and neuronal cell death. Nitric oxide (NO) is an important messenger molecule in the central nervous system, especially in the cerebellum, and it is produced via the enzyme, nitric oxide synthase (NOS). We investigated expression of neuronal-NOS (n-NOS) in the cerebella of all three mutant mice, as revealed by NADPH-diaphorase (NADPH-d) histochemical staining, quantitation of n-NOS protein using Western blotting and quantitation of n-NOS mRNA using in situ hybridization. The expression of n-NOS mRNA and protein as well as the NADPH-d histochemical reaction were elevated in tottering and rolling Nagoya cerebella. n-NOS mRNA and the NADPH-d histochemical reaction were decreased in the leaner cerebellum, but the leaner mouse n-NOS protein concentration was not significantly different compared to age- and gender-matched controls. These findings suggest that NO may act as an important mediator in the production of the neuropathology observed in these mutant mice.

Characterization of chromosomal aberrations in human gastric carcinoma cell lines using chromosome painting

Using chromosome painting, a study of chromosomal abnormalities was performed in six gastric carcinoma cell lines (SNU-484, 601, 620, 638, 668, 719) from Korean patients. Each carcinoma cell line had unique modal karyotypic characteristics and showed a variable number of numerical and structural clonal cytogenetic aberrations. SNU-484, SNU-620, and SNU-668 had near-triploidy; SNU-601, SNU-638, and SNU-719 had near-diploidy. The origins of the marker chromosomes of these cell lines were identified by fluorescence in situ hybridization with constructed painting probes. In all of six cell lines, rearrangement of chromosome 17 resulting in partial deletion of 17p (and/or partial duplication of 17q) was found. The most frequent marker was a partial gain of chromosome 7 with the breakpoints on 7q22 and 7q31. The nonrandom rearrangements of chromosomes were also determined on 1q32, 5q11-q22, 8q, 14q22, 14q34, and 15q15; suggesting that they may be the candidate regions for the isolation of the genes related to gastric cancer.

MK-801, a non-competitive NMDA receptor antagonist, prevents postischemic decrease of inositol 1,4,5-trisphosphate receptor mRNA expression in mongolian gerbil brain

Changes of inositol 1,4,5-trisphosphate receptor (IP3R) mRNA expression after transient brain ischemia and the effect of MK-801, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, on the IP3R mRNA expression was studied in mongolian gerbil brain by in situ hybridization. Transient ischemia was induced by ligating left common carotid artery for 10 min, and the animals were allowed recovery from 15 min to 24 h. MK-801 was introduced intraperitoneally 30 min before ischemia. IP3R mRNA expression was decreased in dentate gyrus and hippocampus from 90 min until 24 h after ischemia. MK-801 pretreatment prevented the change of IP3R mRNA expression after ischemia. These results suggest that IP3R mRNA expression in ischemia may be related with NMDA receptor.