Biomedical subjects

Hee-Sup Shin

Publications and source records attributed to Hee-Sup Shin.

39 records · Page 3Linked to original sources

PubMed2002

Role of synaptic metabotropic glutamate receptors in epileptiform discharges in hippocampal slices.

Application of group I metabotropic glutamate receptor (mGluR) agonists elicits seizure discharges in vivo and prolonged ictal-like activity in in vitro brain slices. In this study we examined 1) if group I mGluRs are activated by synaptically released glutamate during epileptiform discharges induced by convulsants in hippocampal slices and, if so, 2) whether the synaptically activated mGluRs contribute to the pattern of the epileptiform discharges. The GABA(A) receptor antagonist bicuculline (50 microM) was applied to induce short synchronized bursts of approximately 250 ms in mouse hippocampal slices. Addition of 4-aminopyridine (4-AP; 100 microM) prolonged these bursts to 0.7-2 s. The mGluR1 antagonist (S)-(+)-alpha-amino-4-carboxy-2-methylbenzeneacetic acid (LY 367385; 25-100 microM) and the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP; 10-50 microM), applied separately, significantly reduced the duration of the synchronized discharges. The effects of these antagonists were additive when applied together, suggesting that mGluR1 and mGluR5 exert independent actions on the epileptiform bursts. In phospholipase C beta1 (PLCbeta1) knockout mice, bicuculline and 4-AP elicited prolonged synchronized discharges of comparable duration as those observed in slices from wild-type littermates. Furthermore, mGluR1 and mGluR5 antagonists reduced the duration of the epileptiform discharges to the same extent as they did in the wild-type preparations. The results suggest that mGluR1 and mGluR5 are activated synaptically during prolonged epileptiform discharges induced by bicuculline and 4-AP. Synaptic activation of these receptors extended the duration of synchronized discharges. In addition, the data indicate that the synaptic effects of the group I mGluRs on the duration of epileptiform discharges were mediated by a PLCbeta1-independent mechanism.

4-Aminopyridine↗

PubMed2002

Role of the beta(2) subunit of voltage-dependent calcium channels in the retinal outer plexiform layer.

PURPOSE: Mutations in the alpha(1F) subunit of voltage-dependent calcium channels (VDCCs) have been shown to cause incomplete congenital stationary night blindness (CSNB2). The purpose of this study was to dentify which of the four beta subunits of VDCCs participates in the formation of this channel at the photoreceptor synapse and to determine how its absence affects visual processing. METHODS: Mice without each of the four known beta subunits of VDCCs were generated by gene targeting and transgenic rescue (CNS-beta(1), -beta(2)) or by gene targeting alone (beta(3)) or were obtained from a commercial provider (beta(4)). Retinal function and visual sensitivity were examined by electroretinography and an active avoidance behavioral test, respectively. The structure of the retina and expression of the alpha(1F) subunit were examined at the light microscopic level and by immunohistochemistry. RESULTS: Under dark-adapted conditions, CNS-beta(2)-null mice had a normal ERG a-wave, but did not have a normal b-wave. In addition, these mice showed decreased sensitivity to light. Both the a- and b-waves appear normal in the CNS-beta(1)-, beta(3)-, and beta(4)-null mice. Histologic analyses of all four mouse lines indicated that only the CNS-beta(2)-null mice had altered retinal morphology. Eyes of these mice had a thinner outer plexiform layer (OPL) than eyes of control animals. In addition, the labeling pattern of the alpha(1F) subunit in the OPL was altered in CNS-beta(2)-null mice. CONCLUSIONS: The normal distribution of the alpha(1F) subunit of the VDCCs in the OPL is dependent on the expression of the beta(2) subunit. The expression of both of these subunits is required for normal maintenance and/or formation of the OPL and synaptic transmission.

Animals↗

PubMed2002

In vivo differentiation of mouse embryonic stem cells into hepatocytes.

Embryonic stem (ES) cells have been regarded as a powerful resource for cell replacement therapy. In recent reports mouse ES cells have been successfully applied in the treatment of spinal cord injury, hereditary myelin disorder of the central nervous system, and diabetes mellitus. Another type of disease that could benefit from the availability of stem cell therapy is liver disease. However, for this potential to be realized, it is necessary to demonstrate the differentiation of ES cells into hepatocytes. To demonstrate the in vivo differentiation potential of mouse ES cells, we injected ES cells into the spleen of immunosuppressed nude mice. Histological analysis of teratomas derived from injected ES cells revealed that some areas contained typical hepatocytes arranged in a sinusoidal structure. The hepatic nature of these cells was further confirmed by showing that transcripts of liver-specific genes were present in the differentiated teratoma using reverse transcriptase-polymerase chain reaction and immunohistochemistry using several liver-specific antibodies including HEP-PAR, phenylalanine hydroxylase, and mouse N-system aminotransferase to identify the respective proteins in the differentiated hepatocytes. This is the first demonstration that mouse ES cells can differentiate in vivo into a mixed population of hepatocytes of varying maturity. This finding extends the potential use of ES cells in the cell replacement therapy by including its possible application for treating liver diseases.

Animals↗