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Shin Kwak

Publications and source records attributed to Shin Kwak.

24 records · Page 2Linked to original sources
PubMed2003

Human spinal motoneurons express low relative abundance of GluR2 mRNA: an implication for excitotoxicity in ALS.

AMPA receptor-mediated neurotoxicity is currently the most plausible hypothesis for the etiology of amyotrophic lateral sclerosis (ALS). The mechanism initiating this type of neuronal death is believed to be exaggerated Ca2+-influx through AMPA receptors, which is critically determined by the presence or absence of the glutamate receptor subunit 2 (GluR2) in the assembly. We have provided the first quantitative measurements of the expression profile of AMPA receptor subunits mRNAs in human single neurons by means of quantitative RT-PCR with a laser microdissector. Among the AMPA subunits, GluR2 shared the vast majority throughout the neuronal subsets and tissues examined. Furthermore, both the expression level and the proportion of GluR2 mRNA in motoneurons were the lowest among all neuronal subsets examined, whereas those in motoneurons of ALS did not differ from the control group, implying that selective reduction of the GluR2 subunit cannot be a mechanism of AMPA receptor-mediated neurotoxicity in ALS. However, the low relative abundance of GluR2 might provide spinal motoneurons with conditions that are easily affected by changes of AMPA receptor properties including deficient GluR2 mRNA editing in ALS.

Adult↗
PubMed2003

Recent advances in the study of AMPA receptors.

As glutamate is a dominant excitatory neurotransmitter in the central nervous system, glutamate receptors, and especially AMPA receptors, are located ubiquitously in all brain areas. In this paper, we reviewed recent advances of studies on AMPA receptor functions. AMPA receptors are cation-conducting complexes composed of various combinations of four subunits (GluR1 to GluR4). The glutamine residue located in the pore-forming segment of GluR2 subunit (Q/R site) is changed to arginine by RNA editing at the pre mRNA stage in normal adult mammalian animal. The edited GluR2 subunit is a major determination of Ca(2+) permeability of the AMPA receptor; only edited GluR2-lacking receptor shows high-Ca(2+) permeability. The assembly of glutamate AMPA receptor subunit is not completely according to the stochastic theory. The heteromeric subunits assembly is more rapid than the homomeric assembly is. The transfer of AMPA receptor subunit to the plasma membrane is conducted in multiple ways. Many molecules that interact with the intracellular domain of AMPA receptor subunits are reported as the modulators of AMPA receptor subunit transfer. In the motoneuron of sporadic amyotrophic lateral sclerosis (ALS) patients, the efficiency of RNA editing at the GluR2 Q/R site is significantly decreased. Relative low level of edited GluR2 subunit expression is likely responsible for motoneuronal death in ALS. Recently, AMPA receptors in glial cells have been studied. Bergmann glial cells in cerebellum express Ca(2+)-permeable AMPA receptors. Conversion of these AMPA receptors to Ca(2+)-impermeable type receptors induces morphological and functional changes. Glioblastoma cells also express Ca(2+)-permeable AMPA receptors, and their conversion to Ca(2+)-impermeable receptors inhibits cell locomotion and induces apoptosis.

Amyotrophic Lateral Sclerosis↗
PubMed2002

Noise-induced compensation for postural hypotension in primary autonomic failure.

Noise can have a beneficial effect on sensory neurological systems, enhancing detection of small afferent signals and thereby improve efferent neural responses. We hypothesized whether a similar mechanism would facilitate impaired neural transmission associated with neurological disease, and tested whether addition of external noise to baroreceptor signaling could improve blunted autonomic efferent responses to a postural challenge in patients with primary autonomic failure (PAF). Five PAF patients were tested, one in duplicate and another triplicate, for their transient responses of heart rate (measured from electrocardiographic RR intervals; RRIs) and systolic (SBP) and diastolic (DBP) blood pressures to either 30 degrees or 60 degrees head-up tilt, with and without continuous application of beat-to-beat Gaussian white noise to the carotid sinus baroreceptors. Also, the effects of noise were compared with those by a continuous positive pressure applied to the carotid sinus baroreceptors. The data were fit to a first order model to evaluate the speed (by the time constant; tau) and the magnitudes (by the steady state gains; Gs) of RRI and blood pressure responses. The PAF patients exhibited marked drops in SBP and DBP and a blunted increase in heart rate upon transition from a supine to a head-up position. Addition of noise, not the continuous positive pressure, to the arterial baroreceptors significantly (P<0.05) increased the G in RRI and diminished the Gs in SBP and DBP, though the time courses (taus) of both the RRI and blood pressure responses were unaffected. The addition of external noise to baroreceptor signaling ameliorated the marked postural hypotension seen in patients with PAF.

Adaptation, Physiological↗