Moon Young Lee

Effect of MK801 on cFos-like protein expression in the medial vestibular nucleus at early stage of vestibular compensation in uvulonodullectomized rats.

The purpose of this study was to evaluate the effect of uvulonodullectomy (UNL) on the expression of cFos-like protein (FLP) in the medial vestibular nucleus (MVe) during vestibular compensation and effect of MK801, an N-methyl-D-aspartate (NMDA) antagonist, on FLP expression in the brain stem nuclei at 6 h after unilateral labyrinthectomy (ULX) with UNL in Sprague-Dawley rats. Immunohistochemical staining was performed to visualize FLP in the brain stem nuclei and FLP-positive cells were counted by image analyzer. Lesion-induced asymmetric expression of FLP in the bilateral MVe was observed and maintained up to for 72 h in the ULX group, and 120 h in the UNL + ULX group. Moreover, spatial pattern of FLP expression in the bilateral MVe exhibited the marked difference between the ULX and UNL + ULX groups. MK801 treatment 6 h after ULX showed significant increase in the number of FLP in contralateral MVe (cMVe) of the ULX group, but decrease in cMVe of the UNL + ULX group. These results suggest that the lesion of vestibulocerebellum delays the temporal recovery of FLP expression in MVe and the vestibulocerebellar NMDA receptors relate to FLP expression in MVe.

Regulation of contractile activity by magnolol in the rat isolated gastrointestinal tracts.

This study examined the pharmacological property of magnolol, a phenolic compound purified from Magnolia officinalis, on the GI motility using the rat isolated gastrointestinal (GI) strips. Magnolol (0.3-30 microM) dose-dependently stimulated the tone and amplitude of spontaneous contractions in ileum longitudinal muscles. Magnolol at 3 microM significantly increased the contractions of jejunum longitudinal and colon circular muscles, but not the longitudinal muscle contractions in fundus, antrum and colon. Pretreatment of ileum strips with either atropine (0.5 microM) or 4-diphenyllacetoxy-N(2-chloriethyl)-piperidine (4-DAMP, 0.5 microM) dramatically inhibited the acetylcholine (ACh, 0.1 microM)- and magnolol (3 microM)-induced longitudinal muscle contractions, but they were not affected by methoctramine (0.5 microM) and hexamethonium (0.5 microM). Ondansetron (0.1 microM) and GR113808 (2 microM) significantly reduced the tone of ileum longitudinal muscle contractions stimulated by 5-HT (10 microM), but not the amplitude. Magnolol (3 microM)-induced ileum longitudinal muscle contractions, both tone and amplitude, were significantly blocked by GR113808, but not by ondansetron. Taken together, magnolol differently regulates the spontaneous GI motility according to the region of GI tracts and orientation of smooth muscles, and magnolol-induced regulation of smooth muscle contractions in rat GI strips is likely to be mediated, at least in part, by activation of ACh and 5-HT receptors, possibly the M(3) and/or 5-HT(4) receptors.

Role of vestibulocerebellar N-methyl-d-aspartate receptors for behavioral recovery following unilateral labyrinthectomy in rats

The purpose of current study was to elucidate whether vestibulocerebellar N-methyl-D-aspartate (NMDA) receptors are implicated in MK801 induced vestibular decompensation. Sprague-Dawley rats were unilaterally labyrinthectomized (ULX) and some of them were uvulonodullectomized before ULX (UNL + ULX). Number of spontaneous nystagmus (SN) and degree of head deviation (HD) were used as a parameter of behavioral recovery. MK801 treatment 6 h after ULX produced significant increases in SN and decreased HD in ULX rats, indicating decompensation. In marked contrast, however, MK801 treatment resulted in a great reduction of SN and HD in UNL + ULX rats; suggesting involvement of vestibulocerebellar NMDA receptors in MK801 induced decompensation during early stage of vestibular compensation.

The effect of chronic variable stress on bowel habit and adrenal function in rats

Background and Aim:  Increased colonic motility is a well‐known stress response and corticotropin releasing hormone plays an important role in this response, but sequential change of bowel habit and adrenal function during chronic stress has not been reported. The objective of this study was to evaluate the effect of chronic stress on bowel habit and adrenal function.

Fat deposition in the tunica muscularis and decrease of interstitial cells of Cajal and nNOS-positive neuronal cells in the aged rat colon

Little is known about the time course of aging on interstitial cells of Cajal (ICC) of colon. The aim of this study was to investigate the change of morphology, ICC, and neuronal nitric oxide synthase (nNOS)-immunoreactive cells in the aged rat. The proximal colon of 344 Fischer rats at four different ages (6, 31, 74 wk, and 2 yr) were studied. The immunoreactivity of c-Kit, nNOS, anti-protein gene product 9.5, and synaptophysin were counted after immunohistochemistry. The c-kit, stem cell factor (ligand of Kit), and nNOS mRNA were measured by real-time PCR. c-Kit and nNOS protein were assessed by Western blot. Isovolumetric contractile force measurement and electrical field stimulation (EFS) were conducted. The area of intramuscular fat deposition significantly increased with age after 31 wk. c-Kit-immunoreactive ICC and nNOS-immunoreactive neurons and nerve fibers significantly declined with age. mRNA and protein expression of c-kit and nNOS decreased with aging. The functional study showed that the spontaneous contractility was decreased in aged rat, whereas EFS responses in the presence of atropine and L-NG-Nitroarginine methyl ester were increased in aged rat. In conclusion, the decrease of proportion of proper smooth muscle, the density of ICC and nNOS-immunoreactive neuronal fibers, and the number of nNOS-immunoreactive neurons during the aging process may explain the aging-associated colonic dysmotility.

Chronic Administration of Monosodium Glutamate under Chronic Variable Stress Impaired Hypothalamic-Pituitary-Adrenal Axis Function in Rats

The hypothalamic-pituitary-adrenal (HPA) axis is the primary endocrine system to respond to stress. The HPA axis may be affected by increased level of corticotrophin-releasing factors under chronic stress and by chronic administration of monosodium glutamate (MSG). The purpose of this study was to investigate whether chronic MSG administration aggravates chronic variable stress (CVS)-induced behavioral and hormonal changes. Twenty-four adult male Sprague-Dawley rats, weighing 200~220 g, were divided into 4 groups as follows: water administration (CON), MSG (3 g/kg) administration (MSG), CVS, and CVS with MSG (3 g/kg) administration (CVS+MSG). In addition, for the purpose of comparing the effect on plasma corticosterone levels between chronic stress and daily care or acute stress, 2 groups were added at the end of the experiment; the 2 new groups were as follows: naïve mice (n=7) and mice exposed to restraint stress for 2 h just before decapitation (A-Str, n=7). In an open field test performed after the experiment, the CVS+MSG group significant decrease in activity. The increase in relative adrenal weights in the CVS and CVS+MSG group was significantly greater than those in the CON and/or MSG groups. In spite of the increase in the relative adrenal weight, there was a significant decrease in the plasma corticosterone levels in the CVS+MSG group as compared to all other groups, except the naïve group. These results suggest that impaired HPA axis function as well as the decrease in the behavioral activity in adult rats can be induced by chronic MSG administration under CVS rather than CVS alone.

Effects of galvanic stimulation of the mastoid process on the gastric motility induced by caloric stimulation

The effects of galvanic stimulation to the mastoid portion on the vestibuloautonomic symptoms induced by caloric stimulation, such as nausea, vomiting, and vertigo, were evaluated in this study. Gastric motility was measured by electrogastrography (EGG) in 20 healthy volunteers (11 male and nine female) aged 20-30 (average: 25.4) years. Electrical stimulation of the mastoid process with 1.0-3.0 mA, 1.0 ms, 100 Hz was applied using a bipolar-biaural method during caloric stimulation of the external auditory canal. The dominant frequency and power of EGG were determined using running spectral frequency analysis and the time-course of EGG was evaluated in a pseudo three dimensional graphic. Frequency of EGG was classified into normogastria with 3 cpm, bradygastria with lower than 3 cpm, and tachygastria with higher than 3 cpm. At quiescent period, normogastria was 78.7 +/- 3.7%, bradygastria 5.0 +/- 1.1%, and tachygastria 16.4 +/- 3.7%. Caloric stimulation with warm water in the unilateral ear and cold water in the contralateral ear elicited vestibuloautonomic symptoms, with accompanied decreases in normogastria (57.7 +/-4.6%, P < 0.01) and increases in tachygastria (34.8 +/- 4.8%, P < 0.01). Cathodal stimulation to the mastoid process ipsilateral to cold water irrigation during caloric stimulation restored normal pattern of gastric motility: normogastria in 77.1 + 5.3% and tachygastria in 19.3 +/- 4.7%, and relieved vestibuloautonomic symptoms. Cathodal stimulation to the inhibited vestibular system ameliorates the vestibular symptoms induced by caloric stimulation.

Transcriptome of interstitial cells of Cajal reveals unique and selective gene signatures

Transcriptome-scale data can reveal essential clues into understanding the underlying molecular mechanisms behind specific cellular functions and biological processes. Transcriptomics is a continually growing field of research utilized in biomarker discovery. The transcriptomic profile of interstitial cells of Cajal (ICC), which serve as slow-wave electrical pacemakers for gastrointestinal (GI) smooth muscle, has yet to be uncovered. Using copGFP-labeled ICC mice and flow cytometry, we isolated ICC populations from the murine small intestine and colon and obtained their transcriptomes. In analyzing the transcriptome, we identified a unique set of ICC-restricted markers including transcription factors, epigenetic enzymes/regulators, growth factors, receptors, protein kinases/phosphatases, and ion channels/transporters. This analysis provides new and unique insights into the cellular and biological functions of ICC in GI physiology. Additionally, we constructed an interactive ICC genome browser (http://med.unr.edu/physio/transcriptome) based on the UCSC genome database. To our knowledge, this is the first online resource that provides a comprehensive library of all known genetic transcripts expressed in primary ICC. Our genome browser offers a new perspective into the alternative expression of genes in ICC and provides a valuable reference for future functional studies.

Asymmetric activation of extracellular signal-regulated kinase 1/2 in rat vestibular nuclei by unilateral labyrinthectomy.

The expression of phosphorylated extracellular signal-regulated kinase 1/2 (pERK 1/2) was evaluated in the vestibular nuclei (VN) of rats following unilateral labyrinthectomy (UL). Immunohistochemistry revealed a significant asymmetrical increase in pERK 1/2 expression in the VN, 5 min after UL, after which pERK 1/2 immunoreactivity decreased rapidly and was undetectable by 90 min after UL. These results suggest that unilateral deafferentation of the vestibular system triggers intracellular signal pathways that activate ERK 1/2 in the VN.

Radiolabeled Chitosan Hydrogel Containing VEGF Enhances Angiogenesis in a Rodent Model of Acute Myocardial Infarction

Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis in an infarcted myocardium. The purpose of the current investigation was to validate whether a radiolabeled VEGF delivery system can be effectively monitored in vivo, and to ascertain whether the growth factor induces an angiogenic effect to facilitate recovery from infarct conditions in rodent myocardial infarction (MI) models. Rat MI models were divided into three groups, one with left anterior descending coronary artery (LAD) ligation with no injection (the control group), one with LAD ligation and I-131 VEGF injection (the VEGF group), and one with LAD ligation and I-131 VEGF-loaded chitosan injection (the VIC group). On day 7 after injection, autoradiography imaging was performed, followed by semiquantitative and histopathologic analyses. In semi-quantitative analysis, the mean anterior-to-inferior wall ratio of the VIC group was significantly higher than those of the control and VEGF groups (p<0.05). Histopathologic experiments revealed a marked increase in microvascular density in the VIC group compared to those of the control and VEGF groups (p<0.05). Intramyocardially injected VIC was not only effectively monitored in vivo, but also stimulated therapeutic angiogenesis in the infarcted myocardium. Our findings support that the developed VIC is a novel theranostic tool to improve myocardial perfusion following myocardial infarction.