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Ching-Yi Lin

Publications and source records attributed to Ching-Yi Lin.

16 recordsLinked to original sources
PubMed2006

Restoration of long-term potentiation in middle-aged hippocampus after induction of brain-derived neurotrophic factor.

Restoration of neuronal viability and synaptic plasticity through increased trophic support is widely regarded as a potential therapy for the cognitive declines that characterize aging. Previous studies have shown that in the hippocampal CA1 basal dendritic field deficits in the stabilization of long-term potentiation (LTP) are evident by middle age. The present study tested whether increasing endogenous brain-derived neurotrophic factor (BDNF) could reverse this age-related change. We report here that in middle-aged (8- to 10-mo-old) rats, in vivo treatments with a positive AMPA-type glutamate receptor modulator both increase BDNF protein levels in the cortical telencephalon and restore stabilization of basal dendritic LTP as assessed in acute hippocampal slices 18 h after the last drug treatment. These effects were not attributed to enhanced synaptic transmission or to facilitation of burst responses used to induce LTP. Increasing extracellular levels of BDNF by exogenous application to slices of middle-aged rats was also sufficient to rescue the stabilization of basal dendritic LTP. Finally, otherwise stable LTP in ampakine-treated middle-aged rats can be eliminated by infusion of the extracellular BDNF scavenger TrkB-Fc. Together these results indicate that increases in endogenous BDNF signaling can offset deficits in the postinduction processes that stabilize LTP.

Aging↗
PubMed2006

Re-growth of catecholaminergic fibers and protection of cholinergic spinal cord neurons in spinal repaired rats.

The extent of re-growth of catecholaminergic fibers, the survival of cholinergic neurons and the degree of autonomic dysreflexia were assessed in complete spinal cord-transected adult rats that received a repair treatment of peripheral nerve grafts and acidic fibroblast growth factor (aFGF). The rats were randomly divided into three groups: (1) sham control group (laminectomy only); (2) spinal cord transection at T8 (transected group); and (3) spinal cord transection at T8, followed by aFGF treatment and peripheral nerve graft (repaired group). The spinal cords and brains of all rats were collected at 6 months post-surgery. Immunohistochemistry for tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH), and fluoro-gold (FG) retrograde tracing were used to evaluate axon growth across the damage site, and immunocytochemistry for choline acetyl transferase (ChAT) was used to evaluate cholinergic neuronal cell survival following the injury and treatment. When comparing with the transected group, the repaired group showed: (1) lower elevation of mean arterial pressure during colorectal distension; (2) retrogradely labeled neurons in the hypothalamus, zona incerta, subcoeruleus nuclei and rostral ventrolateral medulla following application of FG below the repair site; (3) the presence of TH- and DBH-labeled axons below the lesion site; (4) higher numbers of ChAT-positive neurons in ventral horn and intermediolateral column near the lesion site. We conclude that peripheral nerve graft and aFGF treatments facilitate the re-growth of catecholaminergic fibers, also protect sympathetic preganglionic neurons and spinal motor neurons, and reduce autonomic dysfunction in a T-8 spinal cord-transected rat model.

Acetylcholine↗
PubMed2005

Effects of fermented soy milk on the liver lipids under oxidative stress.

AIM: To investigate the effects of fermented soy milk powder on the antioxidative status and lipid metabolism in the livers of CCl4-injected rats. METHODS: Forty-five healthy male Sprague-Dawley rats were randomly assigned to five groups according to five different diets: control (AIN-76), AIN-76+high-dose fermented soy milk powder, AIN-76+low-dose fermented soy milk powder, AIN-76+high-dose milk yogurt powder and AIN-76+low-dose milk yogurt powder. The experiment lasted for 8 wk. After 4 wk, all the rats received intraperitoneal administration of CCl(4)(0.2 mL/100 g body weight) every week. Total cholesterol (TC), triglyceride (TG), TBARS, ALP, and antioxidative enzymes in the liver were evaluated. RESULTS: There was also no significant difference in TBARS and antioxidative enzymes in the liver. TC and TG in the groups fed with fermented soy milk powder were generally lower than those fed with casein powder. CONCLUSION: Consumption of fermented soy milk was positive in lowering total cholesterol and TG accumulation in the liver under CCl(4)-induced oxidative stress.

Alkaline Phosphatase↗
PubMed2005

Effects of soy components on blood and liver lipids in rats fed high-cholesterol diets.

AIM: To assess the effects of soy protein, isoflavone, and saponin on liver and blood lipid in rats that consumed high-cholesterol diets. METHODS: High-cholesterol diets (1%) with or without soy material were fed to 6-wk-old male Sprague-Dawley rats for 8 wk. Blood lipids, liver lipids, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) levels were measured. The in vitro bile acid-binding ability of soy materials was analyzed. RESULTS: The results of in vitro studies showed that soy protein isolate had a significantly higher bile acid-binding ability (8.4+/-0.8%) than soy saponin (3.1+/-0.7%) and isoflavone (1.3+/-0.4%, P<0.05). On the other hand, at the end of the experimental period, rats that consumed soy protein diets had lower GOT and GPT levels than rats that consumed casein under high-cholesterol diets. Rats that consumed soy protein also had lower total cholesterol (TC) levels in the liver than those that consumed casein under high-cholesterol diets. Rats that consumed the soy protein diet containing both saponin and isoflavone had lower hepatic TC level than those that consumed the soy protein diet without isoflavone alone. The effect of different types of proteins on triglyceride was not significant. CONCLUSION: Consumption of soy provided benefits to control lipid levels under high-cholesterol dieting conditions in this rat model of hypercholesterolemia. The major component that reduced hepatic TC was not saponin, but possibly isoflavone.

Animals↗
PubMed2005

A comparison of maternal age, sex ratio and associated major anomalies among fetal trisomy 18 cases with different cell division of error.

OBJECTIVES: To compare the maternal age, sex ratio, and associated major anomalies among fetal trisomy 18 cases with different cell division of error. METHODS: Thirty-one consecutive cases of fetal trisomy 18 detected perinatally during a period of 6 years were studied. Among these, 18 were 47,XY,+18, and 13 were 47,XX,+18. The average gestational age at diagnosis was 19.7 +/- 4.6 weeks, and the maternal age at diagnosis was 34.5 +/- 5.8 years. DNA polymorphism analysis was applied to determine the parental origin, stage of non-disjunctional error and recombination. RESULTS: Twenty-eight cases were of maternal origin. Among these, 20 had major anomalies, 17 had meiosis II (MII) errors, 10 had meiosis I (MI) errors, and one had a postzygotic mitotic (PZM) or non-crossover MII error. Three cases were of paternal origin. Among these, two had major anomalies, two had MI errors, and one had a PZM or non-crossover MII error. For the 17 cases with maternal MII errors, the average maternal age was 34.5 +/- 6.6 years. Of these cases, 12 had major anomalies, 13 were male, and 4 were female, giving a male:female sex ratio of 3.25:1. For the 10 cases with maternal MI errors, the average maternal age was 34.8 +/- 5.7 years. Of these cases, seven had major anomalies, three were male, and seven were female, giving a male:female sex ratio of 0.429:1. CONCLUSION: In trisomy 18, there is a male preponderance in the fetuses caused by maternal MII errors and a female preponderance in the fetuses caused by maternal MI errors. No significant difference was noted in maternal age or in associated major anomalies between the two groups of maternal MII errors and maternal MI errors. No significant difference was noted in associated major anomalies between the maternal and paternal cases.

Adult↗
PubMed2005

Integrin signaling cascades are operational in adult hippocampal synapses and modulate NMDA receptor physiology.

Integrin class adhesion proteins are concentrated at adult brain synapses. Whether synaptic integrins engage kinase signaling cascades has not been determined, but is a question of importance to ideas about integrin involvement in functional synaptic plasticity. Accordingly, synaptoneurosomes from adult rat brain were used to test if matrix ligands activate integrin-associated tyrosine kinases, and if integrin signaling targets include NMDA-class glutamate neurotransmitter receptors. The integrin ligand peptide Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) induced rapid (within 5 min) and robust increases in tyrosine phosphorylation of focal adhesion kinase, proline-rich tyrosine kinase 2 and Src family kinases. Increases were similarly induced by the native ligand fibronectin, blocked with neutralizing antibodies to beta1 integrin, and not obtained with control peptides, indicating that kinase activation was integrin-mediated. Both GRGDSP and fibronectin caused rapid Src kinase-dependent increases in tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B in synaptoneurosomes and acute hippocampal slices. Tests of the physiological significance of the latter result showed that ligand treatment caused a rapid and beta1 integrin-dependent increase in NMDA receptor-mediated synaptic responses. These results provide the first evidence that, in adult brain, synaptic integrins activate local kinase cascades with potent effects on the operation of nearby neurotransmitter receptors implicated in synaptic plasticity.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2005

AMPA receptor stimulation increases alpha5beta1 integrin surface expression, adhesive function and signaling.

Integrin proteins are critical for stabilization of hippocampal long-term potentiation but the mechanisms by which integrin activities are involved in synaptic transmission are not known. The present study tested whether activation of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate (AMPA) class glutamate receptors increases surface expression of alpha5beta1 integrin implicated in synaptic potentiation. Surface protein biotinylation assays demonstrated that AMPA treatment of COS7 cells expressing GluR1 homomeric AMPA receptors increased membrane insertion and steady-state surface levels of alpha5 and beta1 subunits. Treated cells exhibited increased adhesion to fibronectin- and anti-alpha5-coated substrates and tyrosine kinase signaling elicited by fibronectin-substrate adhesion, as expected if new surface receptors are functional. Increased surface expression did not occur in calcium-free medium and was blocked by the protein kinase C inhibitor chelerythrine chloride and the exocytosis inhibitor brefeldin A. AMPA treatment similarly increased alpha5 and beta1 surface expression in dissociated neurons and cultured hippocampal slices. In both neuronal preparations AMPA-induced integrin trafficking was blocked by combined antagonism of NMDA receptor and L-type voltage-sensitive calcium channel activities but was not induced by NMDA treatment alone. These results provide the first evidence that glutamate receptor activation increases integrin surface expression and function, and suggest a novel mechanism by which synaptic activity can engage a volley of new integrin signaling in coordination with, and probably involved in, stabilization of synaptic potentiation.

Alkaloids↗
PubMed2004

A novel mechanism for the facilitation of theta-induced long-term potentiation by brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF) contributes to the induction of long-term potentiation (LTP) by theta-pattern stimulation, but the specific processes underlying this effect are not known. Experiments described here, using BDNF concentrations that have minor effects on baseline responses, show that the neurotrophin both reduces the threshold for LTP induction and elevates the ceiling on maximal potentiation. The enhanced LTP proved to be as stable and resistant to reversal as that recorded under control conditions. BDNF markedly increased the facilitation of burst responses that occurs within a theta train. This suggests that the neurotrophin acts on long-lasting events that (1) are set in motion by the first burst in a train and (2) regulate the amplitude of subsequent bursts. Whole-cell recordings established that BDNF causes a rapid reduction in the size of the long-lasting afterhyperpolarization (AHP) that follows individual theta bursts. Apamin, an antagonist of type 2 small-conductance Ca2+-activated potassium (SK2) channels, also reduced hippocampal AHPs and closely reproduced the effects of BDNF on theta-burst responses and LTP. The latter results were replicated with a newly introduced, highly selective inhibitor of SK2 channels. Immunoblot analyses indicated that BDNF increases SK2 serine phosphorylation in hippocampal slices. These findings point to the conclusion that BDNF-driven protein kinase cascades serve to depress the SK2 component, and possibly other constituents, of the AHP. It is likely that this mechanism, acting with other factors, promotes the formation and increases the magnitude of LTP.

Animals↗
PubMed2004

Effects of nerve graft on nitric oxide synthase, NAD(P)H oxidase, and antioxidant enzymes in chronic spinal cord injury.

Oxidative stress and nitrosative stress play important roles in the pathogenesis of secondary spinal cord injury. Recently, we demonstrated that peripheral nerve grafts (PNG) with acidic fibroblast growth factor (aFGF) partially restore hind limb locomotion in adult rats with completely transected spinal cords. This study investigated the protein abundances of the superoxide (O2*)-generating enzyme nicotinamide adenine dinucleotide (phosphate) oxidase (NAD(P)H oxidase; gp91phox subunit), nitric oxide synthases (NOS), antioxidant enzymes, superoxide dismutases (Cu Zn SOD, Mn SOD), catalase, and glutathione peroxidase (GPX) as well as nitrotyrosine in the spinal cord tissue 4 months after spinal cord transection in rats with and without PNG and aFGF. The protein abundances of the gp91phox subunit of NAD(P)H oxidase, Mn SOD, catalase, GPX, eNOS, and nitrotyrosine were significantly upregulated, whereas Cu Zn SOD and nNOS were unchanged in the injury group compared to the sham controls. The nerve graft with aFGF treated group showed significantly better hind limb locomotion recovery than the injury group. Although the protein abundances of gp91phox, nitrotyrosine, and Cu Zn SOD were similar in the treated group (nerve graft with aFGF) compared to the injury group, Mn SOD, GPX, catalase, and eNOS protein abundances were significantly higher, whereas nNOS was markedly lower in the treated group. We conclude that the combination of nerve graft and aFGF enhances the local antioxidant defense system after spinal cord transection in rats.

Animals↗
PubMed2004

NAD(P)H oxidase, superoxide dismutase, catalase, glutathione peroxidase and nitric oxide synthase expression in subacute spinal cord injury.

Primary trauma to the spinal cord triggers a cascade of cellular and molecular events that promote continued tissue damage and expansion of the lesion for extended periods following the initial injury. Oxidative and nitrosative stresses play an important role in progression of spinal cord injury (SCI). In an attempt to explore the biochemical origin of oxidative/nitrosative stress associated with secondary SCI, we studied expression of the superoxide (O2*-)-generating enzyme, NAD(P)H oxidase, antioxidant enzymes [superoxide dismutase (CuZn SOD, Mn SOD), catalase, glutathione peroxidase (GPX)], nitric oxide synthases (NOS) and a byproduct of NO-O2*- interaction (nitrotyrosine) in the spinal cord tissues of rats 16 h and 14 days after surgical resections of a 5-mm segment of the cord below T8 or sham-operation. Immunodetectable NAD(P)H oxidase subunits (gp91phox and P67phox), Mn SOD, inducible NOS (iNOS), endothelial NOS (eNOS), and nitrotyrosine were elevated in the transected cords on day 1 and day 14. Neuronal NOS (nNOS) was unchanged on day 1 and significantly depressed on day 14. GPX was unchanged on day 1 and significantly elevated on day 14. Catalase was unchanged in the cord tissue surrounding the transection site at both points. Thus, concurrent upregulations of NAD(P)H oxidase, eNOS and iNOS (but not nNOS), work in concert to maintain oxidative and nitrosative stress in the injured cord tissue.

Acute Disease↗
PubMed2004

Comparisons of urodynamic characteristics between female patients with overactive bladder and overactive bladder plus stress urinary incontinence.

OBJECTIVES: To determine and compare the urodynamic characteristics in patients with overactive bladder (OAB) and patients with OAB plus stress urinary incontinence (OAB+SUI). METHODS: A total of 120 patients (60 each in OAB and OAB+SUI groups) who underwent urodynamic study between January and April 2003 were recruited. A detailed history, physical examination, and multichannel urodynamic data, including uroflowmetry, filling and voiding cystometry, stress urethral pressure profile, and 20-minute pad test were obtained for each patient. The urodynamic findings of each patient were analyzed and the results compared between the two groups. RESULTS: The median age of both groups was 51 years (interquartile range 43 to 64) with a parity of 3 (interquartile range 2 to 4); 54% (n = 65) were menopausal. The urodynamic parameters of bladder storage function showed premature filling sensation with decreased bladder capacity. Additionally, 60 (50%) had genuine stress incontinence, 3 (3%) had idiopathic detrusor overactivity, 11 (9%) mixed type incontinence, and 12 (11%) had voiding dysfunction. Among the urodynamic parameters between the two groups, first desire, strong desire, urgency, functional urethral length, maximal urethral pressure, maximal urethral closure pressure, pad test, and percentage of genuine stress incontinence in the OAB+SUI group were significantly lower statistically than those in the OAB group (P <0.03); the differences in age, parity, and percentage of menopausal status were also statistically significant (P <0.03). CONCLUSIONS: Our data showed that patients in the OAB+SUI group had more impaired urodynamic parameters than those in the OAB group. Age, parity, and menopausal status were contributory factors.

Adult↗
PubMed2004

Motor recovery and anatomical evidence of axonal regrowth in spinal cord-repaired adult rats.

Behavioral assessments of hindlimb motor recovery and anatomical assessments of extended axons of long spinal tracts were conducted in adult rats following complete spinal cord transection. Rats were randomly divided into 3 groups: 1) sham control group (laminectomy only; n = 12); 2) transection-only group, spinal cord transection at T8 (n = 20); and 3) experimental treatment group, spinal cord transection at T8, with peripheral nerve grafts (PNG) and application of acidic fibroblast growth factor (aFGF) (n = 14). The locomotor behavior and stepping of all rats were analyzed over a 6-month survival time using the Basso, Beattie, Bresnahan (BBB) open field locomotor test and the contact placing test. Immunohistochemistry for serotonin (5-HT), anterograde tracing with biotinylated dextran amine (BDA), and retrograde tracing with fluoro-gold were used to evaluate the presence of axons below the damage site following treatment. When compared with the transection-only group, the nerve graft with the aFGF group showed 1) significant improvement in hindlimb locomotion and stepping, 2) the presence of 5-HT-labeled axons below the lesion site at lumbar cord level (these were interpreted as regenerated axons from the raphe nuclei), 3) the presence of anterograde BDA labeling of corticospinal tract axons at the graft site and below, and 4) fluoro-gold retrograde labeling of neuron populations in motor cortex and in red nucleus, reticulospinal nuclei, raphe nuclei, and vestibular nuclei. We conclude that peripheral nerve grafts and aFGF treatments facilitate the regrowth of the spinal axons and improve hindlimb function in a T-8 spinal cord-transected rat model.

Animals↗
PubMed2003

Superoxide dismutase, catalase, glutathione peroxidase and NADPH oxidase in lead-induced hypertension.

BACKGROUND: Earlier studies from this laboratory have revealed the presence of oxidative stress and its role in the pathogenesis of lead-induced hypertension (HTN). We have further shown evidence of increased hydroxyl radical (.OH) and superoxide production in lead-treated rats and cultured endothelial cells. This study was designed to determine whether oxidative stress in animals with lead-induced HTN is associated with dysregulation of the main antioxidant enzymes namely superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) or increased superoxide producing enzyme nicotinamide adenine dinucleotide (phosphate) oxidase [NAD(P)H]. METHODS: Male Sprague-Dawley rats were randomly assigned to lead-exposed and control groups. Animals in the lead-exposed group were provided with drinking water containing 100 ppm lead acetate for 12 weeks. The control group was provided with regular drinking water. At the conclusion of the experiment, immunodetectable Cu Zn SOD, Mn SOD, CAT, GPX and gp91 phox subunit of NAD(P)H oxidase were determined by Western analysis in the kidney, brain and left ventricle of control and lead-exposed rats. Subgroups of the study animals were treated with IV infusion (180 micromol/kg/h) of the superoxide trapping agent, tempol, and arterial pressure and urinary nitric oxide (NO) metabolite (NOx) excretion were determined. RESULTS: Lead exposure for 12 weeks resulted in a marked rise in systolic blood pressure, a significant reduction in urinary NOx excretion, a significant increase in kidney and brain Cu, Zn SOD, a significant increase in brain and insignificant increase in kidney and heart gp91 phox. In contrast, Mn SOD, CAT and GPX in the kidney, brain and left ventricle were unchanged. Incubation with lead acetate did not alter SOD activity in vitro. Infusion of tempol significantly lowered arterial pressure and raised urinary NOx excretion in the lead-exposed group (but had no effect in the control group) pointing to increased superoxide production in the lead-exposed animals. CONCLUSION: Animals with lead-induced hypertension exhibited oxidative stress which was associated with mild up-regulation of superoxide-generating enzyme, NAD(P)H oxidase, with no evidence of quantitative SOD, CAT or GPX deficiencies.

Animals↗
PubMed2002

A developmentally regulated ARF-like 5 protein (ARL5), localized to nuclei and nucleoli, interacts with heterochromatin protein 1.

ARF-like proteins (ARLs) are distinct group of members of the ARF family of Ras-related GTPases. Although ARLs are very similar in primary structure to ARFs, their functions remain unclear. We cloned mouse (m) and human (h) ARL5 cDNAs to characterize the protein products and their molecular properties. mARL5 mRNA was more abundant in liver than in other adult tissues tested. mARL5, similar to mARL4, was developmentally regulated and localized to nuclei. hARL5 interacted with importin-alpha through its C-terminal bipartite nuclear localization signal. When expressed in COS-7 cells, mutant hARL5(T35N), which is predicted to be GDP bound, was concentrated in nucleoli. The N-terminus of hARL5, like that of ARF, was myristoylated. Yeast two-hybrid screening and in vitro protein-interaction assays showed that hARL5(Q80L), predicted to be GTP bound, interacted with heterochromatin protein 1alpha (HP1alpha), which is known to be associated with telomeres as well as with heterochromatin, and acted as a transcriptional suppressor in mammalian cells. The interaction was reproduced in COS cells, where hARL5(Q80L) was co-immunoprecipitated with HP1alpha. hARL5 interaction with HP1alpha was dependent on the nucleotide bound, and required the MIR-like motif. Moreover, hARL5(Q80L), but not hARL5 lacking the MIR-like motif, was partly co-localized with overexpressed HP1alpha. Our findings suggest that developmentally regulated ARL5, with its distinctive nuclear/nucleolar localization and interaction with HP1alpha, may play a role(s) in nuclear dynamics and/or signaling cascades during embryonic development.

ADP-Ribosylation Factors↗