Biomedical subjects

W Tseng

Publications and source records attributed to W Tseng.

12 recordsLinked to original sources

PubMed2004

Trace eyeblink conditioning is hippocampally dependent in mice.

The goal of this study was to determine whether trace eyeblink conditioning is a hippocampally dependent associative learning task in the mouse. First, we examined trace intervals of 0, 250, and 500 ms to determine a relatively long trace interval that would support eyeblink conditioning in young adult C57BL/6 mice. Mice rapidly acquired conditioned responses (CRs) with a 0-ms trace interval, acquired CRs with a 250-ms trace interval in approximately 2 days (2 sessions per day), and showed little acquisition with a 500-ms trace interval. Control mice were presented randomly unpaired stimuli and failed to show conditioning. We then determined the effect of lesioning dorsal hippocampal neurons on trace eyeblink conditioning. The hippocampus was injected bilaterally with vehicle (phosphate-buffered saline), 0.1% ibotenic acid, or 1% ibotenic acid. The vehicle group showed >60% CRs. The 0.1% group showed significantly fewer CRs (35-45%). The 1% group showed a level of CRs similar to that of the control mice. All the lesioned mice exhibited >60% CRs when subsequently trained with a 0-ms trace interval. A regression analysis indicated that the volume of area CA1 lesioned was more predictive of the behavioral impairment than the lesion volume of either CA3 or dentate gyrus, or even the total lesion volume. We conclude that dorsal hippocampal neurons play a critical role in eyeblink conditioning when a 250-ms trace interval is used with the C57BL/6 mouse, and that this paradigm will be useful for studying behavior and the in vivo and in vitro electrophysiology of hippocampal neurons in normal and transgenic or knockout mice.

Animals↗

PubMed2000

Human carbonyl reductase overexpression in the heart advances the development of doxorubicin-induced cardiotoxicity in transgenic mice.

Doxorubicinol (dxol) is the major metabolite formed in the hearts of cancer patients being treated with the widely used chemotherapeutic agent, doxorubicin (dox). The well-documented cardiomyopathy associated with dox treatment has been studied in vitro and ex vivo providing evidence that the C-13 hydroxy metabolite, dxol, might play a key role in the development of dox-induced cardiotoxicity. In this report, we have developed transgenic mice with heart-specific expression of human carbonyl reductase (HCBR), an enzyme that metabolizes dox to dxol. Dox was rapidly converted to dxol in the hearts of the transgenic expressers, which led to advanced development of both acute and chronic cardiotoxicity. Acute cardiotoxicity was evident by a 60% increase in serum creatine kinase activity and a 5-fold increase in cardiac damage measured by electron microscopy. Myofibril degeneration was the major damage observed in acute dox toxicity. Electrocardiograph telemetry, survival data, and electron microscopy were monitored during chronic dox-induced cardiotoxicity. HCBR expressers developed cardiotoxicity 6-7 weeks before the nonexpressers. The HCBR expressers survived for 5 weeks compared with 12 weeks for the controls. Electrocardiograph profiles and necropsies showed the cause of death to be the development of cardiomyopathies leading to congestive heart failure. Levels of dxol were four times higher in the HCBR expresser hearts than in the nonexpressers. Electron microscopy data showed swelling and major structural damage of the mitochondria in the HCBR expressers. These data demonstrate that the C-13 hydroxy metabolite of dox advances the development of dox-induced cardiotoxicity in an in vivo system and suggest that heart carbonyl reductase activity may contribute to dox-induced cardiotoxicity in humans.

Alcohol Oxidoreductases↗

PubMed2000

Neurotoxic lesions of the dorsal hippocampus disrupt auditory-cued trace heart rate (fear) conditioning in rabbits.

The first experiment in this study used the classical heart rate (HR) conditioning paradigm to determine if rabbits could associate an auditory conditioned stimulus (CS) and a fear-producing shock-unconditioned stimulus (US) separated by an empty 10-s trace interval. Trace conditioned rabbits (n = 7) acquired significant bradycardiac conditioned HR responses on CS-alone test trials during a single 35-trial conditioning session. Control animals (n = 7) which received unpaired CSs and USs did not show HR conditioning. During a retention session of CS-alone trials 24 h after the conditioning session, some trace-conditioned animals showed conditioned HR responses immediately following CS onset (n = 3), while others showed responses appropriately timed to the US onset (n = 4) used in trace conditioning 24 h earlier. Thus, rabbits remember the duration of the long 10-s trace interval 24 h after a single day of training. The second part of this study sought to determine if cells in the dorsal hippocampus play a role in trace HR conditioning. Rabbits were given bilateral ibotenic acid lesions in the neocortex (n = 7) or dorsal hippocampus (n = 8). During trace conditioning and retention, neocortical animals showed conditioned HR responses to the CS, whereas the hippocampal group showed no significant HR conditioning. One week after trace conditioning, the same animals received a delay HR conditioning session where no trace interval separated the CS and US. During delay conditioning, hippocampal animals showed significant conditioned HR responses to the CS that were similar to the neocortical group. Thus, the dorsal hippocampus plays a critical role in rabbit HR conditioning when the CS and US are separated by a 10-s trace interval. This paradigm may be ideal for in vivo electrophysiological recording studies because rabbits are easily immobilized during the testing procedure, and learning occurs during a single day of training.

Acoustic Stimulation↗

PubMed2000

Characteristics of a sporulation stimulating factor from Clostridium perfringens type A.

A product in the culture supernatant fluid of Clostridium perfringens NCTC 8239 stimulated the sporulation of a test strain, NCTC 8679, of the same organism. The responsible factor, termed sporulation factor (SF), was present in seven cultures of Cl. perfringens grown in either a defined or complex medium. The SF reversed glucose-mediated catabolite repression of sporulation by this organism. Preliminary characterization of the SF demonstrated a resistance to elevated temperatures and proteases and a molecular weight of less than 500 Da. The known association of Cl. perfringens enterotoxin with sporulation highlights the importance of interactions between strains of this organism as may occur in the human intestine during foodborne illness.

Bacterial Proteins↗

PubMed1999

Airway epithelial tight junctions and binding and cytotoxicity of Pseudomonas aeruginosa.

The role of tight junctions in the binding and cytoxicity of Pseudomonas aeruginosa to apical or basolateral membranes of lung airway epithelial cells was tested with fluorescence microscopy on living cells. Binding of noncytotoxic P. aeruginosa strain O1 was assessed with P. aeruginosa that expressed green fluorescent protein. Binding of cytotoxic P. aeruginosa strain 6206 was assessed with FITC-labeled P. aeruginosa; cytotoxicity was determined from nuclear uptake of the impermeant dye propidium iodide. The role of direct contact of P. aeruginosa to epithelial cells was tested with filters with small (0.45-micrometer) or large (2.0-micrometer) pores. High transepithelial resistance (R(t)) Calu-3 and cultured bovine tracheal monolayers (R(t) > 1,000 Omega. cm(2)) bound P. aeruginosa very infrequently (<1 P. aeruginosa/100 cells) at the apical membrane, but P. aeruginosa bound frequently to cells near "free edges" at holes, wounds, islands, and perimeters; cytotoxicity required direct interaction with basolateral membranes. Wounded high R(t) epithelia showed increased P. aeruginosa binding and cytotoxicity at the free edges because basolateral membranes were accessible to P. aeruginosa, and dead and living cells near the wound bound P. aeruginosa similarly. Compared with high R(t) epithelia, low R(t) CFT1 (R(t) = 100-200 Omega. cm(2)) and EGTA-treated Calu-3 monolayers were 25 times more susceptible to P. aeruginosa binding throughout the monolayer. Cytotoxicity to CFT1 cells (throughout the confluent monolayer, not only at the free edge) occurred after a shorter delay (0.25 vs. 2.0 h) and then five times faster than to Calu-3 cells, indicating that the time course of P. aeruginosa cytotoxicity may be limited by the rate of gaining access through tight junctions and that this occurred faster in low R(t) than in high R(t) airway epithelia. Cytotoxicity appeared to occur in a sequential process that led first to a loss of fura 2 and a later uptake of propidium iodide. P. aeruginosa bound three times more frequently to regions between cells (tight junctions?) than to cell membranes of low R(t) CFT1 cells.

Animals↗

PubMed1998

Hippocampectomy disrupts auditory trace fear conditioning and contextual fear conditioning in the rat.

The hippocampus is believed to be an important structure for learning tasks that require temporal processing of information. The trace classical conditioning paradigm requires temporal processing because the conditioned stimulus (CS) and the unconditioned stimulus (US) are temporally separated by an empty trace interval. The present study sought to determine whether the hippocampus was necessary for rats to perform a classical trace fear conditioning task in which each of 10 trials consisted of an auditory tone CS (1 5-s duration) followed by an empty 30-s trace interval and then a fear-producing floor-shock US (0.5-s duration). Several weeks prior to training, animals were anesthetized and given aspiration lesions of the neocortex (NEO; n = 6), hippocampus and overlying neocortex (HIPP; n = 7), or no lesions at all (control; n = 6). Approximately 24 h after trace conditioning, NEO and control animals showed a significant decrease in movement to a CS-alone presentation that was indicative of a conditioned fear response. Animals in the HIPP group did not show conditioned fear responses to the CS alone, nor did a pseudoconditioning group (n = 7) that was trained with unpaired CSs and USs. Furthermore, all groups except the HIPP group showed conditioned fear responses to the original context in which they received shock USs. One week later, HIPP, NEO, and control animals received delay fear-conditioning trials with no trace interval separating the CS and US. Six of seven HIPP animals could perform the delay version, but none could perform the trace version. This result suggests that the trace fear task is a reliable and useful model for examining the neural mechanisms of hippocampally dependent learning.

Acoustic Stimulation↗

PubMed1991