Sulprostone-Induced Gastric Dysrhythmia in the Ferret: Conventional and Advanced Analytical Approaches.

Nausea and emesis resulting from disease or drug treatment may be associated with disrupted gastric myoelectric activity (GMA). Conventional analytical techniques can determine the relative degrees of brady-, normo-, and tachygastric power, but lose information relative to the basic slow wave shape. The aim of the present study was to investigate the application of advanced analytical techniques in the analysis of disrupted GMA recorded after administration of sulprostone, a prostaglandin E3 / 1 agonist, in ferrets. Ferrets were implanted with radiotelemetry devices to record GMA, blood pressure, heart rate (HR) and core body temperature 1 week before the administration of sulprostone (30 µg/kg) or vehicle (saline, 0.5 mL/kg). GMA was initially analyzed using fast Fourier transformations (FFTs) and a conventional power partitioning. Detrended fluctuation analysis (DFA) was also applied to the GMA recordings to reveal information relative to the fluctuation of signals around local trends. Sample entropy (SampEn) analysis was used for examining the regularity of signals. Conventional signal processing techniques revealed that sulprostone increased the dominant frequency (DF) of slow waves, with an increase in the percentage power of the tachygastric range and a decrease in the percentage power of the normogastric range. DFA revealed that sulprostone decreased the fluctuation function, indicative of a loss of the variability of GMA fluctuations around local trends. Sulprostone increased SampEn values, indicating a loss of regularity in the GMA data. Behaviorally, sulprostone induced emesis and caused defecation. It also increased blood pressure and elevated HR, with an associated decrease in HR variability (HRV). Further analysis of HRV revealed a decrease in both low-frequency (LF) and high-frequency (HF) components, with an overall increase in the LF/HF ratio. Sulprostone did not affect core body temperature. In conclusion, DFA and SampEn permit a detailed analysis of GMA, which is necessary to understand the action of sulprostone to modulate gastric function. The action to decrease HRV and increase the LF/HF ratio may be consistent with a shift toward sympathetic nervous system dominance, commonly seen during nausea.

Transplantation of Retinal Ganglion Cells Derived from Male Germline Stem Cell as a Potential Treatment to Glaucoma.

Glaucoma is characterized by retinal ganglion cell (RGC) degeneration and is the second leading cause of blindness worldwide. However, current treatments such as eye drop or surgery have limitations and do not target the loss of RGC. Regenerative therapy using embryonic stem cells (ESCs) holds a promising option, but ethical concern hinders clinical applications on human subjects. In this study, we employed spermatogonial stem cells (SSCs) as an alternative source of ESCs for cell-based regenerative therapy in mouse glaucoma model. We generated functional RGCs from SSCs with a two-step protocol without applying viral transfection or chemical induction. SSCs were first dedifferentiated to embryonic stem-like cells (SSC-ESCs) that resemble ESCs in morphology, gene expression signatures, and stem cell properties. The SSC-ESCs then differentiated toward retinal lineages. We showed SSC-ESC-derived retinal cells expressed RGC-specific marker Brn3b and functioned as bona fide RGCs. To allow in vivo RGC tracing, Brn3b-EGFP reporter SSC-ESCs were generated and the derived RGCs were subsequently transplanted into the retina of glaucoma mouse models by intravitreal injection. We demonstrated that the transplanted RGCs could survive in host retina for at least 10 days after transplantation. SSC-ESC-derived RGCs can thus potentially be a novel alternative to replace the damaged RGCs in glaucomatous retina.

Establishment of a radiotelemetric recording technique in mice to investigate gastric slow waves: Modulatory role of putative neurotransmitter systems.

NEW FINDINGS: What is the central question of this study? Gastric slow waves originating from the interstitial cells of Cajal-smooth muscle syncytium are usually studied in culture or in tissue segments, but nobody has described recordings of slow waves from awake, freely moving mice. Can radiotelemetry be used to record slow waves, and do they respond predictably to drug treatment? What is the main finding and its importance? Radiotelemetry can be used to record slow waves from awake, freely moving mice, permitting an examination of drug actions in vivo, which is crucial to drug discovery projects for characterizing the effects of drugs and metabolites on gastrointestinal function. ABSTRACT: The mouse is the most commonly used species in preclinical research, and isolated tissues are used to study slow waves from the interstitial cells of Cajal-smooth muscle syncytium of the gastrointestinal tract. The aim of this study was to establish a radiotelemetric technique in awake mice to record gastric myoelectric activity from the antrum to gain insight into the effects of endogenous modulatory systems on slow waves. Under general anaesthesia, two biopotential wires from a telemetry transmitter were sutured into the antrum of male ICR (imprinting control region) mice. The animals were allowed 1 week to recover from surgery before the i.p. administration of drugs to stimulate or inhibit slow waves. The basal dominant frequency of slow waves was 6.96 ± 0.43 c.p.m., and the percentages of power in the bradygastric, normogastric and tachygastric ranges were 6.89 ± 0.98, 37.32 ± 1.72 and 34.38 ± 0.77%, respectively (n = 74). Nicotine at 1 mg kg-1 increased normogastric power, but at 3 mg kg-1 it increased bradygastric power (P < 0.05). Metoclopramide at 10 mg kg-1 increased normogastric power; sodium nitroprusside at 10 mg kg-1 had latent effects on tachygastric power (P < 0.05); and l-NAME at 10 mg kg-1 had no effect (P > 0.05). Nicotine and bethanechol also caused varying degrees of hypothermia (>1°C reductions; P < 0.05). In conclusion, radiotelemetry can be used to record slow waves from awake, freely moving mice. In light of our findings, we recommend that studies assessing slow waves should also assess body temperature simultaneously.