Higher exploratory and vigilant behaviors related to higher central dopaminergic activities of Formosan wood mice (Apodemus semotus) in light-dark exploration tests.

Formosan wood mice (Apodemus semotus) are endemic rodents in Taiwan. Recently Formosan wood mice exhibit similar locomotor behaviors in the laboratory environment as in the field environment has shown. Contemporaneously, Formosan wood mice have higher moving distances of and central dopaminergic (DAergic) activities than C57BL/6 mice in behavioral test. This study tried to compare the behavioral responses between male Formosan wood mice and male C57BL/6 mice in the light-dark exploration tests. We also measured the levels of DA and 3,4-dihydroxyphenylacetic acid (DOPAC), the primary metabolite of DA, to assess the dopaminergic activity of the medial prefrontal cortex, striatum, and nucleus accumbens. Our data show that Formosan wood mice revealed higher exploration and central DAergic activities than did C57BL/6 mice in the light-dark exploration tests, and diazepam (an anxiolytics) treatment reduced the exploratory activity and central dopaminergic activities in Formosan wood mice, but not in C57BL/6 mice. After repeated exposure to light-dark exploration tests, the latency to dark zone was increased, and the duration in light zone as well as the central DAergic activity were decreased in C57BL/6 mice. This study provides comparative findings; Formosan wood mice showed the higher exploratory activities than C57BL/6 mice did, and their central DAergic activities were related to the behavioral responses in these two mice. This could potentially shed light on the reasons behind the prevalence of higher exploration and central dopaminergic activities. Using Formosan wood mice as a model to study human diseases related to hyperactivity adds significant value to the potential research.

Formosan wood mice (Apodemus semotus) exhibit more exploratory behaviors and central dopaminergic activities than C57BL/6 mice in the open field test.

Three-quarters of the lands in Taiwan are over 1000 m above sea level. Formosan wood mice (Apodemus semotus), also called Taiwanese field mice, are largely found at altitudes of 1400 ~ 3700 m and are the dominant rodents in these areas. Notably, Formosan wood mice show high levels of exploratory behaviors, not only in the wild but also in laboratory situations. Therefore, in this study, we examined the behavioral responses and central dopaminergic activities of male C57BL/6J mice and Formosan wood mice in the open field test. Dopamine and its major metabolite 3,4-dihydroxyphenylacetic acid were used as indices of dopaminergic activities. Formosan wood mice showed higher levels of exploration and locomotor activity than C57BL/6J mice in the open field test. Higher central dopaminergic activities in the nucleus accumbens, striatum, and medial prefrontal cortex were found in Formosan wood mice than in C57BL/6J mice in the open field test. Higher levels of locomotion and central dopaminergic activities in Formosan wood mice were consistent after two exposures to the open field test; however, dramatic decreases in levels of locomotion and central dopaminergic activities in C57BL/6J mice were found after two exposures to the open field test. The present study found that Formosan wood mice exhibited higher levels of locomotor activity and exploration and central dopaminergic activities than C57BL/6J mice after one or two exposures to the open field test.

Exploratory and agile behaviors with central dopaminergic activities in open field tests in Formosan wood mice (Apodemus semotus).

Taiwan is a mountainous island, and nearly 75% of its lands are 1000 m above sea level. Formosan wood mice, Apodemus semotus, are endemic rodents and are broadly distributed at altitudes between 1400 and 3700 m in Taiwan. Interestingly, Formosan wood mice show similar locomotor activity in the laboratory as they do in the wild. Hence, we are interested in studying whether exploratory behaviors and central dopaminergic activity are changed in the open field test. We used male C57BL/6J mice as the control, comparing their behavioral responses in the open field, step-down inhibitory avoidance discrimination and novel object recognition tests with those of male Formosan wood mice. We also examined dopamine and its major metabolite 3,4-dihydroxyphenylacetic acid in the medial prefrontal cortex, striatum and nucleus accumbens. In open field tests, Formosan wood mice revealed higher levels of locomotion and exploration than C57BL/6J mice. Learning and memory performance in the novel object recognition test was similar in both Formosan wood mice and C57BL/6J mice, but more agile responses in the inhibitory avoidance discrimination task were found in Formosan wood mice. There was no difference in behavioral responses in the open field test between new second-generation Formosan wood mice and Formosan wood mice that were inbred for more than 10 generations. After repeated exposure to the open field test, high levels of locomotion and exploration as well as central dopaminergic activities were markedly persistent in Formosan wood mice, but these activities were significantly reduced in C57BL/6J mice. Diazepam (anxiolytic) treatment reduced the higher exploratory activity and central dopaminergic activities in Formosan wood mice, but this treatment had no effect in C57BL/6J mice. This study provides comparative findings, as two phylogenetically related species showed differences in behavioral responses.

Corticosterone level and central dopaminergic activity involved in agile and exploratory behaviours in formosan wood mice (Apodemus semotus).

The native Formosan wood mouse (Apodemus semotus) is the dominant rodent in Taiwan. In their natural environment, Formosan wood mice exhibit high locomotor activity, including searching and exploratory behaviours, which is observed similarly in the laboratory environment. How the behavioural responses of Formosan wood mice exhibit in elevated plus maze and marble burying tests remains unclear. How corticosterone levels and central dopaminergic activities are related to the behaviours in these tests is also unclear. This study compared the behaviours of Formosan wood mice with that of C57BL/6J mice using the elevated plus maze and marble burying tests, and measured the corticosterone levels and central dopaminergic activities. Formosan wood mice showed greater locomotor and exploratory activity than the C57BL/6J mice. Similarly, the marble burying and rearing numbers were higher for Formosan wood mice. High locomotor and exploratory behaviours were strongly correlated with corticosterone levels after acute mild restraint stress in Formosan wood mice. The anxiolytic, diazepam, reduced the high exploratory activity, corticosterone levels and central dopaminergic activities. The high locomotor and exploratory behaviours of Formosan wood mice are related to the corticosterone levels and central dopaminergic activities. These data may explain Formosan wood mice dominance in the intermediate altitude of Taiwan.

Circadian Patterns of Rats in Their Home Cages Detected Using a Video Tracking System.

The diurnal rhythm is the common event in nature and specially shows in the behavioral patterns. Using the infrared sensor or photo beam detector to detect this 24-h rhythmicity in behaviors of mammalian, including in the rats and mice, is also the common way. The photo-sensory detecting mean is friendly and its advantage is unrestricted by light density and light-dark transition. However, this kind of equipment is cost-expensive and uneasy to fit for home cage in rodents. In this study, we tried to use the video-tracking system to detect the rhythmic activity of rats in their home cages. Adult male Sprague-Dawley rats, weighing 250-280 g, were used in this study and individual was kept in its own cage. Combined with the infrared sensitive charge-coupled device (CCD) camera and with automatically lights-off sensitive infrared illuminants as the accessory device, we found that animals exhibited the circadian locomotor activity in either light-dark cycles or constant darkness conditions. Moreover, the rhythmic patterns of locomotion in animals were affected by the one-hour exposure of white light under the constant darkness condition. The phase-advanced effects were found by the video tracking system. In summary, the video tracking system is the useful way to detect the rhythmic activity, especially in long-term circadian rhythmicity, in rats.

Spontaneous Intramural Intestinal Hemorrhage versus Acute Mesenteric Ischemia by CT Evaluation.

Objective The purpose of our study was to differentiate the imaging findings of patients with spontaneous intramural intestinal hemorrhage (SIIH) from those with acute mesenteric ischemia (AMI) after abdominal computed tomography (CT) survey in the emergency department. Methods We retrospectively included 83 patients diagnosed with SIIH or AMI after abdominal CT. Results The mean ages of 30 SIIH patients and 53 AMI patients were 74.4±14.6 years and 75.8±11.2 years, respectively. Patients with SIIH had significantly thicker maximal intestinal wall thickening (14.8±3.9 vs. 10.9 ±4.1, p<0.001), a lower rate of ileum involvement (26.7% vs. 77.4%, p<0.001) and a higher rate of ascites (96.7% vs. 64.2%, p<0.001) compared with patients with AMI. Neither pneumatosis intestinalis (p<0.001) nor portomesenteric gas (p<0.01) were detected in SIIH patients but were observed in AMI patients. A receiver-operating characteristic (ROC) curve analysis showed that the optimal cut-off value for maximal intestinal wall thickening between groups was 10.4 mm and the area under the ROC curve between groups was 0.752 (p<0.0001). A multiple logistic regression analysis showed that the independent predictors of SIIH were non-involvement of the ileum (odds ratio, OR, 6.998; p=0.001), maximal intestinal wall thickening ≥10.4 mm (OR, 5.748; p=0.040) and ascites (OR, 13.348; p=0.023). The area under the ROC curve for the model was 0.854 (p<0.001). Conclusion The independent predictors of SIIH from AMI after abdominal CT in acute abdominal patients include non-involvement of the ileum, intestinal wall thickening ≥10.4 mm, and ascites.

Changes in Gene Expression Patterns of Circadian-Clock, Transient Receptor Potential Vanilloid-1 and Nerve Growth Factor in Inflamed Human Esophagus.

Circadian rhythm is driven by the molecular circadian-clock system and regulates many physiological functions. Diurnal rhythms in the gastrointestinal tract are known to be related to feeding pattern, but whether these rhythms are also related to the gastrointestinal damage or injuries; for example, gastroesophageal reflux disease (GERD), is unclear. This study was conducted to determine whether expression of circadian-clock genes or factors involved in vagal stimulation or sensitization were altered in the esophagus of GERD patients. Diurnal patterns of PER1, PER2, BMAL1, CRY2, TRPV1, and NGF mRNA expression were found in patient controls, and these patterns were altered and significantly correlated to the GERD severity in GERD patients. Although levels of CRY1, TIM, CB1, NHE3, GDNF, and TAC1 mRNA expression did not show diurnal patterns, they were elevated and also correlated with GERD severity in GERD patients. Finally, strong correlations among PER1, TRPV1, NGF and CRY2 mRNA expression, and among PER2, TRPV1 and CRY2 expression were found. Expression levels of CRY1 mRNA highly correlated with levels of TIM, CB1, NHE3, GDNF and TAC1. This study suggests that the circadian rhythm in the esophagus may be important for the mediation of and/or the response to erosive damage in GERD patients.

Hepatic circadian-clock system altered by insulin resistance, diabetes and insulin sensitizer in mice.

Circadian rhythms are intrinsic rhythms that are coordinated with the rotation of the Earth and are also generated by a set of circadian-clock genes at the intracellular level. Growing evidence suggests a strong link between circadian rhythms and energy metabolism; however, the fundamental mechanisms remain unclear. In the present study, neonatal streptozotocin (STZ)-treated mice were used to model the molecular and physiological progress from insulin resistance to diabetes. Two-day-old male C57BL/6 mice received a single injection of STZ and were tested for non-obese, hyperglycemic and hyperinsulinemic conditions in the early stage, insulin resistance in the middle stage, and diabetes in the late stage. Gene expression levels of the hepatic circadian-clock system were examined by real-time quantitative PCR. Most of the components of the hepatic circadian-clock gene expression system, such as the mRNAs of Bmal1 (brain and muscle Arnt-like protein-1), Per2 (period 2) and Cry1 (cryptochrome 1), were elevated, and circadian patterns were retained in the early and middle stages of insulin-resistant conditions. The insulin sensitizer, rosiglitazone, returns the physiological and molecular changes associated with the diabetic phenotype to normal levels through peroxisome proliferator-activated receptor γ (PPARγ) rather than PPARα. Early and chronic treatment with rosiglitazone has been shown to be effective to counter the diabetic condition. Over time, this effect acts to attenuate the increased gene expression levels of the hepatic circadian-clock system and delay the severity of diabetic conditions. Together, these results support an essential role for the hepatic circadian-clock system in the coordinated regulation and/or response of metabolic pathways.

Circadian-clock system in mouse liver affected by insulin resistance.

Circadian rhythms are exhibited in the physiological and behavioral processes of all mammals; they are generated by intracellular levels of circadian oscillators, which are named as a set of circadian-clock genes. These genes compose the transcriptional/translational feedback loops to regulate not only circadian rhythmicity, but also energy metabolism. Previous studies have shown that obesity and diabetes cause the dysregulation of the circadian-clock system, and vice versa. However, some diabetes subjects are lean with insulin resistance and the mechanisms of insulin resistance without obesity are much less well known. Therefore, whether insulin resistance alone is enough to influence the expression of circadian-clock genes is uncertain. This study employs a neonatal streptozotocin (STZ)-treated paradigm in mice to model the molecular and physiological progress of nonobese insulin resistance. A single injection of STZ into 2-d-old male C57BL/6 mice induces nonobese, hyperglycemic and hyperinsulinemic conditions, and the levels of gene expression in the liver by a real-time quantitative polymerase chain reaction are then measured. Although the levels of Bmal1 (brain and muscle Arnt-like protein-1), Per2 (period 2), and Cry1 (cryptochrome 1) mRNA expression in the liver change during the progress of insulin resistance conditions, the gene expression patterns still show circadian rhythmicity. This study suggests that changes in the hepatic circadian-clock gene expression mark an early event in the metabolic disruption associated with insulin resistance. Furthermore, 2 wks of treatment with the thiazolidinedione, pioglitazone, fully resolve the dysfunction in metabolic parameters and the changes in circadian-clock gene expression from early insulin resistance conditions. These results indicate that the circadian-clock system is sensitive to insulin resistance, and that treatment with thiazolidinediones can resolve changes in the circadian-clock system in a timely manner. Thus, strengthening the peripheral circadian-clock system may counteract the adverse physiological consequences in the metabolic syndrome.

Anticoagulant-induced intramural intestinal hemorrhage.

BACKGROUND: Long-term use of warfarin can provide benefits in the treatment of many diseases, but adverse bleeding events are unpreventable because of a narrow therapeutic range. OBJECTIVE: The aim of this retrospective chart review with data abstraction was to investigate the clinical presentations of intestinal intramural hemorrhage in emergency department (ED) patients. METHODS: We reviewed the cases of 17 patients with acute abdominal pain in our ED. Medical records including demographic data and results of abdominal computed tomography were retrospectively reviewed and analyzed. RESULTS: The mean ± SD age of the reviewed patients was 77.7 ± 8.5 years (range, 60-93 years). The mean ± SD duration from onset of symptoms to ED visit was 2.5 ± 1.3 days (range, 1-5 days). All patients had abdominal pain, and 64.7% had nausea/vomiting. A total of 64.7% of patients had peritoneal signs. The jejunum was most commonly involved (88.2% of all cases). The maximal mean ± SD wall thickening of the bowel was 14.1 ± 4.4 mm (range, 7.4-26.7 mm), and the estimated mean ± SD length was 35.6 ± 24.4 cm (range, 9-105 cm). The mean ± SD prothrombin time and activated partial thromboplastin time were prolonged to 86.5 ± 26.9 and 116.2 ± 43.1 seconds, respectively. All patients received medical treatment and survived. At the last follow-up (mean, 27.4 months), none of the patients had recurrence of intestinal intramural hemorrhage or intestinal obstruction. CONCLUSION: Prolonged prothrombin time and drug history can indicate the possibility of intramural intestinal hemorrhage, and abdominal computed tomography may help to exclude surgical diseases and prevent unnecessary surgery.

Different patterns of food consumption and locomotor activity among Taiwanese native rodents, Formosan wood mice (Apodemus semotus), and common laboratory mice, C57BL/6 (Mus musculus).

The comparisons of food consumption and locomotor activity among Taiwan native rodents, Formosan wood mice (Apodemus semotus), and laboratory mice, C57BL/6, were examined in this study. The food consumption exhibited the circadian rhythmicity, e.g. higher in the lights-off period and lower in the lights-on period, in either Formosan wood mice (WM) or C57BL/6 mice. We also found that Formosan WM ate more food than C57BL/6 mice in the lights-off period and the whole day in males, but not in females. Similarly, the male Formosan WMs had more locomotor activities than the male C57BL/6 mice in the lights-off period, but this phenomenon did not appear in female mice. These results indicated that even though the Formosan WMs have been successfully inbred in the laboratory, they still keep more native paradigm than the laboratory C57BL/6 mice do. This study is the first report to provide basic physiological comparisons on native and common laboratory mice.

Gonadal hormones-mediated effects on the stimulation of dopamine turnover in mesolimbic and nigrostriatal systems by cocaine- and amphetamine-regulated transcript (CART) peptide in male rats.

Estradiol and testosterone modulated behavioral and neurochemical activities in the mesolimbic and nigrostriatal dopaminergic systems have been reported. We examined whether estradiol and testosterone affect stimulation of cocaine- and amphetamine-regulated transcript (CART) peptide in the mesolimbic and nigrostriatal dopaminergic systems in this study. Intracerebroventricular administration of CART peptide increased dopamine turnover in the nucleus accumbens and striatum in male rats. Stimulation of dopamine turnover in nucleus accumbens and striatum by CART peptide were found in intact male rats, but not in castrated male rats. This stimulation was restored in castrated male rats by testosterone or estradiol priming, or by treatment with the water-soluble form of estradiol, but not by treatment with the membrane-impermeable form of estradiol. Estradiol and testosterone antagonists blocked testosterone's effects, but only estradiol antagonist blocked estradiol's effects. Moreover, treatment of dihydrotestosterone also restored the stimulation in castrated male rats. This dihydrotestosterone's effect was blocked by a testosterone antagonist, but not by an estradiol antagonist. All of these findings indicate that gonadal hormones play a regulatory role in stimulation of CART peptide in mesolimbic and nigrostriatal dopaminergic systems, and suggest that acts through intracellular rather than extracellular mechanisms.

Diurnal rhythmic expression of the rhythm-related genes, rPeriod1, rPeriod2, and rClock, in the rat brain.

High densities of the mRNA of three rhythm-related genes, rPeriod1 (rPer1), rPer2, and rClock, which share high homology in Drosophila and mammals, are found in the rat hypothalamic suprachiasmatic nucleus (SCN). The SCN, however, is not the only brain region that expresses these genes. To understand the possible physiological roles of these rhythm-related genes, we examined expression of these genes in different brain regions at various time points in male Sprague--Dawley rats. Using semi quantitativein situ hybridization with 35S-riboprobes to evaluate mRNA levels, the diurnal rhythmicity of rPer1, and rPer2 mRNA levels was found in the SCN, arcuate nucleus, and median eminence/pars tuberalis. Expression patterns of mRNA for rPer1 and rPer2, however, were not similar in these brain regions. The rhythmicity in these brain regions was specific, because it was not observed in the cerebellum or hippocampus. Moreover, diurnal changes in rClock mRNA expression were not detected in any of the brain regions examined. These findings suggest that the different expression patterns observed for rPer1, rPer2, and rClock mRNAs may be attributed to their different physiological roles in these brain regions, and support previous work indicating that circadian rhythms in the brain are widespread.

Differential effects of melanin concentrating hormone on the central dopaminergic neurons induced by the cocaine- and amphetamine-regulated transcript peptide.

Stimulatory effects of cocaine- and amphetamine-regulated transcript (CART) peptide on central mesolimbic, nigrostriatal and mesocortical dopaminergic (DA) neurons were examined in female Sprague-Dawley rats. We also determined the different blocking effects of melanin concentrating hormone (MCH) on the stimulation by CART peptide in central DA systems. Intracerebroventricular administration of 1 microg CART peptide (55-102) produced increases in 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the nucleus accumbens (NA) at 15 and 45 min, and in the striatum (ST) at 15 min, but not in the medial prefrontal cortex (MPFC). We found that the agonist of alpha-melanocyte stimulating hormone (alpha-MSH), MT II, at 10 microg had a stimulatory effect on the NA and ST DOPAC levels similar to the CART peptide. In contrast, 1 microg MCH and the antagonist of alpha-MSH, HS014, significantly decreased NA and ST DOPAC levels. However, only MCH prevented the stimulatory effect of CART peptide on DOPAC levels in the NA, but not in the ST. These results indicate that the stimulation of CART peptide on central DA neurons is region-specific, and that this effect can be blocked by MCH but not by the antagonist of alpha-MSH.

Effects of the cocaine- and amphetamine-regulated transcript peptide on the turnover of dopamine in tuberoinfundibular neurons and serum prolactin levels: studies using estrogen, melanin concentrating hormone, and melanocortin.

Effects of the cocaine- and amphetamine-regulated transcript (CART) peptide on tuberoinfundibular dopaminergic (TIDA) neurons were examined in female and male Sprague-Dawley rats in the morning and afternoon. We also examined the blocking effects of melanin concentrating hormone (MCH) and the antagonists of alpha-melanocyte stimulating hormone (alpha-MSH), SHU9119 and HS014, on stimulation induced by the CART peptide in TIDA systems. Intracerebroventricular administration of 1 mug CART peptide (55-102) at 45 min, either in the morning or afternoon, produced an increase in the median eminence (ME) DOPAC (3,4-dihydroxyphenylacetic acid) level and a corresponding decrease in serum prolactin (PRL) levels. This resulted from stimulation of TIDA neurons regardless of castration, and whether or not male and female rats were estrogen-primed. The stimulatory effects of the CART peptide on ME DOPAC levels were similar in the morning and afternoon in both male and female rats. Central treatment with 1 microg SHU9119, HS014, or MCH significantly decreased the ME DOPAC levels and elevated serum PRL levels in female rats. However, only MCH prevented the stimulatory effect of the CART peptide on TIDA neurons. These results indicate that stimulation by the CART peptide on TIDA neurons is gender-independent; and this stimulatory effect can be blocked by MCH, but not the antagonists of alpha-MSH.

CART peptide increases the mesolimbic dopaminergic neuronal activity: a microdialysis study.

The effects of cocaine-and amphetamine-regulated transcript (CART) peptide on extracellular concentrations of dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the shell region of the nucleus accumbens (AcbSh) were determined by microdialysis in conscious rats. Intracerebroventricular injections of various doses (0.1-5 microg/5 microl/rat) of CART(55-102) elicited dose-dependent increases of extracellular DOPAC and HVA concentration in the AcbSh, suggesting that CART(55-102) peptide has a psychostimulant-like effect via activation of the mesolimbic dopaminergic system.

Differential effects of colchicine on central dopaminergic neuronal activity and prolactin secretion in estrogen-primed ovariectomized rats.

Colchicine is a potent chemical that disrupts the assembly of microtubulin and affects the integrity of cytoskeleton. It is commonly used to block the axonal transport in neurons. Central administration of colchicine (48 microg/3 microl/rat) two days earlier significantly lowered 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the striatum and nucleus accumbens, both in the morning and in the afternoon. Median eminence DOPAC levels exhibit a diurnal change between morning and afternoon as previously shown. Colchicine treatment lowered and elevated median eminence DOPAC levels in the morning and afternoon, respectively. The estrogen-induced prolactin surge was also blocked. The findings indicate that neuronal inputs are necessary for maintaining basal activities in all dopaminergic neurons, while an inhibitory one predominates in the afternoon for TIDA neurons.

Effects of prolactin-releasing peptide on tuberoinfundibular dopaminergic neuronal activity and prolactin secretion in estrogen-treated female rats.

Both systemic and central effects of a newly discovered prolactin (PRL)-releasing factor (PRF), prolactin-releasing peptide (PrRP), were determined in this study. Systemic injection of PrRP (1 and 10 microg/rat, i.v.) stimulated PRL secretion in ovariectomized, estrogen-treated rats similar to the effect of another PRF, thyrotropin-releasing hormone (TRH). Pretreatment with a dopamine D2 receptor antagonist, sulpiride (1 microg/rat, i.v.), potentiated the stimulatory effect of both PrRP and TRH on PRL secretion. Using the double-labeling immunohistochemical method, PrRP-immunoreactive terminals were found in close contact with tyrosine-hydroxylase-immunoreactive neurons in the hypothalamic arcuate nucleus. Central administration of PrRP (0.1-1,000 ng/rat, i.c.v.) stimulated tuberoinfundibular but not nigrostriatal dopaminergic neuronal activity in 15 min. Levels of 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence and striatum were used as indices for tuberoinfundibular dopaminergic (TIDA) and nigrostriatal dopaminergic neuronal activities, respectively. The serum PRL level, however, was not significantly changed. Similar treatment with TRH (10 ng/rat, i.c.v.) stimulated and inhibited TIDA neuronal activity and serum PRL, respectively, at 30 min. In summary, PrRP may play a role in both the central and peripheral control of PRL secretion.