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Peak bone mass (PBM) achieved at adulthood is a strong determinant of future onset of osteoporosis, and maximizing it is one of the strategies to combat the disease. Recently, pomegranate seed oil (PSO) has been shown to have bone-sparing effect in ovariectomized mice. However, its effect on growing skeleton and its molecular mechanism remain unclear. In the present study, we evaluated the effect of PSO on PBM in growing rats and associated mechanism of action. PSO was given at various doses to 21-day-old growing rats for 90 days by oral gavage. The changes in bone parameters were assessed by micro-computed tomography and histology. Enzyme-linked immunosorbent assay was performed to analyze the levels of serum insulin-like growth factor type 1 (IGF-1). Western blotting from bone and liver tissues was done. Chromatin immunoprecipitation assay was performed to study the histone acetylation levels at IGF-1 gene. The results of the study show that PSO treatment significantly increases bone length, bone formation rate, biomechanical parameters, bone mineral density and bone microarchitecture along with enhancing muscle and brown fat mass. This effect was due to the increased serum levels of IGF-1 and stimulation of its signaling in the bones. Studies focusing on acetylation of histones in the liver, the major site of IGF-1 synthesis, showed enrichment of acetylated H3K9 and H3K14 at IGF-1 gene promoter and body. Further, the increased acetylation at H3K9 and H3K14 was associated with a reduced HDAC1 protein level. Together, our data suggest that PSO promotes the PBM achievement via increased IGF-1 expression in liver and IGF-1 signaling in bone. [ABSTRACT FROM AUTHOR]

A ultra-performance liquid chromatography tandem mass spectrometry method was initially developed and validated for quantification of sophorabioside in rat plasma using kaempferol-3-O-β-D-rutinoside as the internal standard (IS). Analyte and IS were preparation through a protein precipitation procedure with 1.0 mL of methanol to a 0.1 mL plasma sample. The processed samples were separated by C18 analytical column using methanol/water containing 0.1% formic acid with gradient elution as the mobile phase at a flow rate of 0.3 mL/min. Sophorabioside (m/z 577.15 → 269.45) and kaempferol-3-O-β-D-rutinoside (m/z 593.15 → 285.84) were detected by a triple quadrupole tandem mass spectrometer in negative electrospray ionization mode using multiple reaction monitoring. The calibration curve for sophorabioside was linear in the range of 6-1,200 ng/mL (r2 > 0.995) with a lower limit of quantification of 6 ng/mL. The inter- and intra-day precision and accuracy were well within the acceptable limits. The matrix effects were satisfactory in all of the biological matrices examined. The mean recovery of sophorabioside was always >90%. This method was successfully applied to a pharmacokinetic study of sophorabioside in rats after an oral administration of 90 mg/kg sophorabioside. The main pharmacokinetic parameters: Tmax, Cmax and t1/2 were 6.2 ± 0.8 h, 1430.83 ± 183.25 ng/mL, 7.2 ± 0.5 h, respectively. [ABSTRACT FROM AUTHOR]

2,4-Dichlorophenoxyacetic acid (2,4-D) is a chlorophenoxy herbicide used worldwide. We describe a high-performance liquid chromatography (HPLC) method with UV detection for the determination of 2,4-D in female and male rat serum. This allows to observe the change of serum 2,4-D concentration in rats with time and its pharmacokinetics characteristics with a simple, rapid, optimized and validated method. The serum samples are pretreated and introduced into the HPLC system. The analytes are separated in a XDB-C18 column with a mobile phase of acetonitrile (solvent A) and 0.02 M ammonium acetate (containing 0.1% formic acid) (solvent B) using a gradient elution at a flow rate of 1.0 mL/min. The wavelength for UV detection was set at 230 nm. Calibration curve for 2,4-D was constructed over a range of 0.1–400 mg/L. The method was successfully applied to study the pharmacokinetics of 2,4-D in rats in this study. After oral administration of 300 mg/kg and 60 mg/kg 2,4-D, the mean Cmax values were 601.9 and 218.4 mg/L, the AUC0→∞ values were 23,722 and 4,127 mg×h/L and the clearance (Cl) were 1.10 and 0.02 L/(h×kg), respectively. The developed method was found to be specific, precise, reproducible and rapid. [ABSTRACT FROM AUTHOR]

In healthy beings, age is the ultimate reason of cellular malfunction and death. In the rat retina, age causes a functional decline and loss of specific neuronal populations. In this regard, controversial conclusions have been reported for the innermost retina. Here, we have studied the albino and pigmented retina for the duration of the rat life-span. Independent of age (21 days–22 months), the electroretinographic recordings and the volume of the retina and its layers are smaller in albinos. Functionally, aging causes in both strains a loss of cone- and rod-mediated responses. Anatomically, cell density decreases with age because the retina grows linearly with time; no cell loss is observed in the ganglion cell layer; and only in the pigmented rat, there is a decrease in cone photoreceptors. In old animals of both strains, there is gliosis in the superior colliculi and a diminution of the area innervated by retinal ganglion cells. In conclusion, this work provides the basis for further studies linking senescence to neurodegenerative retinal diseases. [ABSTRACT FROM AUTHOR]

Alternative RNA splicing results in the translation of diverse protein products arising from a common nucleotide sequence. These alternative protein products are often functional and can have widely divergent actions from the canonical protein. Studies in humans and other vertebrate animals have demonstrated that alternative splicing events increase with advanced age, sometimes resulting in pathological consequences. Menopause represents a critical transition for women, where the beneficial effects of estrogens are no longer evident; therefore, factors underlying increased pathological conditions in women are confounded by the dual factors of aging and declining estrogens. Estrogen receptors (ERs) are subject to alternative splicing, the spliced variants increase following menopause, and they fail to efficiently activate estrogen-dependent signaling pathways. However, the factors that regulate the alternative splicing of ERs remain unknown. We demonstrate novel evidence supporting a potential biological feedback loop where 17β-estradiol regulates the RNA-binding protein Nova1, which, in turn, regulates the alternative splicing of ERβ. These data increase our understanding of ER alternative splicing and could have potential implications for women taking hormone replacement therapy after menopause. [ABSTRACT FROM AUTHOR]

Several lines of evidence point to alterations in glutamatergic signaling in Parkinson's disease (PD) and levodopa-induced dyskinesia (LID), involving the metabotropic glutamate receptor type 5 (mGluR5). Using small-animal positron emission tomography (PET) with [ 18 F]FPEB and proton magnetic resonance spectroscopy, we investigated cerebral changes in the mGluR5 and glutamate/glutamine availability in vivo in PD rats and following onset of LIDs. In parallel, behavioral tests were performed. Comparing PD to control rats, mGluR5 binding potential was decreased in a cluster comprising the bilateral caudate-putamen (CP), ipsilateral motor cortex and somatosensory cortex, and the contralateral somatosensory cortex and parietal association cortex, with the most pronounced reduction in the ipsilateral CP. mGluR5 binding potentials were not significantly altered upon levodopa (L-DOPA) treatment. However, following L-DOPA, an increase in relative mGluR5 uptake was present in the contralateral motor cortex and somatosensory cortex. Glutamate and glutamine concentrations did not differ between control and untreated PD rats or between hemispheres. Though, glutamine levels were higher in the contralateral CP of saline- and L-DOPA-treated rats as compared to the ipsilateral side. Relative mGluR5 uptake in the CP of levodopa-treated rats was also found positively correlated with abnormal involuntary movement scores. Conclusively, mGluR5 availability and glutamine concentrations in the CP are involved in PD, whereas mGluR5 availability in cortical regions may be involved in LID pathology. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by progressive cognitive decline and the presence of aggregates of amyloid beta (plaques) and hyperphosphorylated tau (tangles). Early diagnosis through neuropsychological testing is difficult due to comorbidity of symptoms between AD and other types of dementia. As a result, there is a need to identify the range of behavioral phenotypes expressed in AD. In the present study, we utilized a transgenic rat (TgF344-AD) model that bears the mutated amyloid precursor protein as well as presenilin-1 genes, resulting in progressive plaque and tangle pathogenesis throughout the cortex. We tested young adult male and female TgF344-AD rats in a spatial memory task in the Morris water maze and for anxiety-like behavior in the elevated plus-maze. Results indicated that regardless of sex, TgF344-AD rats exhibited increased anxiety-like behavior in the elevated plus-maze, which occurred without significant deficits in the spatial memory. Together, these results indicate that enhanced anxiety-like behavior represents an early-stage behavioral marker in the TgF344-AD rat model. [ABSTRACT FROM AUTHOR]

There is still no resolution for arterial remodeling related with hypertension, though hypertension treatment has access to a number of pharmacological agents. The present study aimed at investigating the prevention of Cyathula officinalis Kuan's roots (C. officinalis Kuan) against in arterial remodeling in vitro. Spontaneously hypertensive rats (SHRs) were intragastrically administered 3, 6 or 12 g/kg C. officinalis Kuan or normal saline or enalapril (2.5 mg/kg) once a day for 8 weeks. Hematoxylin and eosin were used to measure blood pressure and stain carotid and arota. The serum concentration of nitric oxide (NO) was measured by NO assay kit (nitrate reductase method). The endothelin-1 transcriptional level, endothelial NO synthase of endothelium as well as angiotensin II receptor type 1 (AT1R) of aorta and carotid was tested by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and the protein level in aorta was also measured by western blotting. The blood pressure in SHR+enalapril, SHR+3 g/kg, SHR+6 g/kg and SHR+12 g/kg C. officinalis Kuan groups was significantly decreased at 4, 6 and 8 weeks post-treatment compared with SHR group. Different doses of C. officinalis Kuan and enalapril treatment showed aortic wall thinness and strengthened NO serum level, but made no impact on the transcriptional level of AT1R in aorta or endothelial NO synthase in carotid. It is suggested by such results that therapy by C. officinalis Kuan is able to fight against arterial remodeling, thus may provide a new means to treat arterial remodeling caused by hypertension. [ABSTRACT FROM AUTHOR]

Oral exposure of rodents to the plasticizer, Di(2-ethyl hexyl) phthalate (DEHP), elicits birth defects and effects upon the reproductive tract. There is currently limited published information regarding potential developmental effects in rodents of another phthalate ester, TEHTM. [ABSTRACT FROM AUTHOR]

Objective Pronociceptive responses to endothelins in the trigeminal system seem to be mediated by ET A and ET B receptors, which have been shown to be expressed in neurons of the trigeminal ganglion of humans and rats. The present study aimed to evaluate the ability of endothelin-1 (ET-1) to induce facial heat hyperalgesia in female rats, the contribution of ET A and ET B receptors to this response, as well as the mechanisms underlying heat hyperalgesia induced by ET-1. Design ET-1 (100 pmol/50 μL) was injected into the upper lip and heat hyperalgesia was evaluated for up to 6 h. Facial heat hyperalgesia induced by ET-1 was assessed in rats pre-treated locally with BQ-123 or BQ-788 (selective ET A and ET B receptor antagonists, respectively, 30 nmol/50 μL); BCTC (TRPV1 receptor antagonist; 300 μg/50 μL); anti-NGF (3 μg/50 μL); K252a (TrkA inhibitor, 1 μg/50 μL); or in rats that received intraganglionar resiniferatoxin injection (RTX, 200 ng/10 μL) to promote C-fibers ablation. Results ET-1 induced facial heat hyperalgesia that persisted up to 6 h and was prevented by BQ-123, BQ-788 or by intraganglionar RTX injection. Likewise, local pre-treatment with BCTC abolished ET-1 induced facial heat hyperalgesia up to 3 h. Local pre-treatment with anti-NGF or K252a was effective to prevent ET-1 induced heat hyperalgesia. Conclusions In conclusion, ET-1 is able to induce heat hyperagelsia in trigeminal primary afferents of female rats, which is mediated by ET A and ET B receptors. Activation of TRPV1 receptors and NGF-signaling pathways may contribute to heat hyperalgesia induced by ET-1. [ABSTRACT FROM AUTHOR]

The dopamine D2-type receptor agonist quinpirole (QNP) facilitates the development of conditioned same-sex partner preference in males during cohabitation, but not in ovariectomized (OVX) females, primed with estradiol benzoate (EB) and progesterone (P). Herein we tested the effects of QNP on OVX, EB-only primed females. Females received a systemic injection (every four days) of either saline (Saline-conditioned) or QNP (QNP-conditioned) and then cohabited for 24 h with lemon-scented stimulus females (CS +), during three trials. In test 1 (female-female) preference was QNP-free, and females chose between the CS + female and a novel female. In test 2 (male-female) they chose between the CS + female and a sexually experienced male. In test 1 Saline-conditioned females displayed more hops & darts towards the novel female, but QNP-conditioned females displayed more sexual solicitations towards the CS + female. In test 2 Saline-conditioned females displayed a clear preference for the male, whereas QNP-conditioned females displayed what we considered a bisexual preference. We discuss the effect of dopamine and ovarian hormones on the development of olfactory conditioned same-sex preference in females. [ABSTRACT FROM AUTHOR]

Prolactin (PRL) and oxytocin (OT) are pituitary hormones essential for lactation, but also promote sexual behavior. OT stimulates social behaviors, such as recognition, approach, and learning, but less is known about PRL in these behaviors. Since PRL and OT have complementary functions in reproduction, we hypothesized that PRL increases social recognition, approach, and learning. Male Long-Evans rats received ovine PRL (oPRL; 0.5, 2.0 or 5.0 mg/kg), the PRL antagonist bromocriptine (0.1, 3.0 or 5.0 mg/kg) or saline 20 mins before testing for recognition of familiar vs. unfamiliar stimulus males. Saline controls preferred the unfamiliar male ( p < 0.05), while bromocriptine blocked this preference. oPRL did not increase preference. To measure social approach, we determined if PRL restores approach 2 h after defeat by an aggressive male. Defeated rats avoided the aggressive male. 2 mg/kg oPRL, before or after defeat, restored approach towards the aggressive male ( p < 0.05). In non-defeated rats, oPRL or 3 mg/kg bromocriptine had no effect. To determine if PRL increases social learning, we tested social transmission of food preference. Rats choose between two unfamiliar flavors, one of which they have previously been exposed to through interaction with a demonstrator rat. Vehicle controls preferred chow with the demonstrated flavor over the novel flavor. oPRL-treated rats were similar. Bromocriptine-treated rats failed to show a preference. When tested one week later, only oPRL-treated rats preferred the demonstrated flavor. The results suggest that PRL is required for social recognition and learning, and that increasing PRL enhances social memory and approach, similar to OT. [ABSTRACT FROM AUTHOR]

Episodic memory was initially believed to be unique to humans. However, studies demonstrate that nonhuman species discriminate items based on the triad what, where and when . Here we addressed the role of the dorsal hippocampal subfield CA1 in an integrative what-where-when task in Wistar rats. We performed bilateral inactivation of dorsal CA1 with the GABA A agonist muscimol previously to the task. As expected, sham-operated animals recollected an integrative memory for objects (what), their places (where) and temporal order (when). However, the inactivation of CA1 impaired the performance of the three components of episodic-like memory. In addition, total time of objects exploration and distance traveled were not different between groups, indicating that rats had similar levels of motivation, thus, alterations in exploration does not account for impaired locomotor performance. Altogether, our data provides evidence that CA1 plays an important role in episodic-like memory. [ABSTRACT FROM AUTHOR]

Taurine lowers blood glucose levels and improves hyperglycemia. However, its effects on glucose transport in the small intestine have not been investigated. Here, we elucidated the effect of taurine on glucose absorption in the small intestine. In the oral glucose tolerance test, addition of 10 mmol/L taurine suppressed the increase in hepatic portal glucose concentrations. To investigate whether the suppressive effect of taurine occurs via down-regulation of active glucose transport in the small intestine, we performed an assay using the everted sac of the rat jejunum. Addition of taurine to the mucosal side of the jejunum suppressed active glucose transport via sodium-glucose cotransporter 1 ( SGLT1). After elimination of chloride ions from the mucosal solution, taurine did not show suppressive effects on active glucose transport. These results suggest that taurine suppressed the increase in hepatic portal glucose concentrations via suppression of SGLT1 activity in the rat jejunum, depending on chloride ions. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of recombinant adenovirus-mediated human β-nerve growth factor (Ad-EGFP-hβ-NGF) on the differentiation of endothelial progenitor cells (EPCs) in rats. Methods: The successfully constructed Ad-EGFP-hβ-NGF and its negative control Ad-EGFP were infected into the isolated and purified rat EPCs to observe their morphological changes. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect the levels of vascular endothelial growth factor (VEGF), von Willebrand factor (vWF) and basic fibroblast growth factor (bFGF) in different rat EPC culture solutions. Western blot was performed to determine the expression of tyrosine kinase receptor A (TrKA) protein in different groups of EPCs. Results: Primary fibrous EPCs were converted into epithelium-like cells. After infection with Ad-EGFPhβ- NGF for 1 week, some EPCs became round and exhibited neural stem cell-like changes. The expression levels of VEGF, vWF and bFGF in the Ad-EGFP-hβ-NGF infection group were significantly higher than those in the control group (p < 0.01). TrKA protein in Ad-EGFP-hβ-NGF infection was also significantly up-regulated compared with that in the negative control and blank control groups (p < 0.01). Conclusion: β-NGF up-regulates the expression of TrKA receptor protein and secretion of angiogenic growth factors (i.e., VEGF, vWF and bFGF), thereby promoting the differentiation of rat EPCs, which may contribute to angiopoiesis or vascular repair. [ABSTRACT FROM AUTHOR]

A microfluidic liver biochip was coupled with a mass spectrometer to detect in real time the drug metabolism of hepatocytes. The hepatocytes were cultivated in the biochip for 35 h. The biochip was placed in a small-scale incubator in which the temperature and CO2 concentration were controlled. The biochip was connected serially to a mass spectrometer, a peristaltic pump and a culture medium reservoir. The injection in the mass spectrometer was performed every 10 min for 11 h. The metabolism of midazolam, phenacetin, omeprazole, dextromethorphan, repaglinide, rosuvastatin, tolbutamide and caffeine was investigated. We monitored the apparition of omeprazole sulfone, hydroxy omeprazole, repaglinide glucuronide, rosuvastatin lactone, dextrorphan, 1-hydroxy midazolam, 4-hydroxy midazolam, 1,4-hydroxy midazolam, paracetamol and 1,3-methylxanthine. Although these were observed, hydroxytolbutamide, 3-methoxymorphinan and midazolam glucuronide, hydroxy repaglinide were not detected. Based on a pharmacokinetic model, we calculated in vitro intrinsic clearances in which adsorption onto the perfusion circuit was taken into account. Then, using a liver organ model, we extrapolated the in vitro intrinsic clearances to the in vivo clearances. The estimated in vivo clearances were in agreement with the literature data on rats for midazolam, dextromethorphan, phenacetin, tolbutamide and caffeine. Rosuvastatin, omeprazole and repaglinide prediction underestimated the in vivo data. [ABSTRACT FROM AUTHOR]

Depolarization of cardiomyocytes triggered by stretch and activation of mechanically gated ion channels can lead to serious arrhythmias. However, stretch-induced signaling activating these channels remain little studied. This study tested the hypothesis on implication of NO in shaping the electrical abnormalities provoked by stretch of the right atrial myocardium in rat via a mechanism engaging a signaling cascade, where NO plays a significant role. This approach showed that in isolated right atrial preparation, NO donor SNAP induces the electrical abnormalities similar to those provoked by stretch, and the latter results from activation of NO synthase. [ABSTRACT FROM AUTHOR]

The expression of Notch2, Numb, and Cas8 genes, whose protein products are involved in regulation of neurogenesis/neuroapoptosis processes, was studied in the relevant cerebral structures of male Wistar rats trained in a spatial habit. The formation of long-term spatial memory was found to be associated with the formation of a specific pattern of transcription activity of the studied genes in different brain structures. The maximum expression of Notch2 gene was found in the hippocampus and cerebellum, the maximum expression of Numb was detected in the prefrontal cortex and cerebellum, and the maximum expression of Cas8 was revealed in the prefrontal cortex of trained animals. [ABSTRACT FROM AUTHOR]

The study examined implication of tributyrin, a metabolic precursor in small intestinal microflora, in stimulation of electrical activity of duodenum and jejunum. Enteral administration of tributyrin enhanced electrical activity of both examined structures in small intestine with elimination of the rest periods. The stimulatory effect was manifested in a prolongation of the periods of irregular activity. The up-regulating effects of tributyrin on electrical activity in upper segments of small intestine are mediated via the cholecystokinin receptors being also associated with activation of cholinergic and blockade of nitrinergic signal transduction pathways. [ABSTRACT FROM AUTHOR]

V1a receptor agonist [Phe, Ile, Orn]-vasopressin produces maximum diuretic and saluretic effects in a dose of 0.1 nmol/100 g body weight: renal excretion of Na increases by 50 times in comparison with the initial level over 90 min, excretion of K, Mg, and Са increases by 3, 2, and 16 times, respectively. New formulas were proposed for calculation of the clearance considering total cation content in the extracellular fluid and the time of total effect of the injected dose. After injection of V1a receptors agonist, clearance of Na was 7% of its total content in the extracellular fluid, the corresponding values for K, Mg, and Ca were 63, 35, and 6%, respectively. The proposed approach differs significantly from the standard cation excretion evaluation and characterizes selective shifts in ion balance induced by physiologically active substances and possible side effects due to unbalanced loss of certain ions. [ABSTRACT FROM AUTHOR]

Ascorbic acid (AsAc) was tested to evaluate its ability to reverse the oxidative stress induced by envenoming. Test groups of rats were envenomed with sub-lethal doses (4.0 mg/kg s. c.) of Bitis arietans venom (BaV) whilst, single doses (500 mg/kg, orally) of AsAc were preadministered in half of them. Blood samples were collected within three periods and levels of lipid peroxidation (LPO) and total-SH increased significantly, whilst, the 'Venom + AsAc' groups were significantly less than both, the respective 'Venom' groups and controls, at different periods. The antioxidant, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzyme level changes were trivial at the three periods, whilst, there were no changes in the 'Venom + AsAc' groups, compared with controls, except SOD which, became significant after 24 h. SCr and BUN levels were significantly higher than the controls within the three periods with variable degrees, whilst, the 'Venom + AsAc' group level changes were insignificant compared with controls and their respective 'Venom' groups at all periods. Blood urea Nitrogen (BUN), became significantly lower after 24 h. After 6 and 24 h AST levels were significantly higher than controls, whilst, ALT was not. Level changes of both AST and ALT 'Venom + AsAc' groups were insignificant, compared with controls at all periods. It is concluded that oxidative stress due to envenoming by BaV induced variable levels of significant changes in levels of nephrotoxic, hepatotoxic markers and antioxidant enzyme parameters. Administration of AsAc relatively adjusted these changes with different degrees, at variable periods of time that demands further deeper research in beneficiary mechanisms of antioxidants. [ABSTRACT FROM AUTHOR]

The chemically carboxymethylated polysaccharide (CPMEP), which is derived from the purified polysaccharide from Morchella angusticepes Peck (PMEP), was prepared. The degree of substitution of CPMEP was 0.461. Fourier transform infrared spectra analysis and 13 C, 1 H, and DEPT135° NMR spectra indicated C6 position was partially substituted by CH 2 COOH. Moreover, serum total cholesterol of hypercholesterolemic rats treated with the high dose of PMEP and CPMEP was 1.54 mmol/L and 1.29 mmol/L compared with that of rats fed with a 2% cholesterol diet (1.74 mmol/L), respectively, indicating CPMEP had a stronger cholesterol-lowering activity than PMEP. CPMEP had a trend in reducing liver total cholesterol while increasing the excretion of total fecal and intestinal bile acids, which were probably mediated by down-regulation of hepatic 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase while up-regulation of cholesterol-7α-hydroxylase. It was therefore concluded that carboxymethylation of PMEP could enhance its cholesterol-lowering ability at least in rats. [ABSTRACT FROM AUTHOR]

Measuring the activity and temperature of rats is commonly required in biomedical research. Conventional approaches necessitate single housing, which affects their behavior and wellbeing. We have used a subcutaneous radiofrequency identification (RFID) transponder to measure ambulatory activity and temperature of individual rats when group-housed in conventional, rack-mounted home cages. The transponder location and temperature is detected by a matrix of antennae in a baseplate under the cage. An infrared high-definition camera acquires side-view video of the cage and also enables automated detection of vertical activity. Validation studies showed that baseplate-derived ambulatory activity correlated well with manual tracking and with side-view whole-cage video pixel movement. This technology enables individual behavioral and temperature data to be acquired continuously from group-housed rats in their familiar, home cage environment. We demonstrate its ability to reliably detect naturally occurring behavioral effects, extending beyond the capabilities of routine observational tests and conventional monitoring equipment. It has numerous potential applications including safety pharmacology, toxicology, circadian biology, disease models and drug discovery. [ABSTRACT FROM AUTHOR]

We investigated the effects of physical exercise (PE) on locomotor activity and anxiety-like behavior in Lewis (LEW) and Spontaneously Hypertensive Rats (SHR) male rats. Rats received either four weeks of forced training, 5 days/week, on a treadmill (experiment 1) or were given 21 days of free access to running wheels (experiment 2). We also tested the effects of social isolation (SI) (seven days of isolation − experiment 3) on behavior. In experiment 1, 20% of LEW rats and 63% of SHR rats completed the training protocol. PE significantly increased central and peripheral locomotion in the open field (OF) and entries into the open arms in the elevated plus-maze (EPM) in both strains. In experiment 2, the distance traveled by SHR rats on running wheels was significantly higher compared with LEW rats. PE on running wheels also increased the time spent in the center of the OF in SHR rats only. In experiment 3, SI decreased central and peripheral locomotion in the OF in both strains. In summary, forced PE on a treadmill reduced anxiety-like behavior and increased locomotion in male rats of both strains, whereas voluntary PE on running wheels decreased anxiety-like behavior in SHR rats only. SI decreased locomotion in both strains in the OF. This study suggests that spontaneous activity levels are genotype-dependent and the effects of PE depend on the type of exercise performed. [ABSTRACT FROM AUTHOR]

The contents of soybean can modify the structure of the reproductive system, especially, when consumed for prolonged periods. In this study, we evaluated the effects of the consumption of transgenic soybean on rat penis morphology after prolonged use. Wistar rats (n = 30) were divided into three groups according to diet: Transgenic Soybean (TS) group, Organic Soybean (OS) group and Control (C) group. After 455 days of intake, the rats were sacrificed and the penises were excised and fixed in formalin for subsequent histological processing. The samples were stained with hematoxylin and eosin, Weigert's resorcin-fuchsin stain and picrosirius red with polarization. The images were scanned for the histomorphometric analyses of the corpora cavernosa, corpus spongiosum, erectile tissue and tunica albuginea as well as the measurement of the thickness of the tunica albuginea. The diameter and areas of the penile arteries with the intima and media tunica were also measured. The elastic fibers of the tunica albuginea, corpora cavernosa and corpus spongiosum were quantified using stereological methods. No significant differences were observed in the collagen and elastic components among the groups. We concluded that no statistically significant differences were found among the groups, demonstrating that the prolonged consumption of OS and TS does not affect the penile structure. [ABSTRACT FROM AUTHOR]

This study investigated the effects of manipulating the load components of aerobic training sessions on the physical performance of rats. To achieve this purpose, adult male Wistar rats were divided into four groups: an untrained control (CON) group and training groups with a predominant overload in intensity (INT) or duration (DUR) or alternating and similar overloads in intensity and duration (ID). Prior to, during, and after 8 weeks of the control or training protocols, the performance of the rats (evaluated by their workload) was determined during fatiguing, incremental-speed treadmill running. Two additional incremental running tests were performed prior to and at the end of the protocols to measure the peak rate of oxygen consumption (VO2peak). As expected, the rats in the trained groups exhibited increased performance, whereas the untrained rats showed stable performance throughout the 8 weeks. Notably, the performance gain exhibited by the DUR rats reached a plateau after the 4th week. This plateau was not present in the INT or ID rats, which exhibited increased performance at the end of training protocol compared with the DUR rats. None of the training protocols changed the VO2peak values; however, these values were attained at faster speeds, which indicated increased running economy. In conclusion, our findings demonstrate that the training protocols improved the physical performance of rats, likely resulting from enhanced running economy. Furthermore, compared with overload in duration, overload in the intensity of training sessions was more effective at inducing performance improvements across the 8 weeks of the study. [ABSTRACT FROM AUTHOR]

Liraglutide, a Glucagon-Like Peptide-1 (GLP-1) receptor agonist, is used as a treatment for Type 2 diabetes mellitus and obesity because it improves glycemia and decreases food intake. Here, we tested whether chronic activation of the GLP-1 receptor system with liraglutide would induce decreases in intake accompanied by changes in proportional food or macronutrient intake similar to those seen following RYGB in rats when a variety of palatable food options are available. A “cafeteria diet” was used that included: laboratory rodent chow, refried beans (low-fat/low-sugar), low-fat yogurt (low-fat/high-sugar), peanut butter (high-fat/low-sugar) and sugar-fat whip (high-fat/high-sugar). Liraglutide (1 mg/kg daily, sc, n = 6) induced significant reductions in body weight and total caloric intake compared to saline–injected control rats ( n = 6). Although access to a cafeteria diet induced increases in caloric intake in both groups relative to chow alone, liraglutide still effectively decreased intake compared with saline-injected rats suggesting that chronic GLP-1 activation competes with the energy density and palatability of available food options in modulating ingestive behavior. Even with the substantial effects on overall intake, liraglutide did not change food choice or relative macronutrient intake when compared to pre-treatment baseline. When drug treatment was discontinued, the liraglutide group increased caloric intake and rapidly gained body weight to match that of the saline group. These results demonstrate that, while liraglutide effectively decreases caloric intake and body weight in rats, it does not cause adjustments in relative macronutrient consumption. Our data also show that drug-induced decreases in intake and body weight are not maintained following termination of treatment. [ABSTRACT FROM AUTHOR]

Atmospheric CO 2 concentrations increased significantly over the last century and continuing increases are expected to have significant effects on current ecosystems. This study evaluated the behavioural and physiological (hormone status, muscle structure) effects of prolonged CO 2 exposure in young female Wistar rats exposed at 700 ppm of CO 2 during 6 h a day for 15 days. Prolonged CO 2 exposure, though not continuous, produced significant disturbances in behaviour with an increase in drinking, grooming and resting, and a reduction in rearing, jumping-play and locomotor activity. Furthermore, CO 2 exposure was accompanied by increased plasma levels of corticosterone, suggesting that prolonged exposure to CO 2 was stressful. The muscular structure can also be modified also when respiratory working conditions change. The expression of myosin heavy chain was significantly affected in the diaphragm and oral respiratory muscles: Masseter Superficialis and Anterior Digastric . Modified behaviour and hormonal changes both appear to be at the origin of the observed muscular adaptation. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 (GLP-1) is an incretin hormone released from intestinal L-cells in response to food entering into the gastrointestinal tract. GLP-1-based pharmaceuticals improve blood glucose regulation and reduce feeding. Specific macronutrients, when ingested, may trigger GLP-1 secretion and enhance the effects of systemic sitagliptin, a pharmacological inhibitor of DPP-IV (an enzyme that rapidly degrades GLP-1). In particular, macronutrient constituents found in dairy foods may act as potent secretagogues for GLP-1, and acute preclinical trials show that ingestion of dairy protein may represent a promising adjunct behavioral therapy in combination with sitagliptin. To test this hypothesis further, chow-maintained or high-fat diet (HFD)-induced obese rats received daily IP injections of sitagliptin (6 mg/kg) or saline in combination with a twice-daily 8 ml oral gavage of milk protein concentrate (MPC; 80/20% casein/whey; 0.5 kcal/ml), soy protein (non-dairy control; 0.5 kcal/ml) or 0.9% NaCl for two months. Food intake and body weight were recorded every 24–48 h; blood glucose regulation was examined at baseline and at 3 and 6.5 weeks via a 2 h oral glucose tolerance test (OGTT; 25% glucose; 2 g/kg). MPC and soy protein significantly suppressed cumulative caloric intake in HFD but not chow-maintained rats. AUC analyses for OGTT show suppression in glycemia by sitagliptin with MPC or soy in chow- and HFD-maintained rats, suggesting that chronic ingestion of dairy or soy proteins may augment endogenous GLP-1 signaling and the glycemic- and food intake-suppressive effects of DPP-IV inhibition. [ABSTRACT FROM AUTHOR]

Background Palatable food access promotes obesity leading some to diet. Here, we modeled the roles of duration, intermittency and choice of access in bingeing, escalation of daily intake, and underacceptance of alternatives. Method Female rats with (“Choice”) or without continuous chow access, received chow or continuous (Chocolate), intermittent (MWF) long (24 h, Int-Long), or intermittent short (30 min, Int-Short) access to a sucrose-rich, chocolate-flavored diet (CHOC). Results Int-Long rats showed cycling body weight; they overate CHOC, had increased feed efficiency on access days and underate chow and lost weight on non-access days, the latter correlating with their reduced brown fat. Int-Short rats had the greatest 30-min intake upon CHOC access, but did not underaccept chow or weight cycle. Individual vulnerability for intermittent access-induced feeding adaptations was seen. Continuous access rats gained fat disproportionate, but in direct relation, to their normalized energy intake and persistently underaccepted chow despite abstinence and return to normal weight. Abstinence reduced the binge-like CHOC intake of Int-Short rats and increased that of continuous access rats, but not to levels associated with intermittent access history. Choice increased daily CHOC intake under Continuous access and binge-like intake under Int-Short access. Conclusions Intermittency and duration of past access to palatable food have dissociable, individually-vulnerable influences on its intake and that of alternatives. With extended access, daily intake reflects the palatability of available food, rather than metabolic need. Ongoing restrictedness of access or a history of intermittency each drive binge-like intake. Aspects of palatable food availability, similar and different to drug availability, promote disordered eating. [ABSTRACT FROM AUTHOR]

This study evaluated the effect of sexual experience on anxiety and hormonal levels associated with the performance of sexual behavior. Two groups of male rats, one with, the second without, sexual experience, were exposed to four different copulatory conditions: ad libitum copulation until ejaculation (ADC-E); enforced interval copulation until ejaculation (EIC-E); ad libitum copulation up to 3 intromissions (ADC-3I); and enforced interval copulation up to 3 intromissions (EIC-E3I). At the end of each condition the animals were subjected to an open-field test to measure anxiety, before being sacrificed to measure corticosterone (CORT) and testosterone (T) levels. The sexually-inexperienced males showed less hyperactivity, lower sexual motivation, and higher anxiety levels. Only in the ADC-E and EIC-E conditions did both the inexperienced and experienced rats have a higher number of entries to the central squares of the open-field test. Both the sexually-inexperienced and experienced male rats showed an increase in CORT levels, but only the latter had increased T levels under all copulatory conditions. These findings reveal that the anxiolytic effect of mating is dependent on previous sexual experience and the degree of control that the male rats had during sexual interaction. The changes in the levels of both hormones could be part of the physiological process necessary to satisfy the demands involved in sexual performance and open filed. These data provide further insight into the role of sexual experience in mediating the release of CORT and T, as well as the anxiolytic effects of ejaculation. [ABSTRACT FROM AUTHOR]

Purpose: To compare the blood-brain barrier permeability changes induced by synchrotron microbeam radiation therapy (MRT, which relies on spatial fractionation of the incident x-ray beam into parallel micron-wide beams) with changes induced by a spatially uniform synchrotron x-ray radiation therapy.Methods and Materials: Male rats bearing malignant intracranial F98 gliomas were randomized into 3 groups: untreated, exposed to MRT (peak and valley dose: 241 and 10.5 Gy, respectively), or exposed to broad beam irradiation (BB) delivered at comparable doses (ie, equivalent to MRT valley dose); both applied by 2 arrays, intersecting orthogonally the tumor region. Vessel permeability was monitored in vivo by magnetic resonance imaging 1 day before (T-1) and 1, 2, 7, and 14 days after treatment start. To determine whether physiologic parameters influence vascular permeability, we evaluated vessel integrity in the tumor area with different values for cerebral blood flow, blood volume, edema, and tissue oxygenation.Results: Microbeam radiation therapy does not modify the vascular permeability of normal brain tissue. Microbeam radiation therapy-induced increase of tumor vascular permeability was detectable from T2 with a maximum at T7 after exposure, whereas BB enhanced vessel permeability only at T7. At this stage MRT was more efficient at increasing tumor vessel permeability (BB vs untreated: +19.1%; P=.0467; MRT vs untreated: +44.8%; P<.0001), and its effects lasted until T14 (MRT vs BB, +22.6%; P=.0199). We also showed that MRT was more efficient at targeting highly oxygenated (high blood volume and flow) and more proliferative parts of the tumor than BB.Conclusions: Microbeam radiation therapy-induced increased tumor vascular permeability is: (1) significantly greater; (2) earlier and more prolonged than that induced by BB irradiation, especially in highly proliferative tumor areas; and (3) targets all tumor areas discriminated by physiologic characteristics, including those not damaged by homogeneous irradiation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to analyze the effect of resistance training (RT) in rats with severe obesity. We examined the effects of 4 sessions·wk-1 for 4 wks of RT in Zucker rats with severe obesity. The animals were divided into 4 groups with 4 animals in each: sedentary lean (SEDL), RT lean (RT-L), sedentary obese (SED-O), and RT obese (RTO). The RT attenuated body weight (BW) gain in obese rats (RT-O) compared to the sedentary obese rats (SED-O; P<0.05). The RT-L group increases MS (P<0.05), and there was a difference in gain with respect to RT-O group (P<0.05), which in turn, RT-O did not increase MS (P>0.05). Both SED-O and RT-O groups have a larger deposit of epididymal and brown fat as compared to healthy rats eutrophic (SED-L and RT-L; P<0.05). The muscle weight is lower in obese rats compared to lean rats (P<0.05). The fasting blood glucose was higher in obese rats compared to lean rats (P<0.05), in turn, no difference was observed in cardiovascular parameters between groups (P>0.05). These data show that a short-term RT program attenuated BW gain in Zucker rats with severe obesity, but does not alter the changes generated by severe obesity. [ABSTRACT FROM AUTHOR]

A series of new 7-bromo-5-(2′-chlorophenyl)-3-arylamino-1,2-dihydro-3 H-1,4-benzodiazepine derivatives ( II- VIII) were synthesized. The series of synthesized compounds included those that had a substantial effect on appetite in rats, exhibiting both orexigenic and anorexigenic effects at low doses (2.07 - 2.21 μM). Compound VI had anorexigenic activity comparable with that of the hormone leptin, which reduces the appetite and food intake. Co-administration of leptin and III, which exhibited a pronounced orexigenic effect, reduced appetite by 73%. [ABSTRACT FROM AUTHOR]

Key points Fructose-containing sugars, including sucrose and high fructose corn syrup (HFCS), have been implicated in the epidemics of obesity and type 2 diabetes., Few studies have evaluated the impact of perinatal exposure to these sugars on metabolic and physiological outcomes in the offspring., Using a rat model, offspring exposed to a maternal sucrose or HFCS diet during the prenatal and/or suckling periods were found to have altered adiposity and liver fat content and composition at weaning., Plasma levels of free fatty acids remained elevated in young adulthood, but consumption of a control diet following weaning appeared to ameliorate most other effects of perinatal exposure to a maternal high-sugar diet., Guidelines for maternal nutrition should advise limiting consumption of fructose-containing sugars, and it is particularly important that these recommendations include maternal nutrition during lactation., Abstract Perinatal exposure to excess maternal intake of added sugars, including fructose and sucrose, is associated with an increased risk of obesity and type 2 diabetes in adult life. However, it is unknown to what extent the type of sugar and the timing of exposure affect these outcomes. The aim of this study was to determine the impact of exposure to maternal consumption of a 10% (w/v) beverage containing sucrose or high fructose corn syrup-55 (HFCS-55) during the prenatal and/or suckling periods on offspring at 3 and 12 weeks, utilising a cross-fostering approach in a rodent model. Perinatal sucrose exposure decreased plasma glucose concentrations in offspring at 3 weeks, but did not alter glucose tolerance. Increased adiposity was observed in 3-week-old offspring exposed to sucrose or HFCS-55 during suckling, with increased hepatic fat content in HFCS-55-exposed offspring. In terms of specific fatty acids, hepatic monounsaturated (omega-7 and -9) fatty acid content was elevated at weaning, and was most pronounced in sucrose offspring exposed during both the prenatal and suckling periods, and HFCS-55 offspring exposed during suckling only. By 12 weeks, the effects on adiposity and hepatic lipid composition were largely normalised. However, exposure to either sucrose or HFCS-55 during the prenatal period only was associated with elevated plasma free fatty acids at weaning, and this effect persisted until 12 weeks. This study suggests that the type of sugar and the timing of exposure (prenatal or suckling periods) are both important for determining the impact on metabolic health outcomes in the offspring. [ABSTRACT FROM AUTHOR]

Key points 5-HT is a neuromodulator released from carotid body (CB) chemoreceptor (type I) cells and facilitates the sensory discharge following chronic intermittent hypoxia (CIH)., In the present study, we show that, in addition to type I cells, adjacent glial-like type II cells express functional, ketanserin-sensitive 5-HT2 receptors, and their stimulation increases cytoplasmic Ca2+ derived from intracellular stores., In type II cells, 5-HT activated a ketanserin-sensitive inward current ( I5-HT) that was similar to that ( IUTP) activated by the P2Y2R agonist, UTP., As previously shown for IUTP, I5-HT was inhibited by BAPTA-AM and carbenoxolone (5 μ m), a putative blocker of ATP-permeable pannexin (Panx)-1 channels; IUTP was reversibly inhibited by the specific Panx-1 mimetic peptide channel blocker, 10Panx peptide., Paracrine stimulation of type II cells by 5-HT, leading to ATP release via Panx-1 channels, may contribute to CB excitability, especially in pathophysiological conditions associated with CIH (e.g. obstructive sleep apnoea)., Abstract Carotid body (CB) chemoreceptor (type I) cells can synthesize and release 5-HT and increased autocrine-paracrine 5-HT2 receptor signalling contributes to sensory long-term facilitation during chronic intermittent hypoxia (CIH). However, recent studies suggest that adjacent glial-like type II cells can respond to CB paracrine signals by elevating intracellular calcium (Δ[Ca2+]i) and activating carbenoxolone-sensitive, ATP-permeable, pannexin (Panx)-1-like channels. In the present study, using dissociated rat CB cultures, we found that 5-HT induced Δ[Ca2+]i responses in a subpopulation of type I cells, as well as in most (∼67%) type II cells identified by their sensitivity to the P2Y2 receptor agonist, UTP. The 5-HT-induced Ca2+ response in type II cells was dose-dependent (EC50 ∼183 n m) and largely inhibited by the 5-HT2A receptor blocker, ketanserin (1 μ m), and also arose mainly from intracellular stores. 5-HT also activated an inward current ( I5-HT) in type II cells (EC50 ∼200 n m) that was reversibly inhibited by ketanserin (1-10 n m), the Ca2+ chelator BAPTA-AM (5 μ m), and low concentrations of carbenoxolone (5 μ m), a putative Panx-1 channel blocker. I5-HT reversed direction at approximately −11 mV and was indistinguishable from the UTP-activated current ( IUTP). Consistent with a role for Panx-1 channels, IUTP was reversibly inhibited by the specific Panx-1 mimetic peptide blocker 10Panx (100 μ m), although not by its scrambled control peptide (scPanx). Because ATP is an excitatory CB neurotransmitter, it is possible that the contribution of enhanced 5-HT signalling to the increased sensory discharge during CIH may occur, in part, by a boosting of ATP release from type II cells via Panx-1 channels. [ABSTRACT FROM AUTHOR]

Key points Ligating the femoral artery of a rat for 72 h, a model for peripheral artery disease, causes an exaggerated exercise pressor reflex in response to muscle contraction., Likewise, the hindlimb muscles of rats with ligated femoral arteries show increased levels of reactive oxygen species., Infusion of tiron, a superoxide scavenger, attenuated the exaggerated pressor reflex and reduced reactive oxygen species production in rats with ligated femoral arteries., Conversely, we found no effect of tiron infusion on the pressor reflex in rats with patent femoral arteries., These results suggest a role of reactive oxygen species with respect to causing the exaggerated pressor response to contraction seen in rats with ligated arteries and peripheral artery disease., Abstract Contraction of muscle evokes the exercise pressor reflex (EPR), which is expressed partly by increases in heart rate and arterial pressure. Patients with peripheral artery disease (PAD) show an exaggerated EPR, sometimes report pain when walking and are at risk for cardiac arrthymias. Previous research suggested that reactive oxygen species (ROS) mediate the exaggerated EPR associated with PAD. To examine the effects of ROS on the EPR, we infused a superoxide scavenger, tiron, into the superficial epigastric artery of decerebrated rats. In some, we simulated PAD by ligating a femoral artery for 72 h before the experiment. The peak EPR in 'ligated' rats during saline infusion averaged 31 ± 4 mmHg, whereas the peak EPR in these rats during tiron infusion averaged 13 ± 2 mmHg ( n = 12; P < 0.001); the attenuating effect of tiron on the EPR was partly reversed when saline was reinfused into the superficial epigastric artery (21 ± 2 mmHg; P < 0.01 vs. tiron). The peak EPR in 'ligated' rats was also attenuated ( n = 7; P < 0.01) by infusion of gp91ds-tat, a peptide that blocks the activity of NAD(P)H oxidase. Tiron infusion had no effect on the EPR in rats with patent femoral arteries ( n = 9). Western blots showed that the triceps surae muscles of 'ligated' rats expressed more Nox2 and p67phox, which are components of NADPH oxidase, compared to triceps surae muscles of 'freely perfused' rats. Tiron added to muscle homogenates reduced ROS production in vitro. The results of the present study provide further evidence indicating that ROS mediates the exaggeration of EPR in rats with simulated PAD. [ABSTRACT FROM AUTHOR]

Key points The brainstem dorsal column nuclei (DCN) process sensory information arising from the body before it reaches the brain and becomes conscious., Despite significant investigations into sensory coding in peripheral nerves and the somatosensory cortex, little is known about how sensory information arising from the periphery is represented in the DCN., Following stimulation of hind-limb nerves, we mapped and characterised the evoked electrical signatures across the DCN surface., We show that evoked responses recorded from the DCN surface are highly reproducible and are unique to nerves carrying specific sensory information., Abstract The brainstem dorsal column nuclei (DCN) play a role in early processing of somatosensory information arising from a variety of functionally distinct peripheral structures, before being transmitted to the cortex via the thalamus. To improve our understanding of how sensory information is represented by the DCN, we characterised and mapped low- (<200 Hz) and high-frequency (550-3300 Hz) components of nerve-evoked DCN surface potentials. DCN surface potentials were evoked by electrical stimulation of the left and right nerves innervating cutaneous structures (sural nerve), or a mix of cutaneous and deep structures (peroneal nerve), in 8-week-old urethane-anaesthetised male Wistar rats. Peroneal nerve-evoked DCN responses demonstrated low-frequency events with significantly longer durations, more high-frequency events and larger magnitudes compared to responses evoked from sural nerve stimulation. Hotspots of low- and high-frequency DCN activity were found ipsilateral to stimulated nerves but were not symmetrically organised. In conclusion, we find that sensory inputs from peripheral nerves evoke unique and characteristic DCN activity patterns that are highly reproducible both within and across animals. [ABSTRACT FROM AUTHOR]

Background and Objective Doxycycline is an antibiotic agent that inhibits the activity of matrix metalloproteinases ( MMPs) present in the extracellular matrix. In this study, the rat incisor was submitted to a hypofunctional condition, and the effects of doxycycline (80 mg/kg/d) on the expression and activity of MMP-2, as well as on eruption rate, were determined in the odontogenic region and in the periodontal ligament for 14 d. Material and Methods Rats were distributed into four groups: normofunctional ( NF); doxycyline normofunctional ( DNF); hypofunctional ( HP); and doxycyline hypofunctional ( DHP). The left lower incisors of 10 rats were shortened every 2 d, using a high-rotation drill, to produce the HP and DHP groups, after starting doxycycline treatment (80 mg/kg) by gavage. Eruption was measured using a millimeter ocular, from the gingival margin to the top of the tooth in the HP and DHP groups, and also by a mark made in the tooth previously, in the NF and DNF groups. The hemimandibles were removed and the teeth were extracted to collect the periodontal and odontogenic tissues for immunohistochemical analyses and zymography. Results The eruption rates were higher in the HP and the DHP groups than in the NF and DNF groups, respectively ( p < 0.05). In the odontogenic region, neither of the treatments changed the expression and activity of MMP-2. In the HP group, the shortening treatment decreased the expression, but not the activity, of MMP-2, while doxycycline was able to inhibit the increase of expression and activity of MMP-2. Conclusion We conclude that the inhibition of MMP-2 by doxycycline, during incisor shortening, was not enough to alter the eruption rate, which suggests that MMP-2 may have an important role in the turnover of extracellular matrix of the periodontal ligament during the tooth-eruption process. [ABSTRACT FROM AUTHOR]

Gestational iron deficiency (ID) can alter developmental programming through impaired nephron endowment, leading to adult hypertension, but nephrogenesis is unstudied. Iron status and renal development during dietary-induced gestational ID (<6 mg Fe kg-1 diet from Gestational Day 2 to Postnatal Day (PND) 7) were compared with control rats (198 mg Fe kg-1 diet). On PND2-PND10, PND15, PND30 and PND45, blood and tissue iron status were assessed. Nephrogenic zone maturation (PND2-PND10), radial glomerular counts (RGCs), glomerular size density and total planar surface area (PND15 and PND30) were also assessed. Blood pressure (BP) was measured in offspring. ID rats were smaller, exhibiting lower erythrocyte and tissue iron than control rats (PND2-PND10), but these parameters returned to control values by PND30-PND45. Relative kidney iron (µg g-1 wet weight) at PND2-PND10 was directly related to transport iron measures. In ID rats, the maturation of the active nephrogenic zone was later than control. RGCs, glomerular size, glomerular density, and glomerular planar surface area were lower than control at PND15, but returned to control by PND30. After weaning, the kidney weight/rat weight ratio (mg g-1) was heavier in ID than control rats. BP readings at PND45 were lower in ID than control rats. Altered kidney maturation and renal adaptations may contribute to glomerular size, early hyperfiltration and long-term renal function. [ABSTRACT FROM AUTHOR]

Paenibacillus alvei, a naturally occurring soil microorganism, may be used in the control and/or elimination of human/animal pathogens present on/within produce commodities associated with human consumption. The safety of oral exposure to P. alvei in male, nulliparous females, the pregnant dam and developing fetus was assessed. Adult male and female rats received a single oral dose (gavage) of P. alvei and tissues were collected at post exposure days 0, 3 and 14. To evaluate the effect of the test organism on fetal development, sperm positive female rats received the test organism every 3 days thereafter throughout gestation. As human exposure would be no more than 1 x 10³ CFU/ml the following dose levels were evaluated in both study phases: 0 CFU/ml tryptic soy broth (negative control); 1 x 108 CFU/ml; 1 x 104 CFU/ml or 1 x 10² CFU/ml. Neither sex specific dose-related toxic effects (feed or fluid consumption, body weight gain, and histopathology) nor developmental/reproductive effects including the number of implantations, fetal viability, fetal weight, fetal length and effects on ossification centers were observed. The test organism did not cross the placenta and was not found in the amniotic fluid. [ABSTRACT FROM AUTHOR]

One of the most challenging adaptations within the therians has been to ensure dynamic stability of the trunk during rapid locomotion in highly structured environments. A reorganization of limb mechanics and development of new sensors has taken place within their stem lineage. Rats, which have a similar lifestyle to the first therians, possess sinus hairs specialized for tactile sensing. It is supposed that carpal sinus hairs have a role in sensing substrate properties and can thus induce adjustments in limb kinematics and body posture according to the different surface diameters and structures detected. This implies a shared sensorimotor control loop of sinus hairs and body posture. To investigate the role of the carpal sinus hairs during locomotion and to explore a possible interaction between limb and spine motion, spatiotemporal and kinematic parameters as well as the contact mechanics of the hairs with regard to the surface were quantified. Locomotion on a treadmill with continuous and discontinuous substrates was compared in the presence/absence of the carpal sinus hairs across a speed range from 0.2 m/s to 0.6 m/s. Recordings were taken synchronously using x-ray fluoroscopy and normal-light high-speed cameras. Our investigation revealed that the three tactile hairs made a triangle-like contact with the ground approximately 30 ms before touchdown of the forelimb. Within that time, it is likely that both the body posture and its oscillation are adjusted according to the different surface textures. The sensory input of the carpal sinus hairs induces a stabilization of the trajectory of the center of mass and, therefore, improves the dynamic stability of the trunk; conversely, the absence of the sensors results in a more crouched frontal body posture, similar to that seen in rats when they are moving in an unknown terrain. The carpal sinus hairs also sense the animal's speed during surface contact. This implicates an adjustment of the limb and spine kinematics, by increasing the speed-dependent effect or by increasing the distance between the trunk and the ground when the rat is walking faster. [ABSTRACT FROM AUTHOR]

The plant Guiera senegalensis is commonly used in improving lactation in the North Western part of Nigeria. Aqueous extract of the plant Guiera senegalensis known as 'Sabara' in Hausa language, was investigated for possible milk production effect in Wistar rats. Six groups of five lactating rats each were dosed. Group A was used as the negative control and Group F which received 0.1 IU of oxytocin was used as positive control. The other four groups (B, C, D, and E) received 50mg, 100mg, 200mg, and 400mg of the extract respectively. Group C showed the highest response with statistical significance at P<0.05 when compared to groups A, D, E, and the positive control (group F). Isolated tissue experiment using the Ugo Basile micro dynamometer showed that the extract was able to stimulate uterine contractions at a dose of 0.3 mg/ml, but no contractions were recorded at 0.6 mg/ml. There were no contractions seen when the extract was tested on intestinal tissue. Acetyl choline was used as a positive control in both the uterine and intestinal tissue. The effect of acetyl choline was compared to the effect of the extract on both tissues. The experiment showed that higher concentrations of the plant extract were not capable of inducing smooth muscle contractions. The lack of smooth muscle contractions at higher doses was similar to what was observed in the milk production activity that was related to pup weight gain. Thus, milk production did not increase significantly with higher doses. In conclusion, the water extract of Guiera senegalensis has a positive galactagogue effect. [ABSTRACT FROM AUTHOR]

Stress contributes, as a risk factor, to such psychological disorders as anxiety. The effects of electrical lesions in the basolateral amygdala nucleus ( BLA) were investigated on the locomotor activity and anxiety-like behaviour in different stress durations. For this purpose, rats were randomly allocated to control, sham, and experimental groups, the latter including groups with and without BLA nucleus subjected to acute, sub-chronic, and chronic stress conditions for 1, 7, and 21 days, respectively, applied 6 h/d. The induced anxiety behaviour was evaluated using the open field test ( OFT) while other variables were measured. Findings revealed that sub-chronic stress led to significantly reduced ( P<.05) anxiety behaviours as measured by entries into and the time spent in the centre area while it also led to significant impairments in exploratory and locomotor activities, indicating intensified anxiety-like behaviour. BLA lesion affected rat behaviour differently such that it significantly ( P<.05) decreased fear under sub-chronic and chronic stress conditions as evidenced by the subjects' greater tendency to enter the centre area in the open field test and their increased number of rearing events ( P<.01). However, BLA lesion led to no significant decrease in the locomotor activity of subjects exposed to sub-chronic or chronic stress conditions as compared with those in similar groups but without BLA lesion. Finally, BLA lesion was found not only to decrease significantly ( P<.01) adrenal gland and body weights, particularly under sub-chronic stress, but also to play a critical role in modulating adrenal functions by decreasing adrenal gland weight, and thereby reducing depression-like symptoms. [ABSTRACT FROM AUTHOR]

The present study was designed to determine the possible protective effects of E. purpurea extracts (EPE) against gamma (γ-) radiation exposure (6Gy) induced biochemical alterations and oxidative tissue damage (liver and testes) in male rats given EPE (100 mg/kg/day for 8 weeks) prior to γ-irradiation. It has been found that γ-irradiation led to hepatic and testicular oxidative stress with concomitant increase in liver function enzymes. Serum lipid profile and hormone level has also been found altered. Rats dosed with EPE before exposure to γ-rays showed significantly less severe damage and remarkable improvement in all of the measured parameters when compared to irradiated rats. It could be concluded that EPE attenuates the deleterious effects of radiation-induced biochemical disorders and tissue damage (liver and testes). [ABSTRACT FROM AUTHOR]

Rationale: The polyglutamine disease spinocerebellar ataxia type 17 (SCA17) is a neurodegenerative disease leading to severe neurological symptoms during development. Additionally, patients affected by SCA17 display psychosis earlier than their motor disorders.Objective: Here the putative psychotic phenotype and endophenotype of transgenic SCA17 rats was examined.Methods: The expression of schizophrenia-like symptoms was evaluated over a longitudinal period before and after the onset of neurological symptoms in SCA17. To this end, transgenic SCA17 rats' monoamine neurotransmission was investigated along with their locomotion at baseline and in response to amphetamine using in-vivo microdialysis in free moving conditions, their sensorimotor gating using pre-pulse inhibition of startle reaction, and their object memory using the novel object recognition test as an index of cognitive impairments.Results: Presymptomatic SCA17 rats displayed dysregulated monoamine levels at baseline and in response to amphetamine compared with control wild-type (wt) rats. At that stage, neither amphetamine-induced hyperlocomotion nor sensorimotor gating differed from that in wt rats. Symptomatic SCA17 rats developed sensorimotor gating deficits and also showed an impaired object memory, while their monoaminergic responses remained supersensitive to amphetamine.Conclusions: The data of the present study demonstrate a neurochemical endophenotype in SCA17 rats resembling that of prodromal schizophrenia. These findings suggest that a sensitization of the monoamine systems arises early in adulthood in SCA17 rats and may predispose them to express schizophrenia-like symptoms later in life. [ABSTRACT FROM AUTHOR]

Convulsive seizures are due to abnormal synchronous and repetitive neuronal discharges in the central nervous system ( CNS). Finding new therapeutics to overcome the side effects of the current drug therapies and to increase their effectiveness is ongoing. Orexin-A and orexin-B are brain neuropeptides originating from postero-lateral hypothalamic neurons. Studies show that orexins, through activation of OX1 and OX2 receptors, have excitatory effects in the CNS. Accordingly, this study was designed to evaluate the effect of OX1 receptor antagonist ( SB-334867) on seizure- and anxiety-related behaviors of pentylenetetrazol ( PTZ)-kindled rats. Kindling was induced by repeated intraperitoneal ( IP) injections of PTZ (32 mg/kg) with two-day intervals for 24 days in male Wistar rats. Three groups received intracerebroventricular ( ICV) injections of SB-334867 (2.5, 5, and 10 μg/rat) before PTZ injections. Two control groups received vehicle (2 μL/rat, ICV) and valproate (26 μg/rat, ICV) before PTZ injections. An extra group of control animals received saline both ICV and IP. Seizure-related behaviors were monitored for 30 min following PTZ administration. The anxiety-like behaviors were also assessed using elevated plus-maze in the first and last days of the study. The results revealed that ICV injection of SB-334867, mainly at the dose of 10 μg/rat, decreased the median of seizure stages, prolonged the latency and reduced the duration of different seizure stages, and reversed the PTZ-induced anxiety-like behaviors. Based on the presented results, it is suggested that pharmacological blockade of the OX1 receptor is a potential target in the treatment of seizure and concomitant anxiety disorders. [ABSTRACT FROM AUTHOR]

Background: Head spot is one of the phenotypes identified in the KFRS4/Kyo rat strain. Although previous linkage analysis suggested that Ednrb, which is frequently involved in coat color variations in various animals, could be the gene responsible for this phenotype, no mutations have been identified in its coding region. Results: To identify mutations causative of this phenotype in KFRS4/Kyo, we analyzed target capture sequencing data that we recently generated. Our target capture method has a unique feature, i.e., it covers not only exonic regions but also conserved non-coding sequences (CNSs) among vertebrates; therefore, it has the potential to detect regulatory mutations. We identified a deletion of approximately 50 kb in length approximately 50 kb upstream of Ednrb. A comparative analysis with the epigenomic data in the corresponding region in humans and mice showed that one of the CNSs might be an enhancer. Further comparison with Hi-C data, which provide information about chromosome conformation, indicated that the putative enhancer is spatially close to the promoter of Ednrb, suggesting that it acts as an enhancer of Ednrb. Conclusions: These in silico data analyses strongly suggest that the identified deletion in the intergenic region upstream of Ednrb, which might contain a melanocyte-specific enhancer, is the mutation causative of the head spot phenotype in the KFRS4/Kyo rat strain. [ABSTRACT FROM AUTHOR]

The typical cause of death in pulmonary hypertension (PH) is right ventricular (RV) failure, with females showing better survival rates than males. Recently, metabolic shift and mitochondrial dysfunction have been demonstrated in RV failure secondary to PH. In light of evidence showing that estrogen protects mitochondrial function and biogenesis in noncardiovascular systems, we hypothesized that the mechanism by which estrogen preserves RV function is via protection of mitochondrial content and oxidative capacity in PH. We used a well-established model of PH (Sugen+Hypoxia) in ovariectomized female rats with/without estrogen treatment. RV functional measures were derived from pressure-volume relationships measured via RV catheterization in live rats. Citrate synthase activity, a marker of mitochondrial density, was measured in both RV and LV tissues. Respiratory capacity of mitochondria isolated from RV was measured using oxygraphy. We found that RV ventricular-vascular coupling efficiency decreased in the placebo-treated SuHx rats (0.78 ± 0.10 vs. 1.50 ± 0.13 in control, P < 0.05), whereas estrogen restored it. Mitochondrial density decreased in placebo-treated SuHx rats (0.12 ± 0.01 vs. 0.15 ± 0.01 U citrate synthase/mg in control, P < 0.05), and estrogen attenuated the decrease. Mitochondrial quality and oxidative capacity tended to be lower in placebo-treated SuHx rats only. The changes in mitochondrial biogenesis and function paralleled the expression levels of PGC-1a in RV. Our results suggest that estrogen protects RV function by preserving mitochondrial content and oxidative capacity. This provides a mechanism by which estrogen provides protection in female PH patients and paves the way to develop estrogen and its targets as a novel RV-specific therapy for PH. [ABSTRACT FROM AUTHOR]