Simvastatin did not prevent nor restore ovariectomy-induced bone loss in adult rats

Current published results on whether statins have beneficial effects on bone metabolism have been conflicting so far. In order to further investigate if statins were promising candidates for the treatment for osteoporosis, we conducted a study in which rats were ovariectomized (OVX) at 6 months of age, allowed to lose bone for 60 days and followed by oral administration of simvastatin at the dose levels of 0.3-10 mg/kg/d for 60 days. PGE2 (6 mg/kg) was used as a positive control. Study endpoints included bone histomorphometry on the proximal tibial metaphysis (PTM) and the tibial diaphysis (TX), dual-energy X-ray absorptiometry on the right femur and micro computed tomography (ICT) on the 5th lumbar vertebra (LV). After 120 days of OVX, cancellous bone lost by 80% in the PTM and 18% in the LV accompanied by increased bone formation and resorption. Simvastatin at all dose levels did not affect bone volume, bone formation rate and bone erosion surface when compared to 120 day ovariectomized animals at all bone sites studied. By contrast, PGE2 restored cancellous and cortical bone area to sham control levels. In conclusion, this study demonstrated that unlike PGE2, oral administration of simvastatin did not have effects on cancellous or cortical bone formation and resorption; and consequently was not able to prevent further bone loss or restore bone mass in the osteopenic, OVX rats.     

Reproductive state but not recent aggressive experience influences behavioral consistency in male Siamese fighting fish

Consistent individual differences in behavior imply that individuals act in the same manner every time they encounter a situation while differing from others. While these differences occur in a variety of contexts in a wide range of organisms, how recent experience affects behavioral consistency remains underexplored. Male Siamese fighting fish exhibit consistent individual differences in behavior when both a male and a female are present. However, whether these responses can be shaped by immediate recent aggressive experience is unknown. In this study, males first were presented with paired dummy male and female conspecifics after they had been isolated to obtain a baseline, no-experience measure. Males then won and lost fights and were retested with the dummies after each fight. These three experience types (no, win, loss) occurred both when males did and did not have nests to determine the effects of nest presence, experience, and the interaction between these factors on behavioral consistency. Overall behavior did not change based on experience with the exception of male-directed tail beats. Repeatability values were affected more by having a nest than fight outcome. This study demonstrates that consistent individual differences in behavior to conflicting stimuli are fairly resistant to short-term aggressive experiential effects.     

Prior host feeding experience influences ovipositional but not feeding preference in a polyphagous insect herbivore

Black vine weevils, Otiorhynchus sulcatus (Fabricius) (Coleoptera: Curculionidae), are globally‐distributed polyphagous pests of many horticultural crops. We investigated how adult weevils were affected by host switching and, in particular, how host plant species nutritional and defensive chemistry affected subsequent host plant species selection and oviposition. Adults were fed one of three host plant species, blackcurrant [Ribes nigrum L. (Grossulariaceae)], raspberry [Rubus idaeus L. (Rosaceae)], or strawberry [Fragaria x ananassa Duchesne (Rosaceae)], throughout their pre‐reproductive periods and then subjected to behavioral choice assays with these plants. Foliar chemistry differed significantly among the three host plant species. Compared to raspberry and strawberry foliage, blackcurrant foliage was 13% lower in nitrogen, 3% higher in carbon, and 28% higher in phenolic compounds. Initial host plant species had a significant effect on weevil mortality, with more weevils dying when previously fed blackcurrant (12%) than strawberry (3%) or raspberry (0%) regardless of subsequent host. Initial host plant species also affected oviposition, with weevils laying only ca. two eggs per week when previously fed blackcurrant, compared to those on raspberry or strawberry (ca. 11 and 15 eggs per week, respectively). When given a choice, weevils discriminated among host plant species and tended to oviposit on plants on which they had previously fed, even when the plant was nutritionally inferior for egg production and adult survival. In contrast, feeding behavior was only affected by the current host plant species. Feeding and oviposition were related to leaf chemistry only in blackcurrant, as leaf consumption was negatively correlated with foliar carbon and zinc concentrations, and positively correlated with foliar phosphorus and potassium concentrations.     

Strength training during pregnancy influences hippocampal plasticity but not body development in neonatal rats

Objective:To describe the effects of strength exercise practice during pregnancy on the offspring’s development parameters: growth and motor performance, hippocampal neuroplasticity, and stress levels.Methods:Pregnant Wistar rats were divided into two groups: sedentary and exercised rats. Exercised pregnant rats were subjected to a strength training protocol (vertical ladder climbing) throughout the gestational period. Male offspring’s body weight, length, and head size were evaluated during the neonatal period (postnatal days [P]2–P21), as well as motor milestones during P0–P8. At P8, a set of male pups were subjected to global hippocampal DNA methylation, hippocampal cell proliferation, and plasma corticosterone concentration.Results:Offspring from trained mothers presented a transient change in body morphometric evaluations, no differences in milestone assessments, enhancement of cell proliferation in the dentate gyrus of the hippocampus, and decreased global hippocampal DNA methylation compared with the offspring from sedentary mothers. Furthermore, strength training during pregnancy did not change the corticosterone concentration of exercised mothers and their offspring.Conclusions:These data indicate that strength training can protect offspring’s development and could impact positively on parameters linked to cognitive function. This study provides a greater understanding of the effects of strength exercise practiced during pregnancy on the offspring’s health.     

Short-term immobilization and recovery affect skeletal muscle but not collagen tissue turnover in humans

Not much is known about the effects of immobilization and subsequent recovery on tendon connective tissue. In the present study, healthy young men had their nondominant leg immobilized for a 2-wk period, followed by a recovery period of the same length. Immobilization resulted in a mean decrease of 6% (5,413 to 5,077 mm(2)) in cross-sectional area (CSA) of the triceps surae muscles and a mean decrease of 9% (261 to 238 N.m) in strength of the immobilized calf muscles. Two weeks of recovery resulted in a 6% increased in CSA (to 5,367 mm(2)), whereas strength remained suppressed (240 N.m). No difference in Achilles tendon CSA was detected between the two legs at any time point. Local tendon collagen synthesis, measured as the peritendinous concentrations of PINP (NH(2)-terminal propeptide of type I collagen; indirect marker for collagen synthesis), was unchanged after 2 wk of immobilization. However, peritendinous levels of PINP were significantly elevated in the immobilized leg (15 to 139 ng/ml) following 2 wk of remobilization compared with preimmobilization levels. In contradiction hereto, systemic concentrations of PINP remained unchanged throughout the study. Immobilization reduced muscle size and strength, while tendon size and collagen turnover were unchanged. While recovery resulted in an increase in muscle size, strength was unchanged. No significant difference in tendon size could be detected between the two legs after 2 wk of recovery, although collagen synthesis was increased in the previously immobilized leg. Thus 2 wk of immobilization are sufficient to induce significant changes in muscle tissue, whereas tendon tissue seems to be more resistant to short-term immobilization.     

Anatomic connections between homotopic transplant of fetal cortical tissue and optic thalamus in adult rats

The present research was planned to study the possibility to reconstruct a damaged neural circuitry by replacing the injured neurons with homotopic fetal cells. In adult rats the motor cortex was injured with intracortical injection of kainic acid solution. After a delay of 10-14 days, a block of cerebral cortex of fetal rats (E17) was transplanted in the cavity produced by the kainic acid in the motor cortex. After 2-3 months, WGA-HRP solution was injected in the thalamus of the host and both anterogradely labeled fiber terminals and retrogradely labeled somata cells were researched in the transplanted cortex. The results showed that: 1) the host thalamus projects to the transplanted cortex with less density compared to the host cortex surrounding the transplant; 2) the thalamic projection to the transplant is not topographically organized whereas the projection to the host cortex is; 3) the transplant was virtually void of a significant projection to the thalamus of the host. In conclusion, the results offer direct evidence that the reconstruction of an injured thalamocortical circuitry of adult rat is not possible by transplanting homotopic fetal neurons.     

Galanin stimulates hCG induced testicular steroidogenesis in adult but not in immature male rats

The present study was undertaken to understand the role of galanin on testosterone secretion. Leydig cells from adult (60-80 days old) and immature (21-30 days old) rat testis were incubated with galanin (100 nM), galantide (100 nM) and Human Chorionic Gonadotropin (hCG, 25 I.U.) alone or in combinations and testosterone release was measured. It was observed that in adults, galanin failed to alter the basal testosterone release from the dispersed Leydig cells but potentiated the hCG induced testosterone release significantly. While galantide, prevented this galanin potentiating effect, but it did not alter the hCG alone induced testosterone release. On the other hand, the Leydig cells obtained from immature male rats were sensitive to hCG alone but not to galanin or galantide, both of which failed to alter the hCG induced testosterone release from these cells. Based on these results it can be postulated that galanin's role at the level of the male gonad is age dependent since its potentiating effects on hCG induced testosterone release were visible only in the adult and not in the immature male rats.     

Selective activation of microglia in spinal cord but not higher cortical regions following nerve injury in adult mouse

Neuronal plasticity along the pathway for sensory transmission including the spinal cord and cortex plays an important role in chronic pain, including inflammatory and neuropathic pain. While recent studies indicate that microglia in the spinal cord are involved in neuropathic pain, a systematic study has not been performed in other regions of the central nervous system (CNS). In the present study, we used heterozygous Cx3cr1 ^GFP/+mice to characterize the morphological phenotypes of microglia following common peroneal nerve (CPN) ligation. We found that microglia showed a uniform distribution throughout the CNS, and peripheral nerve injury selectively activated microglia in the spinal cord dorsal horn and related ventral horn. In contrast, microglia was not activated in supraspinal regions of the CNS, including the anterior cingulate cortex (ACC), prefrontal cortex (PFC), primary and secondary somatosensory cortex (S1 and S2), insular cortex (IC), amygdala, hippocampus, periaqueductal gray (PAG) and rostral ventromedial medulla (RVM). Our results provide strong evidence that nerve injury primarily activates microglia in the spinal cord of adult mice, and pain-related cortical plasticity is likely mediated by neurons.     

Estrogen alters excitability but not morphology of a sexually dimorphic neuromuscular system in adult rats

In rats, motoneurons of the spinal nucleus of the bulbocavernosus (SNB) innervate the bulbocavernosus (BC) muscle, which surrounds the base of the penis. The SNB/BC is a sexually dimorphic, steroid-sensitive neuromuscular system, which is critically important in male reproductive behavior. Androgens are necessary for the development, morphology, and function of the SNB/BC system. However, estradiol (E) is also necessary for the development of the SNB/BC system, and E is capable of maintaining BC EMG activity in adulthood. In this study, we used electrophysiological and anatomical methods to examine estrogenic effects on BC EMG activity. We used a modified H-reflex testing method to investigate polysynaptic reflex characteristics in intact males, castrates, and castrates treated short term with estradiol benzoate (EB). Measures of EMG activity, response latency, and spike count were altered in castrates, but maintained in EB-treated castrates to the levels of intact males. Furthermore, estrogenic effects were found in EMG activity that could be isolated to the periphery of the SNB/BC system. BC NMJ size and muscle fiber area have been demonstrated to be hormone sensitive, and we examined these for possible correlates of E's effects on BC EMG activity. BC muscles of intact males, castrates, and short-term EB-treated castrates were fixed and stained with zinc iodide and osmium tetroxide. NMJ size and muscle fiber area did not differ between groups. Together, these data suggest that E treatment results in changes in the neuromuscular periphery that maintain BC EMG activity, but this effect cannot be accounted for by changes in NMJ size or muscle fiber area.     

Prenatal amphetamine reduces alpha but not beta adrenergic receptor binding in brain of adult rats

Adults offspring of rats treated with daily injection of d,l-amphetamine sulfate (0.5 mg/kg s.c.) during pregnancy showed a significant decrease in brain alpha but not beta adrenergic receptor binding, without apparent changes in receptor affinity. This change may be a consequence of long lasting alterations in the metabolism of brain catecholamines produced by amphetamine administration at fetal age, and may account for the behavioral alterations described in these animals.     

Bone loss in ovariectomized rats: dominant role for estrogen but apparently not for FSH

Estrogen deficiency as the sole factor underlying post‐menopausal osteoporosis was challenged, in light of reports that both follicular stimulation hormone (FSH) receptor and FSHβ knockout mice were resistant to bone loss, suggesting a detrimental role for FSH. We assessed whether lowering FSH levels by gonadotropin realizing (GnRH) analog decapeptyl in ovariectomized female rats (OVX) affects bone. Wistar‐derived 25 days old OVX female rats were injected for 10 weeks with estradiol‐17β (E₂), with GnRH analog (decapeptyl) or with both. FSH and luteinizing hormone (LH) serum levels were markedly increased in OVX rats, with smaller growth plates with disrupted architecture; heavy infiltration of bone marrow with numerous adipocytes and reduced thickness of cortical bone. In OVX rats treated with E₂, FSH, and LH levels were intermediate, the tibia was similar to that of intact rats, but there was reduced thickness of cortical bone. In decapeptyl treated OVX rats, FSH and LH levels were suppressed, the organization of growth plate and the trabecular bone were disrupted, and there were fewer proliferative and chondroblastic cells and a large adipocytes population in bone marrow, but an increased trabecular bone volume (TBV). In the E₂ + decapeptyl treatment, FSH and LH levels were suppressed, with partially restored growth plate architecture and improved TBV. In conclusion, E₂ deficiency is the dominant factor impairing bone loss in OVX and concomitant changes in FSH/LH levels achieved by decapeptyl have some modulating, though complex role in this setting. The role of high FSH levels in post‐menopausal bone loss requires further investigation using combined sub‐optimal doses of the different hormones. J. Cell. Biochem. 112: 128–137, 2011. © 2010 Wiley‐Liss, Inc.     

Characteristics of the recovery processes in the resected thyroid of adult rats after sympathectomy

The investigation was carried out on 65 adult white male rats (12-month-old) after normal development or chemical sympathectomy by guanethidine and subtotal thyroidectomy. By means of electronic microscopic, autoradiographic and radioimmunological methods the increased functional activity in thyroid gland of chemically sympathectomized rats was found. This is mainly due to thyrotropin hyperproduction and intensification of proliferative potential of the organ. Partial resection of sympathectomized rats thyroid gland leads to exhaustion of adenohypophysis compensatory potential manifested in disjunction of integrative connections in hypothalamus-hypophysis-thyroid gland system and delay of thyroid status normalization.     

A weight-loss diet including coffee-derived mannooligosaccharides enhances adipose tissue loss in overweight men but not women

Mannooligosaccharides (MOS), extracted from coffee, have been shown to promote a decrease in body fat when consumed as part of free-living, weight-maintaining diets. Our objective was to determine if MOS consumption (4 g/day), in conjunction with a weight-loss diet, would lead to greater reductions in adipose tissue compartments than placebo. We conducted a double-blind, placebo-controlled weight-loss study in which 60 overweight men and women consumed study beverages and received weekly group counseling for 12 weeks. Weight and blood pressure were measured weekly, and adipose tissue distribution was assessed at baseline and at end point using magnetic resonance imaging. A total of 54 subjects completed the study. Men consuming the MOS beverage had greater loss of body weight than men consuming the Placebo beverage (-6.0 ± 0.6% vs. -2.3 ± 0.5%, respectively, P < 0.05). Men consuming the MOS beverage also had reductions in total body volume (P < 0.0001), total (P < 0.0001), subcutaneous (P < 0.0001), and visceral (P < 0.05) adipose tissue that were greater than changes observed in those consuming the Placebo beverage. In women, changes in body weight and adipose tissue compartments were not different between groups. Adding coffee-derived MOS to a weight-loss diet enhanced both weight and adipose tissue losses in men, suggesting a potential functional use of MOS for weight management and improvement in adipose tissue distribution. More studies are needed to investigate the apparent gender difference in response to MOS consumption.     

Effect of early decrease in the lesion size on late brain tissue loss, synaptophysin expression and functionality after a focal brain lesion in rats

The purpose of the present study is to determine the effects of early decrease in the lesion size on late brain tissue loss, synaptogenesis and functionality after a focal brain lesion in rats. The lesion was induced either to the cortex using the photothrombotic ischemic stroke or to the striatum using the malonate poisoning model. The cortical and striatal lesions amounted to 66-80 mm(3) at day 1 post-lesion and were reduced by 50% after the acute administration of dipyridyl (a liposoluble iron chelator) and aminoguanidine (an inhibitor of the inducible nitric oxide synthase), respectively. Loss of histologically intact tissue and synaptophysin expression as an indicator of synaptogenesis were examined at day 35 post-lesion. Both types of lesion resulted in synaptophysin upregulation in contralateral and ipsilateral cortical areas. On the contrary, brain tissue loss was greater after the striatal (-17%) than the cortical lesion (-5%). Synaptophysin expression and tissue loss were not different between drug- and vehicle-treated rats. Moreover, a set of standard neurological tests revealed a difference in deficit between the both types of lesion, yet only in the acute post-lesion stage. However, it did not distinguish between vehicle- and drug-treated rats whatever the lesion location. Our results indicate that late histological endpoints measurements are not recommended to probe the potential neuroprotective properties of a drug administered within the acute post-lesion stage. They also suggest that inhibition of cytotoxic mechanisms involved in lesion growth is of no clinical interest when it cannot lead to a long-term histological protection and/or increased synaptogenesis.     

Aggregation of detergent-insoluble tau is involved in neuronal loss but not in synaptic loss

Neurofibrillary tangles (NFTs), which consist of highly phosphorylated tau, are hallmarks of neurodegenerative diseases including Alzheimer disease (AD). In neurodegenerative diseases, neuronal dysfunction due to neuronal loss and synaptic loss accompanies NFT formation, suggesting that a process associated with NFT formation may be involved in neuronal dysfunction. To clarify the relationship between the tau aggregation process and synapse and neuronal loss, we compared two lines of mice expressing human tau with or without an aggregation-prone P301L mutation. P301L tau transgenic (Tg) mice exhibited neuronal loss and produced sarcosyl-insoluble tau in old age but did not exhibit synaptic loss and memory impairment. By contrast, wild-type tau Tg mice neither exhibited neuronal loss nor produced sarcosyl-insoluble tau but did exhibit synaptic loss and memory impairment. Moreover, P301L tau was less phosphorylated than wild-type tau, suggesting that the tau phosphorylation state is involved in synaptic loss, whereas the tau aggregation state is involved in neuronal loss. Finally, increasing concentrations of insoluble tau aggregates leads to the formation of fibrillar tau, which causes NFTs to form.     

Neonatal hyperleptinaemia programmes anxiety-like and novelty seeking behaviours but not memory/learning in adult rats

Leptin treatment during lactation programmes for leptin resistance at adulthood, evidenced by hyperleptinaemia, hyperphagia and overweight. Since leptin is known to affect stress response, emotional behaviour and memory/learning performance, the objective of the present study was to evaluate whether neonatal hyperleptinaemia programmes anxiety-like and novelty-seeking behaviours as well as memory/learning in adult male rats. During the first 10 days of lactation (from PN1 to PN10), pups were s.c. injected once per day with either 50 μL of saline (SAL) or murine leptin (LEP — 8 μg/100 g of body mass, saline diluted). Serum leptin was assessed at PN10 and at PN150. Two separate experiments were carried out: 1) experiment one: at PN137, 29 SAL and 30 LEP rats were tested in the elevated plus-maze (EPM) and, at PN142, their behaviour was assessed in the hole board (HB) arena; 2) experiment two: at PN140, a different group of rats consisting of 53 SAL and 56 LEP animals were tested in the radial arm water maze (RAWM). Serum leptin concentration was higher in the LEP group at PN10 and at PN150. LEP animals spent significantly less time in the open arms of the EPM. Furthermore, the number of nose-pokes in the HB arena was higher in LEP rats. There were no differences between groups regarding latency to find the hidden platform in the RAWM. Our results suggests that a central mechanism of leptin resistance at adulthood, caused by neonatal hyperleptinaemia, is associated with an increased level of anxiety and also that it intensifies novelty seeking-behaviour.     

Hyperglycemia contributes insulin resistance in hepatic and adipose tissue but not skeletal muscle of ZDF rats

To determine the contribution of hyperglycemia to the insulin resistance in various insulin-sensitive tissues of Zucker diabetic fatty (ZDF) rats, T-1095, an oral sodium-dependent glucose transporter (SGLT) inhibitor, was administered by being mixed into food. Long-term treatment with T-1095 lowered both fed and fasting blood glucose levels to near normal ranges. A hyperinsulinemic euglycemic clamp study that was performed after 4 wk of T-1095 treatment demonstrated partial recovery of the reduced glucose infusion rate (GIR) in the T-1095-treated group. In the livers of T-1095-treated ZDF rats, hepatic glucose production rate (HGP) and glucose utilization rate (GUR) showed marked recovery, with almost complete normalization of reduced glucokinase/glucose-6-phosphatase (G-6-Pase) activities ratio. In adipose tissues, decreased GUR was also shown to be significantly improved with a normalization of insulin-induced GLUT-4 translocation. In contrast, in skeletal muscles, the reduced GUR was not significantly improved in response to amelioration of hyperglycemia by T-1095 treatment. These results suggest that the contribution of hyperglycemia to insulin resistance in ZDF rats is very high in the liver and considerably elevated in adipose tissues, although it is very low in skeletal muscle.