Effect of Dietary Lipids on Phospholipase D Activity in Rat Brain

Phospholipase D (PLD) is emerging as a major player in many novel signaling pathways. Based on recent studies correlating membrane composition with enzyme function, we speculated that feeding of dietary lipids to the newborns has a major impact on brain PLD activity. To test this hypothesis, the rat dams were fed fat-free powder containing either safflower oil or fish oil, and a control powdered chow. The pups were weaned onto the diet and sacrificed at 30 days of age. PLD activity was measured by transphosphatidylation assays using rat brain membranes. This study shows that microsome GTPS-dependent PLD activity in rats fed safflower oil or fish oil was significantly reduced by 38% and 30% respectively compared to controls. Oleate-dependent PLD activity in the safflower oil group, however, was significantly increased by 38%. In contrast, synaptosome membrane (P2) GTPS-dependent PLD activity in rats consuming safflower oil was significantly increased by 29%, but there was no difference in oleate-dependent PLD activity. Likewise, no difference was observed in microsome oleate-dependent PLD and P2 GTPS-dependent PLD activity between the fish oil and the control groups. These results indicate that dietary lipid intake appears to modulate phospholipid metabolism and differential expression of PLD isozymes in the brain.     

肾脏和肾神经在应激、钠盐所致高血压中的作用

本工作采用电生理、生化、放免、电镜等方法,探讨了慢性应激和盐致高血压大鼠交感神经系统和肾脏功能的改变。实验在雄性ＳＤ大鼠上进行。结果表明：（１）高盐大鼠肾血浆流量（ＲＰＦ）和尿钠排泄明显增加,而应激大鼠ＲＰＦ显著下降。（２）电镜显示高盐大鼠近曲和远曲小管上皮细胞及线粒体变大,应激则使细胞萎缩、线粒体变小。（３）高盐大鼠肾皮质ＮａＫＡＴＰ酶活性下降,应激可使其恢复。（４）频谱分析显示应激大鼠低频波动（０２～０９Ｈｚ）明显增加。（５）应激导致大鼠肾素活性（ＰＲＡ）及血管紧张素Ⅱ（ＡＮＧⅡ）水平升高,并能使高盐大鼠低ＰＲＡ和ＡＮＧⅡ水平升高。（６）大鼠去除双侧肾神经后,应激无法造成血压升高、ＲＰＦ下降和ＰＲＡ、ＡＮＧⅡ上升。上述结果提示：肾交感神经系统兴奋性增加介导的肾脏机制,可能在应激和／或盐致高血压发病过程中具有重要作用。     

Brain glucose and insulin: effects on food intake and brain biogenic amines of rainbow trout

The effects of central (intracerebroventricular, 9 g fish^–1) and peripheral (intraperitoneal, 4 mg kg^–1) administration of bovine insulin, as well as the effect of hyperglycemia (oral administration of 1 g glucose fish^–1) and brain glucodeprivation (intracerebroventricular administration of 2-deoxy-D-glucose) on food intake and levels of brain (telencephalon, preoptic area, and hypothalamus) biogenic amines (serotonin, dopamine, noradrenaline and their metabolites 5-hydroxyindoleacetic acid, and dihydroxyphenylacetic acid) were assessed on rainbow trout (Oncorhynchus mykiss). Treatment with insulin inhibited food intake after 26 or 52 h of administration, central or peripheral, respectively. This effect was still apparent after 74 h of central treatment. When assessing changes in the levels of biogenic amines after 26 h of central insulin administration, there was a significant increase in the levels of 5-hydroxyindoleacetic acid, and in the ratio of dihydroxyphenylacetic acid/dopamine of insulin-treated fish, in telencephalon and hypothalamus, respectively. These results suggest that peripherally administered insulin is involved in a feedback regulatory loop with food intake and body weight. Moreover, at least part of the effects of insulin could be mediated by hypothalamic dopaminergic activity. The strong hyperglycemia induced by oral administration of glucose did not induce significant changes either on food intake (control versus treated), or in brain levels of biogenic amines. The intracerebroventricular administration of 2-deoxy-D-glucose induced an increase in food intake without altering plasma glucose levels, suggesting that fish brain possesses a control system for detecting hypoglycemia in plasma and therefore keep brain glucose levels high enough for brain function.Abbreviations 2-DG 2 Deoxy-D-glucose - 5-HIAA 5-Hydroxyindoleacetic acid - 5-HT 5-Hydroxytryptamine or serotonin - DA Dopamine - DOPAC Dihydroxyphenylacetic acid - EDTA Ethylenediaminetetraacetic acid - FI Food intake - HPLC High pressure liquid chromatography - icv Intracerebroventricular - i.p. Intraperitoneal - MS 222 3-Aminobenzoic acid ethyl esther methanesulfonate salt - NA Noradrenaline     

Central nervous system actions of growth hormone on brain monoamine levels and behavior of juvenile rainbow trout

Growth hormone (GH) has been demonstrated to alter the behavior of juvenile salmonids. However, the mechanisms behind this action are not yet understood. In mammals and birds, peripheral GH treatment has been shown to affect monoaminergic activity in the central nervous system, which may be a mechanism whereby GH alters behavior. To investigate if GH may influence behavior directly at the central nervous system, juvenile rainbow trout were injected with GH into the third ventricle of the brain, whereupon physical activity and food intake were observed during 2 h. Thereafter, brains were sampled and the content of serotonin, dopamine, and noradrenaline and their metabolites were measured in hypothalamus, telencephalon, optic tectum, and brainstem. The GH-treated fish increased their swimming activity relative to sham-injected controls, while appetite remained unchanged, compared with sham-injected controls. Analysis of brain content of monoamines revealed that the GH treatment caused a decrease in the dopamine metabolite homovanillic acid in the hypothalamus, indicating a lowered dopaminergic activity. It is concluded that GH may alter behavior by acting directly on the central nervous system in juvenile rainbow trout. Furthermore, GH seems to alter the dopaminergic activity in the hypothalamus. Whether this is a mechanism whereby GH affects swimming activity remains to be clarified.     

Chronic neuropeptide Y infusion during lactation suppresses pup growth and reduces the length of lactational infertility in rats

In lactating rats, food restriction potentiates the already high levels of hypothalamic neuropeptide Y (NPY). To investigate the role that high levels of NPY might play in the prolongation of lactational infertility that typically accompanies a food restricted lactation we investigated the effects of chronic central infusions of NPY in ad libitum-fed lactating females. First, we compared the effects of intracerebroventricular (icv) infusion of NPY from Days 12-19 postpartum at a dose of 14.4 microg/day with a similar treatment in nonlactating females. In subsequent experiments we examined the effects of NPY infusions into the lateral ventricle at doses of 6 or 20 mug/day or unilaterally into the medial preoptic area at a dose of 1 microg/day from either Days 12-19 or 7-21 postpartum. Effects on food intake; female body weight; and, where appropriate, litter weight and length of lactational diestrus were compared between NPY and vehicle-treated females. As expected NPY infusion produced a robust increase in body weight and food intake in nonlactating females that was accompanied by a suppression of cyclicity. By contrast NPY treatment in lactating rats resulted in a marked decrease in litter growth and an earlier termination of lactational diestrus.     

Intraventricular insulin decreases kappa opioid-mediated sucrose intake in rats

The hormone insulin acts in the central nervous system (CNS) as a regulator of body adiposity and food intake. Recent work from our laboratory has provided evidence that one way by which insulin may decrease food intake is by decreasing the rewarding properties of food. Evidence from others suggests that endogenous opioids may mediate the palatable properties of foods, and insulin may decrease nonfood-related reward via interaction with some CNS kappa opioid systems. In the present study we examined the ability of insulin to interact with exogenous or endogenous kappa opioids to modulate feeding of palatable sucrose pellets by nondeprived rats. Insulin (5 mU intracerebroventricular (i.c.v.), t=−3 h) completely reversed the ability of the exogenous kappa agonist U50,488 (26 μg, i.c.v., t=−15 min) to stimulate 90-min sucrose feeding (211±32% reduced to 125±23% of 90-min baseline intake). Further, i.c.v. insulin (5 mU, t=−3 h) interacted with a subthreshold dose of the kappa receptor antagonist norbinaltorphimine (5 μg, i.c.v., t=−15 min) to decrease the 90-min sucrose intake baseline (77±11% versus 109±10% of 90 min baseline intake, insulin/norbinaltorphimine versus norbinaltorphimine). Together these studies provide new evidence that insulin in the CNS may decrease the action of CNS kappa opioid system(s) that mediate palatable feeding.     

Effect of dietary fibres on constituents of complex carbohydrates in streptozotocin induced diabetic rat tissues

The effect of dietary fibres on constituents of complex carbohydrates in various tissues of streptozotocin induced diabetic rats is presented by analysing different constituents of complex carbohydrates in presence and absence of dietary fibre. Wheat bran was effective in preventing the decrease (14%) in total sugars in spleen and an increase in total sugars in stomach (33%) during diabetes. Decrease in uronic acid content during diabetes in spleen was prevented to the extent of 25% by the presence of wheat bran in the diet. The other parameters which were affected by the presence of wheat bran in the diet during diabetes are amino sugar (brain and stomach), sulphates (liver) and protein (lungs and stomach). Guar gum was effective in preventing the decrease in total sugar content in spleen by 28% and sulphate content in liver by 14% during diabetes. Variation in protein content in lungs was observed in diabetes. The results indicated beneficial role of dietary fibres like wheat bran and guar gum on complex carbohydrates to varying extents in different tissues.     

Accumulation of aluminum in rat brain: does it lead to behavioral and electrophysiological changes?

The present study was undertaken to examine possible aluminum (Al) accumulation in the brain of rats and to investigate whether subchronic exposure to the metal leads to behavioral and neurophysiological changes in both treated and control groups. Each of the groups consisted of 10 animals. Aluminum chloride (AlCl₃) at a low (50 mg/kg/d) or high (200 mg/kg/d) dose was applied to male Wistar rats by gavage for 8 wk. Al-free water by gavage was given to the control group throughout the experiment. Behavioral effects were evaluated by open-field (OF) motor activity and by acoustic startle response (ASR). Electrophysiological examination was done by recording spontaneous activity and sensory-evoked potentials from the visual, somatosensory, as well as auditory cortex. The Al content of each whole brain was determined by electrothermal atomic absorption spectrophotometry. Subchronic Al exposure slightly caused some changes in the evoked potentials and electrocorticograms and in the OF and ASR performance, but these results were not statistically significant. The brain Al levels of the control and the low and high dose of Al-exposed groups were measured as 0.717±0.208 μg/g (wet weight), 0.963±0.491 μg/g (wet weight) and 1.816±1.157 μg/g (wet weight), respectively.     

Nitrogen availability influences the biochemical composition and photosynthesis of tank-cultivated Ulva rigida (Chlorophyta)

Physiological and biochemical changes in relation to inorganic nitrogen availability were studied for tank-cultivated Ulva rigida grown under nitrogen- enriched and nitrogen-depleted seawater. U. rigida was initially cultivated in nitrogen-enriched seawater (daily concentrations of NH4+ and NO3- + NO2- ranged between 0.5–1.7 and 0.06–0.15 mg L-1, respectively), then transferred to nitrogen-depleted seawater where photosynthetic capacity decreased to zero after 23 d. At the time (14 d) when photosynthetic rates were lower than 2.0 μmol O2 g-1 FW min-1 and strong bleaching had occurred, some algae were returned to the initial nitrogen-enriched seawater to study recovery from N-limited growth. Data on biochemical composition (chlorophylls, ash, caloric content, fatty acids and dietary fibres) and colouration varied significantly depending on the nitrogen conditions. C:N ratios correlated significantly with biochemical parameters. Fatty acid (FA) synthesis continued during the N-starvation period; saturated and mono-unsaturated FA increased to a maximun of 72.2%, while poly-unsaturated fatty acids (PUFA) decreased to 27.7%. During the N-enriched recovery period, the reverse was found. C:N ratios above 10 correlated with carbohydrate synthesis as shown by the dietary fibre level. Under nitrogen enriched conditions, C:N ratios decreased along with a decrease in fibre level. Under controlled conditions, nitrogen represents a major influence on the development of intensive tank cultivation of Ulva rigida, not only by affecting parameters closely related to nitrogen metabolism but also some clearly influenced by carbon uptake. This revised version was published online in June 2006 with corrections to the Cover Date.     

Accounting for Missing Data in Noncancer Risk Assessment

Noncancer risk assessments are generally forced to rely on animal bioassay data to estimate a Tolerable Daily Intake or Reference Dose, as a proxy for the threshold of human response. In cases where animal bioassays are missing from a complete data base, the critical NOAEL (no-observed-adverse-effect level) needs to be adjusted to account for the impact of the missing bioassay(s). This paper presents two approaches for making such adjustments. One is based on regression analysis and seeks to provide a point estimate of the adjustment needed. The other relies on non-parametric analysis and is intended to provide a distributional estimate of the needed adjustment. The adjustment needed is dependent on the definition of a complete data base, the number of bioassays missing, the specific bioassays which are missing, and the method used for interspecies scaling. The results from either approach can be used in conjunction with current practices for computing the TDI or RfD, or as an element of distributional approaches for estimating the human population threshold.