Effects of ethanol and low-carbohydrate diet on contents of noradrenaline, dopamine, serotonin and their metabolites in rat brain]

Effects of ethanol consumption and intake of low-carbohydrate (low-CHO) diet on noradrenaline (NA), dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), serotonin (5HT) and its metabolite, 5-hydroxyindoleacetic acid (5HIAA) contents in six brain regions of rats were investigated. 1) Change of DA neuron Ethanol-containing control diet (hypercaloric ethanol diet) did not affect DA content in any area of brain, but decreased HVA in cortex and hypothalamus and increased DOPAC and HVA in midbrain. Low-CHO diet increased DA content in striatum, DOPAC and HVA in midbrain, but decreased DOPAC in hippocampus and hypothalamus, and HVA in cortex, pons and medulla, hippocampus and hypothalamus. Ethanol-containing low-CHO diet (isocaloric ethanol diet) increased DA level in striatum, DOPAC and HVA in midbrain, but decreased HVA in cortex, hippocampus, striatum and hypothalamus. These results suggest that i) hypercaloric ethanol diet has an opposite effect to carbohydrate on DA metabolism: hypercaloric ethanol diet and lowered carbohydrate intake per se enhance DA metabolism in midbrain, whereas inhibit it in cortex and hypothalamus, ii) lowered carbohydrate intake also declines DA metabolism in pons and medulla and hippocampus, whereas enhances DA synthesis in striatum, iii) the combined effect of ethanol and carbohydrate intake on DA metabolism is inhibited each other in the rats of isocaloric ethanol diet feeding, and this diet decreased DA metabolism in striatum. 2) Change of 5HT neuron Hypercaloric ethanol diet did not affect the contents of 5HT and 5HIAA in any region of brain.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distribution, depletion and recovery of docosahexaenoic acid are region-specific in rat brain

The present study examined: (i) age-induced regional changes in fatty acid composition of brain phospholipids; (ii) alpha-linolenic acid deficiency-induced regional depletion and recovery of DHA in the brain. DHA and arachidonic acid (AA) did not distribute evenly in the brain. In weaning and adult rats, the region with the highest DHA percentage was the cortex whereas the medulla had the lowest DHA percentage. In the aged rats, both the cortex and cerebellum were the regions with the highest DHA percentage whereas in the neonatal rats, the striatum had the greatest percentage of DHA, and the hypothalamus and hippocampus had the least percentage of DHA. Regarding AA, the hippocampus was the region that had the highest percentage whereas the medulla was the region with the lowest percentage except for the neonatal rats, whose cerebellum, hypothalamus, striatum and midbrain had AA percentage lower than hippocampus and cortex. DHA was not proportionally depleted in various regions of brain when the rats were maintained on an n-3-deficient diet for two generations. The results demonstrated that the cortex, hippocampus, striatum, cerebellum and hypothalamus had DHA depleted by >71 %, whereas the midbrain and medulla had only 64 and 57 % DHA depleted, respectively. The most important observation was that the diet reversal for 12 weeks resulted in complete DHA recovery in all regions except for the medulla where the recovery was only 62 %. It was concluded that the location of DHA, n-3 deficiency-induced DHA depletion and reversibility of DHA deficiency across the brain were region-specific.     

Subclinical effects of groundwater contaminants. II. Alteration of regional brain monoamine neurotransmitters by benzene in CD-1 mice

Benzene, a common groundwater contaminant, possesses neurotoxic and behavioral effects. Male, adult CD-1 mice were continuously fed drinking waterad libitum containing 0, 31, 166 and 790 mg/L benzene for four weeks. Endogenous levels of the catecholamines norepinephrine (NE) and dopamine (DA), the catecholamine metabolites 3-methoxy-4-hydroxymandelic acid (VMA), 3,4-di-hydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the indoleamine serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), were measured by high-performance liquid chromatography (HPLC) in six discrete brain regions. In the hypothalamus, the brain region richest in NE, concentrations of NE increased by 40, 58 and 61% when mice received doses at 31, 166 and 790 mg/L, respectively. Significant increases of NE were also observed in the medulla oblongata and cerebellum. Dopamine concentrations increased significantly in the hypothalamus and corpus striatum. Increases of catecholamine metabolites were seen in a number of brain regions: midbrain (DOPAC), corpus striatum (VMA, DOPAC, HVA), cerebral cortex (VMA) and cerebellum (VMA). Benzene ingestion significantly increased 5-HT concentrations in the hypothalamus, corpus striatum, midbrain, cerebral cortex and medulla oblongata. Concomitant with increases of 5-HT, 5-HIAA increased in corpus striatum, midbrain, cerebral cortex and medulla oblongata. The findings indicate that oral ingestion of benzene by CD-1 mice induced both synthesis and catabolism of the monoamine neurotransmitters investigated.     

Lifelong low-phylloquinone intake is associated with cognitive impairments in old rats

In a previous report, we showed vitamin K to preferentially accumulate in brain regions rich in white matter and to positively correlate with certain sphingolipids. In rodents, pharmacological vitamin K deficiency has resulted in behavioral perturbations. To gain insight on the role of vitamin K status on brain function, we investigated learning abilities (Morris water maze), motor activity (open field), and anxiety (elevated plus maze) in distinct groups of 6-, 12-, and 20-mo-old female Sprague-Dawley rats that had been fed diets containing low (L; ~80 μg/kg diet), adequate (A; ~500 μg/kg diet), or high (H; ~2000 μg/kg diet) levels of phylloquinone (μg/kg diet; n = 9-12/diet) since weaning. In 20-mo-old rats, sphingolipids (cerebroside, sulfatide, sphingomyelin, ceramide, and gangliosides), phylloquinone, and menaquinone-4 were also assessed in cerebellum, midbrain, pons medulla, striatum, and hippocampus. Lifetime consumption of a low-vitamin K diet resulted in cognitive deficits in the 20-mo-old rats, with those in the L group having longer latencies than those in the H group (P < 0.05); this was associated with higher concentrations of ceramides in the hippocampus (P < 0.05) and lower gangliosides in the pons medulla and midbrain (P < 0.05). The low-vitamin K diet did not affect cognition at 6 and 12 mo of age, nor did it affect motor activity or anxiety at any age. Although much remains to be elucidated about the mechanism of action of vitamin K in cognition, this report points to vitamin K as an important nutritional factor contributing to cognitive health during aging.     

Effects of benzo[a]pyrene on steady-state levels of biogenic amines and metabolizing enzymes in mouse brain regions.

Benzo[a]pyrene (BaP) is a product of incomplete fossil fuel combustion, a well-known pollutant, and a carcinogenic agent. In the present study male CD-1 mice received ip injections of 0, 5, 25, and 100 mg/kg body weight BaP twice a week for 3 weeks. Endogenous levels of brain biogenic amines and their selected metabolites, norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), vanillylmandelic acid, dihydroxyphenylacetic acid (DOPAC), homovanillic acid, and 5-hydroxyindoleacetic acid (5-HIAA) were measured using high performance liquid chromatography and electrochemical detection. The brain regions studied were cortex, striatum, hypothalamus, midbrain, medulla oblongata, and cerebellum. BaP treatment increased the steady-state levels of NE, DA, and 5-HT in the hypothalamus and striatum. Increased levels of DA and 5-HT and their major metabolites DOPAC and 5-HIAA were noticed in the same region, an indication of increased metabolism of these amines. The increase in the 5-HT level in the cortex was not dose-related. Levels of NE and DA were significantly higher in the medulla oblongata. There was a concurrent increase in activities of tyrosine hydroxylase and tryptophan hydroxylase in several brain regions. The effect of BaP on Dopa-decarboxylase was not consistent. Monoamine oxidase was occasionally inhibited. Results indicate that exposure to BaP altered the steady-state levels of biogenic amines in various brain regions and these changes were consistent with the activities of metabolizing enzymes.     

Dietary variation of protein–carbohydrate: Effect on hypothalamic and hippocampal GABA–glutamate in relation to aging

Abstract

Dietary protein variation has been found to alter brain regional neurochemistry with aging. In the present investigation, we studied the effect of short-term treatment of protein–carbohydrate variable diet to rat on hypothalamic and hippocampal γ-amino butyric acid (GABA)–glutamate metabolism with increase of age. Exposure of male albino rats with diet containing normal protein (20%)–normal carbohydrate (68%) increased GABA metabolism and decreased glutamate metabolism in both hypothalamus and hippocampus with the increase of age. GABA–glutamate metabolism of rats having low protein (8%)–high carbohydrate (80%) diet for short-term period (STP), was activated in young age (3 months) and decreased in old age (18 months) in both the brain regions. On the contrary, intake of high protein (50%)–low carbohydrate (38%) diet under similar condition decreased GABA–glutamate metabolism in both hypothalamus and hippocampus of young brain and increased only in hypothalamus of aged brain. In hippocampus of aged brain the same diet decreased glutamate metabolism without changing its GABA metabolism. These results suggest that an age-associated change in GABA–glutamate metabolism depends on the amount of dietary protein and carbohydrate and also on the brain region.     

Dietary variation of protein-carbohydrate: effect on hypothalamic and hippocampal GABA-glutamate in relation to aging

Dietary protein variation has been found to alter brain regional neurochemistry with aging. In the present investigation, we studied the effect of short-term treatment of protein-carbohydrate variable diet to rat on hypothalamic and hippocampal gamma-amino butyric acid (GABA)-glutamate metabolism with increase of age. Exposure of male albino rats with diet containing normal protein (20%)-normal carbohydrate (68%) increased GABA metabolism and decreased glutamate metabolism in both hypothalamus and hippocampus with the increase of age. GABA-glutamate metabolism of rats having low protein (8%)-high carbohydrate (80%) diet for short-term period (STP), was activated in young age (3 months) and decreased in old age (18 months) in both the brain regions. On the contrary, intake of high protein (50%)-low carbohydrate (38%) diet under similar condition decreased GABA-glutamate metabolism in both hypothalamus and hippocampus of young brain and increased only in hypothalamus of aged brain. In hippocampus of aged brain the same diet decreased glutamate metabolism without changing its GABA metabolism. These results suggest that an age-associated change in GABA-glutamate metabolism depends on the amount of dietary protein and carbohydrate and also on the brain region.     

Enhancing effect of Mycoleptodonoides aitchisonii on synthesis of nerve growth factor and releasing dopamine in the rat brain

The effects of edible mushroom Mycoleptodonoides aitchisonii on the synthesis of nerve growth factor (NGF) and neurotransmitter metabolism in rat brain were examined in Wistar strain rats fed a controlled diet for 14 days. Then each brain was dissected to detect the levels of neurotransmitters and NGF in various regions. Dopamine concentration in the cerebral cortex was 1.5-fold significantly increased in the M. aitchisonii feeding group than the control group. However, NGF concentration of the M. aitchisonii feeding was significantly low. NGF concentration in this remaining area of brain from where the cerebral cortex, striatum, hippocampus, cerebellum, hypothalamus and amygdala were removed was significantly higher in the M. aitchisonii feeding. At the same time, in the striatum, the dopamine metabolite DOPAC was significantly increased in the M. aitchisonii feeding. Thereafter, we measured dopamine release from striatal slices using aqueous extract of M. aitchisonii, there was an enhancing effect on dopamine release. These results suggested that M. aitchisonii has enhancing effect on the synthesis of NGF and catecholamine metabolites in the rat brain.     

beta-Naphthoflavone and benzo(a)pyrene alter dopaminergic, noradrenergic, and serotonergic systems in brain and pituitary of rainbow trout (Oncorhynchus mykiss)

In the present study we evaluate for the first time the potential of the flavonoid compound beta-naphthoflavone (BNF) and the high molecular weight- Polycyclic aromatic hydrocarbon (PAH) benzo(a)pyrene (BaP) to alter brain neurotransmitter metabolism in fish. Fish of three different groups were intraperitoneally (i.p.) injected (2 microl g(-1)) with vegetable oil alone (control) or containing BNF or BaP (10 mg kg(-1)) and sacrificed 3, 24, and 72 h after treatment. Contents of dopamine (DA), noradrenaline (NA) and serotonin (5HT), as well as the amine oxidative metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole-3-acetic acid (5HIAA) were assayed in telencephalon, hypothalamus, preoptic region, optic tectum, and brain stem, as well as the pituitary. Fish treated with PAHs showed after 3h decreases in 5HT content in telencephalon, hypothalamus, preoptic region (with both BNF and BaP), and pituitary (with BaP), resulting in increased 5HIAA/5HT ratio. An increased ratio was also observed in hypothalamus 24h after BaP, and in preoptic region 72 h after BNF, in both cases due to an increased 5HIAA content. In other brain regions PAHs effects on 5-HT metabolism were less consistent. With respect to the dopaminergic system, changes induced by PAHs mainly occurred after 24 and 72 h of treatment, with increased DOPAC/DA ratio in preoptic region and brain stem. In hypothalamus, tectum, and pituitary, changes in DA metabolism showed strong variability. Finally, a decreased content of NA was evident in preoptic region (3h) and in telencephalon (24h) after both BNF and BaP treatments. Therefore, both BNF and BaP seem to act in rainbow trout brain by impairing 5HT availability at short term (3h) and increasing neuronal metabolic utilization of both 5HT and DA after 24 and 72 h. Data collected in the present study suggest that brain monoamine neurotransmitters are potential targets of BNF and BaP, and their alteration could have a role in known effects of PAHs on several neuroendocrine processes that are centrally regulated or modulated by brain monoamines.     

Arsenic species, AS3MT amount, and AS3MT gen expression in different brain regions of mouse exposed to arsenite

Human exposure to inorganic arsenic (iAs) has been associated with cancer and serious injury to various internal organs, as well as peripheral neuropathy, endocrine disruption and diverse effects in the central nervous system (CNS). Using rodent models, it is possible to demonstrate As accumulation in the brain that leads to defects in operant learning, behavioral changes, and affect pituitary gonadotrophins. iAs biomethylation in the CNS is a significant process, yielding products that are more reactive and toxic than the parent compound. Mice received 2.5, 5, and 10 mg/kg/day sodium arsenite orally for 9 days. We investigated the distribution of iAs and its metabolites as well as the mRNA and protein expression of arsenic (III) methyltransferase (AS3MT), which encodes the key enzyme in iAs metabolism, in the cerebral cortex, hippocampus, striatum, mesencephalon, thalamus, cerebellum, hypothalamus, pons, medulla oblongata, and pituitary of mouse brain. Our findings show that methylated As metabolites are present in all brain regions studied suggesting that AS3MT is ubiquitously expressed in the brain and it is not inducible by dose of arsenite. There is also a dose-related accumulation of As species in all brain regions, with the highest accumulation observed in the pituitary. The higher distribution of arsenicals in pituitary can help to explain the neuroendocrine effects associated with iAs exposure.     

Pathogenesis of mouse scrapie: patterns of agent replication in different parts of the CNS following intraperitoneal infection

The dynamics of agent replication were studied at 8 levels of spinal cord and in 9 areas of brain of mice infected intraperitoneally with the 139A strain of scrapie agent. Replication in the CNS was first detectable at 2 levels of spinal cord between thoracic vertebrae 4 and 9. The onset of replication was progressively delayed by up to 4 weeks at increasingly lower levels of spinal cord. A similar trend was seen at higher levels of spinal cord and in brain. In brain, agent replication occurred first in medulla, then in the pons and midbrain, thalamus and hypothalamus and, finally, striatum, septum, hippocampus and cerebral cortex. These results are highly suggestive of spread of infection from peripheral sites of agent replication along autonomic fibres to midthoracic cord, followed by an ascending and descending spread of agent at an apparent rate of 0.5 to 1.0 mm/day until the whole CNS is infected. However, experiments involving sympathectomy gave inconclusive results and the evidence for neural spread of scrapie in the peripheral nervous system is circumstantial.     

EFFECT OF PRE- AND POSTNATAL ALCOHOL CONSUMPTION ON GABA LEVELS OF VARIOUS BRAIN REGIONS IN THE RAT OFFSPRING

The effect of maternal alcohol consumption during pregnancyand lactation on -aminobutyric acid (GABA) levels in differentrat brain regions of 3-week-old pups was investigated. Therewas a significant decrease in the thalamus, pons, cerebellumand hippocampus, no change in posterior colliculus, occipitalcortex, temporal cortex, hypothalamus, septum or striatum anda significant increase in frontal cortex, olfactory bulbs, anteriorcolliculus and amygdala. These modifications could be a consequenceof alterations in membrane permeability and may be related tothe behavioural disorders associated with the fetal-alcoholsyndrome.     

Evaluation of toluene exposure via drinking water on levels of regional brain biogenic monoamines and their metabolites in CD-1 mice

Toluene, a potentially neurotoxic substance, is found in trace amounts in groundwater. Adult male CD-1 mice were continuously fed drinking water ad libitum containing 0, 17, 80, and 405 mg/liter toluene. After a 28-day treatment, animals were tested for endogenous levels of the biogenic monoamines norepinephrine (NE), dopamine (DA), and serotonin (5-HT) and their respective metabolites. 3-methoxy-4-hydroxymandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), in six discrete brain regions. The maximum toluene-induced increases of biogenic amines and their metabolites generally occurred at a toluene concentration of 80 mg/liter. In the hypothalamus, a major NE-containing compartment, the concentrations of NE significantly increased by 51, 63, and 34% in groups dosed with 17, 80, and 405 mg/liter, respectively. Significant increases of NE were also observed in the medulla oblongata and midbrain. Concomitantly, concentrations of VMA increased in various brain regions. Concentrations of DA were significantly higher in the corpus striatum and hypothalamus. Alterations in levels of DA metabolites, DOPAC and HVA, were marginal. Toluene significantly increased concentrations of 5-HT in all dissected brain regions, except cerebellum, and increased the 5-HIAA levels in the hypothalamus, corpus striatum, and cerebral cortex.     

Enhancing Effect ofMycoleptodonoides aitchisoniion Synthesis of Nerve Growth Factor and Releasing Dopamine in the Rat Brain

Abstract

The effects of edible mushroom Mycoleptodonoides aitchisonii on the synthesis of nerve growth factor (NGF) and neurotransmitter metabolism in rat brain were examined in Wistar strain rats fed a controlled diet for 14 days. Then each brain was dissected to detect the levels of neurotransmitters and NGF in various regions. Dopamine concentration in the cerebral cortex was 1.5-fold significantly increased in the M. aitchisonii feeding group than the control group. However, NGF concentration of the M. aitchisonii feeding was significantly low. NGF concentration in this remaining area of brain from where the cerebral cortex, striatum, hippocampus, cerebellum, hypothalamus and amygdala were removed was significantly higher in the M. aitchisonii feeding. At the same time, in the striatum, the dopamine metabolite DOPAC was significantly increased in the M. aitchisonii feeding. Thereafter, we measured dopamine release from striatal slices using aqueous extract of M. aitchisonii, there was an enhancing effect on dopamine release. These results suggested that M. aitchisonii has enhancing effect on the synthesis of NGF and catecholamine metabolites in the rat brain.     

G-Protein Pattern and Adenylyl Cyclase Activity in the Brain of Rats After Long-Term Ethanol

Previous studies have described changes in levels of GTP binding proteins (G-proteins) following exposure of rodents to ethanol that did not correlate with the altered activation of the transmembrane signaling pathway. Possible reasons for these inconsistencies were taken into account in the present study by measuring the levels of four different G-protein subunits (G_αs, G_αi1/2, G_αo, G_βγ) in six brain regions. Rats were exposed to ethanol for 4 weeks (forced intake of ethanol liquid diet) and 40 weeks (free-choice ethanol). G-protein levels and activation of adenylyl cyclase (AC) were measured on day 1, day 8, and day 28 after withdrawal. When there were changes in the G-protein levels at all, increases were observed mostly in brain regions from rats with the 40-week exposure and decreases in regions from rats with the 4-week exposure that consumed a higher amount of ethanol per day. In some regions the changes had not normalized by day 28 in the 40-week ethanol group whereas in the 4-week ethanol group changes were observed only at day 1 and day 8. Activation of AC was disturbed in the 4-week ethanol group. Reduced activation was detected in membranes of the cerebral cortex, whereas increased activation was observed in the cerebellum, hypothalamus, pons, and striatum. Addition of ethanol (100 mM) to the tissue homogenate facilitated the stimulating action of Gpp(NH)p only in the hippocampus, cerebellum, and striatum. This in vitro action of ethanol was not affected by the long-term ethanol exposure. Activation of AC in the 40-week ethanol group was reduced in the cerebral cortex, pons, and striatum and increased in the cerebellum and hypothalamus if changes occurred at all. The findings support the contention that changes of the transmembrane signaling pathway in ethanol-exposed rats depend on the brain region and on the mode of application. Furthermore, a clear dissociation was observed between changes of the activation of the adenylyl cyclase and the changes in the levels of G-proteins.     

一次力竭运动小鼠中枢单胺类神经递质的代谢特点

目的：探讨力竭运动中枢单胺类神经递质的代谢变化特点,以期为运动疲劳的中枢机制提供一定实验室依据。方法：4月龄C57/BL小鼠,随机分为安静对照组（SC组）和一次性游泳力竭组（SE组）。力竭游泳即刻取材（皮层、下丘脑、纹状体、海马、脑干和小脑）六个脑区,高功率微波灭活脑组织相关酶类;HPLC测定去甲肾上腺素（NE）、多巴胺（DA）及其代谢产物多巴克（DOPAC）、5羟色胺（5-HT）、5-羟吲哚乙酸（5-HIAA）含量。结果：力竭时皮层、海马和脑干NE含量较安静时明显增加（P〈0.05）,而下丘脑、纹状体和小脑NE含量有降低趋势。海马、脑干组织DA含量力竭时极显著增加（P〈0.01）,皮层、纹状体区仅有增加趋势,而下丘脑DA含量较安静时有降低趋势;DA的代谢产物DOPAC仅在脑干有明显增加。各脑区力竭时5-HT均较安静时明显增加（P〈0.05）,其代谢产物5-HIAA在皮层、下丘脑及小脑也增加显著（P〈0.05）。结论：运动至力竭过程中各脑区单胺类神经元激活程度不相同,其中5-HT和NE可以作为中枢皮层疲劳的一个标志。     

Regional brain contents of serotonin, dopamine and their metabolites in the selectively bred high- and low-alcohol drinking lines of rats

The contents of dopamine (DA), serotonin (5-HT) and their primary acid metabolites were assayed in ten brain regions of the selectively bred high-alcohol drinking (HAD) and low-alcohol drinking (LAD) lines of rats. Compared with the LAD line, the contents of 5-HT and/or 5-hydroxyindoleacetic acid were approximately 10-20% (p less than 0.05) lower in several brain regions of the HAD line (cerebral cortex, striatum, nucleus accumbens, septal nuclei, hippocampus and hypothalamus). The levels of DA, 3,4-dihydroxyphenylacetic acid and homovanillic acid were also 10-20% lower in the nucleus accumbens and anterior striatum (p less than 0.05) of the HAD animals. These data are in agreement with previous findings that comparatively lower levels in 5-HT and DA systems are associated with high-alcohol drinking in rodents and support the involvement of certain 5-HT and DA pathways in the mediation of alcohol drinking behavior.     

Relationships among maternal diet, serotonin metabolism at weaning, and protein selection of progeny

Brain serotonin (5HT) metabolism in rats at weaning was examined in relation to their maternal dietary protein (PC) and tryptophan (TRP) concentration and to their protein feeding behavior. Pup brain TRP, 5HT, and 5-hydroxyindoleaceticacid (5HIAA) concentration was unaffected by maternal diet PC (10, 20, or 40%) but was increased by TRP additions (0.66 or 1.86%) to 40% casein diets. Turnover of brain 5HT, measured at weaning after probenecid injection, was inversely related to maternal diet PC (r = .54, P less than 0.05) but was not affected by TRP supplementation. Pups allowed to select from 10 and 60% casein diets selected during the first 3 days post-weaning, dietary PC which reflected the PC (r = 0.65, P less than 0.01), but not RRP content of their maternal diet, and also reflected brain 5HT turnover (r = .50, P less than 0.05), but not concentration, of their littermates. Thus, the relationship dietary PC to protein selection by the offspring is associated with maternal diet-maternal diet-induced changes in their brain 5HT turnover, at least as measured after probenecid administration.     

Effects of isoenergetic high-carbohydrate compared with high-fat diets on human cholesterol synthesis and expression of key regulatory genes of cholesterol metabolism

BACKGROUND: High-carbohydrate diets improve plasma cholesterol concentrations but increase triacylglycerol concentrations; the latter effect increases the risk of cardiovascular disease (CVD). Triacylglycerol concentrations increase only during very-high-carbohydrate diets consisting mainly of simple sugars. OBJECTIVE: We compared the CVD risk profile, cholesterol metabolism, and glucose tolerance of 7 healthy subjects during 2 isoenergetic diets: a high-fat, low-carbohydrate diet (HF diet) and a moderately high-carbohydrate, low-fat diet (HC diet). DESIGN: In a randomized crossover study, we measured the effects of the HF diet [40% carbohydrate and 45% fat (15% saturated, 15% monounsaturated, and 15% polyunsaturated)] and HC diet [55% carbohydrate (mainly complex) and 30% fat (10% saturated, 10% monounsaturated, and 10% polyunsaturated)] (3 wk each) on plasma lipid concentrations, oral glucose tolerance, cholesterol synthesis rate, and the messenger RNA (mRNA) concentrations of beta-hydroxy-beta-methylglutaryl coenzyme A (HMG-CoA) reductase, the LDL receptor, and the LDL-receptor-related protein (LRP). RESULTS: Compared with the HF diet, the HC diet lowered total, LDL, and HDL cholesterol (P < 0.05 for all) without modifying the ratio of LDL to HDL cholesterol; triacylglycerol concentrations were unchanged. Lower cholesterol concentrations occurred despite a higher cholesterol synthesis rate (P < 0.05) and higher HMG-CoA reductase mRNA concentrations (P < 0.05). LDL receptor mRNA concentrations were unchanged, LRP mRNA concentrations were lower (P < 0.01), and oral glucose tolerance was better (P < 0.05) with the HC diet. CONCLUSION: The beneficial effects of the HC diet on glucose tolerance and plasma cholesterol concentrations without increases in triacylglycerol show that this diet had favorable effects on both insulin sensitivity and the plasma lipid profile.     

Alteration of brain levels of neurotransmitters and amino acids in male F344 rats induced by three-week repeated inhalation exposure to 1-bromopropane

The present study investigated the effects of 1-bromopropane (1BP) on brain neuroactive substances of rats to determine the extent of its toxicity to the central nervous system (CNS). We measured the changes in neurotransmitters (acetylcholine, catecholamine, serotonin and amino acids) and their metabolites or precursors in eight brain regions after inhalation exposure to 1BP at 50 to 1,000 ppm for 8 h per day for 7 d per week for 3 wk. Rats were sacrificed at 2 h (Case 1), or at 19 h (Case 2) after the end of exposure. In Case 1, the level of 5-hydroxyindoleacetic acid (5HIAA) was lowered in some brain regions by 1BP exposure. The decrease of 5HIAA in the frontal cortex was statistically significant at 50 ppm 1BP exposure. In Case 2, gamma-amino butyric acid (GABA) and taurine were decreased in many brain regions of exposed rats, and a significant decrease of taurine in the midbrain occurred at 50 ppm 1BP exposure. In both cases of 2-h and 19-h intervals from the end of exposure to sacrifice, aspartate and glutamine levels were elevated in many brain regions, but the acetylcholine level did not change in any brain region. Three-week repeated exposure to 1BP produced significantly changes in amino acid contents of rat brains, particularly at 1,000 ppm.