Learning and memory impairment in adult rats due to severe zinc deficiency during lactation

In a series of three experiments, adult rats who suffered severe zinc deficiency and/or undernutrition during lactation were tested in a 17-arm radial maze for working memory, reference memory, forgetting and learning. In Experiment 1, eight out of 17 arms were baited. The zinc deficient (ZD) and undernourished (PF) rats revealed a learning deficit when compared to adequately nourished rats (AL). ZD rats also appeared to display a loss of working memory. No evidence of loss of reference memory was observed among any of the groups. A reverse learning procedure was used in Experiment 2 to test the same rats used in Experiment 1. ZD rats were significantly inferior in performance of the reverse learning task compared to the AL and PF rats. No significant differences in performance were noted between the AL and PF rats. Although all groups displayed forgetfulness from Experiment 1 to Experiment 2, no significant differences in forgetfulness were evidenced among the groups. In Experiment 3, all 17 arms were baited. The ZD rats displayed a significant working memory deficit as compared to the AL and PF rats. No significant differences in working memory between the AL and PF rats occurred. The possibility that the differences in performance were due to differences in food motivation or attention was considered and rejected. It was concluded that ZD rats experienced a severe learning deficit and some working memory deficit while the PF rats experienced a mild learning deficit as compared to the AL rats.     

Intra-uterine nutrition and its effects on aggression

Prenatal zinc deficiency and prenatal undernutrition were found to have adverse effects on the food consumption and weight gain of pregnant dams and their offspring. Pups whose dams suffered prenatal zinc deficiency (ZD) consumed less food and gained less weight than pups whose dams suffered prenatal undernutrition (PF). The PF pups consumed less food and gained less weight than pups whose dams were normally fed (AL). The ZD females at age 75 days were significantly more aggressive than the PF females, while the PF females were more aggressive than the AL females. At age 105 days, ZD females were significantly more aggressive than the PF and AL females. There were no differences in aggression between the PF and AL females at 105 days. Among the ZD, PF, and AL male offspring, there were no differences in aggression at either age level except that the 75 day old PF males were significantly less aggressive than the AL males. Thus prenatal malnutrition, especially zinc deficiency, seems to have differential effects on the aggressive tendencies of female and male offspring.     

Water maze performance and changes in serum corticosterone levels in zinc-deprived and pair-fed rats

The aims of the present study were (1) to evaluate the learning and short- and long-term memory of zinc-deprived (ZD) and pair-fed (PF) rats in a Morris water maze (MWM) and (2) to monitor the serum corticosterone levels of these rats before and after swimming. Young Sprague-Dawley rats (aged 27-31 days) consumed AIN-93G diet for 10 days, and then were separated into ad libitum control (CT), PF and ZD groups. The zinc content of the diet was 25-30 ppm (CT and PF) or <1 ppm (ZD). After 17 days on experimental diets, a MWM was used to test spatial cognition. Delayed-matching-to-place (DMP) test results indicate that both zinc deprivation and food restriction had no effect on short-term memory. The PF rats exhibited significantly impaired learning and thigmotaxia (i.e., wall hugging) in the learning test. The PF group also demonstrated less preference for the target zone in the first 15 s of the probing test. When the total 120 s of the probing test was considered, there were no differences in preference for the target zone, but thigmotaxia was greater in the PF than the CT group. The only behavioral change of the ZD group was thigmotaxia observed during the 120-s probing test following training, indicating the increment of anxiety. Morning basal corticosterone levels before swim training were significantly elevated in the PF group on Day 15 of dietary treatment, whereas a significant elevation of the basal corticosterone level in the ZD group was not statistically significant until Day 22. The data indicate an association between impaired learning, poor searching strategy and elevated corticosterone in the PF group. In contrast, the ZD rats showed normal cognitive performance but had elevated corticosterone and increased anxiety-like behavior (thigmotaxia).     

Maternal malnutrition in the rat: Effects on food intake and body weight

The effects of dietary protein level on food intake and body weight were examined in adult female rats during a 35-day pre-mating period and during gestation and lactation. During the pre-mating period, no differences in daily food intake were observed among rats fed a 6% casein, 8% casein or 25% casein diet. However, during this period, rats fed the 6% casein diet gained significantly less weight than those with ad lib access to the 8% or 25% casein diets or than rats pair-fed the 25% casein diet in amounts equivalent to that consumed by rats in the 6% or 8% casein groups. Additionally, rats fed the 6% casein diet displayed decreased efficiency of energy utilization, calculated as weight gain per 100 kilocalories consumed, relative to rats fed the 8% or 25% casein diets. No differences in food intake were observed among the groups during gestation. However, rats fed the 6% casein diet gained less weight than rats fed the 8% or 25% casein diets. During lactation rats fed either the 6% or 8% casein diet consumed significantly less food than animals given the 25% casein diet ad lib. During the second week of lactation, rats receiving ad lib access to the 25% casein diet gained weight while those receiving the 6% or 8% casein diets continued to lose weight. At parturition, body weights of pups did not differ as a function of dietary condition. However, by day 12 of life, pups whose dams had ad lib access to the 25% casein diet weighed significantly more than pups whose dams consumed the 6% or 8% casein diet or whose dams were pair-fed the 25% casein diet in amounts equivalent to those consumed by rats fed the 6% or 8% casein diet.     

锌对大鼠脾脏淋巴细胞功能的影响

通过大鼠锌（ＺＤ），过量锌（ＺＥ）模型，研究３锌对脾脏Ｔ、Ｂ淋巴细胞功能的影响，结果：①ＺＤ、ＺＥ组的脾重及脾脏指数，与对喂（ＰＦ）组、自由喂养（ＡＬ）组，缺锌后再补锌（ＺＤ＋ＡＬ）组比较，差别非常显著。②ＺＤ、ＺＥ组外周血白细胞减低，以淋巴细胞为主。③ＺＤ、ＺＥ组Ｔ、Ｂ淋巴细胞增殖率非常显著低于ＰＦ、ＡＬ和ＺＤ＋ＡＬ组。④ＺＤ、ＺＥ组的总脾淋巴细胞，Ｔ、Ｂ淋巴细胞细胞周期Ｇ０／Ｇ１％增高，而Ｓ％     

Passive avoidance performance of mice fed marginally or severely zinc deficient diets during post-embryonic brain development

Swiss-Webster outbred mice were fed marginally or severely zinc deficient diets (9 or 2 ppm zinc) from day 16 gestation to day 15 postnatal. Control mice were fed a 100 ppm diet either ad lib or in amounts equal to the diet intake of deprived mice (pair fed controls). Male and female offspring were tested at 70 days of age in a one-trial passive avoidance task with a 30 min train-test interval. Both marginally and severely zinc deprived offspring (but not pair fed controls) had shorter avoidance latencies than offspring of ad lib fed zinc replete controls. Zinc deprived offspring did not differ from control mice when either baseline or “stressed” (exposure to novel environment) plasma corticosterone levels were quantitated. Further, zinc staining patterns of the hippocampus (Timm-sulfide stain) were not altered in the nutritionally deprived offspring. Thus marginal dietary zinc deficiency during development can lead to impaired passive avoidance performance in adult mice. This behavioral effect is not associated with altered pituitary-adrenocortical activity or with a permanent reduction in hippocampal zinc staining. This result has significant implications for the influence of zinc deprivation in utero and in the neonatal animal on adult behavior characteristics.     

Rapid neonatal weight gain in rats results in a renal ubiquinone (CoQ) deficiency associated with premature death

We have recently reported that maternal dietary imbalance during pregnancy and lactation can reduce the lifespan of offspring. Rats that were growth restricted in utero by maternal protein restriction and underwent rapid weight gain when suckled by control fed dams died earlier than animals whose mothers were fed a control diet throughout pregnancy and lactation. We demonstrate here that mitochondrial abnormalities and DNA damage occur in the kidney of offspring who die prematurely. We have established by direct measurement and by in vitro supplementation that mitochondrial abnormalities occur because of a functional deficit of the mitochondrial cofactor coenzyme Q9 (CoQ9). These data provide molecular insight into the association between maternal nutrition and determination of offspring lifespan, and identify, a potential dietary intervention to prevent detrimental consequences of imbalanced maternal nutrition.     

The effects of prenatal alcohol exposure on radial arm maze performance in adult rats

The hippocampal formation is sensitive to the in utero exposure to ethanol. It is one brain area thought to play an important role in spatial memory. We examined radial arm maze performance in rats exposed to ethanol prenatally. Pregnant rats were placed into the following treatment groups: LC, 17% EDC (ethanol-derived calories), 35% EDC, PF 35% or PF 17%. The LC group was fed lab chow and water ad lib, the 17% EDC and 35% EDC groups were fed a liquid diet containing either 3.3% or 6.7% v/v ethanol, respectively. Pair-fed controls were fed the same volume of an isocaloric diet as was consumed by their respective ethanol-treated groups. At birth, litters were culled to six and cross fostered to untreated surrogate mothers. Testing was initiated at 60 days of age and continued until the test criterion was satisfied. One-half of the rats in the 35% EDC group did not reach criterion. The remainder of the 35% EDC group and the 17% EDC rats attained criterion but required twice as many trials as their respective pair-fed controls. These results suggest that in utero administration of ethanol affects spatial memory capacity in rat, an observation consistent with other deficits seen in hippocampus of rats prenatally exposed to ethanol.     

Reductions in maternal food and water intake account for prenatal stress effects on neurobehavioral development in B6D2F2 mice

This study evaluated the role of stress-induced reductions in food intake in pregnant B6D2F1 mice in the production of developmental abnormalities in the offspring. One group of dams underwent one hour of physical restraint stress twice daily from days 12 to 17 of gestation. A second group was not restrained but, during this period, each dam was pair-fed to a weight-matched partner in the stressed group. A third group was left undisturbed and allowed unlimited access to lab chow and water. The restraint stress procedure reduced the average daily food and water intake in the dams, resulting in lower maternal weights, with the unstressed pair-fed group being affected more severely than the stressed group. The offspring of both the stressed and pair-fed dams were lighter than the offspring of the dams fed ad lib on day 20 postconception, and exhibited lower brain weights on day 32 postconception. Neurobehavioral development, as assessed on a battery of sensorimotor tests on day 32 postconception, was retarded in the prenatally stressed pups in comparison to the ad lib pups, while the pair-fed pups did not differ from either group. There were no differences among any of the groups on day 50 body or brain weight, body or tail length, anogenital distance, or locomotion, rearing and defecation in the open field.(ABSTRACT TRUNCATED AT 250 WORDS)     

Zinc deficiency and anorexia in rats: normal feeding patterns and stress induced feeding

We report the effects of zinc deficiency on normal feeding behavior in rats and the effects of zinc deficiency on stress-induced eating in rats. Zinc deficient (ZD) rats weighed significantly less than their pair-fed and ad lib controls. Zinc repletion allowed improved growth, but ZD rats never displayed catch-up growth compared to their ad lib controls. ZD rats rapidly developed a depressed food efficiency ratio which normalized with zinc supplementation. Food consumption in ZD rats was approximately one-third that of ad lib controls and water intake was also significantly reduced. Mild tail pinch was able to induce feeding in these normally anorexic ZD rats. We conclude that zinc deficiency represents an interesting model of anorexia which may enhance our understanding of appetite regulation.     

Effects of prenatal nutrition on learning and motivation in rats.

The results of two learning experiments revealed that adult male rats whose dams suffered either prenatal zinc deficiency or undernutrition showed, as compared to rats whose dams were fed ad lib, normal diets during pregnancy (1) more resistance to extinction following partial reinforcement, and (2) a faster occurring negative contrast effect when shifted from large to small reward. An incentive-motivation interpretation of the data suggests that the nutritionally deprived and normal animals differ with respect to the incentive value of the consummatory reward. This effect appears to be long-term.     

Maternal care affects male and female offspring working memory and stress reactivity

Variations in maternal care affect the development of individual differences in learning and memory and neuroendocrine responses to stress in adult male offspring, but it is not known how variations in maternal care affect adult female offspring. The present study investigated the performance of adult Sprague-Dawley male and female offspring exposed to either low or high levels of maternal licking/grooming on a spatial memory task (Experiment 1) and the effects of acute stress on corticosterone levels and spatial memory performance (Experiment 2). In Experiment 1 rats were trained for 24 days on the spatial working/reference memory version of the radial arm maze (RAM). In Experiment 2, rats were trained on the same RAM task, exposed to an acute stress, and the effect of stress on corticosterone levels and subsequent spatial memory was examined. In Experiment 1, adult female offspring of low licking/grooming dams had enhanced working memory compared to all other groups. In Experiment 2, all groups of male and female offspring had enhanced working memory 24 h after exposure to acute 2 h restraint stress while reference memory was enhanced after stress in male and female offspring of low licking/grooming dams. Furthermore, female offspring of low licking/grooming dams showed the largest corticosterone response to the acute restraint stress compared to all other groups. Male offspring of low licking/grooming dams showed a flattened corticosterone response to stress. Thus variations in maternal care differentially affect working memory and stress reactivity in male and female offspring.     

Zinc deficiency and behavior: A developmental perspective

Zinc deficiency was induced in 35 and 300 day-old male Holtzman rats. Group ZDA was fed ad lib a diet deficient in zinc (1 ppm), ZSP controls were pair-fed a diet supplemented with zinc (50 ppm) and ZSA controls were fed ad lib a diet supplemented with zinc (50 ppm). Physical status and six open-field behaviors were evaluated. Food intake, body weight and plasma zinc concentrations were significantly reduced in both age groups. Expanded use of the open-field revealed significantly lower latencies to explore the novel environment and significantly lower ambulation scores in the young and older zinc deficient rats. Older rats spent significantly less time grooming than their controls. Rearing was significantly less in young zinc deficient rats and “kangaroo-like” posture was evident. Young rats made deficient during critical periods of growth and development, were at greater risk for most parameters tested, compared to the older deficient rats. These results do demonstrate, however, that feeding low-zinc diets to older, fully developed animals results in significant physical and behavioral impairment.     

The impact of maternal cafeteria diet on anxiety-related behaviour and exploration in the offspring

Contemporary trends in obesity mean that research into whether unbalanced diets could impact on behavioural traits became increasingly important. The timing of exposure to obesity is particularly important, as sensitive periods during development have been identified where dietary extremes play a critical role in determining adult risk of physiological dysfunction. To this end, female Wistar rats were fed on chow or cafeteria diet (CD) for 8 weeks from weaning until mating. Half of the mated animals within each group were crossed-over to the alternative diet. This generated four treatment groups, differing in their pre-gestational and gestational diets. After birth, offspring of dams from each of the 4 pregnancy groups were further divided into groups, either being fed chow or CD throughout lactation. Anxiety-related behaviour and exploration in the offspring were tested in the Elevated Plus Maze (EMP) and the Open Field (OF) at 10 weeks of age. Maternal obesity significantly reduced the EPM locomotor activity in male and female offspring and grooming in males. Lactational CD had an anxiolytic effect in male offspring as shown in the EPM (increased entries into and more time on open arms) and the OF (shorter latency to enter the centre). In both sexes, lactational CD reduced grooming upon exposure to the EPM and the OF. Post mortem analysis revealed a stimulant effect of lactational CD on adipose tissue growth. The present study demonstrates that pre-gestational, gestational and lactational maternal CD programme behaviour in the offspring with lactational CD reducing anxiety in the male offspring.     

缺锌对大鼠海马结构含生长抑素mRNA神经元的影响

要采用缺锌饲料喂养动物四周后，用原位杂交组织化学结合图象分析技术，研究了缺锌大鼠海马结构内含生长抑素mR-NA神经元的变化。并采用原子吸收分光光度计测定血浆锌含量。结果与对照组相比.缺锌大鼠血浆锌含量明显降低（P＜0.05），海马和齿状回合生长抑素mRNA的神经元数目明显减少（P＜0.01），胞体的灰度值明显降低（P＜0.01），而胞体的截面积无明显改变。结果提示，缺锌时，海马结构生长抑素mRNA的表达下调，海马结构神经元合成生长抑素的能力降低。这种变化可能是缺锌影响脑的学习记忆功能的重要原因之一。     

Effects of Severe and Marginal Maternal Lipotrope Deficiency on Response of Postnatal Rats to Infection

Female rats were fed from weaning on 1 of 4 different diets varying in lipotrope content (I, deficient; II, marginal; III, moderate; and IV, complete). Offspring littered to these dams were divided into 2 groups at weaning, one of which was continued on the mothers'' diet; the other was fed the complete diet (IV). Birth and weaning weights were low in dietary groups I and II, and when the rats were infected with Salmonella typhimurium at about 100 days after weaning, mortality was high in these 2 groups. A switch to diet IV at weaning corrected body weight in groups II and III but not in group I, and decreased mortality in group III but not in groups I and II. Although clinical evidence of deficit induced by maternal deficiency during prenatal and lactation periods was largely eliminated by post-weaning supplementation in group II, biochemical defects were not corrected, as was shown by mortality, serum proteins, and blood cell counts. Results of this study support the hypothesis that maternal nutritional deficiency in lipotropic factors can predispose offspring to infection much later in life even though they appear to be in good clinical condition. These findings are discussed in light of their possible relevance to nutritional problems of some population segments in developing countries.     

Effects of prenatal testosterone propionate treatment on saccharin preference of adult rats exposed to ethanol in utero

Prenatal exposure to alcohol feminizes saccharin consumption patterns in adult male rats. To study the involvement of testosterone in this effect, testosterone propionate (TP) was administered to pregnant dams in an attempt to reverse that feminized saccharin consumption pattern in the male offspring. Female offspring were also studied to determine the effect of TP on saccharin preference in normal males and females. During the last week of gestation, dams were administered a liquid diet containing 35% ethanol derived calories, an isocaloric liquid diet containing no ethanol, or Purina Lab Chow. Half of the dams in each group received twice daily injections of TP, the other half were injected with the oil vehicle. Saccharin consumption of adult fetal alcohol exposed (FAE) males from dams administered oil or TP was significantly greater than controls, indicating that the feminized pattern of saccharin consumption of FAE males cannot be overcome with TP administration during the prenatal period. In controls, prenatal TP exposure alone was found to increase adult saccharin consumption in both sexes. Prenatal administration of TP was also found to markedly depress body weight of offspring of dams receiving the liquid diets compared to offspring from dams receiving the same diets plus oil injections. Body weights of offspring from TP or oil injected dams receiving the chow fed diets during pregnancy did not differ.     

母代高脂饮食对雄性后代小鼠青春期后期运动能力及学习记忆行为的影响

目的:研究母代高脂饮食(high-fat diet,HFD)对雄性后代小鼠青春期后期运动能力及学习记忆行为的影响及机制.方法:通过16周高脂饮食喂养母鼠直至哺乳期结束建立母鼠肥胖模型,以子代雄鼠作为主要研究对象.通过足迹分析和转棒实验研究了子代小鼠的运动协调性,通过旷场实验研究了雄性子代小鼠运动能力的变化,通过水迷宫和...     

Implication of RAS in Postnatal Cardiac Remodeling,Fibrosis and Dysfunction Induced by Fetal Undernutrition

Fetal undernutrition is a risk factor for cardiovascular diseases. Male offspring from rats exposed to undernutrition during gestation (MUN) exhibit oxidative stress during perinatal life and develop cardiac dysfunction in ageing. Angiotensin-II is implicated in oxidative stress-mediated cardiovascular fibrosis and remodeling, and lactation is a key developmental window. We aimed to assess if alterations in RAS during lactation participate in cardiac dysfunction associated with fetal undernutrition. Control dams received food ad libitum, and MUN had 50% nutrient restriction during the second half of gestation. Both dams were fed ad libitum during lactation, and male offspring were studied at weaning. We assessed: ventricular structure and function (echocardiography); blood pressure (intra-arterially, anesthetized rats); collagen content and intramyocardial artery structure (Sirius red, Masson Trichromic); myocardial and intramyocardial artery RAS receptors (immunohistochemistry); plasma angiotensin-II (ELISA) and TGF-β1 protein expression (Western Blot). Compared to Control, MUN offspring exhibited significantly higher plasma Angiotensin-II and a larger left ventricular mass, as well as larger intramyocardial artery media/lumen, interstitial collagen and perivascular collagen. In MUN hearts, TGF-β1 tended to be higher, and the end-diastolic diameter and E/A ratio were significantly lower with no differences in ejection fraction or blood pressure. In the myocardium, no differences between groups were detected in AT1, AT2 or Mas receptors, with MrgD being significantly lower in the MUN group. In intramyocardial arteries from MUN rats, AT1 and Mas receptors were significantly elevated, while AT2 and MrgD were lower compared to Control. Conclusions. In rats exposed to fetal undernutrition, RAS disbalance and associated cardiac remodeling during lactation may set the basis for later heart dysfunction.     

The effects of life-long food restriction on spatial memory in young and aged Fischer 344 rats measured in the eight-arm radial and the Morris water mazes

The effect of life-long 60% ad lib food restriction on performance in two tasks involving spatial memory, the eight-arm radial maze and the Morris water maze, was studied in young and aged Fischer 344 rats. Restricted (R) and ad lib (AL) feeding groups were compared at 8, 16, and 24 months of age on both tasks. A 30-month-old R group was also tested in the Morris water maze. In the eight-arm maze, although 24-month-old animals performed more poorly than 8- and 16-month-old animals during the first week of testing, overall accuracy of performance did not vary significantly as a function of age. Twenty-four-month-old animals took longer to make 10 choices than did younger animals, and there was a significant interaction between feeding regimen and age, reflecting the fact that at the two younger ages, R groups performed more quickly than the AL groups. In the Morris water maze, both distance swum and time to find the platform increased with age. Life-long food restriction led to small but significant improvements in performance in the water maze in aged rats. R groups showed evidence for better retention over 24-hour intervals than did AL groups. By 30 months of age, however, R animals showed impaired performance relative to younger R groups. These differential findings on the two tasks, as they were used here, suggest that there was greater impairment with age on the spatial memory task requiring retention of information over long intervals than there was on the task primarily involving working memory within a trial. Life-long food restriction would appear to delay the impairments of age, but not prevent them.