Low lead exposure during foetal and early postnatal life impairs passive avoidance learning in adulthood in rats

This follow-up study investigated the effects of low-level lead exposure during prenatal and early postnatal period on learning and memory in rats immediately after exposure has ceased at weaning and later in their adulthood. Male Wistar-derived rats were exposed to lead (as 0.2 % lead acetate solution) through their mothers during pregnancy and lactation until they were weaned. Mothers of control rats were given tap water during pregnancy and lactation. All pups were weaned on tap water at 21 days of age and were followed up until 120 days old. Low-level lead exposure did not affect their body weight at any time during the experiment. Blood lead in the exposed rats was significantly higher on postnatal day 22 and dropped to control values by day 120. Passive avoidance test showed impaired memory retention in the exposed rats on postnatal days 25 and 120. This suggests that exposure to low-lead levels during foetal and early postnatal development of brain tissue can cause memory impairment that lasts into adulthood.     

Effects of early thiamin deficiency and subsequent rehabilitation on the cholinergic system in developing rat brain

The effects of thiamin deficiency during pregnancy and/or lactation on brain cholinergic system in rat pups were studied. Dietary rehabilitation for a period of 5 weeks from the 28th day was instituted to study possible 'catch-up' in the brain acetylcholine levels. Brain acetylcholine level was found to be significantly decreased on the 21st and 28th days in pups of the dams fed thiamin deficient diet during gestation and lactation, whereas it was decreased on the 28th day in pups of the dams fed thiamin deficient diet during lactation. Activities of cholinergic enzymes remained unaltered in both the deficient groups. Subsequent dietary rehabilitation was found to reverse the deficits in brain acetylcholine levels.     

Reversal learning after prenatal or early postnatal alcohol exposure in juvenile and adult rats.

Learning tasks that require the reversal of a previously learned contingency are disrupted in animals and humans exposed to alcohol during the perinatal period. The current experiments examined how varying the time of alcohol exposure and the age at which subjects were tested would affect the expression of reversal deficits in a T-maze task. Groups of rats were exposed to alcohol from gestational day (GD) 8 to GD20 or from postnatal day (PN) 4 to PN9, and then tested in a spatial reversal task at either PN28 or PN63. Results indicate that exposure to alcohol during the prenatal period did not lead to substantial dose-dependent reversal learning deficits in males or females at either age tested. However, exposure to alcohol during the early postnatal period, a period that corresponds to the third trimester in human neural development, selectively disrupted reversal learning performance in male rats at PN28 but not PN63. Statistically significant sex differences were seen when subjects were tested at PN63. These results demonstrate how the timing of alcohol exposure leads to variability in the age-dependent expression of learning deficits associated with fetal alcohol effects.     

Effects of peri- and postnatal lead administration on learning of high avoider rats

Effects of administration of lead acetate on Sidman avoidance behavior were assessed in juvenile and adult rats which were obtained by continued selective breeding and which have a high level avoidance ability and small individual differences (THA rat: Tokai high avoider rat). THA rats were administered lead acetate solution at 200-300 mg/kg/day as Pb until 7 wk of age through maternal milk before weaning from mothers which had been administered lead acetate from the 13th day of gestation and per os by gastric tube after weaning. Three series of Sidman avoidance behavior tests were conducted from 49th, 100th and 150th day after birth each for 10 d, 1 h every day. In the first series, a significant delay of shock avoidance acquisition was observed in lead-administered male rats compared with the control subjects, while no acquisition delay was seen in female rats. The lead administered male rats could be divided into two groups with different response patterns; a low susceptible group (LSG) which exhibited as good acquisition rate from the beginning similar to the control rats and a high susceptible group (HSG) which showed a significant delay and individual differences. In the 2nd test series, very high avoidance rates were obtained in all the test groups except in male HSG, but in the 3rd test series, male HSG also attained a final acquisition of high avoidance rate. There was no developmental variation between the groups nor difference in lead contents of the organs of the exposed group. Useful characteristics of THA rats for behavioral toxicology are discussed.     

The effects of single and repeated episodes of thiamin deficiency on memory in alcohol-consuming rats

The underlying pathogenesis of Korsakoff's syndrome, an amnesic disorder most commonly found in alcoholics, is not well understood. Chronic alcoholism is associated with thiamin deficiency and current thinking is that this may be the causal factor. In Experiment 1, rats were given a 20% (v/v) ethanol/water mix as their only source of fluid for 156 days. Three groups were made thiamin deficient through the combination of a thiamin-deficient diet and the centrally acting thiamin antagonist pyrithiamin hydrobromide, after 4, 15, and 26 weeks exposure to ethanol, respectively. The control group was given ad lib access to laboratory chow and water throughout this period. There were no differences between groups on either the working or reference versions of the Morris water tank paradigm. In Experiment 2, to test the hypothesis that a single bout of thiamin deficiency, with or without concurrent alcohol intake, is not sufficient to cause severe memory impairments, two groups of rats were subjected to three bouts of thiamin deficiency. One of these groups consumed an ethanol/water mix, the other tap water. A third group was made thiamin deficient on only one occasion. The control group was not made thiamin deficient and consumed lab chow and tap water throughout. Once again, there were no between-group differences in the data derived from testing in either the eight-arm radial maze or the Morris water tank task. These experiments indicate that the aetiology of Korsakoff's syndrome is more complex than previously thought.     

出生后早期接触速灭威对小鼠空间学习记忆能力的影响

目的观察出生后早期有限次数速灭威染毒对ICR小鼠青春期和成年早期神经行为和空间学习记忆能力的影响以及自主活动能力、感觉运动能力和焦虑情绪是否影响空间学习记忆能力,并探明其影响的发生时间。方法小鼠出生后随机分为5组,即速灭威高、中、低剂量组（5 mg/kg、0.5 mg/kg、0.05 mg/kg,）,溶剂对照组（DMSO）和生理盐水对照组（NS）,于出生后第3、5、7、9、11、13天进行腹腔注射染毒。观察一般生理发育情况,并选用成组的神经行为学实验在青春期（～PND60）和成年早期（～PND90）进行测试。结果青春期小鼠平衡木得分与染毒剂量呈负相关关系（rs=-0.418,P〈0.05）;青春期和成年早期的洞板实验和旷场实验中各指标在同期各组间均无统计学意义;青春期Morris水迷宫空间探索实验中,定位航行结束后和次日的两次穿越平台位置次数与染毒剂量之间均呈负相关关系（rs分别为-0.361和-0.277,P〈0.05）;成年早期Morris水迷宫空间探索实验中,第四象限时间百分比与染毒剂量之间呈负相关关系（rs=-0.390,P〈0.05）;主成分分析发现,反映空间学习记忆能力与自主活动能力、感觉运动能力及焦虑情绪的指标出现在不同的主成分中。结论出生后早期有限次数接触速灭威可能在青春期时已经开始影响到小鼠的空间记忆能力,这可能是成年后空间学习记忆能力损害的重要线索。     

Mechanisms of thiamin deficiency in chronic alcoholism

In the United States and other developed countries thiamin deficiency is often related to chronic alcoholism. A number of mechanisms may be involved in the pathogenesis of thiamin deficiency in the alcoholic population. An important cause is inadequate intake of thiamin. Moreover, there may be decreased converstion of thiamin to the active coenzyme, reduced hepatic storage of the vitamin in patients with fatty metamorphosis, ethanol inhibition of intestinal thiamin transport, and impaired thiamin absorption secondary to other states of nutritional deficiency. The present discussion focuses on the mechanism of ethanol-related thiamin malabsorption. Under normal conditions thiamin transport in animals and humans is biphasic. At low or physiological thiamin concentrations, transport is a saturable, carrier-mediated, active process; but at higher concentrations, the transport of thiamin is predominantly passive. Ethanol reduces the rate of intestinal absorption and the net transmural flux of thiamin. Furthermore, ethanol inhibits only the active and not the passive component of thiamin transport by impeding the cellular exit of thiamin across the basolateral or serosal membrane. The impairment of thiamin movement out of the enterocyte correlates with a fall in the activity of Na-K ATPase. Bound to the basolateral membrane, Na-K ATPase is believed to be involved in the kinetics of active transport. Ethanol also increases the fluidity of enterocyte brush border and basolateral membranes. Since ethanol increases membrane fluidity it is possible that tahe impairment of thiamin transport and the diminution of Na-K ATPase activity may be related, at least partly, to a physical perturbation of the enterocyte membrane.     

Prevalence of thiamin deficiency in anorexia nervosa

OBJECTIVE: Deficiency of thiamin (vitamin B1) causes a range of neuropsychiatric symptoms that resemble those reported in patients with anorexia nervosa (AN) but the prevalence of thiamin deficiency in AN has not been reliably established. This study was designed to investigate the prevalence of thiamin deficiency in AN. METHOD: Thirty-seven patients attending a specialist eating disorders unit and meeting all or some of the DSM-IV criteria for AN were compared with 50 blood donor controls. All subjects underwent measurement of erythrocyte transketolase activation following the addition of thiamin pyrophosphate, the standard biochemical test for thiamin deficiency. Deficiency was defined as a result more than 2 SD above the mean of the control population. RESULTS: Fourteen patients (38%) had results in the deficient range; 7 (19%) met the most stringent published criterion for deficiency. Deficiency was not related to duration of eating restraint, frequency of vomiting, or alcohol consumption. DISCUSSION: Thiamin deficiency may account for some of the neuropsychiatric symptoms of AN and routine screening or supplementation may be indicated.     

发育早期暴露氟西汀对斑马鱼社交行为发展的影响

目的通过研究早期暴露于氟西汀的斑马鱼,探索氟西汀对斑马鱼五羟色胺系统及远期社交功能的影响。方法用氟西汀早期慢性处理斑马鱼(3-6dpf),通过高效液相色谱法(HPLC)检测斑马鱼脑部的主要神经递质及部分代谢产物水平;用社交偏好实验评估斑马鱼社交行为的远期发展(30dpf)。结果随氟西汀剂量的增加,五羟吲哚乙酸(5-HIAA)水平不断升高,而五羟色胺(5-HT)、多巴胺(DA)及3,4-二羟苯酰乙酸(DOPAC)在幼鱼(7dpf)脑内水平先增后减。在社交偏好实验结果中,对照组在毗邻鱼群的区域内总游动距离显著高于4μM组和8μM处理组(P均0.01);游动时间的比较显示,对照组高于4μM组和8μM组(P均0.05)。结论斑马鱼早期暴露于氟西汀,可能通过改变5-HT水平和功能,对神经发育过程产生持续作用,继而影响到其社交能力。     

Effects of postnatal protein malnutrition on learning and memory procedures

Abstract

Protein malnutrition induces structural, neurochemical and functional changes in the central nervous system leading to alterations in cognitive and behavioral development of rats. The aim of this work was to investigate the effects of postnatal protein malnutrition on learning and memory tasks. Previously malnourished (6% protein) and well-nourished rats (16% protein) were tested in three experiments: working memory tasks in the Morris water maze (Experiment I), recognition memory of objects (Experiment II), and working memory in the water T-maze (Experiment III). The results showed higher escape latencies in malnourished animals in Experiment I, lower recognition indexes of malnourished animals in Experiment II, and no differences due to diet in Experiment III. It is suggested that protein malnutrition imposed on early life of rats can produce impairments on both working memory in the Morris maze and recognition memory in the open field tests.     

Effects of postnatal protein malnutrition on learning and memory procedures

Protein malnutrition induces structural, neurochemical and functional changes in the central nervous system leading to alterations in cognitive and behavioral development of rats. The aim of this work was to investigate the effects of postnatal protein malnutrition on learning and memory tasks. Previously malnourished (6% protein) and well-nourished rats (16% protein) were tested in three experiments: working memory tasks in the Morris water maze (Experiment I), recognition memory of objects (Experiment II), and working memory in the water T-maze (Experiment III). The results showed higher escape latencies in malnourished animals in Experiment I, lower recognition indexes of malnourished animals in Experiment II, and no differences due to diet in Experiment III. It is suggested that protein malnutrition imposed on early life of rats can produce impairments on both working memory in the Morris maze and recognition memory in the open field tests.     

Ethanol consumption improves avoidance learning in rats: role of deprivation interval.

Voluntary oral self-administration of ethanol in rats has been used to model ethanol consumption and abuse in human beings, with contradictory results. The purpose of the current study was to assess the effect of voluntary ethanol consumption on acquisition of a lever press escape/avoidance task in rats. Male Wistar rats were exposed to ethanol in a limited-access procedure, and either 1 day or 10 days after their last ethanol exposure, animals received a 4-h lever press escape/avoidance session. Control animals were not exposed to ethanol at any time. Animals in the 1-day ethanol-deprivation group performed significantly better than did the other two groups with respect to avoidance responding. There were no group differences in number of lever presses during a safety period, a measure of anxiety. Further, we obtained a significant negative correlation between behavioral performance and change in ethanol consumption after the escape/avoidance session, as well as a significant positive correlation between baseline ethanol consumption and avoidance performance. Results are discussed in terms of the potential neural mediators of the improved avoidance effect in animals in the 1-day ethanol-deprivation group.