Involvement of retinoic acid receptor α in the autistic-like behavior of rats with vitamin A deficiency by regulating neurexin 1 in the visual cortex: a mechanism study. / è§†é»„é ¸å—ä½“α通过调控视皮质轴突蛋白1å‚ä¸Žç»´ç”Ÿç´ Aç¼ºä¹å¤§é¼ å­¤ç‹¬ç—‡æ ·è¡Œä¸ºçš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To study the mechanism of retinoic acid receptor α (RARα) signal change to regulate neurexin 1 (NRXN1) in the visual cortex and participate in the autistic-like behavior in rats with vitamin A deficiency (VAD). METHODS: The models of vitamin A normal (VAN) and VAD pregnant rats were established, and some VAD maternal and offspring rats were given vitamin A supplement (VAS) in the early postnatal period. Behavioral tests were performed on 20 offspring rats in each group at the age of 6 weeks. The three-chamber test and the open-field test were used to observe social behavior and repetitive stereotyped behavior. High-performance liquid chromatography was used to measure the serum level of retinol in the offspring rats in each group. Electrophysiological experiments were used to measure the long-term potentiation (LTP) level of the visual cortex in the offspring rats. Quantitative real-time PCR and Western blot were used to measure the expression levels of RARα, NRXN1, and N-methyl-D-aspartate receptor 1 (NMDAR1). Chromatin co-immunoprecipitation was used to measure the enrichment of RARα transcription factor in the promoter region of the NRXN1 gene. RESULTS: The offspring rats in the VAD group had autistic-like behaviors such as impaired social interactions and repetitive stereotypical behaviors, and VAS started immediately after birth improved most of the behavioral deficits in offspring rats. The offspring rats in the VAD group had a significantly lower serum level of retinol than those in the VAN and VAS groups (P<0.05). Compared with the offspring rats in the VAN and VAS groups, the offspring rats in the VAD group had significant reductions in the mRNA and protein expression levels of NMDAR1, RARα, and NRXN1 and the LTP level of the visual cortex (P<0.05). The offspring rats in the VAD group had a significant reduction in the enrichment of RARα transcription factor in the promoter region of the NRXN1 gene in the visual cortex compared with those in the VAN and VAS groups (P<0.05). CONCLUSIONS: RARα affects the synaptic plasticity of the visual cortex in VAD rats by regulating NRXN1, thereby participating in the formation of autistic-like behaviors in VAD rats.

A weekly vitamin A supplementary program alleviates social impairment in Chinese children with autism spectrum disorders and vitamin A deficiency.

BACKGROUND: Children in China with Autism Spectrum Disorders (ASD) are prone to vitamin A deficiency (VAD). The present study compared two vitamin A supplements (VAS) in two groups of children with ASD and VAD to explore a better VAS program for children with ASD. METHOD: A total of 138 3-8-year-old children with ASD (118 males and 20 females) were enrolled in this 6-month study. Of these 138 children, 82 who had VAD (ASD-VAD) were divided into two VAS groups that received the recommended VAS program (RNI-VAS) or a weekly dose of VAS (WD-VAS). The 56 children who had normal vitamin A levels (ASD-VAN) served as a control group. The Social Responsiveness Scale (SRS) was used to assess the severity of social impairment before and after the interventions. Their serum retinol (VA) and oxytocin (OXT) concentrations, the mRNA expression of retinoic acid receptors (RARs), and CD38 gene in peripheral blood was measured before and after the 6-month intervention. RESULTS: The WD-VAS program increased VA levels better than the RNI-VAS program did (P < 0.01), and it significantly decreased SRS scores (P < 0.05). In addition, the change in VA was positively correlated with the change in mRNA levels in RARß (r = 0.2441, P = 0.0092), the CD38 in PBMC (r = 0.2729, P = 0.0033), and the change in OXT concentration in serum (r = 0.3735, P < 0.0001). VA was also negatively correlated with changes in SRS scores across the three groups (r = -0.2615, P = 0.0026). CONCLUSION: The WD-VAS might be more suitable for children with ASD and VAD than other interventions to improve both VA and social functioning, which may be mediated through the RARß-CD38-OXT axis.

Simultaneous Determination of Ten Constituents in Chaiqin Qingning Capsule by High-performance Liquid Chromatography Coupled with Triple-quadrupole Mass Spectrometry.

BACKGROUND: Chaiqin Qingning Capsule (CQQNC) was a prescription of Traditional Chinese Medicine with the effects of clearing away heat and removing toxin, harmonizing the exterior and interior, it was widely used in Asian, for example, China and Japan, different batches of the raws materials and different processing time may be the vital factor which raised a challenge to control the quality of the CQQNC. EXPERIMENTAL METHODS: In this experiment, a high-performance liquid chromatography-mass spectrometry/MS (HPLC-MS/MS) method was developed to simultaneously determine ten bioactive components for the quality control of CQQNC. Chromatographic separation was achieved using an XBridge BEH C18 column (150 mm × 4.6 mm, 2.5 µm) with a mobile phase composed of 10 mm aqueous ammonium acetate and acetonitrile using a gradient elution in 20 min. This study was conducted by multiple reaction monitoring mode through electrospray ionization resource with a negative ionization mode. RESULTS: The established method was validated with good performance of precision, accuracy, stability, and reproducibility and was utilized to simultaneously quantify ten constituents of CQQNC obtained from seven different batches. CONCLUSION: It is the first time to report the rapid and simultaneous analysis of the ten compounds in CQQNC by HPLC-MS/MS and apply to determine 10 constituents in 7 batches of CQQNC bought from drug store in china. This method could be considered as good quality criteria to control the quality of CQQNC. SUMMARY: In this paper, a simple, specific, and rapid high-performance liquid chromatogram coupled with triple-quadrupole mass spectrometry method for simultaneous quantification of ten constituents in Chaiqin Qingning Capsule has been developed for the first time. This method could be considered as good quality criteria to control the quality of CQQNC. Abbreviations used: CHM: Chinese herbal medicine; TCM: Traditional Chinese Medicine; CQQNC: Triple-quadrupole mass spectrometry Chaiqin Qingning Capsules; HPLC-MS/MS: High liquid chromatography equipped with tandem mass spectrometry; ESI: Electrospray ionization; DP: Declustering potential; CE: Collision energy; RSD: Relative standard deviation; LOD: Limit of detection; LOQ: Limit of quantity.

Effect of vitamin A supplementation on gut microbiota in children with autism spectrum disorders - a pilot study.

BACKGROUND: Dysbiosis of gut microbiota are commonly reported in autism spectrum disorder (ASD) and may contribute to behavioral impairment. Vitamin A (VA) plays a role in regulation of gut microbiota. This study was performed to investigate the role of VA in the changes of gut microbiota and changes of autism functions in children with ASD. RESULTS: Sixty four, aged 1 to 8 years old children with ASD completed a 6-month follow-up study with VA intervention. High-performance liquid chromatography was used to assess plasma retinol levels. The Autism Behaviour Checklist (ABC), Childhood Autism Rating Scale (CARS) and Social Responsiveness Scale (SRS) were used to assess autism symptoms. CD38 and acid-related orphan receptor alpha (RORA) mRNA levels were used to assess autism-related biochemical indicators' changes. Evaluations of plasma retinol, ABC, CARS, SRS, CD38 and RORA mRNA levels were performed before and after 6 months of intervention in the 64 children. Illumina MiSeq for 16S rRNA genes was used to compare the differences in gut microbiota before and after 6 months of treatment in the subset 20 of the 64 children. After 6 months of intervention, plasma retinol, CD38 and RORA mRNA levels significantly increased (all P < 0.05); the scores of ABC, CARS and SRS scales showed no significant differences (all P > 0.05) in the 64 children. Meanwhile, the proportion of Bacteroidetes/Bacteroidales significantly increased and the proportion of Bifidobacterium significantly decreased in the subgroup of 20 (all false discovery rate (FDR) q < 0.05). CONCLUSIONS: Bacteroidetes/Bacteroidales were the key taxa related to VA. Moreover, VA played a role in the changes in autism biomarkers. It remains unclear whether the VA concentration is associated with autism symptoms. TRIAL REGISTRATION: The study protocol was peer reviewed and approved by the institutional review board of Children's Hospital, Chongqing Medical University in 2013 and retrospectively registered in Chinese Clinical Trial Registry (ChiCTR) on November 6, 2014 (TRN: ChiCTR-ROC-14005442 ).

Effects of vitamin A, vitamin A plus zinc, and multiple micronutrients on anemia in preschool children in Chongqing, China.

This study is to clarify the impact of vitamin A or vitamin A combined with other micronutrients supplementation on anemia and growth in preschoolers. In the present study, a total of 290 preschoolers, aged 36-72 months old were randomly assigned to 3 treatment groups: vitamin A (A group), vitamin A plus zinc (AZ group), and vitamin A combined with additional multiple-micronutrient (AMM group). After 6-month supplementation, the height and height-for-age z-score gains of the AZ group were significantly higher than the other groups; the weight gain of the AMM group was greater than the other groups. Compared with baseline values, the concentrations of hemoglobin, and zinc at the end significantly increased in all 3 groups. The incremental concentrations of hemoglobin in the AMM group were significant higher than in the other two groups. Furthermore, the incremental concentrations of serum retinol in the AMM group, and the increase in serum zinc concentrations in the AZ group were significantly higher, respectively, than in the other groups. These 3 kinds of supplements in the present study are effective in enhancing height gains and are effective in reducing the prevalence of anemia. Supplementation of zinc plus vitamin A is a better way for improving children's height and height-for-age z-score. Vitamin A combined with multiple-micronutrient is more effective in improving the hemoglobin concentrations in preschool children.

Effect of vitamin A, vitamin A plus iron and multiple micronutrient-fortified seasoning powder on infectious morbidity of preschool children.

OBJECTIVE: Improvement of hemoglobin and serum retinol and facilitation of the mobilization of iron storage were achieved with a multiple-micronutrient-fortified diet in preschoolers for 6 mo in a suburb of Chongqing, China. We investigated whether fortification with multiple micronutrients in a diet for preschool children results in changes in children's infectious morbidity compared with diets fortified solely with vitamin A and with vitamin A plus iron. METHODS: From December 2005 to June 2006, 226 2- to 6-y-old preschool children were recruited from three nurseries randomly assigned to three different fortified-diet groups for 6 mo. Group I was fortified with vitamin A; groups II and III were fortified with vitamin A plus iron and vitamin A plus iron, thiamine, riboflavin, folic acid, niacinamide, zinc, and calcium, respectively. The secondary functional outcomes, morbidity of diarrhea and respiratory infection, were collected during supplementation. RESULTS: The groups were comparable concerning compliance and loss to follow-up. There was evidence of a lower incidence rate of respiratory-related illnesses, diarrhea-related illness, fewer symptoms of runny nose, cough, and fever, and shorter duration of respiratory-related illnesses and cough for children in group III compared with children in groups I and II. However, there was no significantly or clinically important difference between children in groups I and II. CONCLUSION: The beneficial effects on infectious morbidity over 6 mo, in addition to some biochemical improvements, highlight the potential of this micronutrient-fortified seasoning powder supplied in a diet for preschool children.

[Effects of vitamin A, vitamin A plus iron and multiple micronutrient-fortified seasoning powder on iron metabolic homeostasis].

OBJECTIVE: To evaluate the effect of vitamin A, vitamin A plus iron and "7 + 1" multiple micronutrient-fortified seasoning powder on iron metabolic homeostasis in preschool children. METHODS: This was a randomized, controlled and blinded interventional field trial. A total of 226 2 - 7 years old preschool children were recruited from three nurseries in the area, and they were randomly assigned into three different fortified diet groups for 6 months. The subjects in Group I were fortified with vitamin A; those in Group II and III were fortified with vitamin A plus iron and vitamin A plus iron, thiamine, riboflavin, folic acid, niacinamide, zinc and calcium (7 + 1), respectively. The concentration of serum vitamin A was measured by high-performance liquid chromatography (HPLC), serum ferritin (SF) was measured by enzyme-linked immunosorbent assay (ELISA), soluble transferrin receptor (sTfR) was measured by microparticle-enhanced, and hemoglobin (HB) by hemiglobincyanide, the sTfR-SF index (TFR-F index) and total body iron content were computed respectively before and after intervention. Simultaneously, children's demographic data, socio-economic status and eating habits, etc. were investigated by questionnaires. RESULTS: A total of 226 preschool children were included in the study with age ranged from 2 to 7 years with average age (4.0 ± 0.85) (means ± standard deviation). The prevalence of anemia, deficient iron storage, vitamin A deficiency (VAD) and suspect sub-clinical vitamin A deficiency (SSVAD) were 23.5%, 15.0%, 6.3% and 25.9%, respectively. The levels of SF and sTfR significantly decreased after intervention in all groups (χ(2) = 8.3298, χ(2) = 16.1471, χ(2) = 15.1371, χ(2) = 15.1171, χ(2) = 5.2617, χ(2) = 4.8844, P < 0.05) especially in group II and group III for SF (χ(2) = 16.1471, χ(2) = 15.1371, P < 0.05) and group I for sTfR (χ(2) = 15.1171, P < 0.05). No marked change of TFR-F index and total body iron contents was observed in group I (t = 0.1817, t = 1.7736, P > 0.05), while TFR-F index decreased and total body iron contents increased in group II and group III (t = 5.3561, t = 6.5979, t = 11.1663, t = 8.7306, P < 0.05) after intervention. CONCLUSION: Vitamin A intervention has significant effect on iron storage and mobilization but seldom effect on iron absorption in small intestine. The combination of vitamin A and other micronutrients might be a better intervention for the improvement of iron deficiency for preschool-children.

[Primary culture of rat hippocampal neurons and detection of the neuronal excitability].

OBJECTIVE: To improve the efficiency of primary culture of hippocampal neurons and obtain highly purified neurons with good in vitro growth and minimal risk of contamination. METHODS: The hippocampal neurons of neonatal Wistar rats were isolated and the single cell suspension was prepared by mechanical trituration and sedimentation in stead of trypsin digestion and filteration. Twenty-four hours after the cell plating, the culture medium was removed and replaced by serum-free DMEM/F12 with B27 supplementation. Half of the culture medium was changed 2-3 times every week. The morphological changes of the neurons were observed under inverted phase-contrast microscope. Immunofluorescence staining for NSE was performed to identify the neurons, and the purity of neurons was calculated. The hippocampal neurons were stained with calcium-sensitive fluorescent dye to monitor the effect of KCl on neuronal excitability by a calcium imaging system. RESULTS AND CONCLUSION: This simplified method is time-saving and cost-effective for primary culture of hippocampal neurons with reduced risk of contamination, and the neurons obtained showed high uniformity, purity and long-term viability.

Effect of biscuits fortified with different doses of vitamin A on indices of vitamin A status, haemoglobin and physical growth levels of pre-school children in Chongqing.

OBJECTIVE: To investigate the efficacy of biscuits fortified with different doses of vitamin A on improving vitamin A deficiency (VAD), anaemia and physical growth of pre-school children. DESIGN: A randomised double-masked population-based field interventional trial with a positive control group. SETTING: Banan district of Chongqing, China. SUBJECTS: A total of 580 pre-school children aged 3-6 years were randomly recruited into four groups. Children in groups I and II were given biscuits fortified with vitamin A at 30 % of the recommended daily intake (RDA) and 100 % of the RDA once a day for 9 and 3 months, respectively. Children in group III received biscuits containing 20,000 IU of vitamin A once a week for 3 months. Initially, the children in group IV received a 200,000 IU vitamin A capsule just once. At the beginning and end of the study, blood samples were collected to measure Hb, serum retinol, retinol-binding protein and prealbumin, and weight and height were measured. RESULTS: All the fortification types significantly decreased the prevalence of VAD and anaemia in each group (P < 0.05). The effect of 9-month intervention on group I was the most efficient (P < 0.0045). After intervention, the Z-scores of height-for-age, weight-for-age and weight-for-height in all groups increased markedly compared with baseline (P < 0.05), but no significant difference was observed among the groups. CONCLUSIONS: Data indicated that consuming vitamin A-fortified biscuits with daily 100 % RDA for 3 months has the same effect on the improvement of VAD, anaemia and physical growth as did the weekly 20,000 IU and single 200,000 IU administration in pre-school children.

Co-assessment of iron, vitamin A and growth status to investigate anemia in preschool children in suburb Chongqing, China.

BACKGROUND: Anemia is a widespread public health problem, which is due to many factors, nutritional or non-nutritional. Iron, vitamin A and growth status were assessed to investigate anemia of preschool children in suburb Chongqing, China. METHODS: A descriptive, cross-sectional survey was performed on 459 preschool children aged 2 to 7 years randomly chosen from the kindergartens in 6 suburban districts of Chongqing. Weight and height levels, hemoglobin, erythrocyte protoporphyrin, serum retinol, and ferritin concentrations were measured to evaluate the anthropometric and nutritional status. RESULTS: The rates of stunt, underweight, overweight, wasting, obesity, anemia, iron deficiency, vitamin A deficiency (VAD), and marginal VAD were 6.3%, 3.9%, 3.7%, 1.5%, 3.1%, 23.5%, 15.0%, 6.3% and 25.9%, respectively. Serum retinol concentration was significantly lower in children with anemia than in those without anemia (P=0.003), and the retinol concentration was associated with hemoglobin (Pearson's correlation coefficient, r=0.22, P<0.01). Children with VAD had a significantly increased risk for anemia (odds ratio, 2.56; 95% confident interval, 1.15-5.70). In all 108 children with anemia, only 42 were related to VAD and 12 related to iron deficiency, suggesting that almost half of the anemia children cannot be explained solely by iron deficiency or VAD. CONCLUSIONS: Vitamin A and iron deficiency are still public health problems in some localities of China. Public health interventions in anemia control should be used to eliminate deficiencies of vitamin A, iron, and other micronutrients by deliberate supplementation. Attention must be paid to such deficiencies in high-risk groups, especially in preschool children.

Marginal vitamin A deficiency affects lung maturation in rats from prenatal to adult stage.

UNLABELLED: Mild or marginal vitamin A deficiency (MVAD) is still a serious and widespread public health problem in pregnant women and children in developing countries. This study investigated rat lung maturation from prenatal to adult stage during pregnancy and postnatal MVAD and the recovery after postnatal vitamin A supplementation (VAS). Adult female rats and their offspring were randomized into three groups. 1. CONTROL: the mothers and offspring received a normal diet.2. MVAD: The mothers and offspring received a MVAD diet.3. VAS: the mothers received MVAD diet till parturition, and then received the normal diet. The offspring of the VAS group were given low-dose vitamin A from postnatal day 1 to day 7 and received the normal diet after weaning. The lung development, structure, and collagen and elastic fiber of offspring were monitored by morphometric analysis at age 1 d, 2 and 8 wk, respectively. Lower body weight, lung weight, reduced numbers of alveoli and total alveolar surface area as well as increased alveoli septa thickness was observed in MVAD compared to that in the control animals. Increased collagen deposits and decreasing elastic fiber were found in MVAD rats. However, all of these were significantly improved in VAS-treated animals. These data suggest that the rat lung is sensitive to MVAD during the developing stage. Early postnatal vitamin A supplementation can partially restore the normal lung structure.

Effects of vitamin A, vitamin A plus iron and multiple micronutrient-fortified seasoning powder on preschool children in a suburb of Chongqing, China.

Preschool children in developing countries are likely to have multiple, concurrent micronutrient deficiencies. This study was designed to evaluate the effectiveness of different combinations of nutritional fortified diet to improve the blood levels of iron, vitamin A and other essential micronutrients in the preschool population of Banan District of Chongqing, China. From December 2005 to June 2006, a total of 226 2-6 y old preschool children were recruited from three nurseries in the area, and they were randomly assigned to three different fortified diet groups for 6 mo. Group I was fortified with vitamin A; groups II and III were fortified with vitamin A plus iron and vitamin A plus iron, thiamine, riboflavin, folic acid, niacinamide, zinc and calcium, respectively. Subjects' weight and height were measured for assessing the children's growth and development. Blood samples were taken at the beginning and the end of the 6-mo study period for measuring serum levels of micronutrients. Group III with the multiple micronutrient fortified diet was the most effective to improve the serum level of retinol from [media (P25, P75): 1.06 (0.89, 1.32)] micromol/L to 1.29 (1.04, 1.39) micromol/L (p<0.05) and retinol binding protein from 17.0 (12.6, 25.6) mg/L to 31.6 (24.4, 44.0) mg/L (p<0.05) and to mobilize the stored iron in the liver (p<0.05). In addition, the three groups' hemoglobin levels were elevated from 117.0 (109.0, 124.1) g/L, 114.0 (109.2, 119.7) g/L and 115.0 (109.5, 122.7) g/L to 125.7 (119.2, 133.1) g/L, 126.5 (122.2, 135.9) g/L and 125.1 (119.8, 131.6) g/L over the 6 mo of intervention period, but there were no difference among the three groups (p>0.05). Nevertheless, unexpected results were obtained when comparing the effects on growth status among the different supplement groups. Our study has demonstrated that a multiple micronutrient fortified diet for 6 mo is more effective to improve the levels of hemoglobin, serum retinol, and RBP as well as to facilitate the mobilization of iron storage in preschool children.

[Effects of early intervention on learning and memory in young rats of marginal vitamin A deficiency and it's mechanism].

OBJECTIVE: In recent years, some experiments on vitamin A-deprived animals reveal a progressive and ultimately profound impairment of hippocampal CA1 area's long-term potentiation and these losses are fully reversible by dietary vitamin A replenishment in vivo. Our previous study revealed that marginal vitamin A deficiency (MVAD) beginning from embryonic period impairs learning, memory and long-term potentiation (LTP) in young rats. But the losses might not be reversible if the vitamin A supplementation is late, especially when the critical period of hippocampus development is missed. The present study aimed to observe the recovery of learning and memory in vitamin A marginally deficient young rats after early intervention with vitamin A supplementation and begin to study the mechanism. METHODS: Rats were divided into control, MVAD, vitamin A intervention 1 (VAI1) and VAI2 groups in this study. In control group (10 young rats) the dams and pups were fed with normal diet (VA 6500 U/kg). In MVAD group (19 young rats) the dams and pups were fed with MVAD diet (VA 400 U/kg). In VAI1 group (10 young rats) the dams were fed with MVAD diet till day 14 of pregnancy, then were fed with normal diet and the pups were fed with normal diet. In VAI2 group (13 young rats) the dams were fed with MVAD diet till delivery, then were fed with normal diet and the pups were fed with normal diet too. All the young rats were killed at the age of 7 weeks. During the last week of the experiment, the shuttle box active avoidance reaction tests were carried out. At week 7, the hippocampal CA1 LTP was detected by electrophysiological technique. The expression of RAR-alpha, RAR-beta, RXR-beta, RXR-gamma, RC3 and tTG mRNA was detected by using semi-quantified RT-PCR in hippocampus. RESULTS: (1) The times to reach the learning standard in MVAD group (45.6 +/- 12.1) were more than those in control group (17.1 +/- 4.4) (P < 0.01), in both VAI1 group (20.8 +/- 3.1) and VAI2 group (22.1 +/- 4.0) were more than those in group MVAD (P < 0.01), and there were no significant differences among groups VAI1, VAI2 and control (P > 0.05) in active avoidance reaction tests. (2) The changes of field excitatory postsynaptic potentials (fEPSP) slope for MVAD group [(22.9 +/- 9.4)%] and VAI2 group [(39.1 +/- 4.33)%] were less than that of control group [(57.5 +/- 27.3)%], respectively (P < 0.05). No significant difference was found between VAI1 and control group (P > 0.05). (3) The expression of RAR-beta and RXR-beta mRNA decreased by 48.72% and 37.84% respectively (P < 0.05) compared with control, but the expression of RAR-beta mRNA in group VAI1 was higher than that in group MVAD (P = 0.065). The expression of RC3 mRNA in MVAD group was lower than that in control (P = 0.061) and RAR-alpha mRNA in MVAD group was higher than that in control (P = 0.061). The expression of RXR-gamma and tTG mRNA had no significant difference among different groups as determined with semi-quantified RT-PCR in hippocampus. CONCLUSION: Early vitamin A intervention may make the impaired learning and memory behavior due to marginal vitamin A deficiency recover to the normal level in young rats, but lip losses in group VAI2 might not be reversible. Vitamin A may modulate the expression of RC3 mRNA by affecting RAR-alpha, RAR-beta and RXR-beta to influence the LTP, learning and memory.

[Effects of marginal vitamin A deficiency and intervention on learning and memory in young rats].

OBJECTIVE: Previous studies have demonstrated that vitamin A and its active derivatives function as essential competence factors for long-term synaptic plasticity within the adult brain. But little is known if marginal vitamin A deficiency (MVAD) beginning from embryonic period affects the brain development and the ability of learning and memory in young rats. The aim of this study was to identify the effects of MVAD and vitamin A intervention (VAI) on learning, memory and the hippocampal CA1 long-term potentiation (LTP) in young rats. METHODS: Rats were divided into control, MVAD and VAI groups in this study. In control group (10 young rats) the dams and pups were fed with normal diet (VA 6500 IU/kg). In MVAD group (19 young rats) the dams and pups were fed with MVAD diet (VA 400 IU/kg). In VAI group (9 young rats) the dams were fed with MVAD diet and the pups were fed with normal diet from postnatal week 4. All the young rats were killed at the age of 7 weeks. During the last week of the experiment, the shuttle box active avoidance reaction tests were carried out. At week 7, the hippocampal CA1 LTP was detected by electrophysiological technique and relative intensity of fluorescence in cells in hippocampal slices was measured by confocal laser scanning microscopy labeled by fluo-3. RESULTS: (1) The times to reach the learning standard in both VAI group (28.8 +/- 4.1) and MVAD group (45.6 +/- 12.1) were more than control group (17.1 +/- 4.4) (P < 0.01), and that of MVAD group was more than VAI group (P < 0.05) in active avoidance reaction tests. (2) The changes of field excitatory postsynaptic potentials (fEPSP) slope for MVAD group (22.9% +/- 9.4%) and VAI group (29.5% +/- 13.7%) were less than that of control group (57.5% +/- 27.3%), respectively (P < 0.01). No significant difference was found between VAI and MVAD groups (P > 0.05). (3) No significant differences of relative intensity of fluorescence in cells were found among the three groups before the tetanus stimulation. However, the significantly low relative intensity of fluorescence in cells was seen in MVAD (65.1 +/- 17.0) and VAI (85.8 +/- 17.1) groups compared with control group (113.6 +/- 20.5) after the tetanus stimulation (P < 0.01), and that of VAI group was higher than that of MVAD group (P < 0.05). CONCLUSION: MVAD beginning from embryonic period impairs learning, memory and LTP in young rats. But the losses might not be reversible if the vitamin A supplementation is late especially missing the critical period of hippocampus development. According to the experimental data, it is speculated that vitamin A may modulate the influx of calcium ion to influence the LTP and lead to the change of learning and memory.