Memory In Young Rats Research Articles

Taurine ameliorates volatile organic compounds-induced cognitive impairment in young rats via suppressing oxidative stress, regulating neurotransmitter and activating NMDA receptor.

Long-term exposure to volatile organic compounds (VOCs) in children leads to intellectual and cognitive impairment. Taurine is an essential nutritional amino acid for children, which can improve neurological development in children. However, the neuroprotective effect of taurine on VOCs-induced cognitive impairment in children remains unclear. The aim of this study was to investigate the neuroprotective effects of taurine on VOCs-induced cognitive impairment in young rats. The rats were nose-only exposed to VOCs for a period of 4 weeks to create a model of cognitive impairment, and 0.5% and 1% taurine in tap water were administered throughout the trial period, respectively. Our results showed that young rats adjusted the recovery of their physiological functions by voluntarily increasing the intake of taurine in tap water when exposed to excessive VOCs by inhalation. In addition, taurine enhanced grasp, shortened the latency period of escape, and improved the learning and memory function of young rats. Moreover, taurine decreased malondialdehyde (MDA), γ-aminobutyric acid (GABA), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Urea, Creatinine (CREA) and injury biomarker level, enhanced superoxide dismutase (SOD), reduced glutathione (GSH) and glutamic acid (Glu) activities, up-regulated the protein expression of brain derived neurotrophic factor (BDNF) and N-Methyl-d-aspartate receptor 1 (NMDAR1) in model rats, and in most of cases 1% but not 0.5%, ameliorated the defects induced by VOCs. Collectively, these findings suggested that taurine protected against VOCs-induced cognitive-behavioral impairment in young rats through inhibiting oxidative stress and regulating neurotransmitter homeostasis. In addition, taurine were capable of restoring abilities of learning and memory in young rats exposed to VOCs by activating the N-Methyl-d-aspartate (NMDA) receptor. The findings suggest taurine as a potential novel drug for the treatment of cognitive behavioral disorders in children.

Spatial learning and memory of young and aging rats following injection with human Wharton’s jelly‐mesenchymal stem cells

Human Wharton’s jelly‐mesenchymal stem cells (hWJ‐MSC) are an emerging potential source of stem cells derived from the umbilical cord. Previous studies have shown their potential as treatment for traumatic brain injury and Parkinson’s disease. However, no study has yet investigated the effect of hWJ‐MSC injections in countering spatial learning and memory impairment in aging rats. The effect of hWJ‐MSC injection on young rats is also unknown. The objective of this research was to analyze the effect of an hWJ‐MSC injection on spatial learning, memory, density of putative neural progenitor cells (pNPC), and neuronal apoptosis in the dentate gyrus (DG) of young and aging rats. Injection of hWJ‐MSC did not change spatial learning and memory in young rats until two months post‐injection. This might be due to retained pNPC density and neuronal apoptosis in the DG of young rats after injection of hWJ‐MSC. In contrast, injection of hWJ‐MSC promoted both spatial learning and memory in aging rats, a finding that might be attributable to the increased pNPC density and attenuated neuronal apoptosis in DG of aging rats during the two months post‐injection. Our study suggests that a single injection of hWJ‐MSC might be sufficient to promote improvement in long‐term learning and memory in aging rats.

Prenatal Exposure to Cadmium During Organogenesis Impairs Memory in Young Rats.

Pregnant rats were treated with 0.3 and 0.6 mg cadmium (CdCl2)/kg injected subcutaneously on a daily basis from gestational day 7 to day 15 (organogenesis period). One control group was not injected and other received saline. The 45-day-old offspring were tested in a step-down inhibitory avoidance to evaluate short-term and long-term memory and in a radial maze for the study of spatial memory. These studies showed that gestational exposure to 0.6 mg Cd/kg produced in the male offspring a significant impairment in the retention of long-term memory evaluated 24 hours after training in the step-down inhibitory avoidance. The radial maze also demonstrated that the male offspring prenatally exposed to 0.6 mg Cd presented a significant deficit in the retention of spatial memory evaluated 42 days after training. These results demonstrate that the exposure to Cd during organogenesis may affect the retention of some types of memory.

What is the combined effect of intense intermittent exercise and Ginkgo biloba plant on the brain neurotrophic factors levels, and learning and memory in young rats?

The present study was conducted to investigate the effect of intense intermittent exercise and Ginkgo biloba on the hippocampal levels of brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) and also memory and learning in young rats. Forty two eight-week-old rats were randomly divided into six groups including control, low dose of Ginkgo biloba (65 mg/kg), high dose of Ginkgo biloba (100 mg/kg), exercise, exercise + low dose of Ginkgo biloba, exercise + high dose of Ginkgo biloba. The exercise protocol or Ginkgo biloba administration was six days a week for six weeks. The hippocampal levels of BDNF and NT-4 were measured by ELISA method, and learning and memory were evaluated by Morris water maze test in all groups. Data were analyzed using SPSS software. Increase in hippocampal levels of BDNF and NT-4 appeared following exercise (p < 0.01). The levels do not change following exercise + Ginkgo biloba administration. However, the NT-4 level decreased in the high dose of Ginkgo biloba group (p < 0.01). Disorder in learning and memory was indicated following the use of low dose of Ginkgo biloba or exercise + low dose Ginkgo biloba administration (p < 0.001). Learning elevated in the exercise group (p < 0.05). Exercise in young rats may increase brain neurotrophin levels and lead to improved learning. The preventative or protective role of Ginkgo biloba against some diseases has been suggested, but its consumption in young athletes is recommended with caution.

Intraventricular infusion of quinolinic acid impairs spatial learning and memory in young rats: a novel mechanism of lead-induced neurotoxicity

BackgroundLead (Pb), a heavy metal, and quinolinic acid (QA), a metabolite of the kynurenine pathway of tryptophan metabolism, are known neurotoxicants. Both Pb and QA impair spatial learning and memory. Pb activates astrocytes and microglia, which in turn induce the synthesis of QA. We hypothesized increased QA production in response to Pb exposure as a novel mechanism of Pb-neurotoxicity.MethodsTwo experimental paradigms were used. In experiment one, Wistar rat pups were exposed to Pb via their dams’ drinking water from postnatal day 1 to 21. Control group was given regular water. In the second protocol, QA (9 mM) or normal saline (as Vehicle Control) was infused into right lateral ventricle of 21-day old rats for 7 days using osmotic pumps. Learning and memory were assessed by Morris water maze test on postnatal day 30 or 45 in both Pb- and QA-exposed rats. QA levels in the Pb exposed rats were measured in blood by ELISA and in the brain by immunohistochemistry on postnatal days 45 and 60. Expression of various molecules involved in learning and memory was analyzed by Western blot. Means of control and experimental groups were compared with two-way repeated measure ANOVA (learning) and t test (all other variables).ResultsPb exposure increased QA level in the blood (by ~ 58%) and increased (p < 0.05) the number of QA-immunoreactive cells in the cortex, and CA1, CA3 and dentate gyrus regions of the hippocampus, compared to control rats. In separate experiments, QA infusion impaired learning and short-term memory similar to Pb. PSD-95, PP1, and PP2A were decreased (p < 0.05) in the QA-infused rats, whereas tau phosphorylation was increased, compared to vehicle infused rats.ConclusionPutting together the results of the two experimental paradigms, we propose that increased QA production in response to Pb exposure is a novel mechanism of Pb-induced neurotoxicity.

Can coconut oil and treadmill exercise during the critical period of brain development ameliorate stress-related effects on anxiety-like behavior and episodic-like memory in young rats?

Virgin coconut oil (CO) and treadmill exercise have been reported to improve memory performance in young rats. CO has also been associated with antistress properties in young, stressed mice. Therefore, in this study we aimed to investigate whether CO and treadmill exercise could synergistically ameliorate the effects of chronic stress on anxiety-like behavior and episodic-like memory in young rats. The rats received CO and were exercised (Ex) from the 15th to the 45th day of life. The animals were supplemented with CO (10 mL kg-1 day-1) or a vehicle (V, distilled water and 0.009% Cremophor) via oral gavage. The Ex animals were placed for 30 min day-1 on a treadmill, with the speed gradually increasing from the first week to the last. From the 46th to the 54th postnatal day, with the exception of the 51st and the 52nd day, all rats were subjected to restraint stress. Afterwards, all rats underwent the open-field test to evaluate locomotor activity and anxiety-like behavior. To evaluate episodic-like memory, all animals underwent tests to recognize object identity and special location. Lastly, lipid profile and murinometric parameters were evaluated. A two-way ANOVA test followed by a Tukey test demonstrated that the CO&Ex group explored more of the unprotected central area of the OFT (27.04 ± 4.03 s, p < 0.01), when compared to the control group (15.36 ± 2.54 s). CO&Ex spent more time exploring the novel location of the object (71.62 ± 3.04%, p < 0.01), when compared to the control group (58.62 ± 2.48%). CO and exercise during lactation can ameliorate the effects of stress on anxiety-like behavior and episodic-like memory in young rats.

Effect of khat extract on young rat's memory

Consumption of khat is still pressing issue in Jazan region. The present study was imperative to know the effect of khat use on memory of young rats. The current study used rats in age comparable to adult humans that mimic the stages of education and grouped in four groups. 1-control normal, 2-scopolamine, 3-khat extract administered group for four weeks, 4- khat withdrawal group administered khat extract for four weeks then left for one week without khat administration. All groups of rats were trained using Morris water maze task before treatment then the behavioral test was performed after treatments and cortex acetylcholinesterase (AChE) enzyme activities were determined in all groups. The body weights were detected weekly. The study showed that khat extract impaired performance in the water maze test, increased cortical AChE activity and reduced the body weight in a time related manner, meanwhile khat withdrawals showed partial retention of the maze performance, reduction in AChE activity and body weight gain. The study knocks alarm on cognitive impairment due to khat consumption especially on youth.

Regulation of structural and functional synapse density by L-threonate through modulation of intraneuronal magnesium concentration

Oral administration of the combination of L-threonate (threonate) and magnesium (Mg2+) in the form of L-Threonic acid Magnesium salt (L-TAMS) can enhance learning and memory in young rats and prevent memory decline in aging rats and in Alzheimer’s disease model mice. Recent results from a human clinical trial demonstrate the efficacy of L-TAMS in restoring global cognitive abilities of older adults. Previously, we reported that neuronal intracellular Mg2+ serves as a critical signaling molecule for controlling synapse density, a key factor that determines cognitive ability. The elevation of brain Mg2+ by oral administration of L-TAMS in intact animals plays a significant role in mediating the therapeutic effects of L-TAMS. The current study sought to elucidate the unique role of threonate. We aimed to understand if threonate acts directly to elevate intraneuronal Mg2+, and why Mg2+ given without threonate is ineffective for enhancing learning and memory ability. We discovered that threonate is naturally present in cerebrospinal fluid (CSF) and oral treatment with L-TAMS elevated CSF threonate. In cultured hippocampal neurons, threonate treatment directly induced an increase in intracellular Mg2+ concentration. Functionally, elevating threonate upregulated expression of NR2B-containing NMDAR, boosted mitochondrial membrane potential (ΔΨm), and increased functional synapse density in neuronal cultures. These effects are unique to threonate, as other common Mg2+ anions failed to have the same results. Mechanistically, threonate’s effects were specifically mediated through glucose transporters (GLUTs). We also evaluated the effects of threonate in human neural stem cell-derived neurons, and found it was equally effective at upregulating synapse density. The current study provides an explanation for why threonate is an essential component of L-TAMS and supports the use of L-TAMS to promote cognitive abilities in human.

Low-Dose Exposure to Lead during Pregnancy Affects Spatial Learning, Memory and Neurogenesis in Hippocampus of Young Rats

Lead is toxic to all organ systems. Central nervous system has received much attention because of the impact of lead exposure on cognitive and behavioral development in children. We investigated the effects of in utero lowdose exposure to lead on neurogenesis in hippocampus and spatial learning and memory in young rats. Wistar rats, after establishing pregnancy, were given drinking water with 0.1% lead acetate until parturition. Control animals received deionized water. The hippocampus of lead-exposed rats showed significantly higher level of lead when compared to age matched controls on postnatal day 0, 21, 30, 40 and 50. Spatial learning and memory determined with Morris water maze test revealed significant memory deficit in lead exposed rats when tested on postnatal day 21 and deficit in relearning ability on postnatal day 37. It also revealed significant memory deficit in lead exposed rats when tested on postnatal day 30, but good relearning ability on postnatal day 47. Doublecortin immunostaining showed significantly decreased number of new neurons in the lead-exposed rats in comparison to control rats. Our data show that low-dose exposure to lead during pregnancy decreased neurogenesis in the hippocampus of young rats that resulted in impairment of spatial learning and memory.

Repeated exposure to propofol impairs spatial learning, inhibits LTP and reduces CaMKIIα in young rats

Propofol is one of the most widely used intravenous anesthetics. We investigated the effects of propofol injected during development on synaptic plasticity and long-term spatial learning and memory in young rats. Propofol (75mg/kg) was administered to 7-day-old rats either as a single dose or in 7 doses at 24-h intervals. At postnatal day 28, spatial learning in the Morris water maze and long-term potentiation (LTP) in the CA1 region of the hippocampus were significantly reduced in the rats that had received 7 doses of propofol. This treatment also significantly decreased the expression of CaMKIIα and pCaMKIIα in the hippocampus, and reduced the pCaMKIIα/CaMKIIα ratio, as measured by immunochemistry and Western blotting. We conclude that repeated exposure to propofol impairs learning and memory in the developing rat brain, and this finding may be associated with down-regulation of CaMKIIα and pCaMKIIα.

Lanthanum chloride impairs spatial learning and memory and downregulates NF-κB signalling pathway in rats

Exposure to rare earth elements (REEs) is known to impair intelligence in children and cause neurobehavioral abnormalities in animals. However, the mechanisms underlying these phenomena are not clear. Lanthanum is often used to study the effects of REEs. The aim of this study was to investigate the influence of lanthanum chloride (LaCl3) on spatial learning and memory and a possible underlying mechanism involving nuclear factor-kappa B (NF-κB) signalling pathway expression in the hippocampus. The rats were exposed to 0, 0.25, 0.50 or 1.00 % LaCl3 in drinking water during pregnancy and lactation (i.e. while feeding their offspring). After weaning, young rats continued to receive 0, 0.25, 0.50 and 1.00 % LaCl3 in the drinking water for 1 month. LaCl3 exposure impaired the spatial learning and memory of young rats and significantly decreased the expression of phosphorylated IκB kinase complex, phosphorylated IκBα, NF-κB, c-fos, c-jun and brain-derived neurotrophic factor in the hippocampus. These results indicate that LaCl3 exposure impairs spatial learning and memory in rats by inhibiting NF-κB signalling pathway.

Antioxidant administration prevents memory impairment in an animal model of maple syrup urine disease

Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder resulting from deficiency of branched-chain α-keto acid dehydrogenase complex leading to branched chain amino acids (BCAA) leucine, isoleucine, and valine accumulation as well as their corresponding transaminated branched-chain α-keto acids. MSUD patients present neurological dysfunction and cognitive impairment. Here, we investigated whether acute and chronic administration of a BCAA pool causes impairment of acquisition and retention of avoidance memory in young rats. We have used two administration protocols. Acute administration consisted of three subcutaneous administrations of the BCAA pool (15.8μL/g body weight at 1-h intervals) containing 190mmol/L leucine, 59mmol/L isoleucine, and 69mmol/L valine or saline solution (0.85% NaCl; control group) in 30 days old Wistar rats. Chronic administration consisted of two subcutaneous administrations of BCAA pool for 21 days in 7 days old Wistar rats. N-acetylcysteine (NAC; 20mg/kg) and deferoxamine (DFX; 20mg/kg) co administration influence on behavioral parameters after chronic BCAA administration was also investigated. BCAA administration induced long-term memory impairment in the inhibitory avoidance and CMIA (continuous multiple-trials step-down inhibitory avoidance) tasks whereas with no alterations in CMIA retention memory. Inhibitory avoidance alterations were prevented by NAC and DFX. BCAA administration did not impair the neuropsychiatric state, muscle tone and strength, and autonomous function evaluated with the SHIRPA (SmithKline/Harwell/ImperialCollege/RoyalHospital/Phenotype Assessment) protocol. Taken together, our results indicate that alterations of motor activity or emotionality probably did not contribute to memory impairment after BCAA administration and NAC and DFX effects suggest that cognition impairment after BCAA administration may be caused by oxidative brain damage.

Over activation of hippocampal serine/threonine protein phosphatases PP1 and PP2A is involved in lead-induced deficits in learning and memory in young rats

Serine/threonine protein phosphatases regulate several key cellular events in the brain, including learning and memory. These enzymes, when over-activated, are known to function as a constraint on learning and memory. We investigated whether these phosphatases are implicated in lead (Pb)-induced deficits in learning and memory. Wistar rat pups were exposed to 0.2% Pb-acetate via their dams’ drinking water from postnatal day (PND) 1–21 and directly in drinking water until PND 30. Pb levels in blood, brain and hippocampus were measured and expression of PP1, PP2A, PP2B and PP5 in hippocampus was analyzed. Total phosphatase activity, and PP1 and PP2A activities were determined. Tau phosphorylation at various epitopes was determined by Western blot. Spatial learning and memory was determined by Morris water maze test. Pb exposure significantly increased levels of Pb in blood, brain and hippocampus, reduced the number of synapses in hippocampus and impaired learning and long-term memory (LTM). Short-term memory (STM) was only affected in rats at PND21. Pb exposure increased the expression and activity of PP1 and decreased phosphorylation of tau at threonine-231 in hippocampus at both PND21 and PND30. Pb-induced phosphorylation of tau at serine-199/202 (AT8) paralleled with PP2A activity; at PND21 PP2A activity increased and AT8 phosphorylation decreased; at PND30 PP2A activity decreased and AT8 phosphorylation increased. Increased PP1 activity in hippocampus by Pb is associated with learning and LTM impairment, whereas, increased PP2A activity is associated with STM impairment. These findings suggest the overactivation of PP1 and PP2A, together with changes in tau phosphorylation, as a potential mechanism of lead-induced deficits in learning and memory.

The mechanism of sleep deprivation on the learning and memory of young rats

Objective To explore the effect of total sleep deprivation on learning and memory ability of young rats and to find out some clues of its mechanism.Methods 12 weaned (3-week-old) male Spraque-Daw-lcy rats were randomly divided into sleep deprivation(SD) group and control group(CC).SD was introduced by Flower pot technique,and lasted for 48 hours.The Morris water maze was used to test the spatial learning and memory of young rats before SD and after SD 24h,SD 48h.All the rats were decapitated after 48h SD ,and the cerebral cortex and hippocampus were dissected for cDNA microarray containing 1176 cDNA.The genes whose rations (SD/CC) were>2.0 or<0.5 were considered significant different between two groups.Results The impairment of retention of spatial reference memory was showed in SD group after 48 hours total sleep deprivation,while memory acquisition was not effected by 48h SD.The differences were not found in the spatial learning and working memory between SD and CC group.Among 85 genes which were screened out with 40 upregulated and 45 downregulated,there were 11 genes related to learning and memory.The upregulated genes were Rasal,Fgf2,Bid3 and Gnao,and the downregulated were Cd9 ,Fgf1 ,China6 and four glutamate receptors including Grin2b,Gria1,Gria4 and Grml.Conclusion Compared with the effect of short term total sleep deprivation on adult rats,the impairment of memory retention after 48 hours sleep deprivation was newly found,and the changes of synaptic conduction related gene expression may be contribute to the mechanism of this memory impariment. Key words: Sleep deprivation; Young rat; Learning and memory; cDNA mirooarray

The influence of forepaw palmar sensorimotor deprivation on learning and memory in young rats

This study examined the effects of early palmar forepaw sensorimotor deprivation on learning and memory in rats. Sensorimotor deprivation was performed on 18-day-old male rats. Controls were sham operated. Studies were performed on rats aged 18, 25, 35, 45 and 60 days. Morris water maze testing was used to assess learning and memory. Long-term potentiation (LTP) was assessed by electrophysiological means in slices obtained from the hippocampal Schaffer collateral pathway. Nissl staining was performed to assess pyramidal cell number in hippocampal CA1 and CA3 regions. Hippocampal N-methyl- d-aspartate receptor 1 (NMDAR1) mRNA and protein levels were assessed. Learning and short-term memory were significantly depressed in 25 and 35 day old sensorimotor deprived rats ( P < 0.01). LTP was also significantly depressed in sensorimotor deprived rats at these ages, while hippocampal CA1 pyramidal cell counts were significantly decreased ( P < 0.05). CA3 cell numbers were significantly lower in 25-day-old sensorimotor deprived rats ( P < 0.05). Both NMDAR1 mRNA and protein levels were significantly lower in sensorimotor deprived rats aged 25 and 35 days ( P < 0.05). These findings indicate that palmar surface forepaw sensorimotor deprivation impairs subsequent learning and memory in young rats. Decreased hippocampal pyramidal cell numbers and altered NMDAR1 expression may underlie this impairment.

Effect of behavior training on learning and memory of young rats with fetal growth restriction

Objective To investigate the effect of behavior training on the learning and memory of young rats with fetal growth restriction (FGR). Methods The model of FGR was established by passive smoking method to pregnant rats. The new-born rats were divided into FGR group and normal group, and then randomly subdivided into trained and untrained group respectively. Morris water maze behavior training was performed on postnatal months 2 and 4, then learning and memory abilities of young rats were measured by dark-avoidance testing and step-down testing. Results In the dark-avoidance and step-down testing, the young rats' performance of FGR group was worse than that of control group, and the trained group was better than the untrained group significantly. Conclusion FGR young rats have descended learning and memory abilities. Behavior training could improve the young rats' learning and memory abilities, especially for the FGR young rats.

EFFECTS OF TESTOSTERONE AND GROWTH HORMONE ON LONG-TERM RETENTION AND EXTINCTION OF A PASSIVE AVOIDANCE RESPONSE IN YOUNG AND AGED RATS

Wistar rats were divided into two blocks: young and aged. Each block was then randomly divided into the following groups: (1) Control (saline solution), (2) Growth Hormone (GH), (3) Testosterone enanthate, and (4) GH plus testosterone enanthate. Animals were trained on a one-trial passive avoidance conditioning and tested for retention 24 h after training and thereafter twice a week until the extinction response occurred. Results showed that GH, testosterone, and GH plus testosterone improved long-term memory in young rats. Both GH and testosterone delayed the extinction process in young and aged rats. The GH-testosterone interaction delayed the extinction only in young rats.

Choline supplementation facilitates short-term memory consolidation into intermediate long-term memory of young sprague-dawley rats

Choline is important for the synthesis of acetylcholine, an integral neurotransmitter involved in memory formation. In order to investigate the effect of choline supplementation on memory consolidation, the study utilized a T-maze to facilitate passive avoidance learning and memory in young female Sprague-Dawley rats. Rats were placed in two groups; choline-supplemented that received choline chloride daily for two weeks, and control that received vehicle daily for two weeks. Rats were evaluated to determine their ability to avoid an aversive electric foot-shock (0.1 mA at 60V) when they characteristically entered the preferred dark area (DA) of the T-maze. Both groups of rats showed preference, without significant difference, for entry into DA of the T-maze. However, fifteen minutes after passive avoidance both choline supplemented and control rats avoided entry into DA. This display of DA avoidance 15 minutes after training, suggests that both groups of rats had acquired short-term memory of the aversive stimulus. However, when the test was repeated 24 hours after training, the control group did not avoid entry into DA, whereas the choline-supplemented group either avoided entry or entered after a significantly longer latency period (p < 0.01). These results suggest that supplementation with choline facilitated the consolidation of short-term memory of the avoidance learning into intermediate long-term memory in young rats.

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

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. 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. (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. 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.

Glucose and age-related changes in memory

Epinephrine, released from the adrenal medulla, enhances memory in young rats and mice and apparently does so, at least in part, by increasing blood glucose levels. Like epinephrine, administration of glucose enhances cognitive functions in humans and rodents, including reversing age-related impairments in learning and memory. Epinephrine responses to training are increased in aged rats but the subsequent increase in blood glucose levels is severely blunted. The absence of increases in blood glucose levels during training might contribute to age-related deficits in learning and memory. Also, extracellular glucose levels in the hippocampus are depleted during spontaneous alternation testing to a far greater extent in aged than in young rats. Importantly, systemic injections of glucose block the depletion in the hippocampus and also enhance performance on the alternation task. Thus, the extensive depletion of extracellular glucose during training in aged rats may be associated with age-related memory impairments, an effect that might be related to – or may exacerbate – the effects on learning and memory of an absence of the increases in blood glucose levels to training as seen in young rats. Together, these findings suggest that age-related changes in both peripheral and central glucose physiology contribute to age-related impairments in memory.