OBJECTIVETo investigate the relationship between the effects of zinc on hippocampal cholecystokinin (CCK) positive neurons and learning and memory ability of lead-exposed rats.

METHODSThirty-six Wistar rats were divided into control group, lead-exposed group (drunk 6.15 mmol/L of lead solution) and lead-zinc group (drunk 6.15 mmol/L of lead + 3.10 mmol/L of ZnSO(4) solution) randomly. Y-maze test was used to study learning and memory ability in rats; Atomic absorption method was used to determine serum and hippocampal lead content; ABC immunohistochemistry and quantitative graphic analysis were used to investigate the changes of CCK positive neurons in different hippocampal subfields in lead-exposed rats.

RESULTSThe learning and memory ability in lead-exposed rats were significantly lower (P < 0.05) while the serum and hippocampal lead content in lead-exposed rat were significantly higher (P < 0.05) than those in control and lead-zinc group. The number and optical density of CCK positive neurons in CA(1) and CA(3) areas of lead-exposed rats were significantly lower (P < 0.05) than those in control and lead-zinc group. No differences in these indexes between the control and lead-zinc group were found (P > 0.05).

CONCLUSIONLead may damage the learning and memory ability and affect the number of CCK positive neurons in lead-exposed rats. Zinc might play an important role in preventing lead-induced damages.

Animals ; Cholecystokinin ; metabolism ; Hippocampus ; drug effects ; metabolism ; Lead ; toxicity ; Maze Learning ; drug effects ; Memory ; drug effects ; Neurons ; drug effects ; metabolism ; Rats ; Rats, Wistar ; Zinc ; pharmacology

Animals ; Epilepsy ; genetics ; metabolism ; Genes, MDR ; Hippocampus ; drug effects ; metabolism ; Male ; Rats ; Rats, Wistar ; Triazines ; pharmacology

OBJECTIVETo evaluate the influence on the synaptic protein expression in different brain regions of ICR mice after lambda-cyhalothrin (LCT) exposure during postnatal period.

METHODSTwo male and 4 female healthy ICR mice were put in one cage. It was set as pregnancy if vaginal plug was founded. Offspring were divided into 5 groups randomly, and exposed to LCT (0.01% DMSO solution) at the doses of 0.1, 1.0 and 10.0 mg/kg by intragastric rout every other day from postnatal days (PND) 5 to PND13, control animals were treated with normal saline or DMSO by the same route. The brains were removed from pups on PND 14, the synaptic protein expression levels in cortex, hippocampus and striatum were measured by western blot.

RESULTSGFAP levels of cortex and hippocampus in the LCT exposure group increased with doses, as compared with control group (P < 0.05), while Tuj protein expression did not change significantly in the various brain regions of ICR mice. GAP-43 protein expression levels in the LCT exposed mouse hippocampus and in female ICR mouse cortex increased with doses, as compared with control group (P < 0.05). Presynaptic protein (Synapsin I) expression levels did not change obviously in various brain regions. However, postsynaptic density protein 95 (PSD95) expression levels of the hippocampus and striatum in male offspring of 10.0 mg/kg LCT group, of cortex of female LCT groups, and of female offspring in all exposure groups, of striatum, in 1.0 or 10.0 mg/kg LCT exposure groups significantly decreased (P < 0.05).

CONCLUSIONSEarly postnatal exposure to LCT affects synaptic protein expression. These effects may ultimately affect the construction of synaptic connections.

Animals ; Animals, Newborn ; Brain ; drug effects ; metabolism ; Corpus Striatum ; drug effects ; metabolism ; Female ; Hippocampus ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred ICR ; Nitriles ; toxicity ; Pyrethrins ; toxicity ; Synapsins ; metabolism

OBJECTIVETo study the effects of benzo[a]pyrene (B[a]P) on capability of learning and memory and the content of amino acid neurotransmitters in hippocampus of rats.

METHODSThirty-two healthy, male SD rats were randomly divided into 4 groups according to their weights after intubated into ventricles: the solvent control group, 2.5, 5.0 and 10.0 mmol/L groups. 10 microl of B[a]P olive oil solutions, of different concentrations 2.5, 5.0 and 10.0 mmol/L, were injected into rats' lateral ventricles, respectively. Rats in the solvent control group were injected into the same volume of olive oil as that in B[a]P group. Rats' capability of learning and memory was tested by Morris water maze. The content of amino acid neurotransmitters in rats' hippocampus were determined by high performance liquid chromatogram with a fluorescence detector.

RESULTSCompared with the controls, the performances of learning and memory of rats decreased significantly in B[a]P treated groups (P<0.01). Levels of glutamate (Glu) were lower significantly in treated groups than that in controls (P<0.01). No significant differences were found in contents of aspartic acid (Asp), glycine (Gly) and aminobutyric acid (GABA) among the four groups.

CONCLUSIONB[a]P can damage rats' spatial learning and memory, and which could be related to decreased contents of excitatory amino acids in hippocampus.

Amino Acids ; metabolism ; Animals ; Benzo(a)pyrene ; toxicity ; Hippocampus ; drug effects ; metabolism ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; Neurotransmitter Agents ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effects of enriched environment and impoverished environment on the learning and memory ability of manganese-exposed mice and the mechanism.

METHODSForty female Kunming mice were randomly and equally divided into 4 group: control group (CG), standard environment and manganese exposure group (SEG), enriched environment and manganese exposure group (EEG), and impoverished environment and manganese exposure group (IEG). The mouse model of manganese poisoning was established by intraperitoneal injection of manganese chloride. The learning and memory ability was tested by Morris water maze. The expression of cAMP response element-binding protein (CREB) in area CA1 of the hippocampus was measured by immunohistochemistry.

RESULTSIn place navigation test, the SEG had a significantly longer escape latency than the CG (P < 0.05), and the EEG had a significantly shorter escape latency than the SEG (P < 0.05); there was no significant difference in escape latency between IEG and SEG (P > 0.05). In spatial probe test, the EEG had a significantly greater number of platform crossings than the SEG (P < 0.05), and the IEG had a significantly smaller number of platform crossings than the SEG (P < 0.05). The expression of CREB in area CA1 of the hippocampus was significantly lower in IEG and SEG than in CG (P < 0.05), and it was significantly higher in EEG than in SEG (P < 0.05).

CONCLUSIONIn the enriched environment, the learning and memory ability of manganese-exposed mice can be improved, which may be due to the increased expression of CREB in the hippocampus.

Animals ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Disease Models, Animal ; Environment ; Female ; Hippocampus ; drug effects ; metabolism ; Learning ; drug effects ; Manganese Poisoning ; metabolism ; Memory ; drug effects ; Mice

OBJECTIVETo observe the effect of chronic lead contaminant on mRNA expression of protein kinase C (PKC) and calmodulin (CaM) in hippocampus of baby rats.

METHODSThe Wistar pregnant rats were randomly divided into 3 groups fed with distilled water and lead contained water (0.2% and 1.0% lead acetate) respectively. The lead exposure period was from the 0 day of pregnancy to the day when the offspring weaned. Then the baby rats were fed with lead water the same as their mothers. The cliff avoidance reflex within postnatal day 8 and step down test at postnatal day 50 were performed. Then pups were killed at postnatal day 8 and 50 respectively. Atomic absorption spectrometry was used to determine lead content of rats' brain. RT-PCR was used to observe mRNA expression of PKC and CaM in hippocampus of baby rats.

RESULTSThe brain lead content of test groups were much higher than that of the control group. The completion rate of cliff avoidance reflex and the score of step down test of test groups were lower than those in the control group (P < 0.05). Compared with control group, PKC and CaM mRNA expression of chronic lead exposure baby rats in the hippocampus had the down trend (P < 0.05).

CONCLUSIONThe decrease of PKC and CaM mRNA expression level in hippocampus has a great link with the impairment of learning and memory induced by lead in baby rats, which might be one of the molecule mechanisms of lead induced impairment of learning and memory.

Animals ; Calmodulin ; genetics ; metabolism ; Female ; Hippocampus ; drug effects ; metabolism ; Lead ; toxicity ; Learning ; drug effects ; Male ; Memory ; drug effects ; Protein Kinase C ; genetics ; metabolism ; RNA, Messenger ; genetics ; Rats

Animals ; Arginine Vasopressin ; metabolism ; Female ; Hippocampus ; drug effects ; metabolism ; Lead ; toxicity ; Learning ; drug effects ; Memory ; drug effects ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Sprague-Dawley

This study aims to investigate the effects of fibroblast growth factor 21 (FGF-21) on learning and memory abilities and antioxidant capacity of D-galactose-induced aging mice. Kunming mice (37.1 +/- 0.62) g were randomly divided into normal control group, model group and FGF-21 high, medium and low dose groups (n = 8). Each group was injected in cervical part subcutaneously with D-galactose 180 mg x kg(-1) x d(-1) once a day for 8 weeks. At the same time, FGF-21-treated mice were administered with FGF-21 by giving subcutaneous injection in cervical part at the daily doses of 5, 2 and 1 mg x kg(-1) x d(-1). The normal control group was given with normal saline by subcutaneous injection in cervical part. At seventh week of the experiment, the learning and memory abilities of mice were determined by water maze and jumping stand tests. At the end of the experiment, the mice were sacrificed and the cells damage of hippocampus was observed by HE staining in each group. Reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and total antioxidant capacity (T-AOC) in the brain of mice were determined. The results showed that different doses of FGF-21 could reduce the time reaching the end (P < 0.01 or P < 0.05) and the number of touching blind side (P < 0.01 or P < 0.05) in the water maze comparing with the model group. It could also prolong the latency time (P < 0.05) and decrease the number of errors (P < 0.01 or P < 0.05) in the step down test. The result of HE staining showed that FGF-21 could significantly reduce brain cell damage in the hippocampus. The ROS and MDA levels of three different doses FGF-21 treatment group reduced significantly than that of the model group [(5.58 +/- 1.07), (7.78 +/- 1.92), (9.03 +/- 1.77) vs (12.75 +/- 2.02) pmol (DCF) x min(-1) x mg(-1), P < 0.01 or P < 0.05], [(2.92 +/- 0.71), (4.21 +/- 0.81), (4.41 +/- 0.97) vs (5.62 +/- 0.63) nmol x mg(-1) (protein), P < 0.01]. Comparing with the model group, the activities of SOD, GPx, CAT and T-AOC of the three different doses FGF-21 treatment groups were also improved in a dose-dependent manner. This study demonstrates that FGF-21 can ameliorate learning and memory abilities of D-galactose induced aging mice, improve the antioxidant abilities in brain tissue and delay brain aging. This finding provides a theoretical support for clinical application of FGF-21 as a novel therapeutics for preventing aging.
Aging ; drug effects ; Animals ; Antioxidants ; metabolism ; Brain ; drug effects ; Catalase ; metabolism ; Fibroblast Growth Factors ; pharmacology ; Galactose ; Glutathione Peroxidase ; metabolism ; Hippocampus ; drug effects ; Malondialdehyde ; metabolism ; Maze Learning ; drug effects ; Memory ; drug effects ; Mice ; Superoxide Dismutase ; metabolism

To explore the relationship between beta-amyloid (A beta) and the pathogenesis of Alzheimer disease (AD), after injection of beta-amyloid into the rat brain, the apoptosis of nerve cells and acetylcholine (Ach) content in rat hippocampus were examined by employing TUNEL technique and base hydroxylamine colorimetry respectively. The influence of age and glucocorticoid on the neurotoxic effect of A beta was also analyzed. A beta peptide could strongly induce the apoptosis of neurons in hippocampus, cortex and striate body (P < 0.05 or P < 0.01). In addition, the senility and glucocorticoid pre-treatment could enhance the toxic effect of A beta (P < 0.05 or P < 0.01). It is concluded that A beta may play an important role in the pathogenesis of Alzheimer disease via its induction of apoptosis of neurons and by decreasing the content of the Ach.
Acetylcholine/metabolism ; Aging ; Alzheimer Disease/etiology ; Amyloid beta-Protein/*toxicity ; Apoptosis/*drug effects ; Dexamethasone/*pharmacology ; Drug Synergism ; Hippocampus/metabolism ; Hippocampus/*pathology ; Injections, Intraventricular ; Neurons/pathology ; Rats, Wistar

Animals ; Cognitive Dysfunction ; metabolism ; Cystatin C ; pharmacology ; Hippocampus ; drug effects ; Insulin Resistance ; physiology ; Neurons ; drug effects ; Rats ; Rodentia