OBJECTIVETo explore the changes in spatial learning performance and long-term potentiation (LTP) which is recognized as a component of the cellular basis of learning and memory in normal and lead-exposed rats after administration of melatonin (MT) for two months.

METHODSExperiment was performed in adult male Wistar rats (12 controls, 12 exposed to melatonin treatment, 10 exposed to lead and 10 exposed to lead and melatonin treatment). The lead-exposed rats received 0.2% lead acetate solution from their birth day while the control rats drank tap water. Melatonin (3 mg/kg) or vehicle was administered to the control and lead-exposed rats from the time of their weaning by gastric gavage each day for 60 days, depending on their groups. At the age of 81-90 days, all the animals were subjected to Morris water maze test and then used for extracellular recording of LTP in the dentate gyrus (DG) area of the hippocampus in vivo.

RESULTSLow dose of melatonin given from weaning for two months impaired LTP in the DG area of hippocampus and induced learning and memory deficit in the control rats. When melatonin was administered over a prolonged period to the lead-exposed rats, it exacerbated LTP impairment, learning and memory deficit induced by lead.

CONCLUSIONMelatonin is not suitable for normal and lead-exposed children.

Animals ; Female ; Lead ; toxicity ; Learning ; drug effects ; Long-Term Potentiation ; drug effects ; Male ; Maze Learning ; drug effects ; Melatonin ; administration & dosage ; toxicity ; Rats ; Spatial Behavior ; drug effects

OBJECTIVETo study the effects of quercetin, a flavonoid, on the learning and memory ability of 3-day-old neonatal rats with hypoxic-ischemic brain white matter damage (WMD).

METHODSSixty 3-day-old Sprague-Dawley rats were randomly divided into four groups: control, WMD model,and quercetin treatment groups (20 and 40 mg/kg). There were 15 rats in each group. Rats in the WMD model and the two quercetin treatment groups were subjected to right common carotid artery ligation followed by 2 hrs of exposure to 8% O2 to induce periventricular white matter injury. After the operation quercetin was administered daily in the two quercetin treatment groups for 6 weeks. Six weeks later, Morris water maze and open-field tests were carried out to test memory and learning ability as well as behavior and cognition.

RESULTSFrom the second day of training, escape latency in the Morris water maze test was more prolonged in the WMD model group than in the control group (P<0.01). The escape latency in the two quercetin treatment groups was shortened significantly compared with the WMD model group (P<0.05). The WMD model group crossed the original platform fewer times compared with the control and quercetin treatment groups (P<0.05). The open-field test indicated that the number of rearings increased and time spent in the centre was extended in the WMD model group compared with the control group. Compared with the WMD model group, the number of rearings was significantly reduced (P<0.05) and time spent in the centre was significantly shortened in the quercetin treatment groups (P<0.05).

CONCLUSIONSQuercetin treatment can improve memory and learning ability as well as cognitive ability in neonates with WMD, suggesting that quercetin protects against WMD resulting from hypoxia-ischemia.

Animals ; Hypoxia-Ischemia, Brain ; drug therapy ; psychology ; Learning ; drug effects ; Maze Learning ; drug effects ; Memory ; drug effects ; Quercetin ; pharmacology ; Rats ; Rats, Sprague-Dawley

Animals ; Female ; Injections, Intraventricular ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; Mice ; Mice, Inbred Strains ; Toluene ; administration & dosage ; toxicity

OBJECTIVETo explore the effect of tetramethylpyrazine on learning, memory, and cholinergic system in D-galactose-lesioned mice.

METHODSC57BL/6J mice were given subcutaneous injection of 2% D-galactose for 40 days (100 mg.kg-1.d-1). Normal saline, tetramethylpyrazine (TMP) and Huperzine A (HupA) were given respectively by intragastric administration in different study groups from the third week on. Learning and memory ability were tested by Morris water maze for 5 days at the sixth week. Acetylcholinesterase (AchE) activity, the binding sites (Bmax) and the affinity (KD) of M-cholinergic receptor were determined.

RESULTSThe learning and memory dysfunction, with lowered AchE activity and M-cholinergic receptor binding sites were found in the model group as compared with the normal control group. The tetramethylpyrazine, especially at the dose of 100 mg.kg-1.d-1, could markedly attenuate cognitive dysfunction, while elevate the lowered AchE activity (P < 0.05) and M-cholinergic receptor binding sites (P < 0.005) in the cerebral cortex of mice treated with D-galactose.

CONCLUSIONSThe tetramethylpyrazine can significantly improve central cholinergic system function, and thus enhance the learning and memory ability in D-galactose-lesioned mice.

Acetylcholinesterase ; metabolism ; Animals ; Avoidance Learning ; drug effects ; Cognition ; drug effects ; Galactose ; Learning ; drug effects ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; Mice ; Mice, Inbred C57BL ; Pyrazines ; pharmacology ; Receptor, Muscarinic M1 ; metabolism ; Receptors, Cholinergic ; drug effects ; physiology

OBJECTIVETo study the effects of prenatal exposure to benzo[a]pyrene (B[a]P) on the physical development, early behavioral development, the adaptability to new environment and the learning and memory ability of rat offspring.

METHODSPregnant rats were randomly divided into five groups: control group, olive oil group, 3 exposure groups (25, 50 and 100 mg/kg B [a]P). The rats were exposed to B [a]P) by intraperitoneal injection on the 17th-19th days during gestation. The offspring were weighed on postnatal days (PND)1, PND 4, PND 7 and PND 28, the indices of physical development, reflective ability and sensory function were detected for offspring, the Morris water maze and Open-field tests were used to measure the ability of learning and memory and the adaptability to new environment of offspring.

RESULTSThe time of ear opening in middle and high-dose groups [(4.1 +/- 0.4),(5.0 +/-0.4) d] was posterior to that in untreated and solvent groups [(3.3 +/- 0.5), (3.4 +/- 0.6) d ](P < 0.01). The attainment rate (6.5%) of the surface righting reflex test in high-dose group on the 4th day was significantly lower than that (36.1%) in untreated group, the attainment rate (50.0%) in high-dose group on PND7 was significantly lower than those (81.3% and 79.3%) in untreated group and solvent group (P < 0.05). Compared to the untreated group, the time of forelimb hanging test in all exposure groups on PND12 and PND14 significantly decreased; compared to the solvent group the time of forelimb hanging test decreased in high-dose group on the 14th day significantly decreased (P < 0.01). The attainment rate (61.9%) of olfactory discrimination in high-dose group on PND12 was significantly lower than that (94.3%) in untreated group (P < 0.05). The results of Morris water maze test showed that the escape latency of different dose groups significantly increased, and the time of spatial probe and the times of traversing flat in high-dose group decreased significantly, as compared to the untreated and solvent groups (P < 0.01). The results of open-field test indicated that the center retention time in middle and high-dose groups significantly prolonged, the times of crossing lattice obviously reduced, and the rearing times decreased in high-dose group, as compared to untreated (P < 0.05).Compared to the solvent group, the times of crossing lattice in all exposure groups reduced significantly (P < 0.01 or P < 0.05).

CONCLUSIONThe prenatal exposure to B[a]P could inhibit the physical development and early behavioral development, and influence the adaptability to new environment and learning and memory ability for offspring.

Animals ; Benzo(a)pyrene ; toxicity ; Female ; Learning ; drug effects ; Maze Learning ; Memory ; drug effects ; Motor Activity ; Neurotoxicity Syndromes ; physiopathology ; Pregnancy ; Prenatal Exposure Delayed Effects ; physiopathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of ginsenoside Rg1 (G-Rg1) on the morphology of the hippocampal neurons of rats with electrical hippocampal injuries and evaluate its protective effects on the learning and memory function.

METHODSForty female SD rats were randomly divided into G-Rg1 group, saline group, sham-operated group and G-Rg1+Sham operation group. Using the stereotactic apparatus, electrical hippocampal injury was induced, not in the two sham groups, by application of direct electrical current, followed by treatments with intragastric administration of G-Rg1 or saline for 14 consecutive days. The learning and memory function of the rats was assessed with Morris water maze test. The viability and arrangement of the hippocampal neurons and the number of Nissl bodies were observed after the treatments.

RESULTSTreatment with G-Rg1 significantly improved the learning and memory function of rats with electrical hippocampal injury. The viability of the hippocampal neurons showed no significant changes in the two sham-operated groups (P>0.05), and the number of Nissl bodies was much lower in saline group than in the other groups (P<0.05).

CONCLUSIONSG-Rg1 can improve the learning and memory function of rats with electrical hippocampal injury, the mechanism of which is probably associated with its protective effect on the hippocampal neurons against electrical injury.

Animals ; Female ; Ginsenosides ; pharmacology ; Hippocampus ; cytology ; drug effects ; pathology ; Maze Learning ; drug effects ; Memory ; drug effects ; Neurons ; drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo compare brain lead accumulation and neurotoxicity induced by lead under drinking purified water and tap water on rat.

METHODSAll 104 male weaning SD rats were randomly divided into eight groups, matched-four pairs according to drinking water: tap water, purified water, tap water with lead 50 mg/L(lead acetate water-solution), purified water with lead 50 mg/L, tap water with lead 200 mg/L, purified water with lead 200 mg/L, tap water with lead 800 mg/L. All were fed with normal food and environmental cognitions kept consistent Morris water maze(including Place Navigation, Spatial Probe Test, Visible Platform Trial) was measured to test rat spatial learning at the 12 and 24 week. At the end of the experiment (28 week), rats were killed and the lead of brain and blood was measured by Graphite furnace atomic absorption spectrometric method; the NR1, NR2A, NR2B of NMDAR (N-methyl-D-aspartame receptor) in hippocampus were analyzed by RT-PCR.

RESULTSUnder the same lead exposure, no significant differences were observed in blood lead, however, brain lead level showed higher in drinking purified water group than that in tap water group. Expression of NR1, NR2A and NR2B in hippocampus of the rats drinking purified water was lower than those drinking tap water, especially at low lead exposure (50 mg/L) (P < 0.05). In the 24 week Morris water maze, place navigation test's escape latency showed significantly prolonged at the rats drinking purified water as compared with those drinking tap water on the pairs of 50 mg/L and 200 mg/L pb2+ groups (P < 0.05), and the differences occurred in early 1-2 days.

CONCLUSIONCompared with drinking tap water, drinking purified water might increase the accumulation of brain lead, lower NR1, NR2A, NR2B expression and delay the spatial learning and memory ability under chronic lead exposure in water.

Animals ; Drinking ; Intelligence ; drug effects ; Lead ; toxicity ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; N-Methylaspartate ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; drug effects

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

OBJECTIVETo study the role of oxiracetam on traumatic brain injury in rats.

METHODSThirty Wistar rats were randomly divided into 3 groups: sham operation group, model group and treatment group. Feeney method were used to establish traumatic brain injury (TBI) model in rats in model and treatment group, and rats in sham group were only broached without hydraumatic fitted. Rats in treatment group were successive administration for 21 days with oxiracetam (100 mg/kg, ig). Neurologic impairment scores were undertook after operation of 1 d, 4 d, 7 d, 14 d and 21 d, and Morris water maze test were proceeded during 15 to 19 days after operation. Average escape latency, searching time in target quadrant and number of crossing target platform in rats were recorded.

RESULTSNeurologic impairment scores of rats in treatment group were significantly less than those of model group after operation of 7, 14 and 21 d (P < 0.05). Average escape latency of model group were significantly higher than those of sham operation group and treatment group (P < 0.05, P < 0.01). Searching time in target quadrant and number of crossing target platform of model group were lower than those of sham operation and treatment group (P < 0.05)).

CONCLUSIONOxiracetam could decrease neural injury and increase ability of learning, memory and space cognition in traumatic brain injury rats.

Animals ; Brain Injuries ; drug therapy ; psychology ; Male ; Maze Learning ; drug effects ; Pyrrolidines ; pharmacology ; therapeutic use ; Rats ; Rats, Wistar

OBJECTIVETo study the effect of nano-SiO2 on spatial learning and memory.

METHODSTwenty-four male rats were randomly divided into 3 groups: control group (C group), low dose group (L group) and high dose group (H group). The rats were intragastrically administrated with nanometer particles at 25 and 100 mg/kg body weight every day for 4 weeks. After exposure, the ability of learning and memory of rats was tested by Morris water maze, and electrophysiological brain stereotactic method was used to test long-tear potentiation (LTP) in dentate gyrus (DG) of the rats.

RESULTSThe increase rate of body weight in H group was reduced significantly compared with C group ( P < 0.05). In the space exploration experiment of Morris water maze test, the escape latency of H group was longer than that of C group (P < 0.05). The rats of H group spent less time in finding the target quadrant (P < 0.05) . The rate of LP induction of H group was significantly lower than that of C group (P < 0.05). After high fre quency stimulation (HFS), The changes of amplitude of population spike (PS) of L group and H group were lower than those of C group significantly (P < 0.05, P < 0.01).

CONCLUSIONNano-SiO₂may result in impairment of spatial learning and memory ability by reducing the rate of LTP induction and the increase of PS in hippocampus.

Animals ; Dentate Gyrus ; drug effects ; Long-Term Potentiation ; drug effects ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; Nanoparticles ; adverse effects ; Rats ; Silicon Dioxide ; adverse effects ; Spatial Learning ; drug effects