OBJECTIVETo study the effects of 1-bromopropane (1-BP) on the functions of learning-memory and the central cholinergic system in rats.

METHODSForty male Wistar rats were randomly divided into four groups: low 1-BP group (200 mg/kg), middle 1-BP group (400 mg/kg), high 1-BP group (800 mg/kg) and control group, and the exposure time was 7 days. The Morris water maze (MWM) test was applied to evaluate the learning-memory function in rats. After the MWM test, the rats were sacrificed, the cerebral cortex and hippocampus were quickly dissected and homogenized in ice bath. The activity of acetylcholine esterase (AChE) and choline acetyltransferase (ChAT) in supernatant of homogenate were detected.

RESULTSThe latency and swim path-length of rats in middle and high 1-BP groups prolonged significantly in place navigation test and the efficiency of searching strategy obviously decreased, as compared with control group (P < 0.05 or P < 0.01). In spatial probe test, the number of crossing platform in three 1-BP groups decreased significantly, as compared with control group (P < 0.05 or P < 0.01). The cortical AChE activity of rats in middle and high 1-BP groups was significantly higher than that of control and low 1-BP group (P < 0.05 or P < 0.01). The AChE activity in rat hippocampus of high 1-BP group obviously increased, as compared with control group as compared with control group (P < 0.05). There was no significant difference of cortical ChAT activity between three 1-BP groups and control group (P > 0.05). In the hippocampus, there was no difference of ChAT activity among the groups (P > 0.05).

CONCLUSION1-BP exposure could significantly influence the learning-memory function in rats due to the increase of AChE activity.

Acetylcholinesterase ; metabolism ; Animals ; Cerebral Cortex ; drug effects ; enzymology ; Choline O-Acetyltransferase ; metabolism ; Hippocampus ; drug effects ; enzymology ; Hydrocarbons, Brominated ; toxicity ; Male ; Maze Learning ; drug effects ; Rats ; Rats, Wistar

OBJECTIVETo investigate the change of free Ca(2+) in cytoplasma in the neurotoxicity of the manganese (Mn).

METHODSThe cortical neurons were separated from the neonatal Wistar rats and cultured in vitro. The neurons were grouped as the Mn-treated groups and the untreated group. The neurons in the Mn-added groups were incubated in the culture media containing lower, medium and high dosage manganese chloride (MnCl(2 x 4) H2O) with the concentration at 0.2, 0.6, 1.0 mmol/L respectively. Meanwhile, neurons in control were cultured in the normal culture media. All treatments stopped 24 h later. Neurons were labeled Ca(2+) sensitive prober, Fluo-3/AM. The fluorescence intensity of Fluo-3 combined with Ca(2+) was examined by LSCM (Laser scanning confocal microscope) and was treated by the picture analysis technique. The intensity was equal to the free Ca(2+) concentrations in cytoplasma of neurons.

RESULTSMnCl(2) can induce free Ca(2+) overloaded in cytoplasma of neurons, but the increasing degree varied in MnCl(2) dosage. Cytoplasma Ca(2+) concentration in the moderate dosage The moderate dosage MnCl(2) group and the high dosage MnCl(2) group were significantly higher than that in the lower dosage MnCl(2) group and the control group (P < 0.05).

CONCLUSIONThe Ca(2+) overload is involved in the neurotoxicity of manganese, and a dosage response relationship is found between the manganese chloride dose and Ca(2+) overload in cortical neurons.

Animals ; Animals, Newborn ; Calcium ; metabolism ; Cells, Cultured ; Cerebral Cortex ; drug effects ; metabolism ; Dose-Response Relationship, Drug ; Manganese ; toxicity ; Neurons ; drug effects ; metabolism ; Rats ; Rats, Wistar

OBJECTIVETo investigate the effect of propofol on the expression of thrombospondin-1 (THBS-1) mRNA and protein in purified newborn rat cortical astrocytes in vitro.

METHODSAstrocytes were isolated from newborn rat cortex and grown in culture before exposure to propofol at 3, 10, 30, 100 or 300 µmol/L for 6 h, 12, or 24 h. The mRNA level of THBS-1 was detected by RT-PCR, and the protein level of THBS-1 was detected by immunofluorescence cytochemistry and Western blotting.

RESULTSPropofol exposure caused significantly upregulated THBS-1 level in cultured astrocytes (P<0.05) to a level about 1.3 times higher than that in control cells. The mRNA and protein levels of THBS-1 in cultured rat cortical astrocytes were upregulated by exposures to 10, 30 and 100 µmol/L propofol (P<0.01). High expression of THBS-1 mRNA and protein was detected in the cells with exposures for different durations (P<0.05), especially in the 12 h group (P<0.01).

CONCLUSIONPropofol at clinically relevant concentrations can modulate the level of THBS-1 secreted by astrocytes of rat cerebral cortex in vitro.

Animals ; Astrocytes ; drug effects ; metabolism ; Cells, Cultured ; Cerebral Cortex ; cytology ; Propofol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Thrombospondin 1 ; metabolism

OBJECTIVETo probe into the prelude marker of central nervous system injury in response to methyl mercury chloride (MMC) stimulation and the signal transduction molecular mechanism of injury in rat brain induced by MMC.

METHODSThe expression of c-fos mRNA in brain and the expression of c-FOS protein in cortex, hippocampus and ependyma were observed using reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemical methods. The control group was injected with physiological saline of 0.9%, while the concentrations for the exposure groups were 0.05 and 0.5, 5 mg/kg MMC respectively, and the sampling times points were 20, 60, 240, 1440 min.

RESULTSThe expression of c-FOS protein in cortex and hippocampus increased significantly, the accumulation of mercury in the brain induced by 0.05 mg/Kg MMC for 20 min had no significant difference compared with the control group. The mean value was 0.0044 mg/Kg, while the protein c-FOS expression had significant difference compared with the control group (P < 0.01). More sensitive expression occurred in hippocampus and cortex, but not in ependyma. Conclusion The expression of c-FOS protein in cortex and hippocampus can predict the neurotoxicity of MMC in the early time, and immediately early gene (IEG) c-fos participates in the process of brain injury induced by MMC.

Animals ; Biomarkers ; metabolism ; Brain ; drug effects ; metabolism ; Cerebral Cortex ; drug effects ; metabolism ; Gene Expression Regulation ; drug effects ; Hippocampus ; drug effects ; metabolism ; Methylmercury Compounds ; pharmacokinetics ; toxicity ; Proto-Oncogene Proteins c-fos ; biosynthesis ; genetics ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the lipid peroxidation induced by deltamethrin (DM) in the cerebral cortex and hippocampus of rat.

METHODSWistar male rats were administrated with DM (daily dose was 3.125, 12.500 mg/kg respectively). The content of malondialdehyde (MDA) and the activity of total-superoxide dismutase (T-SOD, including Mn-SOD and CuZn-SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) in cerebral cortex and hippocampus tissue were determined. The reduced glutathione (GSH) content and gamma-glutamylcysteine synthetase (gamma-GCS) activity in cytosolic fraction of cerebral cortex and hippocampus tissue was determined by reversed-phase high performance liquid chromatographic assay with o-phthalaldehyde pre-column derivation.

RESULTS(1) MDA content in cerebral cortex of the high dose group was significantly higher than those in the low dose group, and MDA content in hippocampus tissue of the high dose group was significantly higher than those in both the control and the low dose group after 5 d of DM exposure. (2) The activity of T-SOD and CuZn-SOD in cerebral cortex of both high and low dose group were significantly lower than that in the control group, and there was no effect on CAT activity in cerebral cortex (P < 0.01 or P < 0.05). (3) GSH content in cerebral cortex of the high dose group was significantly higher than that in control group (P < 0.05), and that in hippocampus tissue of high dose was significantly lower than that in both control and low dose group (P < 0.05). GR activity of low dose group in cerebral cortex was significantly lower than that in both control and high group [(11.80 +/- 5.15) vs (18.98 +/- 3.68), (17.35 +/- 2.47) U/mg pro] (P < 0.01). Gamma-GCS activity in hippocampus tissue of the high dose group was significantly lower than that in both control and low dose group [(1.75 +/- 0.60) vs (3.17 +/- 0.79), (2.72 +/- 0.75) nmol x mg pro(-1) x min(-1)] (P < 0.01). GR activity in hippocampus tissue of both high and low dose group was significantly lower than that in the control group [(21.63 +/- 4.92), (21.46 +/- 8.89) vs (31.22 +/- 6.97) U/mg pro] (P < 0.05).

CONCLUSIONThe oxidative stress in nerve tissue, which could be resulted from effect of DM on the activity of SOD, gamma-GCS and GR and GSH content, is one of the mechanisms of neuro-toxicity induced by DM; The decreased activity of gamma-GCS and GR may be the primary cause of DM-induced decrease in that GSH content in hippocampus tissue.

Animals ; Cerebral Cortex ; drug effects ; metabolism ; Dose-Response Relationship, Drug ; Hippocampus ; drug effects ; metabolism ; Insecticides ; toxicity ; Lipid Peroxidation ; drug effects ; Male ; Malondialdehyde ; metabolism ; Nitriles ; toxicity ; Oxidative Stress ; drug effects ; Oxidoreductases ; metabolism ; Pyrethrins ; toxicity ; Rats ; Rats, Wistar

OBJECTIVETo investigate the effect of Cedemex on cAMP and cGMP contents in different brain regions in morphine withdrawal rats precipitated by naloxone.

METHODA physical morphine dependent model of rats was established by subcutaneous injection of morphine in gradually increasing dosage within 7 days. cAMP and cGMP contents of VTA, cortex and hippocampus of the rat brains were determined by radioimmunoassay.

RESULTThe morphine withdrawal symptoms of rats were relieved significantly by ig Cedemex. Compared with the controls, cAMP content in the region of VTA, cortex and hippocampus of the morphine dependent rats were significantly higher (P < 0.05), while cGMP contents in those regions were significantly lower (P < 0.05). cAMP contents in the area of VTA, cortex and hippocampus of the morphine dependent rats were significantly reduced, while cGMP contents were significantly increased by ig Cedemex.

CONCLUSIONCedemex may significantly attenuate the morphine withdrawal symptoms in rats. The mechanism of this effect may be related to adjusting the contents of cAMP and cGMP in some brain regions.

Animals ; Brain ; drug effects ; metabolism ; pathology ; Cerebral Cortex ; drug effects ; metabolism ; Cyclic AMP ; metabolism ; Cyclic GMP ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Hippocampus ; drug effects ; metabolism ; Morphine ; adverse effects ; Rats ; Substance Withdrawal Syndrome ; metabolism

OBJECTIVETo investigate the effects of nano-lead exposure on learning and memory and iron homeostasis in the brain of the offspring rats on postnatal day 21 (PND21) and postnatal day 42 (PND42).

METHODSTwenty adult pregnant female Sprague-Dawley rats were randomly divided into control group and nano-lead group. Rats in the nano-lead group were orally administrated 10 mg/kg nano-lead, while rats in the control group were administrated an equal volume of normal saline until PND21. On PND21, the offspring rats were weaned and given the same treatment as the pregnant rats until 42 days after birth. The learning and memory ability of offspring rats on PND21 and PND42 was evaluated by Morris water maze test. The hippocampus and cortex s amples of offspring rats on PND21 and PND42 were collected to determine iron and lead levels in the hippocampus and cortex by inductively coupled plasma-mass spectrometry. The distributions of iron in the hippocampus and cortex were observed by Perl's iron staining. The expression levels of ferritin, ferroportin 1 (FPN1), hephaestin (HP), and ceruloplasmin (CP) were measured by enzyme-linked immunosorbent assay.

RESULTSAfter nano-lead exposure, the iron content in the cortex of offspring rats on PND21 and PND42 in the nano-lead group was significantly higher than those in the control group (32.63 ± 6.03 µg/g vs 27.04 ± 5.82 µg/g, P<0.05; 46.20 ±10.60 µg/g vs 36.61 ± 10.2µg/g, P<0.05). The iron content in the hippocampus of offspring rats on PND42 in the nano-lead group was significantly higher than that in the control group (56.9 ± 4.37µg/g vs 37.71 ± 6.92µg/g, P<0.05). The Perl's staining showed massive iron deposition in the cortex and hippocampus in the nano-lead group. FPNl level in the cotfex of offspring rats on PND21 in the nano-lead group was significantly lower than that in the control group (3.64 ± 0.23 ng/g vs 4.99 ± 0.95 ng/g, P<0.05). FPN1 level in the hippocampus of offspring rats on PND42 in the nano-lead group was significantly lower than that in the control group (2.28 ± 0.51 ng/g vs 3.69 ± 0.69 ng/g, P<0.05). The escape latencies of offspring rats on PND21 and PND42 in the nano-lead group were longer than those in the control group (15.54 ± 2.89 s vs 9.01 ± 4.66 s; 6.16 ± 1.42 s vs 4.26 ± 1.51 s). The numbers of platform crossings of offspring rats on PND21 and PND42 in the nano- lead group were significantly lower than those in the control group (7.77 ± 2.16 times vs 11.2 ± 1.61 times, P<0.05; 8.12 ± 1.51 times vs 13.0 ± 2.21 times, P<0.05).

ONCLUSIONn Nano-lead exposure can result in iron homeostasis disorders in the hippocampus and cortex of offspring rats and affect their learning and memory ability.

Animals ; Cerebral Cortex ; drug effects ; metabolism ; Female ; Hippocampus ; drug effects ; metabolism ; Homeostasis ; Iron ; metabolism ; Lead ; toxicity ; Learning ; drug effects ; Maternal Exposure ; adverse effects ; Memory ; drug effects ; Pregnancy ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the effects of deltamethrin on intracellular free Ca2+ concentration and apoptosis in rat neural cells.

METHODSWister rats were randomly divided into 4 groups(3 treated groups and 1 control). Intracellular free Ca2+ concentration in rat neural cells was measured by using the fluorescent Ca2+ indicator Fura-2/AM. Apopotic rate of neural cells was measured by using FACS420 Flow Cytometer.

RESULTSIntracellular free Ca2+ concentration at 5 h after deltamethrin exposure [hippocampus: (389.94 +/- 43.64) nmol/L, cerebral cortex: (449.33 +/- 23.23) nmol/L], at 24 h[hippocampus: (340.47 +/- 32.36) nmol/L, cerebral cortex: (311.62 +/- 25.48) nmol/L] and at 48 h[hippocampus: (287.13 +/- 24.29) nmol/L, cerebral cortex: (346.55 +/- 36.87) nmol/L] were all higher than those of the control group[hippocampus: (203.24 +/- 18.53) nmol/L, cerebral cortex: (226.85 +/- 14.81) nmol/L, P < 0.01]; Apoptotic rate in neural cells 24 h and 48 h later [hippocampus: (8.45 +/- 1.02)%, (9.44 +/- 1.14)%, cerebral cortex: (7.90 +/- 0.49)%, (8.01 +/- 0.87)%] were also higher than those of the control group[hippocampus: (2.97 +/- 0.36)%, cerebral cortex: (3.50 +/- 0.48)%, P < 0.01)] and increased with time prolonged.

CONCLUSIONExposure to high dose of deltamethrin would interfere with intracellular free Ca2+ concentration and apoptotic rate in rat neural cells, suggesting that there may be certain relation between them.

Animals ; Apoptosis ; drug effects ; Calcium ; metabolism ; Cerebral Cortex ; drug effects ; metabolism ; pathology ; Flow Cytometry ; Hippocampus ; drug effects ; metabolism ; pathology ; Insecticides ; toxicity ; Neurons ; cytology ; drug effects ; metabolism ; Nitriles ; toxicity ; Pyrethrins ; toxicity ; Rats ; Rats, Wistar

Animals ; Binding Sites ; drug effects ; Brain ; metabolism ; Calcium ; metabolism ; Cerebral Cortex ; metabolism ; Cyclic AMP ; metabolism ; Hippocampus ; metabolism ; Insecticides ; toxicity ; Male ; Organothiophosphorus Compounds ; toxicity ; Phosphoramides ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the effect of Wulongdan on the learning and memory abilities of rats with chronic cerebral ischemia and explore the mechanisms.

METHODSMale SD Rat models of chronic cerebral ischemia were established by permanent ligation of the bilateral carotid arteries. Three weeks after the operation, the rats were randomly divided into sham-operated group, chronic cerebral ischemia group (model group), high-dose drug group, low-dose drug group and Yinxingye group and received the corresponding treatments on a daily basis for 5 consecutive weeks. Morris water maze was used to assess the learning and memory abilities of the rats, and Western blotting was carried out for detecting the expressions of NR1 and NR2B in the hippocampus and cerebral cortex.

RESULTSCompared with the model group, the rats in high-dose drug, low-dose drug and Yinxingye groups showed significantly shorter time of finding platform in Morris water maze test (P<0.05 or 0.01). The rats in the model group showed significantly lowered expressions of NR1 and NR2B of the cortex and hippocampus than those in the sham-operated group (P<0.01). In comparison with the model group, the high-dose Wulongdan group and Yinxingye group both showed significantly increase expressions of NR1 and NR2B (P<0.01), but their expression levels still remained significantly lower than those in the sham-operated group (P<0.01).

CONCLUSIONWulongdan can enhance the learning and memory abilities of rats with chronic cerebral ischemia, the mechanisms of which may involve increased expressions of NR1 and NR2B in the hippocampus and cortex.

Animals ; Brain Ischemia ; drug therapy ; psychology ; Cerebral Cortex ; drug effects ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hippocampus ; drug effects ; metabolism ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; metabolism