While inflammatory bowel disease (IBD) might be a risk factor in the development of brain dysfunctions, the underlying mechanisms are largely unknown. Here, mice were treated with 5% dextran sodium sulfate (DSS) in drinking water and sacrificed on day 7. The serum level of IL-6 increased, accompanied by elevation of the IL-6 and TNF-α levels in cortical tissue. However, the endotoxin concentration in plasma and brain of mice with DSS-induced colitis showed a rising trend, but with no significant difference. We also found significant activation of microglial cells and reduction in occludin and claudin-5 expression in the brain tissue after DSS-induced colitis. These results suggested that DSS-induced colitis increases systemic inflammation which then results in cortical inflammation via up-regulation of serum cytokines. Here, we provide new information on the impact of colitis on the outcomes of cortical inflammation.
Animals ; Calcium-Binding Proteins ; metabolism ; Caspase 3 ; metabolism ; Cerebral Cortex ; pathology ; Claudin-5 ; metabolism ; Colitis ; chemically induced ; complications ; pathology ; Cytokines ; genetics ; metabolism ; Dextran Sulfate ; toxicity ; Disease Models, Animal ; Encephalitis ; etiology ; Gene Expression Regulation ; drug effects ; Mice ; Microfilament Proteins ; metabolism ; Occludin ; metabolism ; Polysaccharides ; blood ; toxicity ; Time Factors

OBJECTIVETo investigate the protective effect of histone acetylation against hypoxic-ischemic cortical injury in neonatal rats.

METHODSA total of 90 neonatal rats aged 3 days were divided into three groups: sham-operation, cortical injury model, and sodium butyrate (a histone deacetylase inhibitor) treatment. The rats in the model and the sodium butyrate treatment groups were intraperitoneally injected with lipopolysaccharide (0.05 mg/kg), and then right common carotid artery ligation was performed 2 hours later and the rats were put in a hypoxic chamber (oxygen concentration 6.5%) for 90 minutes. The rats in the sham-operation group were intraperitoneally injected with normal saline and the right common carotid artery was only separated and exposed without ligation or hypoxic treatment. The rats in the sodium butyrate treatment group were intraperitoneally injected with sodium butyrate (300 mg/kg) immediately after establishment of the cortical injury model once a day for 7 days. Those in the sham-operation and the model groups were injected with the same volume of normal saline. At 7 days after establishment of the model, Western blot was used to measure the protein expression of histone H3 (HH3), acetylated histone H3 (AH3), B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-2-associated X protein (BAX), cleaved caspase-3 (CC3), and brain-derived neurotrophic factor (BDNF). Immunofluorescence assay was used to measure the expression of 5-bromo-2'-deoxyuridine (BrdU) as the cortex cell proliferation index.

RESULTSThe sodium butyrate treatment group had a significantly lower HH3/AH3 ratio than the model group (P<0.05), which suggested that the sodium butyrate treatment group had increased acetylation of HH3. Compared with the model group, the sodium butyrate treatment group had a significant increase in Bcl-2/Bax ratio, a significant reduction in CC3 expression, and a significant increase in BDNF expression (P<0.05). The sodium butyrate treatment group had a significant increase in the number of BrdU-positive cells in the cortex compared with the model group (P<0.05), and BrdU was mainly expressed in the neurons.

CONCLUSIONSIncreased histone acetylation may protect neonatal rats against cortical injury by reducing apoptosis and promoting regeneration of neurons. The mechanism may be associated with increased expression of BDNF.

Acetylation ; Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Brain-Derived Neurotrophic Factor ; analysis ; Butyric Acid ; therapeutic use ; Cerebral Cortex ; pathology ; Female ; Histones ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of corticosterone on the expression of the neuronal migration protein lissencephaly 1 (LIS1) in developing cerebral cortical neurons of fetal rats.

METHODSThe primary cultured cerebral cortical neurons of fetal Wistar rats were divided into control group, low-dose group, and high-dose group. The neurons were exposed to the medium containing different concentrations of corticosterone (0 μmol/L for the control group, 0.1 μmol/L for the low-dose group, and 1.0 μmol/L for the high-dose group). The neurons were collected at 1, 4, and 7 days after intervention. Western blot and immunocytochemical staining were used to observe the change in LIS1 expression in neurons.

RESULTSWestern blot showed that at 7 days after intervention, the low- and high-dose groups had significantly higher expression of LIS1 in the cytoplasm and nucleus of cerebral cortical neurons than the control group (P<0.05), and the high-dose group had significantly lower expression of LIS1 in the cytoplasm of cerebral cortical neurons than the low-dose group (P<0.05). Immunocytochemical staining showed that at 1, 4, and 7 days after corticosterone intervention, the high-dose group had a significantly lower mean optical density of LIS1 than the control group and the low-dose group (P<0.05). At 7 days after intervention, the low-dose group had a significantly lower mean optical density of LIS1 than the control group (P<0.05).

CONCLUSIONSCorticosterone downregulates the expression of the neuronal migration protein LIS1 in developing cerebral cortical neurons of fetal rats cultured in vitro, and such effect depends on the concentration of corticosterone and duration of corticosterone intervention.

1-Alkyl-2-acetylglycerophosphocholine Esterase ; analysis ; genetics ; Animals ; Cells, Cultured ; Cerebral Cortex ; drug effects ; metabolism ; Corticosterone ; pharmacology ; Dose-Response Relationship, Drug ; Female ; Fetus ; drug effects ; Microtubule-Associated Proteins ; analysis ; genetics ; Pregnancy ; Rats ; Rats, Wistar

OBJECTIVETo investigate acrylamide (ACR)-induced subacute neurotoxic effects on the central nervous system (CNS) at the synapse level in rats.

METHODSThirty-six Sprague Dawley (SD) rats were randomized into three groups, (1) a 30 mg/kg ACR-treated group, (2) a 50 mg/kg ACR-treated group, and (3) a normal saline (NS)-treated control group. Body weight and neurological changes were recorded each day. At the end of the test, cerebral cortex and cerebellum tissues were harvested and viewed using light and electron microscopy. Additionally, the expression of Synapsin I and P-Synapsin I in the cerebral cortex and cerebellum were investigated.

RESULTSThe 50 mg/kg ACR-treated rats showed a significant reduction in body weight compared with untreated individuals (P < 0.05). Rats exposed to ACR showed a significant increase in gait scores compared with the NS control group (P < 0.05). Histological examination indicated neuronal structural damage in the 50 mg/kg ACR treatment group. The active zone distance (AZD) and the nearest neighbor distance (NND) of synaptic vesicles in the cerebral cortex and cerebellum were increased in both the 30 mg/kg and 50 mg/kg ACR treatment groups. The ratio of the distribution of synaptic vesicles in the readily releasable pool (RRP) was decreased. Furthermore, the expression levels of Synapsin I and P-Synapsin I in the cerebral cortex and cerebellum were decreased in both the 30 mg/kg and 50 mg/kg ACR treatment groups.

CONCLUSIONSubacute ACR exposure contributes to neuropathy in the rat CNS. Functional damage of synaptic proteins and vesicles may be a mechanism of ACR neurotoxicity.

Acrylamide ; toxicity ; Animals ; Cerebellum ; cytology ; drug effects ; Cerebral Cortex ; cytology ; drug effects ; Drug Administration Schedule ; Gait ; Gene Expression Regulation ; drug effects ; Male ; Neurons ; drug effects ; Neurotoxicity Syndromes ; pathology ; Rats ; Rats, Sprague-Dawley ; Synapses ; drug effects ; Synapsins ; genetics ; metabolism ; Synaptic Vesicles ; drug effects ; physiology ; Weight Loss ; drug effects

OBJECTIVETo explore the role of P53 phosphorylation in neuron apoptosis of rats by chronic aluminum exposure.

METHODSA total of male 40 SD rats were divided randomly into 4 groups (n = 10/dose), the exposed groups were fed with normal diet with different concentration of AlCl3 · 6H2O for 6 months respectively. The dosage of low, middle and high groups were 10.73, 107.33, 1073.33 mg/kg in sequence. The control group received normal diet. The neuron apoptosis was measured by method of Tunel. The expressions of P53 and pP53-ser15 protein in the cortex were detected by Western-blot.

RESULTSTunel staining showed that the low, middle and high group rats had increased apoptosis rate than control group (P < 0.01). Western-blot test demonstrated that the expression of P53 protein in the cortex of high group rats were significantly higher than the control and low groups (P < 0.05). The expression of pP53-ser15 protein in the cortex of middle and high group rats were also higher than the control and low groups (P < 0.05).

CONCLUSIONChronic aluminum exposure can lead to over expression of P53 and pP53-ser15 protein in cerebral cortex, which maybe one of the most important mechanisms of neuron apoptosis induced by AlCl3.

Aluminum ; toxicity ; Aluminum Compounds ; toxicity ; Animals ; Apoptosis ; Cerebral Cortex ; metabolism ; Chlorides ; toxicity ; Male ; Neurons ; cytology ; drug effects ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo study the toxicity of methomyl to acetylcholinesterase (AChE) in different regions.

METHODSThe optimal temperature and time for measurement of AChE activity were determined in vitro. The dose- and time-response relationships of methomyl with AChE activity in human erythrocyte membrane, rat erythrocyte membrane, cortical synapses, cerebellar synapses, hippocampal synapses, and striatal synapses were evaluated. The half maximal inhibitory concentration (IC50) and bimolecular rate constant (K) of methomyl for AChE activity in different regions were calculated, and the type of inhibition of AChE activity by methomyl was determined.

RESULTSAChE achieved the maximum activity at 370 °C, and the optimal time to determine initial reaction velocity was 0-17 min. There were dose- and time-response relationships between methomyl and AChE activity in the erythrocyte membrane and various brain areas. The IC50 value of methomyl for AChE activity in human erythrocyte membrane was higher than that in rat erythrocyte membrane, while the Ki value of methomyl for AChE activity in rat erythrocyte membrane was higher than that in human erythrocyte membrane. Among synapses in various brain areas, the striatum had the highest IC50 value, followed by the cerebellum, cerebral cortex, and hippocampus, while the cerebral cortex had the highest Ki value, followed by the hippocampus, striatum, and cerebellum. Lineweaver-Burk diagram demonstrated that with increasing concentration of methomyl, the maximum reaction velocity (Vmax) of AChE decreased, and the Michaelis constant (Km) remained the same.

CONCLUSIONMethomyl is a reversible non-competitive inhibitor of AChE. AChE of rat erythrocyte membrane is more sensitive to methomyl than that of human erythrocyte membrane; the cerebral cortical synapses have the most sensitive AChE to methomyl among synapses in various brain areas.

Acetylcholinesterase ; metabolism ; Animals ; Cerebellum ; drug effects ; Cerebral Cortex ; drug effects ; Erythrocyte Membrane ; drug effects ; enzymology ; Hippocampus ; drug effects ; Humans ; Inhibitory Concentration 50 ; Methomyl ; toxicity ; Rats ; Synapses ; drug effects ; Toxicity Tests

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 examine the expression of calreticulin (CRT) and the changes of intracellular free calcium and neuronal apoptosis in the cerebral cortex of neonatal rats with hypoxic-ischemic brain damage (HIBD), and to investigate the intervention effects of Shenfu injection.

METHODSSeven-day-old rats were randomly assigned to three groups: control, hypoxic-ischemia (HI) and Shenfu-treated. Each group (n=50) was subdivided into 5 groups sacrificed at 3, 6, 12, 24 and 72 hours. Rat models of HIBD were prepared according to the Rice's method. Rats in the control group only underwent the separation of right common carotidartery. Shenfu injection was administered by intraperitoneal injections right after HI insults and then once daily at a dosage of 10 mL/kg for 3 days in the Shenfu-treated group. The expression of CRT in the cerebral cortex was detected by RT-PCR and Western blot. The free calcium concentrations were determined under a fluorescent microscope. The apoptosis rate was measured by the flow cytometry.

RESULTSCompared with the control group, the expression levels of CRT in the HI and the Shenfu-treated groups were obviously up-regulated (P<0.05), and the expression levels of CRT in the Shenfu-treated group were notably higher than those in the HI group (P<0.05) at all time points. The concentrations of intracellular free calcium and the apoptosis rate of neurons in the cerebral cortex in the Shenfu-treated group were significantly reduced compared with those in the HI group (P<0.05), but increased significantly compared with those in the control group at all time points (P<0.05).

CONCLUSIONSShenfu injection may have neuroprotective effects against HIBD by up-regulation of CRT expression and relief of calcium overload.

Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Calcium ; metabolism ; Calreticulin ; analysis ; Cerebral Cortex ; metabolism ; pathology ; Drugs, Chinese Herbal ; pharmacology ; Female ; Hypoxia-Ischemia, Brain ; drug therapy ; metabolism ; pathology ; Injections ; Male ; Neurons ; drug effects ; Rats, Sprague-Dawley

OBJECTIVETo explore the protective effects of rutin against learning and memory impairment induced by trimethyltin (TMT) and investigate the possible mechanism.

METHODSForty 6- to 9-week-old male BALB/c mice were randomized equally into saline group (control), TMT group, TMT+rutin group, and rutin group. Mouse models of learning and memory impairment were establish by acute TMT (2.25 mg/kg) exposure. In TMT+rutin and rutin treatment groups, the mice received intraperitioneal injection of rutin (10 mg/kg) for 1 week before TMT exposure. Twenty-four hours after TMT exposure, Morris water maze test was employed to test the escape latency of the mice, and the synaptophysin expression in the hippocampus and cortex were analyzed by Western blotting.

RESULTSCompared that in TMT group, the escape latency of the mice in water maze test was significantly shorter in the other 3 groups (P<0.05); the escape latency in TMT +rutin group was similar with that in the control and rutin groups (P>0.05). Western blotting showed significantly decreased synaptophysin expression in the hippocampus and cortex in TMT group (P<0.05); synaptophysin expression in TMT +rutin group increased significantly compared with that in TMT group (P<0.05) but showed no statistical significance from that in rutin and control groups (P>0.05).

CONCLUSIONRutin pretreatment offers protective effect against TMT-induced learning and memory impairment in mice possibly by antagonizing decreased synaptophysin in the hippocampus and cortex.

Animals ; Cerebral Cortex ; drug effects ; metabolism ; Hippocampus ; drug effects ; metabolism ; Learning ; drug effects ; Male ; Memory Disorders ; chemically induced ; drug therapy ; Mice ; Mice, Inbred BALB C ; Neuroprotective Agents ; pharmacology ; Rutin ; pharmacology ; Synaptophysin ; metabolism ; Trimethyltin Compounds ; adverse effects

To assess the neurotoxic effects and redox responses of Aroclor 1254 (A1254) on perinatally exposed rat offspring, A1254 was administered by gavage from gestational day (GD) 6 to postnatal day (PND) 21. Neurobehavioral development, antioxidant enzyme activities, lipid peroxidation (LPO), nitric oxide (NO), and NO synthase (NOS) levels were analyzed in the offspring. Neurobehavioral development analysis revealed delayed appearance of the righting reflex, negative geotaxis, and cliff drop test responses in A1254 exposed group. Developmental A1254 exposure also caused oxidative stress in the brain of PND 22 offspring via reductions in the activity of SOD and GSH-Px, and by promoting a rise in the levels of NO and NOS.
Aging ; metabolism ; Animals ; Cerebral Cortex ; drug effects ; enzymology ; metabolism ; Chlorodiphenyl (54% Chlorine) ; toxicity ; Female ; Glutathione Peroxidase ; metabolism ; Kidney ; drug effects ; enzymology ; metabolism ; Lipid Peroxidation ; drug effects ; Liver ; drug effects ; enzymology ; metabolism ; Mice ; Nervous System ; drug effects ; growth & development ; metabolism ; physiopathology ; Nervous System Diseases ; chemically induced ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Oxidative Stress ; drug effects ; Pregnancy ; Prenatal Exposure Delayed Effects ; chemically induced ; Random Allocation ; Rats ; Superoxide Dismutase ; metabolism