In order to explore the role of acetylcholine in the pathogenesis of Parkinson's disease (PD), the changes in the concentration of acetylcholine (Ach) in the striatum, the apoptosis of substantia nigra cells, the ultrastructure and the changes of Nissl cells in rats during the morbidity of PD, and the corresponding behaviors in rats with PD were observed. Rat PD model was established by using the modified Thomas method. Eighty-one rats were randomly divided into normal control, sham operation and PD groups and their behavior features were observed at post-operative day (POD) 7, 14 and 21 as three subgroups (n=9 each). The concentration of Ach in the striatum was determined by using high-performance liquid chromatography. The apoptosis of substantia nigra cells was assayed by using TUNEL method. The ultrastructural changes in the substantia nigra were observed under the electron microscopy, and the survival of neurons in the substantia nigra area was examined by using Nissl staining. In PD group at POD 7 to 21, the damage in the substantia nigra area was gradually aggravated, the concentration of Ach, apoptosis rate and turns of rotation were gradually increased, and the number of Nissl cells was gradually reduced over the time as compared with the normal control and sham operation groups (all P<0.05). It was concluded that there exist dynamic changes in Ach concentration, ethology and apoptosis of the substantia nigra cells during the morbidity of PD, suggesting the contribution of apoptosis to the morbidity of PD, and critical role of Ach in the pathogenesis of PD.
Acetylcholine ; pharmacology ; Animals ; Corpus Striatum ; drug effects ; metabolism ; pathology ; Disease Models, Animal ; Male ; Parkinson Disease ; metabolism ; pathology ; Rats ; Rats, Wistar

OBJECTIVEIn vivo Proton Magnetic Resonance Spectroscopy (1H-MRS) can be used to evaluate the levels of specific neurochemical biomarkers of pathological mechanisms in the brain.

METHODSWe conducted T2-Weighted Magnetic Resonance Imaging (MRI) and 1H-MRS with a 3.0-Tesla animal MRI system to investigate the early microstructural and metabolic profiles in vivo in the striatum of rats following carbon monoxide (CO) poisoning.

RESULTSCompared to baseline, we found significant cortical surface deformation, cerebral edema changes, which were indicated by the unclear gray/white matter border, and lateral ventricular volume changes in the brain. A significant reduction in the metabolite to total creatine (Cr) ratios of N-acetylaspartate (NAA) was observed as early as 1 h after the last CO administration, while the lactate (Lac) levels increased marginally. Both the Lac/Cr and NAA/Cr ratios leveled off at 6 h and showed no subsequent significant changes. In addition, compared to the control, the choline (Cho)/Cr ratio was slightly reduced in the early stages and significantly increased after 6 h. In addition, a pathological examination revealed mild cerebral edema on cessation of the insult and more severe cerebral injury after additional CO poisoning.

CONCLUSIONThe present study demonstrated that 1H-MRS of the brain identified early metabolic changes after CO poisoning. Notably, the relationship between the increased Cho/Cr ratio in the striatum and delayed neuropsychologic sequelae requires further research.

Animals ; Biomarkers ; Carbon Monoxide Poisoning ; metabolism ; Corpus Striatum ; drug effects ; metabolism ; Magnetic Resonance Spectroscopy ; methods ; Male ; Rats ; Rats, Sprague-Dawley

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

AIMTo study the protective effect of Quinacrine(QA) on rat striatum neurons from the injury caused by heat environment treatment, to probe the relationship between cell membrane injury and cellular injury protection, and to seek the possibility of QA as a preventive agent to heat injury.

METHODSPrimary cultured striatum neurons from newborn rats were pretreated with QA at different concentration for 1 h, and then heat-treated at 43 degrees C for another 1 h. Cell necrosis was detected by Trypan blue staining, and apoptosis was evaluated through Activated Caspase-3 dye and TdT dye.

RESULTSHeat treatment effected the survival of striatum neurons and resulted in great number of cell death, which was mainly mediated by cell necrosis process. It was shown that treatment of QA itself had little effect on the survival of striatum neurons, while QA pretreatment decreased cellular necrosis caused by following heat treatment.

CONCLUSIONQA protects striatum neurons from heat environment injury at about 20 pmol/L, and the protection may mediated by reduction of necrosis.

Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Death ; drug effects ; Cells, Cultured ; Corpus Striatum ; cytology ; Heat-Shock Response ; Neurons ; drug effects ; Quinacrine ; pharmacology ; Rats ; Rats, Wistar

OBJECTIVETo study the oxidative damage of SWCNTs in striaturn and hippocampi of mice.

METHODSForty male ICR mice were divided into experiment group (12.5 mg/kg SWCNTs) and control group (saline containing 0.1% Tween80) randomly. Each group was subdivided into 1, 7, 14 and 28 days group, 5 mice in each subgroup, then treated with tail intravenous injection for 5 continuous days. The striatum and hippocampus were isolated on the ice bath and homogenized in saline. SOD, GSH-Px, and MDA in the supernatants were measured with xanthine oxidize, GSH consumption in enzymatic reaction and TBA methods.

RESULTSAfter exposure to 12.5 mg/kg SWCNTs for 5 d, SOD activity in striaturn and hippocampi decreased on 1st day and reached the minimum on 7th day, then increased gradually. The SOD activity in the SWCNTs treatment groups on 7th day were significantly decreased when compared to control (P < 0.05). Comparison with control group, GSH-Px activity in striaturn obviously decreased on 7th day then increased on 14th day, the difference between 7th day and 14th day was significantly (P < 0.05). GHS-Px activity in the hippocampi in SWCNTs group on 7th day and 14th day was significantly lower than that in control group (P < 0.05), then increased to the level of control group on 28th day. MDA contents of striaturn and hippocampi in SWCNTs group reduced on 1st day, then gradually increased on 7th day and 14th day, then reduced, MDA contents on7th day and 14th day n SWCNTs group were significantly higher than that in control group (P < 0.05).

CONCLUSIONSThe results of present study indicated that SWCNTs could decrease antioxidase activity and increase the Lipid peroxide in striaturn and hippocampi of mice.

Animals ; Corpus Striatum ; drug effects ; metabolism ; Hippocampus ; drug effects ; metabolism ; Lipid Peroxidation ; drug effects ; Male ; Mice ; Mice, Inbred ICR ; Nanotubes, Carbon ; adverse effects ; Oxidation-Reduction ; Oxidative Stress ; drug effects ; Superoxide Dismutase ; metabolism

OBJECTIVETo investigate the effect and mechanism of prepared Radix Polygoni Multiflori (RPM) on the elevation of extracellular hydroxyl radical in striatum of rats induced by intracerebral perfusion of 6-hydroxy dopamine (6-OHDA).

METHODSCerebral microdialysis was used to establish the model. Hydroxyl radical was captured by salicylic acid, and 2,3-dihydroxy benzyl acid (2,3-DHBA) and 2,5-dihydroxy benzyl acid (2,5-DHBA) formed by hydroxyl radical in vital brain were measured by high performance liquid chromatography-electrochemical detector (HPLC-ED).

RESULTSAfter perfusion of 6-OHDA in brain of rats, the levels of 2,3-DHBA and 2,5-DHBA in the model group increased rapidly. The former was higher during the whole course of observation (P<0.01), while the latter was higher at most time points than that in the control group (P<0.05 or P<0.01). The level of 2,3-DHBA in the RPM group was lower than that in the model group at 5 time points (P < 0.05, P < 0. 01).

CONCLUSIONRPM could inhibit the elevating of extracellular hydroxyl radical in striatum of rats induced by intracerebral perfusion of 6-OHDA, indicating one of the brain protective mechanisms of RPM may be related to its anti-oxidation effect.

Animals ; Corpus Striatum ; drug effects ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Hydroxyl Radical ; metabolism ; Male ; Microdialysis ; Neuroprotective Agents ; pharmacology ; Oxidopamine ; Polygonum ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the effects of chlorpromazine combined with Platycodon grandiflorum on the striatal extracellular dopamine level in rats and to research the interaction and the mechanism of action after combining traditional Chinese medicine with western medicine.

METHODTwenty four rats were randomly assigned into four groups: the control group, Platycodon group, chlorpromazine group and chlorpromazined combined with P. grandiflorum group. The level of dopamine in CSF microdialysis samples was detected with high performance liquid chromatography with electrochemical detector after administration for 10 days.

RESULTThe CSF level of DA (1.52 +/- 0.34) microg x L(-1) was significantly higher (P < 0.01) in chlorpromazine combined with P. grandiflorum group than that in the chlorpromazine group (1.25 +/- 0.22) microg x L(-1) (P < 0.05) and that in the normal control (1.06 +/- 0.24) microg x L(-1) (P < 0.01).

CONCLUSIONThe combining utilization of P. grandiflorum and chlorpromazine may increase the DA concentration of monoamine neurotransmitters, which results in under the therapeutic effect is maintained, the dosage of chlorpromazine used to individuals are decreased and the incidence rate of the adverse reactions of chlorpromazine will descend.

Animals ; Chlorpromazine ; chemistry ; Corpus Striatum ; drug effects ; metabolism ; Dopamine ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Male ; Microdialysis ; Platycodon ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo examine the protective effect of nicotinamide on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) in mouse model and its mechanisms.

METHODSParkinson's disease was induced by injection of MPTP in adult male C57BL/6 mice, nicotinamide (500 mg/kg,i.p.) was given prior to subacute (30 mg/kg/d × 5 d,i.p.) MPTP administration. Locomotor activities, striatal dopamine levels, lactate dehydrogenase (LDH) and NO synthase (NOS) activities of whole brains and striatum were analyzed at d5 after last MPTP injections.

RESULTSPretreatment with nicotinamide significantly improved the locomotor activity in the open-field test (P<0.01), but not in the swimming test and grip & climbing test. Nicotinamide administration resulted in sparing striatal dopamine levels from MPTP-induced dopamine depletion. There was no significant difference in LDH and NOS activities in the whole brains among the groups; but the activities in the striatum were drastically elevated after MPTP treatment. Nicotinamide pretreatment markedly inhibited MPTP-induced LDH and NOS activities (P<0.01) and showed no significant difference compared to controls (P>0.05).

CONCLUSIONNicotinamide protects dopaminergic neurons against MPTP-induced neurodegeneration,which suggests that the neuroprotective effects be associated with the inhibition of cell injuries and NOS activities.

Animals ; Corpus Striatum ; drug effects ; metabolism ; Disease Models, Animal ; Dopamine ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity ; drug effects ; physiology ; Neurons ; drug effects ; metabolism ; Niacinamide ; pharmacology ; Parkinson Disease ; drug therapy ; metabolism

The present study is to assess the prophylactic effect of quinacrine (QA) , an anti-malarial drug, against heatstroke in rats. Conscious rats were orally given equal volume normal saline or QA (dissolved in normal saline and final dosage for rats was 4.5, 9.0 and 18 mg x kg(-1)). An hour later rats were put into a warm water circulated hot chamber (41.0 +/- 0.5) degrees C. Rectal temperature (core temperature, T(co)) of rats in hot chamber was continuously monitored by a thermocouple. T(co) and survival time of rats showed that QA pre-treatment postponed the hyperthermia, and increased the survival time of rats in hot chamber. Primary striatum neurons' culture from new born rats was maintained with D-MEM and 10% FBS. After immuno-cytochemistry identification with antibodies against neural specific proteins, culture received 20 micromol x L(-1) QA only for 1 h and followed by 43.0 degrees C heat treatment for another hour, or 20 micromol x L(-1) QA for 1 h followed by 43.0 degrees C heat treatment for another hour. Control culture received heat treatment only. Cultures were labeled with the fluorescent indicator DPH and the relative membrane fluidity of neurons was measured with the help of fluorescent polarized spectrophotometer. [3H] Arachidonic acid (AA) labeled membrane of E. Coli cells was used as substrate to determine cPLA2 activity of neurons. Gas chromatography and mass spectrum were also employed to detect on the level of fatty acids level in rat striatum neurons. Results from cells indicated that inhibition of cPLA2, reduction the release of active fatty acids such as AA, and possibly, stabilization of the cell membrane which was disturbed by hot treatment, may contribute to the mechanism underlying heat protection and heatstroke preventive effects of quinacrine.
Animals ; Cells, Cultured ; Corpus Striatum ; drug effects ; pathology ; Fatty Acids ; metabolism ; Heat Stroke ; metabolism ; physiopathology ; prevention & control ; Hot Temperature ; adverse effects ; Male ; Membrane Fluidity ; drug effects ; Neurons ; enzymology ; metabolism ; physiology ; Phospholipases A2 ; metabolism ; Quinacrine ; pharmacology ; Rats ; Rats, Wistar

OBJECTIVETo investigate effect and mechanisms on dopamine contents of striatum (Str) in the 6-OHDA induced rat model of Parkinson's disease (PD) by ginsenoside Rg1.

METHODOvariectomized PD rats were treated with vehicle, ginsenoside Rg1, (10 mg x kg(-1)) or estrogen receptor (ER) antagonist ICI 182,780 for 14 d. The change of apomorphine-linduced rotational behavior in PD rats were observed. The high performance lipid chromotophotography (HPLC) was used to determine the contents of DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)in striatum.

RESULTRg1 treatment could ameliorate the PD rat's rotational behavior induced by apomorphine (P < 0.01). This effect could be blocked by ER antagonist ICI 182,780. The DA, DOPAC and HVA levels in the injured side of Str for PD rats were significantly decreased compared with the intact side (P < 0.01). Rg1, treatment could increase DA contents in the injured side of Str (P < 0.01). ICI 182,780 could completely block the neuroprotective effects of Rg1. The DA contents and its metabolites in the injured side of the ICI treatment group were significantly decreased compared with the Rg1 group (P < 0.01).

CONCLUSIONGinsenoside Rg1 may have protective effects on the dopaminergic neurons for the 6-OHDA induced OVX rat model of PD, ER. May be involved in the protection action.

3,4-Dihydroxyphenylacetic Acid ; Animals ; Behavior, Animal ; drug effects ; Central Nervous System Agents ; pharmacology ; Corpus Striatum ; drug effects ; metabolism ; Disease Models, Animal ; Dopamine ; metabolism ; Female ; Ginsenosides ; pharmacology ; Homovanillic Acid ; metabolism ; In Vitro Techniques ; Ovariectomy ; Parkinson Disease ; drug therapy ; metabolism ; Rats ; Rats, Wistar