To study the effects of 6-hydroxydopamine (6-OHDA) and reduced glutathione (GSH) on the nigral dopaminergic neurons in brain slices in vitro, immolunohistochemical technique was used to observe the changes of TH-stained neurons, including cell bodies and the dendrites, in the substantia nigra (SN) of midbrain slices of rats after incubation for 1 h in the presence of GSH 15 min before and during the period of incubation with 6-OHDA. The results showed that cell bodies remained intact but dendrites were fragmented and truncated after treatment with 6-OHDA. The antioxidant GSH alone did not significantly affect the dendrites of SN neurons but prevented 6-O-HDA-induced damage of dendrites. It was concluded that glutathione may prevent 6-OHDA-induced dopaminergic neurodegeneration and play a protective role in dopaminergic neurons.
Glutathione/*therapeutic use ; Neurons/pathology ; Oxidopamine ; Parkinson Disease, Secondary/chemically induced ; Parkinson Disease, Secondary/*drug therapy ; Random Allocation ; Rats, Sprague-Dawley ; Substantia Nigra/pathology ; Tyrosine 3-Monooxygenase/metabolism

In order to investigate the neurotoxicity of lipopolysaccharide (LPS) on the dopaminergic neurons of substantia nigra and the pathogenesis of Parkinson disease, LPS was stereotaxically infused into substantia nigra (SN). At different dosages and different time points with 5 microg LPS, the damage of the dopaminergic neurons in SN was observed by using tyrosine-hydroxylase (TH) immunohistochemical staining. The results showed that 14 days after injection of 0.1 microg to 10 microg LPS into the rat SN, TH-positive (TH+) neurons in the SN were decreased by 5%, 15%, 20%, 45 %, 96% and 99% respectively. After injection of 5 microg LPS, as compared with the control groups, TH+ neurons began to decrease at 3rd day and obviously decrease at 14th day, only 5% of total cells, and almost disappeared 30 days later. The results suggested that LPS could induce the degeneration of dopaminergic neurons in the SN in a dose- and time-dependent manner.
Animals ; Dopamine ; metabolism ; Dose-Response Relationship, Drug ; Female ; Lipopolysaccharides ; toxicity ; Nerve Degeneration ; Neurons ; pathology ; Parkinson Disease, Secondary ; chemically induced ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; pathology

To study the effects of 6-hydroxydopamine (6-OHDA) and reduced glutathione (GSH) on the nigral dopaminergic neurons in brain slices in vitro, immolunohistochemical technique was used to observe the changes of TH-stained neurons, including cell bodies and the dendrites, in the substantia nigra (SN) of midbrain slices of rats after incubation for 1 h in the presence of GSH 15 min before and during the period of incubation with 6-OHDA. The results showed that cell bodies remained intact but dendrites were fragmented and truncated after treatment with 6-OHDA. The antioxidant GSH alone did not significantly affect the dendrites of SN neurons but prevented 6-O-HDA-induced damage of dendrites. It was concluded that glutathione may prevent 6-OHDA-induced dopaminergic neurodegeneration and play a protective role in dopaminergic neurons.
Animals ; Glutathione ; therapeutic use ; Male ; Neurons ; pathology ; Oxidopamine ; Parkinson Disease, Secondary ; chemically induced ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; pathology ; Tyrosine 3-Monooxygenase ; metabolism

In order to investigate the neurotoxicity of lipopolysaccharide (LPS) on the dopaminergic neurons of substantia nigra and the pathogenesis of Parkinson disease, LPS was stereotaxically infused into substantia nigra (SN). At different dosages and different time points with 5 microg LPS, the damage of the dopaminergic neurons in SN was observed by using tyrosine-hydroxylase (TH) immunohistochemical staining. The results showed that 14 days after injection of 0.1 microg to 10 microg LPS into the rat SN, TH-positive (TH+) neurons in the SN were decreased by 5%, 15%, 20%, 45 %, 96% and 99% respectively. After injection of 5 microg LPS, as compared with the control groups, TH+ neurons began to decrease at 3rd day and obviously decrease at 14th day, only 5% of total cells, and almost disappeared 30 days later. The results suggested that LPS could induce the degeneration of dopaminergic neurons in the SN in a dose- and time-dependent manner.
Dopamine/metabolism ; Dose-Response Relationship, Drug ; Lipopolysaccharides/*toxicity ; *Nerve Degeneration ; Neurons/pathology ; Parkinson Disease, Secondary/*chemically induced ; Random Allocation ; Rats, Sprague-Dawley ; Substantia Nigra/*pathology

Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes, public health decision making, and primary prevention synthesis. Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies. Biomarkers are generally classified into three groups: biomarkers of exposure, effect, and susceptibility.The main body compartments that store lead are the blood, soft tissues, and bone; the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurological disorders, such as brain damage, mental retardation, behavioral problems, nerve damage, and possibly Alzheimer's disease, Parkinsons disease, and schizophrenia. This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.
Alzheimer Disease ; chemically induced ; metabolism ; pathology ; physiopathology ; psychology ; Animals ; Behavior ; drug effects ; Biomarkers ; metabolism ; Brain ; metabolism ; pathology ; physiopathology ; Brain Diseases ; chemically induced ; pathology ; physiopathology ; Environmental Exposure ; adverse effects ; Humans ; Lead ; pharmacokinetics ; toxicity ; Lead Poisoning ; etiology ; metabolism ; pathology ; physiopathology ; psychology ; Neurotoxicity Syndromes ; etiology ; metabolism ; pathology ; physiopathology ; psychology ; Parkinson Disease, Secondary ; chemically induced ; metabolism ; pathology ; physiopathology ; psychology ; Schizophrenia ; chemically induced ; metabolism ; pathology ; physiopathology

The use of prokinetics/antiemetics is one of the leading causes of drug-induced parkinsonism (DIP) observed in neurology clinics. Cognitive dysfunction in DIP has recently been recognized, but pathologies related with cognitive dysfunction is unknown. Among our retrospective cohort of 385 consecutive parkinsonian patients enrolled in our parkinsonism registry, 14 patients were identified who satisfied our inclusion criteria: parkinsonism caused by prokinetics/antiemetics, existing T1-weighted 3D volumetric MR images, and normal [18F]-N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane PET scan images. For the comparison of volumetric MR data, 30 age- and sex-matched healthy individuals were included in this study. Among 14 patients with DIP, 4 patients were diagnosed with dementia, and all other patients had mild cognitive impairment (MCI). Comparisons of MR volumetric data between DIP patients with MCI and controls show that cortical gray matter volumes are reduced bilaterally in DIP (P=0.041) without changes in either total white matter volume or total intracranial volume. Among subcortical structures, the volume of the right hippocampus is reduced in DIP patients compared with controls (P=0.011, uncorrected). In DIP, cortical thickness is reduced in the bilateral lingual (P=0.002), right fusiform (P=0.032) and part of the left lateral occipital gyri (P=0.007). Our results suggests that cognitive dysfunction in DIP caused by prokinetics/antiemetics is common. Structural changes in the brain by 3D MRI may be associated with cognitive decline in DIP.
Aged ; Aged, 80 and over ; Antiemetics/*adverse effects ; Brain/drug effects/pathology ; Cognition Disorders/*chemically induced/*pathology ; Female ; Gastrointestinal Agents/*adverse effects ; Humans ; Male ; Parkinson Disease, Secondary/*chemically induced/*pathology ; Republic of Korea ; Retrospective Studies ; Risk Assessment ; Treatment Outcome

BACKGROUNDParaquat (PQ; 1, 1'-dimethyl-4, 4'-bipyridinium), a widely used herbicide that is structurally similar to the known dopaminergic neurotoxicant MPTP (1-methyl-1, 2, 3, 6-tetrahydropyridine), has been suggested as a potential etiologic factor for the development of Parkinson's disease (PD). Aging is an accepted risk factor for idiopathic Parkinson's disease. The aim of this study was to test the hypothesis that paraquat could induce PD-like nigrostriatal dopaminergic degeneration in aging C57BL/6 mice.

METHODSSenile male C57BL/6 mice were intraperitoneally injected with either saline or PQ at 2-day intervals for a total of 10 doses. Locomotor activity and performance on the pole test were measured 7 days after the last injection and animals were sacrificed one day later. Level of dopamine (DA) and its metabolites levels in the striatum were measured by high-performance liquid chromatography with an electrochemical detector (HPLC-ECD), and numbers of tyrosine hydroxylase (TH) positive neurons were estimated using immunohistochemistry.

RESULTSLocomotor activities were significantly decreased and the behavioral performance on the pole test were significantly impaired in the PQ treated group. Level of DA and its metabolites levels in the striatum were declined by 8 days after the last injection. Immunohistochemical analyses showed that PQ was associated with a reduction in numbers of tyrosine hydroxylase positive neurons.

CONCLUSIONSLong-term repeated exposes to PQ can selectively impair the nigrostriatal dopaminergic system of senile mice, suggesting that PQ could play an important role in the pathogenesis of Parkinson's disease (PD). Our results also validate a novel model of PD induced by exposure to a toxic environmental agent.

Aging ; pathology ; Animals ; Corpus Striatum ; drug effects ; Disease Models, Animal ; Dopamine ; analysis ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity ; drug effects ; Paraquat ; toxicity ; Parkinson Disease, Secondary ; chemically induced ; Substantia Nigra ; drug effects ; enzymology ; Tyrosine 3-Monooxygenase ; analysis

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; Female ; MPTP Poisoning ; drug therapy ; pathology ; physiopathology ; Male ; Materia Medica ; therapeutic use ; Mice ; Mice, Inbred C57BL ; Microglia ; drug effects ; pathology ; Parkinson Disease, Secondary ; chemically induced ; drug therapy ; physiopathology ; Scorpion Venoms ; chemistry

AIMTo investigate the role of ginsenoside Rg1 in preventing against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced apoptosis of the substantia nigra neurons in the mouse model of Parkinson's disease (PD).

METHODSC57B1 male mice were given MPTP i.p. in the PD model group. Different doses of ginsenoside Rg1 (2.5, 5.0 and 10.0 mg.kg-1) were given i.p. 3 days prior to MPTP in the pretreatment group. Nissl staining, tyrosine hydroxylase (TH) immunostaining and TdT-mediated duTP nick-end labeling (TUNEL) staining were used to observe the damage of nigral neurons. The method of immunostaining was used to detect the caspase-3 activity, expression of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS).

RESULTSPretreatment with ginsenoside Rg1 was shown to prevent the loss of Nissl staining neurons and TH-positive neurons, and decrease the percent of TUNEL-positive. Simultaneously, Rg1 was found to reduce caspase-3 activity and the expression of iNOS.

CONCLUSIONGinsenoside Rg1 showed protective effect on MPTP-induced apoptosis in the mouse nigral neurons and this effect may be attributable to reducing the expression of iNOS and inhibiting the activation of caspase-3.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; Apoptosis ; Caspase 3 ; Caspases ; metabolism ; Ginsenosides ; pharmacology ; therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Neurons ; drug effects ; pathology ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Nitric Oxide Synthase ; metabolism ; Nitric Oxide Synthase Type I ; Parkinson Disease, Secondary ; chemically induced ; metabolism ; pathology ; prevention & control ; Random Allocation ; Substantia Nigra ; pathology

OBJECTIVETo investigate the protective effects of cistanche total glycosides (CTG) on dopaminergic neuron in substantia nigra (SN) of model mice of Parkinson's disease (PD).

METHODSExperimental mice were randomly divided into 5 groups, the normal control group, the model group, the high (400 mg/kg), moderate (200 mg/kg) and low (100 mg/kg) dose CTG groups. Mouse model of chronic PD was induced by peritoneal injection of MPTP (1-methyl-4-phenyl-1,2,3,6-ttrahydropyridine) 30 mg/kg for 5 successive days. Climbing test was used to estimate the neurobehavior of mice on the 7th and 14th day (D7 and D14) after initiating MPTP injection; meantime, quantitative immunohistochemistry was conducted to detect the number of dopaminergic neuron in SN and expression of tyrosine hydroxylase (TH) in striatum.

RESULTSThe average time of climbing in the high dose CTG group on D7 and D14 was significantly shorter than that in the model group (P < 0.01). The mean optic density (OD) of TH in striatum was higher in the three CTG groups than that in the model group on D7 (P < 0.01); but on D14, significance only showed in the high and moderate dose CTG groups (P < 0.01). Moreover, the MPTP induced decrease of TH positive neuron could be antagonized by CTG, but significant difference only showed between the high dose CTG group and the model group at the two time points of observation (P < 0.05).

CONCLUSIONCTG could improve the neurobehavior of PD model mice significantly, and inhibit the decrease of nigral dopaminergic neurons and TH expression in striatum.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; Behavior, Animal ; drug effects ; Cistanche ; chemistry ; Dopamine ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Glycosides ; pharmacology ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred C57BL ; Neurons ; drug effects ; metabolism ; pathology ; Neuroprotective Agents ; pharmacology ; Parkinson Disease, Secondary ; chemically induced ; physiopathology ; Random Allocation ; Substantia Nigra ; drug effects ; metabolism ; pathology ; Tyrosine 3-Monooxygenase ; metabolism