BACKGROUNDBoth Parkinson's disease (PD) and multiple system atrophy (MSA) have associated sleep disorders related to the underlying neurodegenerative pathology. Clinically, MSA with predominant parkinsonism (MSA-P) resembles PD in the manifestation of prominent parkinsonism. Whether the amount of rapid eye movement (REM) sleep without atonia could be a potential marker for differentiating MSA-P from PD has not been thoroughly investigated. This study aimed to examine whether sleep parameters could provide a method for differentiating MSA-P from PD.

METHODSThis study comprised 24 MSA-P patients and 30 PD patients, and they were of similar age, gender, and REM sleep behavior disorder (RBD) prevalence. All patients underwent clinical evaluation and one night of video-polysomnography recording. The tonic and phasic chin electromyogram (EMG) activity was manually quantified during REM sleep of each patient. We divided both groups in terms of whether they had RBD to make subgroup analysis.

RESULTSNo significant difference between MSA-P group and PD group had been found in clinical characteristics and sleep architecture. However, MSA-P patients had higher apnea-hypopnea index (AHI; 1.15 [0.00, 8.73]/h vs. 0.00 [0.00, 0.55]/h, P = 0.024) and higher tonic chin EMG density (34.02 [18.48, 57.18]% vs. 8.40 [3.11, 13.06]%, P < 0.001) as compared to PD patients. Subgroup analysis found that tonic EMG density in MSA + RBD subgroup was higher than that in PD + RBD subgroup (55.04 [26.81, 69.62]% vs. 11.40 [8.51, 20.41]%, P < 0.001). Furthermore, no evidence of any difference in tonic EMG density emerged between PD + RBD and MSA - RBD subgroups (P > 0.05). Both disease duration (P = 0.056) and AHI (P = 0.051) showed no significant differences during subgroup analysis although there was a trend toward longer disease duration in PD + RBD subgroup and higher AHI in MSA - RBD subgroup. Stepwise multiple linear regression analysis identified the presence of MSA-P (β = 0.552, P < 0.001) and RBD (β = 0.433, P < 0.001) as predictors of higher tonic EMG density.

CONCLUSIONTonic chin EMG density could be a potential marker for differentiating MSA-P from PD.

Aged ; Body Mass Index ; Electromyography ; methods ; Female ; Humans ; Male ; Middle Aged ; Multiple System Atrophy ; diagnosis ; physiopathology ; Parkinson Disease ; physiopathology ; Parkinsonian Disorders ; physiopathology ; Polysomnography ; Retrospective Studies

The thalamostriatal pathway is implicated in Parkinson's disease (PD); however, PD-related changes in the relationship between oscillatory activity in the centromedian-parafascicular complex (CM/Pf, or the Pf in rodents) and the dorsal striatum (DS) remain unclear. Therefore, we simultaneously recorded local field potentials (LFPs) in both the Pf and DS of hemiparkinsonian and control rats during epochs of rest or treadmill walking. The dopamine-lesioned rats showed increased LFP power in the beta band (12 Hz-35 Hz) in the Pf and DS during both epochs, but decreased LFP power in the delta (0.5 Hz-3 Hz) band in the Pf during rest epochs and in the DS during both epochs, compared to control rats. In addition, exaggerated low gamma (35 Hz-70 Hz) oscillations after dopamine loss were restricted to the Pf regardless of the behavioral state. Furthermore, enhanced synchronization of LFP oscillations was found between the Pf and DS after the dopamine lesion. Significant increases occurred in the mean coherence in both theta (3 Hz-7 Hz) and beta bands, and a significant increase was also noted in the phase coherence in the beta band between the Pf and DS during rest epochs. During the treadmill walking epochs, significant increases were found in both the alpha (7 Hz-12 Hz) and beta bands for two coherence measures. Collectively, dramatic changes in the relative LFP power and coherence in the thalamostriatal pathway may underlie the dysfunction of the basal ganglia-thalamocortical network circuits in PD, contributing to some of the motor and non-motor symptoms of the disease.
Animals ; Brain Waves ; physiology ; Corpus Striatum ; physiopathology ; Cortical Synchronization ; physiology ; Dopaminergic Neurons ; physiology ; Electrocorticography ; Male ; Neural Pathways ; physiopathology ; Oxidopamine ; Parkinsonian Disorders ; physiopathology ; Rats, Wistar ; Thalamic Nuclei ; physiopathology ; Walking ; physiology

Animals ; Disease Progression ; Dopaminergic Neurons ; physiology ; Free Radical Scavengers ; blood ; Hydroxyl Radical ; antagonists & inhibitors ; Male ; Oxidopamine ; Parkinsonian Disorders ; blood ; chemically induced ; physiopathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the changes in the expression of divalent metal transporter 1 (DMT1) and ferroportin 1 (FP1) in the substantia nigra (SN) of rats with manganese-induced parkinsonism.

METHODSEighty Sprague-Dawley rats were randomly divided into four groups. Rats in the control group were injected intraperitoneally with saline solution. Rats in the low-dose, medium-dose, and high-dose groups were injected intraperitoneally with 5, 15, and 20 mg/kg MnC12 solution, respectively, for 16 weeks. Three behavioral tests were performed at the 16th week. The concentration of Mn2+ in the SN was determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES), and the positive expression of tyrosine hydroxylase (TH) was measured by immunohistochemical staining to determine whether rats with manganese-induced parkinsonism were successfully produced. The expression of DMT1 and FP1 in SN was measured by immunohistochemical staining and fluorescent quantitative polymerase chain reaction.

RESULTSRats with manganese-induced parkinsonism were successfully produced using the above method. Compared with that in the control group, the concentrations of Mn2+ in the SN of rats exposed to 5, 15, and 20 mg/kg Mn2+ were significantly higher (1.72?0.33 vs 0.56 ± 0.20 µg/g, P<0.01; 2.92±0.77 vs 0.56±0.20 µg/g, P<0.01; 5.65±1.60 vs 0.56±0.20 µg/g, P<0.01). The mean ODs of TH-positive cells in the SN of rats exposed to 5, 15, and 20 mg/kg Mn+ were significantly lower than that in the control group (0.054±0.008 vs 0.109±0.019, P<0.01; 0.016±0.004 vs 0.109±0.019, P<0.01; 0.003±0.001 vs 0.109±0.019, P<0.01). Compared with that in the control group, the mean optical densities (ODs) of DMT1-positive cells in the SN of rats exposed to 15, and 20 mg/kg Mn2+ were significantly higher (0.062±0.004 vs 0.015±0.007, P<0.01; 0.116±0.064 vs 0.015±0.007, P<0.01). The mean ODs of FP1-positive cells in the SN of rats exposed to 5, 15, and 20 mg/kg Mn2+ were significantly lower than that in the control group (0.092±0.011 vs 0.306±0.081, P<0.01; 0.048±0.008 vs 0.306±0.081, P<0.01; 0.008±0.002 vs 0.306±0.081, P< 0.01). Rats exposed to 15 and 20 mg/kg Mn2+ had significantly higher expression of DMT1 mRNA in the SN than those in the control group (0.052±0.0126 vs 0.001±0.0004, P<0.05; 0.124±0.0299 vs 0.001±0.0004, P<0.05). However, rats exposed to 5, 15, and 20 mg/kg Mn2 had significantly lower expression of FP1 mRNA in the SN than those in the control group (0.059±0.0076 vs 0.162±0.0463, P<0.05; 0.033±0.0094 vs 0.162±0.0463, P< 0.05; 0.002±0.0007 vs 0.162±0.0463, P<0.05).

CONCLUSIONThe increased expression of DMT1 and reduced expression of FP1 may be involved in the processes of Mn2+ accumulation in the SN and dopaminergic neuron loss in rats with manganese-induced parkinsonism.

Animals ; Cation Transport Proteins ; metabolism ; Disease Models, Animal ; Manganese ; adverse effects ; Parkinsonian Disorders ; chemically induced ; metabolism ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; metabolism ; physiopathology

Intermittent administrations of dopaminergic agents in hemiparkinsonian rat enhances the behavioral response to subsequent administration of the drugs. This phenomenon is known as "priming" and thought as comparable to drug-induced dyskinesia in patients with Parkinson's disease. We investigated the behavioral and electrophysiological changes in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats after repeated administrations of apomorphine. Administration of apomorphine (0.32 mg/kg, intraperitoneal, i.p.) twice daily for 6 days enhanced the rotation induced by apomorphine from 341 turns/hour at the beginning to 755 turns/hr at the end. At the same time, the response to selective D2 agonist quinpirole (0.26 mg/kg, i.p.) was also enhanced from 203 to 555 turns/hr. Extracellular single unit recording revealed no significant difference in the basal firing rates of substantia nigra pars reticulata (SNr) neurons between the ipsilateral and contralateral side of the 6-OHDA lesion regardless of the repeated administrations of apomorphine. In SNr of the lesion side, the units with burst firing pattern were found more frequently after repeated administrations of apomorphine and the suppressive effect of quinpirole on the firing rate was enhanced. These findings suggest that the increased percentage of the burst units is the important electrophysiological change in the development of enhanced response to selective D2 agonist.
Animal ; Apomorphine/*pharmacology ; Dopamine Agonists/*pharmacology ; MPTP Poisoning/physiopathology ; Male ; Oxidopamine/toxicity ; Parkinsonian Disorders/*physiopathology ; Quinpirole/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine D2/*drug effects ; Substantia Nigra/*drug effects/physiology

Epidemiological studies have suggested an association between pesticide exposure and Parkinson's disease. In this study, we examined the neurotoxicity of an organochlorine pesticide, heptachlor, in vitro and in vivo. In cultured SH-SY5Y cells, heptachlor induced mitochondria-mediated apoptosis. When injected into mice intraperitoneally on a subchronic schedule, heptachlor induced selective loss of dopaminergic neurons in the substantia nigra pars compacta. In addition, the heptachlor injection induced gliosis of microglia and astrocytes selectively in the ventral midbrain area. When the general locomotor activities were monitored by open field test, the heptachlor injection did not induce any gross motor dysfunction. However, the compound induced Parkinsonism-like movement deficits when assessed by a gait and a pole test. These results suggest that heptachlor can induce Parkinson's disease-related neurotoxicities in vivo.
Animals ; *Apoptosis ; Astrocytes/drug effects/pathology ; Cell Line, Tumor ; Cells, Cultured ; Dopaminergic Neurons/*drug effects/pathology ; Gait ; Heptachlor/*toxicity ; Humans ; *Locomotion ; Mice ; Neurotoxicity Syndromes/etiology/physiopathology ; Parkinsonian Disorders/chemically induced ; Pesticides/*toxicity ; Substantia Nigra/*drug effects/pathology/physiopathology

In the present study, changes in the neuronal activity of serotonergic neurons in the dorsal raphe nucleus (DRN) and the effect of the selective 5-HT(1A) receptor antagonist WAY-100635 in a rat model of Parkinson's disease (PD) were investigated by using extracellular single unit recording. Rat model of PD was produced by microinjection of 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta on the right side of the brain. The results showed that the mean spontaneous firing rate of DRN serotonergic neurons in the control and 6-OHDA-lesioned rats were (1.76+/-0.11) spikes/s (n=24) and (2.43+/-0.17) spikes/s (n=21), respectively. The firing rate of serotonergic neurons in 6-OHDA-lesioned rats was significantly higher than that in the control rats (P<0.001). In the control rats, 92% (22/24) of the neurons fired regularly and 8% (2/24) fired in bursts. In rats with 6-OHDA lesions, 9% (2/21) of neurons fired regularly, 43% (9/21) exhibited irregular pattern and 48% (10/21) fired in bursts. The percentage of DRN serotonergic neurons firing in bursts was obviously higher in 6-OHDA-lesioned rats than that in the control rats (P<0.001). Local injection of WAY-100635 (3 microg in 200 nL) into the DRN significantly increased the firing rate of serotonergic neurons with no change in firing pattern in the control rats (n=19, P<0.002), but did not change the firing rate and firing pattern of serotonergic neurons in 6-OHDA-lesioned rats (n=17, P>0.05). These results suggest the dysfunction of 5-HT(1A) receptor in 6-OHDA-lesioned rats and the involvement of the DRN in the pathophysiological mechanism of PD.
Action Potentials ; physiology ; Animals ; Disease Models, Animal ; Male ; Neurons ; physiology ; Oxidopamine ; Parkinsonian Disorders ; chemically induced ; physiopathology ; Piperazines ; pharmacology ; Pyridines ; pharmacology ; Raphe Nuclei ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Serotonin ; metabolism ; Serotonin Antagonists ; pharmacology

OBJECTIVETo evaluate the role of thrombin-activated microglia in the neurodegeneration of nigral dopaminergic neurons in the rat substantia nigra (SN) in vivo.

METHODSAfter stereotaxic thrombin injection into unilateral SN of rats, immunostaining, reverse transcription polymerase chain reaction (RT-PCR) and biochemical methods were used to observe tyrosine hydroxylase (TH) immunoreactive positive cells, microglia activation, nitric oxide (NO) amount and inducible nitric-oxide synthase (iNOS) expression.

RESULTS(1) Selective damage to dopaminergic neurons was produced after thrombin injection, which was evidenced by loss of TH immunostaining in time-dependent manner; (2) Strong microglial activation was observed in the SN; (3) RT-PCR demonstrated the early and transient expression of neurotoxic factors iNOS mRNA in the SN. Immunofluorescence results found that thrombin induced expression of iNOS in microglia. The NO production in the thrombin-injected rats was significantly higher than that of controls (P < 0.05).

CONCLUSIONThrombin intranigral injection can injure the dopaminergic neurons in the SN. Thrombin-induced microglia activation precedes dopaminergic neuron degeneration, which suggest that activation of microglia and release of NO may play important roles in dopaminergic neuronal death in the SN.

Animals ; Disease Progression ; Dopamine ; biosynthesis ; Encephalitis ; chemically induced ; metabolism ; physiopathology ; Female ; Gliosis ; chemically induced ; metabolism ; physiopathology ; Immunohistochemistry ; Inflammation Mediators ; toxicity ; Injections ; Microglia ; drug effects ; metabolism ; Nerve Degeneration ; chemically induced ; metabolism ; physiopathology ; Neurons ; drug effects ; metabolism ; pathology ; Nitric Oxide ; biosynthesis ; Nitric Oxide Synthase Type II ; drug effects ; metabolism ; Oxidative Stress ; drug effects ; physiology ; Parkinsonian Disorders ; chemically induced ; metabolism ; physiopathology ; RNA, Messenger ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Substantia Nigra ; drug effects ; metabolism ; physiopathology ; Thrombin ; toxicity ; Time Factors ; Tyrosine 3-Monooxygenase ; drug effects ; genetics ; metabolism ; Up-Regulation ; drug effects ; physiology

OBJECTIVENeuroinflammation with microglial activation has been implicated to have a strong association with the progressive dopaminergic neuronal loss in Parkinson's disease (PD). The present study was undertaken to evaluate the activation profile of microglia in 1-methyl-4-phenyl pyridinium (MPP+)-induced hemiparkinsonian rats. Triptolide, a potent immunosuppressant and microglia inhibitor, was then examined for its efficacy in protecting dopaminergic neurons from injury and ameliorating behavioral disabilities induced by MPP+.

METHODSThe rat model of PD was established by intranigral microinjection of MPP+. At baseline and on day 1, 3, 7, 14, 21 following MPP+ injection, the degree of microglial activation was examined by detecting the immunodensity of OX-42 (microglia marker) in the substantia nigra (SN). The number of viable dopaminergic neurons was determined by measuring tyrosine hydroxylase (TH) positive neurons in the SN. Behavioral performances were evaluated by counting the number of rotations induced by apomorphine, calculating scores of forelimb akinesia and vibrissae-elicited forelimb placing asymmetry.

RESULTSIntranigral injection of MPP+ resulted in robust activation of microglia, progressive depletion of dopaminergic neurons, and ongoing aggravation of behavioral disabilities in rats. Triptolide significantly inhibited microglial activation, partially prevented dopaminergic cells from death and improved behavioral performances.

CONCLUSIONThese data demonstrated for the first time a neuroprotective effect of triptolide on dopaminergic neurons in MPP+-induced hemiparkinsonian rats. The protective effect of triptolide may, at least partially, be related to the inhibition of MPP+-induced microglial activation. Our results lend strong support to the use of immunosuppressive agents in the management of PD.

1-Methyl-4-phenylpyridinium ; antagonists & inhibitors ; toxicity ; Animals ; Biomarkers ; metabolism ; CD11b Antigen ; analysis ; metabolism ; Cell Count ; Cell Survival ; drug effects ; physiology ; Disability Evaluation ; Diterpenes ; pharmacology ; therapeutic use ; Dopamine ; metabolism ; Encephalitis ; drug therapy ; immunology ; prevention & control ; Epoxy Compounds ; pharmacology ; therapeutic use ; Gliosis ; drug therapy ; immunology ; prevention & control ; Herbicides ; antagonists & inhibitors ; toxicity ; Immunosuppression ; methods ; Immunosuppressive Agents ; pharmacology ; therapeutic use ; Male ; Microglia ; drug effects ; immunology ; Neurons ; drug effects ; immunology ; pathology ; Parkinsonian Disorders ; drug therapy ; immunology ; physiopathology ; Phenanthrenes ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; drug effects ; immunology ; physiopathology ; Treatment Outcome ; Tyrosine 3-Monooxygenase ; analysis ; metabolism

OBJECTIVETo study the effects of intranigral injection of different doses of CuSO4.5H2O on dopaminergic neuron in the nigrostriatal system of rats.

METHODSWistar rats were divided into four groups, including control group, 10 nmol, 50 nmol and 200 nmol copper injected into left substantia nigra (SN) groups. Seven days after the intranigral injection of copper, dopamine (DA) contents in the striatum (Str) were measured by high performance lipid chromotophotography (HPLC); the density of tyrosine hydroxylase (TH) positive axons in the Str was measured by TH staining method; TH and Caspase-3 mRNA expression in the SN were measured by semi-quantitative RT-PCR. We detected the activity of superoxide dismutase (SOD) in the lesioned midbrain of rats using biochemical methods.

RESULTSDA and its metabolites contents had no significant difference between control group and low dose (10 nmol) copper group. But from 50 nmol copper group, DA contents in the lesioned sides were reduced with the increase in the copper doses injected, showing a significant linear correlation (F = 34.16, P < 0.01). In the 50 nmol copper group, TH positive axons in the Str decreased compared with those of the control and unlesioned sides (F = 121.9, P < 0.01). In the 50 nmol copper group, TH mRNA expression decreased (t = 3.12, P < 0.01) while Caspase-3 mRNA expression increased (t = 8.96, P < 0.01) in the SN compared with the control. SOD activity decreased in the midbrain of rats treated with 50 nmol copper compared with that of the control (t = 2.33, P < 0.01).

CONCLUSIONCopper could induce damage of dopaminergic neurons in the SN of rats through destroying antioxidant defenses and promoting apoptosis.

Animals ; Apoptosis ; drug effects ; physiology ; Axons ; drug effects ; metabolism ; pathology ; Caspase 3 ; drug effects ; genetics ; metabolism ; Copper ; toxicity ; Corpus Striatum ; drug effects ; metabolism ; pathology ; Dopamine ; metabolism ; Dose-Response Relationship, Drug ; Male ; Nerve Degeneration ; chemically induced ; metabolism ; pathology ; Neural Pathways ; drug effects ; metabolism ; pathology ; Neurons ; drug effects ; metabolism ; pathology ; Neurotoxins ; toxicity ; Oxidative Stress ; drug effects ; physiology ; Parkinsonian Disorders ; chemically induced ; metabolism ; physiopathology ; RNA, Messenger ; drug effects ; metabolism ; Rats ; Rats, Wistar ; Substantia Nigra ; drug effects ; metabolism ; pathology ; Superoxide Dismutase ; drug effects ; genetics ; metabolism ; Superoxide Dismutase-1 ; Tyrosine 3-Monooxygenase ; drug effects ; genetics ; metabolism ; Wallerian Degeneration ; chemically induced ; metabolism ; pathology