Previous studies have shown that electroacupuncture (EA) promotes recovery of motor function in Parkinson's disease (PD). However the mechanisms are not completely understood. Clinically, the subthalamic nucleus (STN) is a critical target for deep brain stimulation treatment of PD, and vesicular glutamate transporter 1 (VGluT1) plays an important role in the modulation of glutamate in the STN derived from the cortex. In this study, a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD was treated with 100 Hz EA for 4 weeks. Immunohistochemical analysis of tyrosine hydroxylase (TH) showed that EA treatment had no effect on TH expression in the ipsilateral striatum or substantia nigra pars compacta, though it alleviated several of the parkinsonian motor symptoms. Compared with the hemi-parkinsonian rats without EA treatment, the 100 Hz EA treatment significantly decreased apomorphine-induced rotation and increased the latency in the Rotarod test. Notably, the EA treatment reversed the 6-OHDA-induced down-regulation of VGluT1 in the STN. The results demonstrated that EA alleviated motor symptoms and up-regulated VGluT1 in the ipsilateral STN of hemi-parkinsonian rats, suggesting that up-regulation of VGluT1 in the STN may be related to the effects of EA on parkinsonian motor symptoms via restoration of function in the cortico-STN pathway.
Adrenergic Agents ; toxicity ; Animals ; Apomorphine ; pharmacology ; Disease Models, Animal ; Dopamine Agonists ; pharmacology ; Electroacupuncture ; methods ; Functional Laterality ; drug effects ; Male ; Medial Forebrain Bundle ; injuries ; Motor Activity ; drug effects ; physiology ; Neurons ; drug effects ; metabolism ; Oxidopamine ; toxicity ; Parkinson Disease, Secondary ; chemically induced ; physiopathology ; therapy ; Rats ; Rats, Sprague-Dawley ; Subthalamic Nucleus ; drug effects ; metabolism ; pathology ; Tyrosine 3-Monooxygenase ; metabolism ; Up-Regulation ; drug effects ; physiology ; Vesicular Glutamate Transport Protein 1 ; metabolism

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

OBJECTIVETo discuss the protective effect of alkaloids from Piper longum (PLA) in rat dopaminergic neuron injury of 6-OHDA-induced Parkinson's disease and its possible mechanism.

METHODThe rat PD model was established by injecting 6-OHDA into the unilateral striatum with a brain solid positioner. The PD rats were divided into the PLA group (50 mg x kg(-1) x d(-1)), the madorpa group (50 mg x kg(-1) x d(-1)) and the model group, with 15 rats in each group. All of the rats were orally given drugs once a day for 6 weeks. Meanwhile, other 15 rats were randomly selected as the sham operation group, and only injected with normal saline in the unilateral striatum. The behavioral changes were observed with the apomorphine (APO)-induced rotation and rotary rod tests. The number of tyrosine hydroxylase (TH)-positive cells in rat substantia nigra and the density of TH-positive fibers in striatum were detected by tyrosine hydroxylase immunohistochemistry. The content of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione (GSH), catalase (CAT), malondialdehyde (MDA), nitric oxide (NO) and nitric oxide synthase (NOS) in rat substantia nigra and striatum were measured by the spectrophotometric method.

RESULTAfter being induced by APO, PD rats showed obvious rotation behaviors, with decreased time stay on rotary rod and significant reduction in the number of TH-positive cells in sustantia nigra and the density of TH-positive fibers in striatum. The activities of SOD, GSH-Px, CAT, the content of GSH and the total antioxidant capacity significantly decreased, whereas the activities of NOS and the content of MDA, NO significantly increased. PLA could significantly improve the behavioral abnormality of PD rats and increase the number of TH-positive cells in sustantia nigra and the density of TH-positive fibers in striatum. It could up-regulate the activities of SOD, GSH-Px, CAT, the content of GSH and the total antioxidant capacity, and decrease the content of NOS and the content of MDA, NO.

CONCLUSIONAlkaloids from P. longum shows the protective effect in substantia nigra cells of 6-OHDA-induced PD model rats. Its mechanism may be related with their antioxidant activity.

Administration, Oral ; Alkaloids ; administration & dosage ; pharmacology ; Animals ; Apomorphine ; pharmacology ; Catalase ; metabolism ; Dopamine Agonists ; pharmacology ; Dopaminergic Neurons ; drug effects ; metabolism ; pathology ; Glutathione ; metabolism ; Glutathione Peroxidase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Motor Activity ; drug effects ; Neostriatum ; drug effects ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Oxidopamine ; Parkinson Disease, Secondary ; chemically induced ; physiopathology ; prevention & control ; Piper ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; drug effects ; metabolism ; Superoxide Dismutase ; metabolism ; Tyrosine 3-Monooxygenase ; metabolism

The aim of this study is to investigate the protective effect of N-[2-(4-hydroxyphenyl)ethyl]-2-(2, 5-dimethoxyphenyl)-3-(3-methoxy-4-hydroxyphenyl)acrylamide (FLZ), a novel synthetic squamosamide cyclic derivative, against Parkinson's disease (PD) model mice induced by the inflammatory bacterial endotoxin, lipopolysaccharides (LPS) and the neurotoxin 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). C57/BL mice were ip injected LPS (5 mg x kg(-1)) once. One week following the LPS injection, mice received a subcutaneous injection of MPTP (25 mg x kg(-1)) once daily for 2 days. Eight weeks later, FLZ (25, 50 and 75 mg x kg(-1)) was orally administered to mice once daily for 60 days. The motor ability of the mice was evaluated by rod climbing test and footprint test. The dopamine (DA) levels in mouse striatum were determined by high performance liquid chromatography system. The tyrosine hydroxylase (TH)-positive cells were showed by immunohistochemical analysis. FLZ treatment significantly improved motor dysfunction of mice challenged by LPS plus MPTP. The increase of TH-positive cell numbers and elevation of DA levels may be contributed to the beneficial effects of FLZ on motor behavior. This study showed FLZ has significant therapeutic effect on LPS plus MPTP induced chronic PD model, which indicates its potential as a new candidate drug to treat PD.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; 3,4-Dihydroxyphenylacetic Acid ; metabolism ; Acrylamides ; pharmacology ; Animals ; Caffeic Acids ; pharmacology ; Corpus Striatum ; metabolism ; Dopamine ; metabolism ; Homovanillic Acid ; metabolism ; Lipopolysaccharides ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity ; drug effects ; Neurons ; drug effects ; metabolism ; Parkinson Disease, Secondary ; chemically induced ; metabolism ; pathology ; physiopathology ; Random Allocation ; Tyrosine 3-Monooxygenase ; metabolism

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

PURPOSE: The purpose of this study was to determine the effect of dehydroepiandrosterone (DHEA) on recovery of muscle atrophy induced by Parkinson's disease. METHODS: The rat model was established by direct injection of 6-hydroxydopamine (6-OHDA, 20 microg) into the left striatum using stereotaxic surgery. Rats were divided into two groups; the Parkinson's disease group with vehicle treatment (Vehicle; n=12) or DHEA treatment group (DHEA; n=22). DHEA or vehicle was administrated intraperitoneally daily at a dose of 0.34 mmol/kg for 21 days. At 22-days after DHEA treatment, soleus, plantaris, and striatum were dissected. RESULTS: The DHEA group showed significant increase (p<.01) in the number of tyrosine hydroxylase (TH) positive neurons in the lesioned side substantia nigra compared to the vehicle group. Weights and Type I fiber cross-sectional areas of the contralateral soleus of the DHEA group were significantly greater than those of the vehicle group (p=.02, p=.00). Moreover, extracellular signal-regulated kinase (ERK) phosphorylation significantly decreased in the lesioned striatum, but was recovered with DHEA and also in the contralateral soleus muscle, Akt and ERK phosphorylation recovered significantly and the expression level of myosin heavy chain also recovered by DHEA treatment. CONCLUSION: Our results suggest that DHEA treatment recovers Parkinson's disease induced contralateral soleus muscle atrophy through Akt and ERK phosphorylation.
Animals ; Corpus Striatum/drug effects/metabolism ; Dehydroepiandrosterone/*pharmacology/therapeutic use ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Male ; Muscle Fibers, Slow-Twitch/drug effects ; Muscle, Skeletal/drug effects/metabolism ; Muscular Atrophy/drug therapy/*etiology/*pathology ; Myosins/metabolism ; Neurons/drug effects/enzymology ; Oxidopamine/toxicity ; Parkinson Disease, Secondary/*chemically induced/*complications ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Rats, Sprague-Dawley ; Tyrosine 3-Monooxygenase/metabolism

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

OBJECTIVETo explore the mechanism of electroacupuncture scalp point penetration therapy in treatment of the Parkinson's disease (PD).

METHODSForty Wistar rats were randomly divided into a normal group, a sham-operation group, a model group and an electroacupuncture (EA) group. 6-OHDA was injected into the left striatum to make lateralization PD rat model. Acupuncture at "Baihui" (GV 20)-through-"Taiyang" (EX-HN 5), once each day, 6 days constituting one course. Immunohistochemical method was used to observe the facio-density and the integral optical density of brain-derived neurotrophic factor (BDNF) in the left substantia nigra, and TUNEL method was used to observe the apoptotic amount, and high performance liquid chromatography was used to observe DA contents of the left striatum in each group.

RESULTSAs compared with the model group, in the acupuncture group, the facio-density and the integral optical density in the left substantia nigra increased significantly (P < 0.05), the amount of apoptosis decreased significantly (P < 0.05), and the content of striatum DA increased significantly (P < 0.05).

CONCLUSIONEA scalp point-through-point therapy may enhance BDNF protein expression level in the substantia nigra to decrease the amount of apoptosis in the PD model rat.

Acupuncture Points ; Animals ; Apoptosis ; Brain-Derived Neurotrophic Factor ; metabolism ; Electroacupuncture ; methods ; Female ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Oxidopamine ; administration & dosage ; toxicity ; Parkinson Disease, Secondary ; chemically induced ; therapy ; Random Allocation ; Rats ; Rats, Wistar ; Scalp ; pathology ; Substantia Nigra ; metabolism ; pathology ; Treatment Outcome

OBJECTIVETo investigate the role of P38 signaling pathway in modulating the expression of cyclooxygenase-2 (COX-2) in the substantia nigra (SN) of mice with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson disease (PD), and explore the possible mechanism of the dopaminergic (DA) neuron death in PD and the effects of ginsenoside Rg1 on the P38 signaling pathway and DA neurons.

METHODSC57BL6 mice were treated with MPTP to produce the subacute PD model, and the behavioral changes were observed. Immunohistochemistry and Western blotting for tyrosine hydroxylase (TH), COX-2, prostaglandin E2 (PGE2) and phosphorylated P38 (p-P38) were used to observe the changes of positive cell number in the midbrain after treatment with ginsenoside Rg1.

RESULTSCompared with the control mice, the mice with PD presented with typical symptoms of PD. The number of p-P38-, COX-2-, and PGE2-positive cells significantly increased in the SN area 6 h after the 3rd injection of 30 mg/kg MPTP (P<0.01). The number of TH-positive neurons in the PD model group was substantially reduced by about 60% (P<0.01) in 24 h after the 5th injection of MPTP. In mice with ginsenoside Rg1 treatment, the number of p-P38-, COX-2-, and PGE2-positive cells was reduced obviously 6 h after the 3rd injection of MPTP as compared with that in the model group (P<0.01). The number of TH-positive neurons in the SN was decreased by only 30% (P<0.01 vs control group) 24h after the 5th injection of MPTP.

CONCLUSIONP38 signaling pathway may play an important role in modulating COX-2 expression in the SN in the early stage of MPTP-induced subacute PD, and ginsenoside Rg1 may act on the P38 signaling pathway to protect the DA neurons in PD.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; Blotting, Western ; Cyclooxygenase 2 ; biosynthesis ; Ginsenosides ; pharmacology ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred C57BL ; Neurons ; drug effects ; metabolism ; pathology ; Parkinson Disease, Secondary ; chemically induced ; metabolism ; physiopathology ; Signal Transduction ; drug effects ; Substantia Nigra ; drug effects ; metabolism ; pathology ; p38 Mitogen-Activated Protein Kinases ; metabolism

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