In this study, the effects of Radio Electric Asymmetric Conveyer (REAC), a non-invasive physical treatment, on neuroinflammatory responses in a mouse model of parkinsonism induced by intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), were investigated in vivo. We found that the REAC tissue optimization treatment specific for neuro-regenerative purposes (REAC TO-RGN-N) attenuated the inflammatory picture evoked by MPTP-induced nigro-striatal damage in mice, decreasing the levels of pro-inflammatory molecules and increasing anti-inflammatory mediators. Besides, there was a significant reduction of both astrocyte and microglial activation in MPTP-treated mice exposed to REAC TO-RGN-N. These results indicated that REAC TO-RGN-N treatment modulates the pro-inflammatory responses and reduces neuronal damage in MPTP-induced parkinsonism.
Animals ; Corpus Striatum ; pathology ; Electric Stimulation ; methods ; Inflammation ; pathology ; Male ; Mice ; Nerve Degeneration ; pathology ; Nerve Regeneration ; physiology ; Parkinsonian Disorders ; pathology

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

OBJECTIVETo explore the mechanism of acupuncture in treatment of Parkinson's disease.

METHODSFifty Wistar rats were randomly divided into a normal control group, a sham-operation control group, a model group, a Fengfu-Taichong group and a Shuanggu Yitong group. The hemilateral rotation Parkinson's disease model was prepared by micro-injection of 6-hydroxyl-dopamine into the right striatum. Effects of acupuncture at "Fengfu" (GV 16), "Taichong" (LR 3) hy Shoanggu Yitong needling method on proliferation and differentiation of nerve stem cells in the Parkinson's disease model rat were compared. Proliferation and numher changes of the nerve stem cells in the suhstantia nigra and the striatum were investigated with immunohistochemical method, and the number of nerve stem cells transforming neurons were observed with immunohistochemical double-labeling method.

RESULTSIn the two acupuncture groups, the proliferative cells in the substantia nigra and thestriatum of the destroyed side increased significantly (P < 0.01), and the number of nerve stem cells and the number of transformed neurons in the destroyed side of the substantia nigra and the striatum increased significantly only in the Shuanggu Yitong group (P < 0.01).

CONCLUSIONShuanggu Yitong needling method can induce proliferation and differentiation of nerve stem cells in the substantia nigra and the striatum regions in the Parkinson's disease model rat.

Acupuncture Therapy ; methods ; Animals ; Bromodeoxyuridine ; metabolism ; Cell Differentiation ; Cell Proliferation ; Corpus Striatum ; pathology ; Male ; Neurons ; cytology ; Parkinson Disease ; therapy ; Rats ; Rats, Wistar ; Stem Cells ; cytology ; Substantia Nigra ; pathology

Although the mammalian brain has long been thought to be entirely postmitotic, the recent discovery has confirmed an existence of neural stem or progenitor cells in various regions of the adult mammalian brain. Like embryonic stem cells, adult neural progenitor cells possess the capacity of self-renewal and differentiation potential for neurogenesis or gliogenesis. In addition to the subventricular zone and hippocampus where active cell division naturally occurs, adult neural progenitors with neurogenic potential exist in the striatum and the vicinity of dopaminergic neurons in the substantia nigra. Normally, progenitors in those regions proliferate at a low level, and most proliferated cells remain uncommitted. In response to the selective lesion of nigrostriatal dopaminergic pathway by the neurotoxins, such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine, progenitors in the injured areas markedly increase their proliferation rate. Depending upon the magnitude and kinetics of the lesion, neurogenesis and gliogenesis were induced in the lesion sites at varying extents. A large number of growth and neurotrophic factors influence proliferation and/or differentiation of progenitor cells under normal and lesioned conditions. Some factors (epidermal and basic fibroblast growth factors and brain-derived neurotrophic factor) are facilitatory, while others (usually bone morphogenetic proteins) are inhibitory, for controlling division and fate of neuronal or glial progenitors. Expression of endogenous factors and their respective receptors in existing and newborn cells are also subject to be altered by the lesion. These genomic responses are considered to be important elements for the formation of a local molecular niche for a given phenotypic cell regeneration. Taken together, adult neural progenitor cells in the nigrostriatal dopaminergic system have the ability to respond to the lesion to repopulate missing cells. The regenerative neuro- or gliogenesis in situ can, at least in part, endogenously compensate injured neural elements, and achieve a self-repair of neurodegenerative disorders such as Parkinson's disease.
Adult Stem Cells ; physiology ; Animals ; Cell Differentiation ; physiology ; Corpus Striatum ; pathology ; physiopathology ; Humans ; Neurodegenerative Diseases ; physiopathology ; Neuronal Plasticity ; physiology ; Neurons ; cytology ; Parkinson Disease ; physiopathology ; Substantia Nigra ; pathology ; physiopathology

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder characterized by severe loss of substantia nigra dopamine (DA) neurons. The target region of substantia nigra DA neurons is the dorsal striatum. According to the classic model, activation of DA receptors on striatal medium spiny neurons (MSNs) modulates their intrinsic excitability. Activation of D1 receptors makes MSNs in the direct "Go" pathway more excitable, whereas activation of D2 receptors makes MSNs in the indirect "NoGo" pathway less excitable. Therefore increased DA increases the responsiveness of the Go pathway while decreases the responsiveness of the NoGo pathway. Both mechanisms increase motor output. Conversely, diminished DA will favor the inhibitory NoGo pathway. Therefore, DA has direct, "on-line" effect on motor performance. However, in addition to modulating the intrinsic excitability of MSNs "on-line", DA also modulates corticostriatal plasticity, therefore could potentially produce cumulative and long-lasting changes in corticostriatal throughput. Studies in my lab suggest that DA blockade leads to both direct motor performance impairment and D2 receptor dependent NoGo learning ("learned" motor inhibition) that gradually deteriorates motor performance. NoGo learning is experience dependent and task specific. It is different from blocked learning since NoGo learning impairs future performance even after DA is restored. More recent data from my lab suggest that NoGo learning in the absence of DA arises from increased LTP at the indirect pathway corticostriatal synapses and contributes significantly to PD-like motor symptoms. Our data and hypotheses suggest a novel therapeutic strategy for PD that targets directly signaling molecules for corticostriatal plasticity (e.g. the cAMP pathway and downstream signaling molecules) and prevents aberrant plasticity under conditions of DA denervation.
Corpus Striatum ; cytology ; Dopamine ; physiology ; Dopaminergic Neurons ; pathology ; Humans ; Neuronal Plasticity ; Parkinson Disease ; physiopathology ; Receptors, Dopamine D1 ; physiology ; Receptors, Dopamine D2 ; physiology ; Substantia Nigra ; pathology

OBJECTIVETo investigate the effect of Bushen Yanggan Recipe (BSYGR) on the function and morphology of nigrostriatal system in Parkinsonian model rats with long-term levodopa treatment.

METHODSUnilateral Parkinsonian rat models were established by injecting 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta (SNpc) and ventral segmental area (VTA). Animals were randomly divided into four groups, the sham control group, model control group, levodopa group and levodopa plus BSYGR group. The content of striatal dopa (DA), digydroxy-phenyl acetic acid (DOPAC) and homovanilic acid (HVA) or the THmRNA expression level in the midbrain were measured.

RESULTS(1) Levels of striatal DA, DOPAC, HVA, DOPAC/DA, HVA/DA decreased in the model control group by about 90% as compared with those in sham control group (P < 0.05). These parameters in the levodopa group were higher than those in the sham control group, while in the levodopa plus BSYGR group, they were lower than those in the levodopa group (P < 0.01), approaching the levels in the sham control group (P > 0.05). (2) Striatal TH activity in the model group was lower than that in the sham control group significantly, but higher than that in the levodopa group, while in the levodopa plus BSYGR group, it showed a level obviously higher than that in the levodopa group (P < 0.05). (3) Levodopa plus BSYGR group had a higher midbrain THmRNA expression level than that in the levodopa group.

CONCLUSIONBSYGR could effectively reduce the side effects resulting from the long-term treatment of levodopa.

Animals ; Corpus Striatum ; pathology ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; Levodopa ; pharmacology ; Male ; Parkinson Disease ; pathology ; physiopathology ; Phytotherapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley

AIMTo investigate the effect of hyperthermia on apoptosis of cultivated striatum neurons in the rat.

METHODSAfter 30 min hyperthermia in 43 degrees, the Ca2+ concentration, the mitochondria membrane potential of the neuron were detected by Laser Scanning Confocal Microscopy (LSCM). The apoptosis of striatum neurons was detected by TUNEL staining.

RESULTSHeat stress at 43 degrees C for 40 min caused an increase in the Ca2+ concentration of striatum neurons and a decrease in the mitochondria membrane potential of the striatum neurons.

CONCLUSIONThe striatum shows more apoptosis neurons after heat stress.

Animals ; Animals, Newborn ; Apoptosis ; Cells, Cultured ; Corpus Striatum ; cytology ; Heat-Shock Response ; Hot Temperature ; adverse effects ; Membrane Potential, Mitochondrial ; Neurons ; cytology ; pathology ; Rats ; Rats, Wistar

We studied the effect of carbon monoxide (CO)-induced hypoxia on synaptosomal uptake and release of dopamine (DA) in rat striatum. When the rats were intoxicated at a blood level of carboxyhemoglobin (HbCO), 60-70% for 3-4hrs, [3H] DA uptake was inhibited as much as 80% of control activity. This suppressed activity remained as long as 12 hrs after termination of the intoxication. After a week recovery period, the suppressed uptake activity was restored completely. When the rats were intoxicated maintaining a blood level of HbCO at 30-40% for 6-7hrs, the uptake was inhibited to 57% of the control actvity and this suppressed activity was restored within 12hrs. For the rats maintaining a blood level of HbCO at 15-25% for 6-7hrs, uptake inhibition was not shown. Acute CO intoxication(at 60-70% of HbCO for 3-4 hrs) caused an increase in K+-stimulated DA release to 147% of the control value. In conclusion, the diminished uptake and increased release of striatal DA in a CO intoxicated brain would cause an extraneuronal accumulation of DA with depletion of intraneuronal DA level, which may play a role in CO-induced hypoxic cell damage.
Animal ; Carbon Monoxide Poisoning/*complications ; Corpus Striatum/*ultrastructure ; Culture Media ; Dopamine/*metabolism ; Female ; Hypoxia, Brain/chemically induced/*pathology ; In Vitro ; Male ; Rats ; Synaptosomes/*metabolism

The mechanism of chorea underlying nonketotic hyperglycemia was controversial. Serial follow up of brain MRI, 99mTc-ECD SPECT, and 18F-FDG PET in conjunction with clinical observation was done to clarify the pathologic localization. From the functional neuroimages, according to the clinical improvement, the relevant pathology was localized on the lentiform nucleus, mainly on the putamen. In caudate, the mismatch between glucose metabolism and blood flow was observed during and after choreoballistic movement which suggested an important cue to understand the pathogenesis of chorea.
Basal Ganglia* ; Brain ; Chorea ; Corpus Striatum ; Cues ; Fluorodeoxyglucose F18 ; Follow-Up Studies* ; Glucose ; Humans ; Hyperglycemia* ; Magnetic Resonance Imaging ; Metabolism ; Pathology* ; Putamen ; Tomography, Emission-Computed, Single-Photon

OBJECTIVE: To investigate the activation characteristics of microglia (MG) in the rats striatum with MA-induced neurotoxicity. METHODS: Male Wistar rats were divided randomly into control group (n=24) and experimental group (n=24). The rats of experimental group were injected intraperitoneally with MA (15 mg/kg x 8 injections, at 12 hours interval). The rats of control group were administrated with saline. The tissues of striatum of two rat groups were harvested at 0.5 d, 1 d, 2 d, 3 d, 4 d, 5 d, 6 d and 7 d post initial administrations of MA or saline. The structure changes were observed by transmission electron microscopy and CD-11b immunohistochemistry. The ratio of activated MG was calculated and statistically analyzed. RESULTS: In the control group, the morphological characteristics of the MG showed that the cell bodies were small with slender processes, high electronic density nucleus, and fewer organelles known as the "fork-type". In contrast, the MG in the MA-induced neurotoxicity group displayed larger cell body, shorter cell processes or disappeared, lower electronic density nucleus and rich organelles, resembling "bush-like" or "amoeba-like". The ratio of activated MG in control group was below 0.15 at all timepoints, whereas in the experimental group, the ratio of activated MG increased significantly from day 1 to day 7 (P<0.001). CONCLUSION The continuous MA stimulation of the CNS results in prominent MG activation.
Animals ; Corpus Striatum/pathology* ; Immunohistochemistry ; Male ; Methamphetamine/toxicity* ; Microglia/ultrastructure* ; Microscopy, Electron, Scanning ; Random Allocation ; Rats ; Rats, Wistar ; Staining and Labeling ; Time Factors