The etiology of nervous system diseases is complicated, posing significant harm to patients and often resulting in poor prognoses. In recent years, the role of dopaminergic system in nervous system diseases has attracted much attention, and its complex regulatory mechanism and therapeutic potential have been gradually revealed. This paper reviews the role of dopaminergic neurons, the neurotransmitter dopamine, dopamine receptors and dopamine transporters in neurological diseases (including Alzheimer's disease, Parkinson's disease and schizophrenia), with a view to further elucidating the disease mechanism and providing new insights and strategies for the treatment of neurological diseases.
Humans ; Dopamine/metabolism* ; Nervous System Diseases/physiopathology* ; Parkinson Disease/physiopathology* ; Receptors, Dopamine/metabolism* ; Dopaminergic Neurons/physiology* ; Dopamine Plasma Membrane Transport Proteins/metabolism* ; Alzheimer Disease/physiopathology* ; Schizophrenia/physiopathology* ; Animals

OBJECTIVES: To investigate the effects of early life intervention with Bifidobacterium bifidum BD-1 (B. bifidum BD-1) on hyperactivity in a female mouse model of attention deficit hyperactivity disorder (ADHD) and explore the underlying mechanisms. METHODS: Eight newborn female Wistar-Kyoto (WKY) rats and 6 spontaneous hypertensive rats (SHRs) were gavaged with saline and another 6 SHRs were gavaged with B. bifidum BD-1 (10⁹ CFU) daily for 3 weeks. Open field test of the rats was conducted at 7 weeks, and fecal samples were collected at weaning (3 weeks) and at 7 weeks for 16S rRNA sequencing. Immunofluorescent staining was used to detect dopamine transporter (DAT) and tyrosine hydroxylase (Th) levels in the striatum and activated microglia in the prefrontal cortex. Treg cells in the mesenteric lymph nodes, spleen and blood were analyzed using flow cytometry. RESULTS: The SHRs traveled a significantly greater distance in open fields test than WKY rats, and this behavior was significantly attenuated by B. bifidum BD-1 intervention. The expression of DAT and Th in the striatum was significantly lower in the SHRs than in WKY rats, while B. bifidum BD-1 treatment obviously increased Th levels in the SHRs. B. bifidum BD-1 intervention significantly deceased the number of activated microglia and increased Treg cell counts in the spleen of SHRs. The treatment also enhanced α diversity in gut microbiota of the SHRs and resulted in a decreased Firmicutes/Bacteroidota ratio, more active Muribaculaceae growth, and suppression of Clostridia_UCG-014 proliferation. CONCLUSIONS Early life intervention with B. bifidum BD-1 alleviates hyperactivity in female SHRs by modulating the gut microbiota and peripheral immune response, suppressing neuroinflammation and improving dopaminergic system function. These findings provide evidence for early prevention strategies and support the development and application of psychobiotics for ADHD.
Animals ; Female ; Rats ; Rats, Inbred WKY ; Rats, Inbred SHR ; Attention Deficit Disorder with Hyperactivity/therapy* ; Bifidobacterium bifidum ; Probiotics/therapeutic use* ; Dopamine Plasma Membrane Transport Proteins/metabolism* ; Tyrosine 3-Monooxygenase/metabolism* ; Gastrointestinal Microbiome ; Disease Models, Animal

To investigate the effect of Rehmanniae Radix on depression-like behavior and monoamine neurotransmitters of chronic unpredictable mild stress(CUMS) model rats. CUMS combined with isolated feeding was used to induce the depression model of rats. The depression-like behavior of rats was evaluated by sucrose preference test, open field test, and forced swim test. Hematoxylin-Eosin(HE) staining was used to investigate the pathological changes of neurons in the CA1 and CA3 area of hippocampus. Ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS) was used to detect the contents of 5-hydroxytryptamine(5-HT), 5-hydroxyindoleacetic acid(5-HIAA), dopamine(DA), 3,4-dihydroxyphenylacetic acid(DOPAC), homovanillic acid(HVA), norepinephrine(NE), and 3-methoxy-4-hydroxyphenyl glycol(MHPG) in rats. Western blot was used to detect the protein expressions of tryptophan hydroxylase 2(TPH2), serotonin transporter(SERT), and monoamine oxidase A(MAO-A) in the hippocampus of rats. Compared with the normal group, depressive-like behavior of rats was obvious in the model group. The arrangements of neurons in the CA1 and CA3 area of hippocampus were loose and disorderly. The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in the hippocampal area were decreased(P<0.01). The protein expression of TPH2 was decreased(P<0.01), but those of SERT and MAO-A were increased(P<0.01). In the Rehmanniae Radix groups with 1.8 g·kg~(-1) and 7.2 g·kg~(-1), the depression-like behavior of CUMS rats and pathological changes of neurons in CA1, CA3 area of hippocampus were improved. The protein expression of TPH2(P<0.05, P<0.01) was increased, and those of SERT and MAO-A were down-regulated(P<0.05, P<0.01). The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in hippocampus were increased(P<0.05, P<0.01). The changes in DA, DOPAC, HVA, DA/(DOPAC +HVA), NE, DHPG, and NE/DHPG were not statistically significant. The results suggested that Rehmanniae Radix improved depression-like behavior of CUMS rats, and the mechanism might be related to the regulation of synthesis, transportation, and metabolism of 5-HT neurotransmitter in the hippocampus.
3,4-Dihydroxyphenylacetic Acid/pharmacology* ; Animals ; Antidepressive Agents/therapeutic use* ; Chromatography, Liquid ; Depression/drug therapy* ; Disease Models, Animal ; Dopamine ; Eosine Yellowish-(YS)/pharmacology* ; Hematoxylin/pharmacology* ; Hippocampus/metabolism* ; Homovanillic Acid/pharmacology* ; Hydroxyindoleacetic Acid/metabolism* ; Methoxyhydroxyphenylglycol/pharmacology* ; Monoamine Oxidase/metabolism* ; Neurotransmitter Agents/metabolism* ; Norepinephrine/pharmacology* ; Plant Extracts ; Rats ; Rehmannia/chemistry* ; Serotonin/metabolism* ; Serotonin Plasma Membrane Transport Proteins/pharmacology* ; Stress, Psychological/metabolism* ; Tandem Mass Spectrometry ; Tryptophan Hydroxylase/metabolism*

OBJECTIVETo investigate the mRNA expression of dopamine receptor D2 (DRD2) and dopamine transporter (DAT) in peripheral blood lymphocytes before and after treatment in children with tic disorder (TD).

METHODSRT-PCR was used to measure the mRNA expression of DRD2 and DAT in peripheral blood lymphocytes before and after treatment in 60 children with TD. The correlations between mRNA expression of DRD2 and DAT and the severity of TD were analyzed. Sixty healthy children served as the control group.

RESULTSBefore treatment, the children with TD had a significant increase in the mRNA expression of DRD2 and DAT compared with the control group (P<0.05). After 3 months of treatment with oral aripiprazole, the mRNA expression of DRD2 decreased significantly (P<0.05), while that of DAT showed no significant changes in children with TD. In the children with moderate or severe TD, the mRNA expression of DRD2 was positively correlated with Yale Global Tic Severity Scale (YGTSS) score (P<0.05). In the children with moderate TD, the mRNA expression of DAT was positively correlated with YGTSS score (P<0.05).

CONCLUSIONSIn children with TD, the mRNA expression of DRD2 in peripheral blood lymphocytes can be used as one of the indicators for diagnosing TD, assessing the severity of TD, and evaluating clinical outcomes.

Adolescent ; Child ; Child, Preschool ; Dopamine Plasma Membrane Transport Proteins ; genetics ; Female ; Humans ; Lymphocytes ; metabolism ; Male ; RNA, Messenger ; blood ; Receptors, Dopamine D2 ; genetics ; Tic Disorders ; drug therapy ; metabolism ; mortality

A double toxin-double lesion strategy is well-known to generate a rat model of striatonigral degeneration (SND) such as multiple system atrophy-parkinsonian type. However, with this model it is difficult to distinguish SND from Parkinson's disease (PD). In this study, we propose a new rat model of SND, which is generated by simultaneous injection of 6-hydroxydopamine into the medial forebrain bundle and quinolinic acid into the striatum. Stepping tests performed 30 min after intraperitoneal L-dopa administration at 6 weeks post-surgery revealed an L-dopa response in the PD group but not the SND group. Apomorphine-induced rotation tests revealed no rotational bias in the SND group, which persisted for 2 months, but contralateral rotations in the PD group. MicroPET scans revealed glucose hypometabolism and dopamine transporter impairment on the lesioned striatum in the SND group. Tyrosine hydroxylase immunostaining in the SND group revealed that 74.7% of nigral cells on the lesioned side were lost after lesion surgery. These results suggest that the proposed simultaneous double toxin-double lesion method successfully created a rat model of SND that had behavioral outcomes, multitracer microPET evaluation, and histological aspects consistent with SND pathology. This model will be useful for future study of SND.
Animals ; Apomorphine/pharmacology ; Behavior, Animal/drug effects ; Corpus Striatum/drug effects/pathology ; Disease Models, Animal ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Glucose/metabolism ; Injections, Intraperitoneal ; Levodopa/pharmacology ; Male ; Medial Forebrain Bundle/drug effects/pathology ; Oxidopamine/*toxicity ; Parkinson Disease/metabolism/pathology ; Positron-Emission Tomography ; Quinolinic Acid/*toxicity ; Rats ; Rats, Wistar ; Striatonigral Degeneration/*chemically induced/metabolism/pathology ; Touch/drug effects

Sporadic spastic paraplegia (SSP) and hereditary spastic paraplegia (HSP) belong to a clinical and genetically heterogeneous group of disorders characterized by progressive spasticity and weakness in the lower extremities. The symptoms are associated with pyramidal tract dysfunction and degeneration of the corticospinal tracts. Parkinsonism is uncommon in SSP/HSP patients. However, both disorders are associated with damage to the nigrostriatal dopaminergic system. In the present study, the clinical features of patients with SSP/HSP were investigated, and nigrostriatal dopaminergic binding potential was assessed using dopamine transporter (DAT) single-photon emission computer tomography (SPECT). Nine patients with spastic paraplegia participated in the present study. The subjects underwent DAT SPECT using the agent [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato (3-)-N2,N20,S2,S20]oxo-[IR-(exo-exo)])-[99mTc]technetium ([99mTc]TRODAT-1). The [99mTc]TRODAT-1 SPECT images of five patients appeared normal, whereas the images of four patients revealed reduced striatal ligand uptake. Among the four patients with reduced uptake, two had parkinsonism, and one exhibited periodic limb movements and restless leg syndrome. Our DAT SPECT imaging study shows that reduced DAT density may be observed in patients with parkinsonism. The results of the present study offer an explanation for the spectrum of spastic paraplegia symptoms and the progression of the disorder.
Adult ; Aged ; Brain/*radionuclide imaging ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Female ; Humans ; Male ; Middle Aged ; Organotechnetium Compounds/diagnostic use ; Paraplegia/diagnosis/genetics/*radionuclide imaging ; Parkinsonian Disorders/complications/genetics/*radionuclide imaging ; Pyramidal Tracts ; Radiopharmaceuticals/diagnostic use ; Spastic Paraplegia, Hereditary/diagnosis/genetics/*radionuclide imaging ; Tomography, Emission-Computed, Single-Photon

OBJECTIVETo observe the effect of Bushen Huoxue Granule (BHG) on dopamine (DA) neurotransmitter and dopamine transporter (DAT) in the brain of patients with Parkinson's disease (PD) as an adjunctive therapy.

METHODSNinety-four PD patients were randomly assigned to two groups, 47 in each group. Madopar was given to all as the basic treatment group. The placebo was given to those in the control group while BHG was given to those in the treatment. The therapeutic course for all was three months. Before and after treatment DA levels in the brain of patients were detected by encephalofluctuograph (EFG) technique. Changes of DAT in the striatum of patients in the treatment group were detected by positron emission tomography (PET) and region of interest (ROI) analysis.

RESULTS(1) Before treatment the DA level was lower in the two groups than the normal value, showing significant difference (P < 0.01), but with no significant difference between the two groups (P > 0.05). After treatment the DA level obviously increased in the two groups, showing significant difference from that before treatment (P < 0.01). No significant difference existed in the DA level in the two groups when compared with the normal value (P > 0.05), but with significant difference between the two groups (P < 0.05). Better results were obtained in the treatment group than in the control group. (2) The DAT radioactive accumulation inside the striatum increased obviously in the treatment group after treatment. ROI analysis showed the total ratio of striatum/cerebellum before and after treatment was 1.86 +/- 0.32 and 2.61 +/- 0.53 respectively, showing statistical difference (P < 0.05).

CONCLUSIONBHG could improve the DA level of PD patients, and increasing DAT contents in the striatum, thus playing a role in effectively treating PD.

Aged ; Brain ; metabolism ; Dopamine ; metabolism ; Dopamine Plasma Membrane Transport Proteins ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease ; drug therapy ; metabolism ; Phytotherapy

BACKGROUNDParaquat (PQ; 1,1'-dimethyl-4,4'-bipyridinium), a widely used herbicide, has been repeatedly suggested as a potential etiologic factor for the development of Parkinson's disease (PD), owing to its structural similarity to the known dopaminergic neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This study aimed to observe the influence of paraquat on nigrostriatal dopaminergic neurons in C57BL/6 mice.

METHODSA total of 24 male C57BL/6 mice were assigned randomly to 3 groups: control group (treated by saline), PQ treated group, and MPTP treated group. Mice in PQ treated group were taken orally with PQ (10 mg/kg) daily for four months. Locomotor activity was measured. 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 tyrosine hydroxylase (TH) positive neurons were detected by using immunohistochemistry. At the same time, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and the content of malondialdehyde (MDA) in substantia nigra were measured by spectrophotometry. mRNA expression of dopamine transporter (DAT) in dopaminergic neurons of substantia nigra was also determined by reverse transcription (RT)-PCR technique.

RESULTSLocomotor activities were significantly impaired in the PQ treated group. Level of DA and its metabolites levels in the striatum were declined. The activities of SOD and GSH-PX were decreased, and the content of MDA was increased in PQ treated mice compared with that in control group. Numbers of TH positive neurons and the mRNA expression of DAT in substantia nigra of mice were also decreased after PQ taken orally for four months.

CONCLUSIONSThe present study suggests that chronic oral administration of PQ could trigger dopaminergic neuron degeneration. Oxidative stress could be involved in the pathogenic mechanism of PD induced by PQ.

Administration, Oral ; Animals ; Behavior, Animal ; drug effects ; Corpus Striatum ; drug effects ; Dopamine ; analysis ; metabolism ; Dopamine Plasma Membrane Transport Proteins ; analysis ; genetics ; Glutathione Peroxidase ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Oxidative Stress ; Paraquat ; toxicity ; Parkinson Disease ; etiology ; RNA, Messenger ; analysis ; Substantia Nigra ; drug effects ; Superoxide Dismutase ; metabolism

OBJECTIVETo explore the mechanism of electroacupuncture scalp point-through-point therapy in the treatment of Parkinson's disease.

METHODSThirty-six Wistar rats were randomly divided into a normal group, a sham-operation group, a model group and a point-through-point therapy group. 6-()HDA was injected into left striatum to made lateralization Parkinson's disease rat model. The point-through-point therapy group was treated with electroacupuncture at "Baihui" (GV 20 )-through-"Taiyang" (EX-NH 5), once each day, 6 days constituting one course, for 2 courses, and the rats of other groups were not treated. HE staining method was used for observation of the histo-morphologic changes of the substantia nigra neurons, and RT-PCR for the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) mRNAs.

RESULTSThe expressions of TH mRNA (1.22 +/- 0. 19) and DAT mRNA (0.62-0.11) in the point-through-point therapy group were significantly higher than (0.65 +/- 0.17) and (0.41 +/- 0.08) in the model group, respectively (all P < 0.05). As compared with the model group, the number of neurons in the substantia nigra increased and degeneration of the neurons relieved in the point-through-point therapy group.

CONCLUSIONThe electroacupuncture scalp point-through-point therapy can increase expressions of TH mRNA and DAT mRNA in the substantia nigra in the Parkinson's disease model rat, and promote synthesis and reuptake of dopamine, hence Parkinson's disease is cured.

Acupuncture Points ; Animals ; Disease Models, Animal ; Dopamine Plasma Membrane Transport Proteins ; genetics ; metabolism ; Electroacupuncture ; Female ; Gene Expression ; Humans ; Male ; Parkinson Disease ; genetics ; metabolism ; therapy ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Substantia Nigra ; metabolism ; Tyrosine 3-Monooxygenase ; genetics ; metabolism

This study was conducted to evaluate the applicability of 99mTc-2beta-[ N, N'-bis (2-mercaptoethyl) ethylenediamino]methyl,3beta(4-chlorophenyl)tropane(TRODAT-1) dopamine transporter(DAT) SPECT imaging in children with autism, and thus to provide an academic basis for the etiology, mechanism and clinical therapy of autism. Ten autistic children and ten healthy controls were examined with 99mTc-TRODAT-1 DAT SPECT imaging. Striatal specific uptake of 99mTc-TRODAT-1 was calculated with region of interest analysis according to the ratics between striatum and cerebellum [(STR-BKG)/BKG]. There was no statistically significant difference in semiquantitative dopamine transporter between the bilateral striata of autistic children (P=0.562), and between those of normal controls (p=0.573); Dopamine transporter in the brain of patients with autism increased significantly as compared with that in the brain of normal controls (P=0.017). Dopaminergic nervous system is dysfunctioning in the brain of children with autism, and DAT 99mTc-TRODAT-1 SPECT imaging on the brain will help the imaging diagnosis of childhcod autism.
Autistic Disorder ; diagnostic imaging ; metabolism ; Brain ; diagnostic imaging ; metabolism ; Child ; Child, Preschool ; Dopamine Plasma Membrane Transport Proteins ; metabolism ; Humans ; Male ; Organotechnetium Compounds ; Tomography, Emission-Computed, Single-Photon ; Tropanes