Research progress on the pathogenesis of attention deficit hyperactivity disorder based on the theory of Dopamine deficits / 中华实用儿科临床杂志

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood, which seriously affects physical and mental health in children.Its etiology and pathogenesis are complex and have not been fully elucidated.Currently, the theory of Dopamine (DA) deficits has been widely recognized and studied in the international academic community.The DA system is considered as the key to the pathogenesis of ADHD.The causes of DA deficits are complex.In addition to the well-established reuptake disorder caused by abnormal DA transporter function, DA deficits are also associated with the activation of DA vesicle cycle enzymatic inactivation, vesicle transport dysfunction, and receptor dysfunction, which are of great significance in analyzing disease pathogenesis and drug development.This article reviews the research on the causes of DA deficits proposed in recent years based on the theory of DA deficits, aiming to provide ideas and references for the research on the pathogenesis of ADHD in China.

Study on predictive role of dopamine transporter imaging in Parkinson′s disease with wearing-off phenomenon / 中华神经科杂志

Objective:To investigate whether the presynaptic dopamine neuronal depletion in different striatal subregions predicts future development of wearing-off (WO) in Parkinson′s disease (PD) patients.Methods:A retrospective longitudinal study included 57 PD patients who were referred to the Department of Neurology of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2019 to September 2020, and completed 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane dopamine transporter (DAT) positron emission tomography scans at the initial evaluation and received dopaminergic drugs for at least 12 months during follow-up. The time of starting dopaminergic drug treatment and the occurrence of WO were recorded. After adjusting for clinical related factors, the predictive value of DAT uptake and related parameters in striatal subregions for WO was evaluated by Cox proportional hazards model. Results:During a median follow-up period of 23 months, 10 patients (18.18%) developed WO. Patients with WO exhibited less DAT uptake in the caudate nucleus and anterior putamen nucleus (0.66±0.52 vs 1.08±0.42, t=2.76, P=0.008 and 0.66±0.20 vs 0.87±0.28, t=2.27, P=0.027 respectively), especially in these subregions contralateral to the less-affected side of the body, compared to those without WO. Cox proportional hazard models revealed that after adjusting for gender, age, course of disease, baseline Unified Parkinson′s Disease Rating Scale Ⅲ score and increment of levodopa equivalent dosage, the lower the DAT uptake of the caudate ipsilateral to the less-affected side of the body ( HR=0.20, 95% CI 0.07-0.63, P=0.006), as well as the lower the DAT uptake of the caudate nucleus and posterior putamen nucleus ( HR=0.28, 95% CI 0.11-0.69, P=0.006 and HR=0.08, 95% CI 0.01-0.64, P=0.018 respectively) and the higher the ratio of putamen/caudate contralateral to the less-affected side of the body ( HR=2.33, 95% CI 1.02-5.33, P=0.045), the higher the risk of WO. Conclusion:The presynaptic dopamine neuronal loss, particularly bilateral caudate nucleus dopaminergic depletion at the early stage, has predictive value of development of WO in PD.

Effect of Modified Xiaoyaosan on Dopamine Transporter in Rats with Hyperprolactinemia / 中国实验方剂学杂志

ObjectiveTo investigate the effect of modified Xiaoyaosan on central dopamine transporter （DAT）/protein kinase C （PKC）-dependent signaling pathway in hyperprolactinemia （HPRL） rats. MethodHPRL rat model was established by chronic combined stress combined with intraperitoneal injection of metoclopramide. Ninety-six rats were randomly divided into six groups， namely， the blank group， model group， western medicine （bromocriptine， 0.001 g·kg-1·d-1） group， and high-， medium-， and low-dose （60， 30， 15 g·kg-1·d-1） modified Xiaoyaosan groups. After 14 days of administration， the serum prolactin （PRL） content was detected by enzyme-linked immunosorbent assay， the expression of tyrosine hydroxylase （TH） in rat hypothalamus by immunohistochemistry， and the protein expression of DAT and PKC in hypothalamus by Western blot. ResultCompared with the blank group， the model group exhibited significantly increased PRL and DAT （P<0.01）， but decreased TH and PKC （P<0.01）. Compared with the model group， bromocriptine and modified Xiaoyaosan at the medium dose significantly lowered the content of PRL （P<0.01）. The modified Xiaoyaosan at the medium and high doses elevated the expression of TH （P<0.05， P<0.01）. The expression levels of PKC in the medium- and low-dose modified Xiaoyaosan groups and the western medicine group were significantly increased （P<0.01）， while the DAT expression levels in the high-， medium-， and low-dose modified Xiaoyaosan groups and the western medicine group were decreased （P<0.01）. ConclusionThe modified Xiaoyaosan is able to up-regulate the expression of TH and down-regulate the level of DAT through PKC-dependent signaling pathway， thereby regulating the PRL.

DRD4 genotyping may differentiate symptoms of attention-deficit/hyperactivity disorder and sluggish cognitive tempo

Objective: Studies to reduce the heterogeneity of attention-deficit/hyperactivity disorder (ADHD) have increased interest in the concept of sluggish cognitive tempo (SCT). The aim of this study was to investigate if the prevalence of two variable-number tandem repeats (VNTRs) located within the 3′-untranslated region of the DAT1 gene and in exon 3 of the dopamine D4 receptor (DRD4) gene differ among four groups (31 subjects with SCT but no ADHD, 146 individuals with ADHD but no SCT, 67 subjects with SCT + ADHD, and 92 healthy controls). Methods: We compared the sociodemographic profiles, neurocognitive domains, and prevalence of two VNTRs in SCT and ADHD subjects versus typically developing (TD) controls. Results: The SCT without ADHD group had a higher proportion of females and lower parental educational attainment. Subjects in this group performed worse on neuropsychological tests, except for psychomotor speed and commission errors, compared to controls. However, the ADHD without SCT group performed significantly worse on all neuropsychological domains than controls. We found that 4R homozygosity for the DRD4 gene was most prevalent in the ADHD without SCT group. The SCT without ADHD group had the highest 7R allele frequency, differing significantly from the ADHD without SCT group. Conclusion: The 7R allele of DRD4 gene was found to be significantly more prevalent in SCT cases than in ADHD cases. No substantial neuropsychological differences were found between SCT and ADHD subjects.

Reduced Uptake on Dopamine Transporter Imaging by Methylphenidate

No abstract available.

Heterogeneous Patterns of Striatal Dopamine Loss in Patients with Young- versus Old-Onset Parkinson's Disease: Impact on Clinical Features

OBJECTIVE: Ample evidence has suggested that age at onset of Parkinson's disease (PD) is associated with heterogeneous clinical features in individuals. We hypothesized that this may be attributed to different patterns of nigrostriatal dopamine loss. METHODS: A total of 205 consecutive patients with de novo PD who underwent 18F-FP-CIT PET scans (mean follow-up duration, 6.31 years) were divided into three tertile groups according to their age at onset of parkinsonian motor symptoms. Striatal dopamine transporter (DAT) availability was compared between the old- (n = 73) and young-onset (n = 66) groups. In addition, the risk of developing freezing of gait (FOG) and longitudinal requirements for dopaminergic medications were examined. RESULTS: The old-onset PD group (mean age at onset, 72.66 years) exhibited more severe parkinsonian motor signs than the young-onset group (52.58 years), despite comparable DAT availability in the posterior putamen; moreover, the old-onset group exhibited more severely decreased DAT availability in the caudate than the young-onset group. A Cox regression model revealed that the old-onset PD group had a higher risk for developing FOG than the young-onset group [hazard ratio 2.523, 95% confidence interval (1.239–5.140)]. The old-onset group required higher doses of dopaminergic medications for symptom control than the young-onset group over time. CONCLUSION: The present study demonstrated that the old-onset PD group exhibited more severe dopamine loss in the caudate and were more likely to develop gait freezing, suggesting that age at onset may be one of the major determinants of the pattern of striatal dopamine depletion and progression of gait disturbance in PD.

Effect of Single-Nucleotide Polymorphisms on Decline of Dopamine Transporter Availability in Parkinson's Disease

BACKGROUND AND PURPOSE: We aimed to determine the association between the annual changes in dopamine transporter (DAT) availability as measured by 123I-ioflupane (123I-FP-CIT) single-photon-emission computed tomography and single-nucleotide polymorphisms (SNPs) known to be risk factors in Parkinson's disease (PD). METHODS: In total, 150 PD patients were included from the Parkinson's Progression Markers Initiative database. Specific SNPs that are associated with PD were selected for genotyping. SNPs that were not in Hardy-Weinberg equilibrium or whose minor allele frequency was less than 0.05 were excluded. Twenty-three SNPs met the inclusion criteria for this study. The Kruskal-Wallis test was used to compare annual percentage changes in DAT availability for three subgroups of SNP. RESULTS: None of the 23 SNPs exerted a statistically significant effect (p < 0.0022) on the decline of DAT availability in PD patients. However, we observed trends of association (p < 0.05) between three SNPs of two genes with the annual percentage change in DAT availability: 1) rs199347 on the putamen (p=0.0138), 2) rs356181 on the caudate nucleus (p=0.0105), and 3) rs3910105 on the caudate nucleus (p=0.0374). A post-hoc analysis revealed that DAT availability was reduced the most for 1) the putamen in the CC genotype of rs199347 (vs. CT, p=0.0199; vs. TT, p=0.0164), 2) the caudate nucleus in the TT genotype of rs356181 (vs. CC, p=0.0081), and 3) the caudate nucleus in the CC genotype of rs3910105 (vs. TT, p=0.0317). CONCLUSIONS: Significant trends in the associations between three SNPs and decline of DAT availability in PD patients have been discovered.

Acute Restraint Stress Augments 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Neurotoxicity via Increased Toxin Uptake into the Brain in C57BL/6 Mice / 神经科学通报·英文版

As an environmental risk factor, psychological stress may trigger the onset or accelerate the progression of Parkinson's disease (PD). Here, we evaluated the effects of acute restraint stress on striatal dopaminergic terminals and the brain metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which has been widely used for creating a mouse model of PD. Exposure to 2 h of restraint stress immediately after injection of a low dose of MPTP caused a severe loss of striatal dopaminergic terminals as indicated by decreases in the dopamine transporter protein and dopamine levels compared with MPTP administration alone. Both striatal 1-methyl-4-phenylpyridinium ion (MPP) and MPTP concentrations were significantly increased by the application of restraint stress. Striatal monoamine oxidase-B, which catalyzes the oxidation of MPTP to MPP, was not changed by the restraint stress. Our results indicate that the enhanced striatal dopaminergic terminal loss in the stressed mice is associated with an increase in the transport of neurotoxin into the brain.

Atypical parkinsonism with marked asymmetry due to a superimposed developmental venous anomaly

@#Intracranial developmental venous anomalies (DVAs) are the most common cerebral vascular malformation and are usually asymptomatic. Movement disorders are rarely associated with DVAs within basal ganglia regions. We report a case of markedly asymmetric parkinsonism due to unilateral DVA in the basal ganglia, which occurred together with symmetrical nigrostriatal dopaminergic deficits. A 57-year-old woman presented with resting tremor in the right hand lasting for 6 months. She also experienced problems with gait and started falling while walking one month ago. The neurological examination found a resting tremor in the right hand and moderate rigidity and bradykinesia in the right extremities. She reported light headedness on standing up. The patient displayed minimal response to treatment with 300 mg levodopa. The FP-CIT PET scan revealed symmetrical decrease of radiotracer uptake in bilateral basal ganglia. Brain MRI and cerebral angiography identified a large DVA draining the basal ganglia, thalamus, and surrounding deep white matter in the left side. Conclusion: A DVA may contribute to the prominent asymmetrical manifestation in our patient, in combination with symmetrical dopaminergic loss from neurodegenerative Parkinsonian syndrome. A marked asymmetry in patients with signs of atypical Parkinsonism can be a clue for further imaging investigation to exclude superimposed structural lesions such as DVAs.

Role of Positron Emission Tomography as a Biologic Marker in the Diagnosis of Primary Progressive Aphasia: Two Case Reports / 대한핵의학회잡지

Primary progressive aphasia (PPA) is a heterogenous neurodegenerative disorder characterized by declining language and speech ability. Various underlying neuropathologies can induce PPA, and the disorder is divided into three subtypes—progressive non-fluent aphasia, semantic variant aphasia, and logopenic aphasia—according to clinical features. Accurate disease classification and prediction of underlying diseases are necessary for appropriate treatment, but proper use of imaging tests is important because clinical information alone often makes it difficult to make accurate decisions. Because there is a characteristic metabolic pattern according to the subtypes, F-18 fluorodeoxyglucose positron emission tomography (PET) can indicate subtype classification. In addition, PETstudies for imaging amyloid or dopamine transporters play an important role in demonstrating underlying disease. The present case showed that PET imaging studies are useful in diagnosis and could be used as a biomarker in PPA.

Abuse-related effects of synthetic cathinones:importance of DAT/SERT relationships / 中国药理学与毒理学杂志

OBJECTIVE Wide spread abuse of synthetic cathinones found in bath salts preparations has resulted in regulation of some cathinones internationally. Chemists skirt these laws by altering the chemical structures of first-generation cathinones (ie, MDPV, methylone, and mephedrone), resulting in second-generation cathinones (eg, α-PVP, α-PPP, MDPPP, and MDPBP). Although MDPV is a more effective reinforcer than cocaine, little is known about the reinforcing effectiveness of second-generation cathinones. To test the hypothesis that synthetic cathinones with higher selectivity for DAT relative to SERT are more effective reinforcers. METHODS Monoamine transporter inhibition was determined using synaptosomes prepared from rat brains. The relative reinforcing effectiveness of intravenously self-administered MDPV, MDPBP, MDPPP, α-PVP, α-PPP, and cocaine were directly compared through evaluations of ① dose- response curves under a progressive ratio (PR) schedule of reinforcement and ② demand curves obtained for each drug in male Sprague-Dawley rats. RESULTS Rank order selectivity for DAT/SERT was α-PVP>MDPV>α-PPP≈MDPBP>MDPPP>cocaine. Comparisons of the maximum number of infusions obtained under a PR schedule of reinforcement (α-PVP>MDPV>α-PPP>MDPBP≈MDPPP>cocaine) and the essential value obtained for each drug in demand analyses (α-PVP>MDPV>α-PPP≈MDPBP≈MDPPP>cocaine) suggest relative reinforcing effectiveness is related to DAT/SERT selectivity. CONCLUSION These data provide evidence that DAT/SERT selectivity accounts for select synthetic cathinones functioning as more effective reinforcers than cocaine and may predict the abuse-related effects of novel synthetic cathinones in humans.

Association between methylation status of CpG island in DAT1 and DRD4 genes and clinical symptoms of ADHD / 中国神经精神疾病杂志

Objective To investigate the correlation of methylation status in DA T1 and DRD4 genes and severity of clinical manifestations in ADHD patients.Methods One hundrd eleven DSM-Ⅳ defined ADHD patients were enrolled in this study and the demographic data were collected.Clinical symptoms were also assessed by Attention Deficit Hyperactivity Disorder Rating Scale-Ⅳ Home Version (ADHD-RS-Ⅳ) and self-developed Oppositional Defiant Disorder (ODD) rating scale.Bisulfite genomic sequencing (BGS) was used to detect the methylation status of every CpG site in DA T1 and DRD4 promoter CpG island in peripheral venous blood.Results The DNA methylation level in total CpG island for DA T1 was higher in individuals without depression,anxiety or ADHD family history compared to individuals with above family histories (P＜0.05).The differences on methylation levels for DA T1 and DRD4 were not significant between high and low ADHD-RS-Ⅳ total score (≤30 vs.＞30),ADHD-RS-Ⅳ inattention score (≤ 17 vs.＞17),and ADHD-RS-Ⅳ hyperactivity/impulsivity score (≤13 vs.＞13) subgroups (all P＜0.05).The methylation levels in total CpG island in DA T1 was higher in individuals whose ODD score were ＜9 compared to those whose ODD score were ≥9 (P＜0.05).Conclusions Methylation status of CpG island in DAT1 may influence the severity of oppositional defiant symptom in ADHD patients,which is correlated with depression,anxiety and ADHD family histories.

Clinical and neuroimaging features of frontotemporal dementia with parkinsonism linked to chromosome 17 / 中华神经科杂志

Objective To explore the clinical and neuroimaging features of a frontotemporal dementia with parkinsonism linked to chromosome 17 ( FTDP-17 ) pedigree caused by mutation of microtubule-associated protein tau ( MAPT) gene.Methods The proband and one patient from a FTDP-17 pedigree were assessed through standardized clinical evaluation , neuropsychology assessment , video-electroencephalogrom ,MRI, genetic sequencing , as well as 18 F fludeoxyglucose ( FDG) SPECT for brain metabolism and 11 C 2β-carbomethoxy-3β-( 4-fluoro ) tropane ( CFT ) PET for dopamine transporter ( DAT ) distribution, respectively.Results A FTDP pedigree with 15 patients (6 still alive) was recruited to this study.The proband and one affected patient were genotyped and confirmed as MAPT c .1788T>G mutation. Parkinsonism was the first symptom for both two patients . Personality, speech changes and dementia accompanied with brain atrophy were developed at the later stage in one patient .The 18 F FDG SPECT studies illustrated asymmetric hypometabolism of the temporal , frontal lobes and basal ganglia in two patients . Regarding to the 11 C CFT PET, one affected patient showed asymmetric decreased uptake of tracer in basal ganglia regions.Conclusions FTDP-17 can display a confusingly broad clinical phenotype , with the parkinsonism as the first symptom . Brain glucose metabolism and DAT distribution could be potential biomarkers in early diagnosis of FTDP-17.

Longitudinal Decline of Striatal Subregional ¹⁸FFP-CIT Uptake in Parkinson's Disease / 대한핵의학회잡지

PURPOSE: Dopamine transporter imaging is suggested to be a useful imaging biomarker for Parkinson's disease (PD) progression and monitoring drug effects.We investigated the longitudinal decline characteristics of striatal [¹⁸F]FP-CIT uptake in PD.METHODS: We retrospectively reviewed 35 PD patients and 9 non-PD patients. All patients underwent [¹⁸F]FP-CIT PET at the initial diagnosis and follow-up. PET images were spatially normalized and analyzed with eight striatal and one occipital VOI templates. We measured the specific to non-specific binding ratio (SNBR) of the striatal subregions and calculated the absolute annual reduction (AAR) and relative annual reduction (%RAR) of the SNBRs.RESULTS: Total striatal SNBRs in PD patients were significantly lower than those in non-PD patients, with the most significant difference in the posterior putamen. Both AAR (0.26 ± 0.14 vs. 0.09 ± 0.19, p < 0.05) and %RAR (6.9 ± 3.5 vs. 1.2 ± 2.7, p < 0.001) of total striatal SNBRs were significantly greater in PD than non-PD patients. There were no significant differences in the AAR and %RAR of total striatal SNBRs between elderly and young onset PD. The AARs of the posterior putamen were higher in early PD than in advanced PD. Conversely, the %RARs were not significantly different between early and more advanced PD. The disease duration was significantly negatively correlated with the AAR but not with the %RAR of the posterior putamen.CONCLUSIONS: The longitudinal decline of striatal [¹⁸F]FP-CIT uptake in PD was nonlinear and significantly faster than that in non-PD, with a different rate of decline among the striatal subregions.

Clinical Features Indicating Nigrostriatal Dopaminergic Degeneration in Drug-Induced Parkinsonism

OBJECTIVE: Patients with drug-induced parkinsonism (DIP) may have nigrostriatal dopaminergic degeneration. We studied the clinical features that may indicate nigrostriatal dopaminergic degeneration in patients with DIP. METHODS: Forty-one DIP patients were classified into normal and abnormal [¹⁸F] FP-CIT scan groups. Differences in 32 clinical features and drug withdrawal effects were studied. RESULTS: Twenty-eight patients had normal (Group I) and 13 patients had abnormal (Group II) scans. Eight patients of Group I, but none of Group II, had taken calcium channel blockers (p = 0.040). Three patients of Group I and six of Group II had hyposmia (p = 0.018). After drug withdrawal, Group I showed greater improvement in Unified Parkinson's Disease Rating Scale total motor scores and subscores for bradykinesia and tremors than Group II. Only hyposmia was an independent factor associated with abnormal scans, but it had suboptimal sensitivity. CONCLUSION: None of the clinical features were practical indicators of nigrostriatal dopaminergic degeneration in patients with DIP.

Evaluation of the therapeutic efficacy for methamphetamine dependence through visual digital neural molecular imaging techniques / 中华行为医学与脑科学杂志

Objective To evaluate the therapeutic effects of methamphetamine (MA) dependence and the repairment of DA neuronal function by SPECT corpus striatum DAT visual digital neural molecular imaging techniques.Methods 25 MA dependent patients (BPRS score ≥ 35) were treated by self-designed treatment program for more than 6 months.The clinical therapeutic effects were scored with reducing rate of BPRS.MA dependent patients were examined by SPECT corpus striatum DAT imaging before and after treatment,while healthy volunteers were examined only once.The SPECT corpus striatum DAT images were analyzed visually and quantitatively.Results The reducing rate of BPRS showed that the total effective rate was 80.0％.Visual analysis of SPECT corpus striatum DAT images showed that the distribution of DAT in the corpus striatum was regionally reduced or defected in various degrees before treatment,and was significantly increased after treatment.Quantitative analysis showed that the bilateral striatal V ((19.26 ± 2.85) cm3),m((20.22±2.99) g) and Ra(4.78±0.79) ％) of MA dependent patients were significantly lower compared with those of the healthy volunteers(respectively (35.39±4.42) cm3,(37.16±4.64) g and (7.93± 0.86) ％) (all P＜ 0.01) before treatment and were significantly improved (P＜ 0.01) after treatment (V:(22.80±4.28) cm3,m:(23.93± 4.49) g and Ra:(5.64 ± 0.99) ％) with a 76.0％ corpus striatum DAT improvement rate.However,the bilateral striatal V,m and Ra of MA dependent patients after treatment were still lower than those of the healthy volunteers (P＜0.01).There was no significant difference between the striatal DAT improvement rate and the BPRS reduction rate (P＞ 0.05).Conclusion SPECT corpus striatum DAT visual digital neural molecular imaging techniques are reliable in the evaluation of the treatment programs for MA dependence and the repair of DA neuronal function.

Functional Regulation of Dopamine D₃ Receptor through Interaction with PICK1

PICK1, a PDZ domain-containing protein, is known to increase the reuptake activities of dopamine transporters by increasing their expressions on the cell surface. Here, we report a direct and functional interaction between PICK1 and dopamine D₃ receptors (D₃R), which act as autoreceptors to negatively regulate dopaminergic neurons. PICK1 colocalized with both dopamine D₂ receptor (D₂R) and D₃R in clusters but exerted different functional influences on them. The cell surface expression, agonist affinity, endocytosis, and signaling of D₂R were unaffected by the coexpression of PICK1. On the other hand, the surface expression and tolerance of D₃R were inhibited by the coexpression of PICK1. These findings show that PICK1 exerts multiple effects on D₃R functions.

Experimental animal models in attention deficit hyperactivity disorder / 中华行为医学与脑科学杂志

Objective To review the advantages and disadvantages of common attention deficit hyperactivity disorder(ADHD) animal models,published in 2000-2014 at home and abroad,with an attempt to provide new ideas for the future study of the pathogenesis in ADHD.Methods Major online database including CNKI,Wan Fang databases,OVID,Pubmed databases were searched in January 2015,using the key wordsattention deficit hyperactivity disorder, animal modelsand so on,to analysis the advantages and disadvantages of each type of experimental animal models and research value in ADHD.Results Totally 29 studies were enrolled,and the analysis show that the current commonly used experimental animal models of ADHD are spontaneously hypertensive rats,dopamine transporter gene knockout mice,lack of mutant mice model,neonatal 6 hydroxy dopamine damage of juvenile rat model,neonatal hypoxic rats model,X-ray irradiation injury model of rat hippocampus and other brain tissue damage model and isolated feeding model,and each animal model has the advantages,disadvantages and special research value of the pathogenesis of ADHD.Conclusion The specific pathogenesis of ADHD is unclear,but the neuroendocrine changes especially HPA axis attracted much attention in recent years.this paper summarizes the research at home and abroad comparison of several common animal models of ADHD.neuroendocrine changes in SHR and ADHD children have a certain degree of consistency in HPA axis,looking for ADHD children and SHR in neuroendocrine aspects of consistency is likely to open a new path to search the pathogenesis in ADHD.

DRD4/DAT1 mRNA expression in attention deficit hyperactivity disorder children before and after methylphenidate treatment / 中华行为医学与脑科学杂志

Objective To investigate mRNA expression level changes of dopamine transporter gene (DAT1) and dopamine receptor gene(DRD4) in attention deficit hyperactivity disorder(ADHD) children's peripheral blood before and after methylphenidate treatment,and to explore associations between the mRNA expression level and symptom severity,as well as methylphenidate response.Methods Forty five ADHD children by DSM-Ⅳ diagnostic criteria,aged six to fifteen years old participated in a six-week drug titration treatment of metbylphenidate.ADHD-RS-Ⅳ Home Version, WCST and VCPT were used to evaluate the ADHD clinical symptoms and cognitive functions.RNA Simple Total RNA Kit was used to extract the total RNA.After reverse transcription, the obtained c-DNA was used in the following qRT-PCR to evaluate relative mRNA expression of the candidate genges before and after medication.Results The DRD4 mRNA relative expression level after taking methylphenidate was significantly higher than that before methylphenidate treatment (0.23 ± 0.23 vs 0.16± 0.18, P =0.041).There was no significant difference between DAT1 mRNA relative expression level before (0.43 ± 0.40) and after (0.43±0.40) methylphenidate treatment.No significant difference was found on eitber basal DAT1/DRD4 mRNA expression or fold change of DAT1/DRD4 mRNA expression before and after medication between methylphenidate treatment responders and non-responders groups.There was a positively significant correlation between baseline DRD4 mRNA relative expression level and erroneous T score of CPT(r=0.424, P=0.025) , however, no other statistically significant correlation was found between basal DRD4 mRNA relative expression level and ADHD-RS-Ⅳ total score,WCST conceptual level, CPT missing T score, and CPT reaction T sco~ (all P＞0.05).There was also no statistical significant correlation between basal DAT1 mRNA relative expression level and ADHD-RS-Ⅳ total score,WCST conceptual level,and CPT T scores(all P＞0.05).Conclusion DRD4 gene function may be increased after methylphenidate treatment and play an important role in impulsivity behavior of ADHD.Therefore, DRD4 mRNA expression level might be a biomarker for ADHD diagnosis and a predicting indicator of drug efficacy.

Effect of Electroacupuncture on Striatal D1R and DAT Expressions in Cerebral Ischemia-reperfusion Rats / 上海针灸杂志

ObjectiveTo investigate the effects of dopamine D1 receptor (D1R) tool drugs and combined acupuncture and medicine on striatal expressions of D1R and dopamine transporters (DAT) in middle cerebral artery occlusion (MCAO)-reperfusion rats.MethodForty-seven male SD rats were randomly grouped, used to make a model and given corresponding interventions. The materials were taken and fixed six hrs later. Striatal D1R and DAT expressions were detectedby an immunohistochemical method in different groups.ResultThe neurological deficit score was significantly higher in the model group than in the blank group. Electroacupuncture treatment decreased the score significantly (P0.05). DAT expression was significantly down-regulated in the other groups compared with the model group (P0.05).ConclusionCerebral ischemia-reperfusion can result in high D1R and DAT expressions in rat striatum on the ischemic side. Electroacupuncture, D1R antagonists and a combination of the two can significantly down-regulate D1R expression and have a protective effect on the brain. The effects of electroacupuncture and D1R antagonists can not be added to each other. D1R signaling pathway may be one of ways by which electroacupuncture produces a protective effecton the brain.