[Mathematical cognitive function in children with attention deficit hyperactivity disorder: a behavior and event-related potential study].

OBJECTIVE: To explore the mathematics cognitive function of children with attention deficit hyperactivity disorder and explore neural mechanisms with event-related potential(ERP) and behaviors. METHODS: Behavior data and ERP elicited by performing mental calculation tasks were recorded in 27 children with ADHD and 29 normal controls from July to October 2012 at Third Affiliated Hospital of Soochow University.The differences of behaviors and N2 component of ERP were compared and analyzed. RESULTS: The reaction time of the children with ADHD were longer than the control group in addition, subtraction and multiplication ((949 ± 144) vs (829 ± 166) ms, (981 ± 129) vs (856 ± 170) ms, (944 ± 136) vs (825 ± 172) ms, all P < 0.05). While the correct rate were less than normal control in all three arithmetic operations (0.80% (0.72%, 0.88%) vs 0.90% (0.85%,0.96%), 0.78% (0.64%,0.85%) vs 0.90% (0.84%,0.93%), 0.86% (0.74%,0.92%) vs 0.93%(0.90%,0.98%), all P < 0.05). N2 component could be elicited by all subjects in forehead. The amplitude of N2 of children with ADHD were significantly lower than control group in all three arithmetic operations at left frontal (F3: (-3.5 ± 5.2) vs (-6.7 ± 3.5)µV, (-3.8 ± 4.0) vs (-7.4 ± 4.5)µV, -5.8 (-7.6,1.6) vs -6.4(-10.3, -4.9) µV, all P < 0.05) and Fz ((-4.3 ± 6.4) vs ( -7.4 ± 4.2) µV, (-5.0 ± 5.4) vs (-7.9 ± 4.6)µV, -5.2(-9.7, -0.6) vs -7.9 (-10.5, -5.1)µV, all P < 0.05), the latency of ADHD group were prolonger than controls in subtraction operations at right and left frontal ((328 ± 36) vs (307 ± 27)ms, 325 (307,354)vs 309 (280, 330)ms) and frontal electrodes ((331 ± 35) vs (311 ± 30) ms, all P < 0.05). In addition and multiplication operations, there was no significant difference in latency (all P > 0.05). CONCLUSIONS: The children with ADHD have weak capacities of inhibition irrelevant information and paying attention to control. Their deficits in mental arithmetics may be due to the difficulties of selecting the best strategy during cognitive tasks.

Effects and mechanism of amyloid ß1-42 on mitochondria in astrocytes.

Amyloid ß (Aß)1-42 is strongly associated with Alzheimer's disease (AD). The effects of Aß1­42 on astrocytes remain largely unknown. The present study focused on the effects of Aß1­42 on U87 human glioblastoma cells as astrocytes for in vitro investigation and mouse brains for in vivo investigation. The mechanism and regulation of mitochondria and cytochrome P450 reductase (CPR) were also investigated. As determined by MTT assays, low doses of Aß1­42 (<1 µM) marginally promoted astrocytosis compared with the 0 µM group within 24 h, however, after 48 h treatment these doses reduced cellular growth compared with the 0 µM group. Furthermore, Aß1­42 doses >5 µM inhibited the growth of U87 cells compared with the 0 µM group after 24 and 48 h treatment. Immunofluorescence analysis demonstrated that astrocytosis was also observed in early stage AD mice compared with wild­type (WT) mice. In addition, concentrations of Aß1­42 were also significantly higher in early stage AD mice compared with WT mice, however, the levels were markedly lower compared with later stage AD mice, as determined by ELISA. In addition to increased levels of Aß1­42 in mice with later stage AD, reduced astrocyte staining was observed compared with WT mice. Western blotting indicated that the effect of Aß1­42 on U87 cell apoptosis may be regulated via Bcl­2 and caspase­3 located in mitochondria, whose functions, including adenosine triphosphate generation, electron transport chain and mitochondrial membrane potential, were inhibited by Aß1­42. During this process, the expression and activity of cytochrome P450 reductase was also downregulated. The current study provides novel insight into the effects of Aß1­42 on astrocytes and highlights a potential role for astrocytes in the protection against AD.

The delta-opioid receptor and Parkinson's disease.

Parkinson's disease (PD) is a common degenerative neurological disease leading to a series of familial, medical, and social problems. Although it is known that the major characteristics of PD pathophysiology are the dysfunction of basal ganglia due to injury/loss of dopaminergic neurons in the substantia nigra pars compacta dopaminergic and exhaustion of corpus striatum dopamine, therapeutic modalities for PD are limited in clinical settings up to date. It is of utmost importance to better understand PD pathophysiology and explore new solutions for this serious neurodegenerative disorder. Our recent work and those of others suggest that the delta-opioid receptor (DOR) is neuroprotective and serves an antiparkinsonism role in the brain. This review summarizes recent progress in this field and explores potential mechanisms for DOR-mediated antiparkinsonism.

In vivo and in vitro studies on the roles of p38 mitogen-activated protein kinase and NADPH-cytochrome P450 reductase in Alzheimer's disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disease with an increasing morbidity rate. As one of the most important signaling pathways that responds to inflammation and degeneration, the p38 mitogen-activated protein kinase (MAPK) signaling pathway is active in the cortexes of AD mice. At the cellular level the same effect can be observed with p38 MAPK when induced by amyloid ß (Aß)1-42, a 42-residue Aß fragment. Inhibition of p38 MAPK in the present study protected SH-SY5Y cells from the toxicity of Aß1-42, and alleviated the formation of senile plaques and cognitive impairment in AD mice. The expression of cytochrome P450 reductase (CPR) in the brains of mice with AD, in addition to Aß1-42-treated SH-SY5Y cells, also increased. However, the inhibition of CPR did not protect SH-SY5Y cells from the toxicity of Aß1-42. The results of the present study suggest that p38 MAPK is a potential therapeutic target for the treatment of AD. In addition, the main enzyme that metabolizes drugs, CPR, could serve a more complex role in AD.

Catalpol preserves neural function and attenuates the pathology of Alzheimer's disease in mice.

Alzheimer's disease (AD) is the most common form of dementia and there currently are no effective treatment strategies available. Catalpol is an iridoid glucoside, and large quantities can be isolated from the genus Rehmannia (Orobanchaceae). The present study assessed whether catalpol had any protective effects against Alzheimer's disease using a murine model. Reactive oxygen species (ROS)-associated enzymes as well as soluble Aß40 and Aß42 were detected using kits. Thioflavin­S staining was performed to detect senile plaques and reverse-transcription quantitative polymerase chain reaction was used to assess iroquois homeobox protein 3 (IRX3) and obesity­associated genes, while western blot analysis was used for ß­secretase 1 (BACE1), insulin­degrading enzyme (IDE) and neprilysin (NEP) detection. The Morris water maze was used to detect the learning ability and spatial memory. The results revealed that catalpol was able to reduce the oxidative stress in the cerebral cortex by regulating the activities and concentration of ROS­associated enzymes superoxide dismutase, glutathione peroxidase and catalase, however not malondialdehyde. Catalpol was also identified to be able to reduce the levels of soluble Aß40 and Aß42 in the cerebral cortex and thus inhibit the formation of senile plaques. These effects were observed to be regulated by IDE, however not by BACE1 or NEP. It is suggested that catalpol is not capable of directly regulating the expression of IRX3 and obesity­associated genes. Subsequent to the treatment with catalpol, impairments in learning and memory were also observed to be relieved using the Morris water maze test. The results of the present study indicate that catalpol may be a potential drug for the treatment of neurodegenerative diseases such as AD.

dl-3-n-Butylphthalide prevents oxidative damage and reduces mitochondrial dysfunction in an MPP(+)-induced cellular model of Parkinson's disease.

The aim of the present study was to explore the neuroprotective effects and mechanisms of action of dl-3-n-butylphthalide (NBP) in a 1-methyl-4-phenylpyridiniumion (MPP(+))-induced cellular model of Parkinson's disease (PD). NBP was extracted from seeds of Apium graveolens Linn. (Chinese celery). MPP(+) treatment of PC12 cells caused reduced viability, formation of reactive oxygen, and disruption of mitochondrial membrane potential. Our results indicated that NBP reduced the cytotoxicity of MPP(+) by suppressing the mitochondrial permeability transition, reducing oxidative stress, and increasing the cellular GSH content. NBP also reduced the accumulation of alpha-synuclein, the main component of Lewy bodies. Given that NBP is safe and currently used in clinical trials for stroke patients, NBP will likely be a promising chemical for the treatment of PD.

Combination of autologous fascia lata and fat injection into the vocal fold via the cricothyroid gap for unilateral vocal fold paralysis.

OBJECTIVES: To apply the technique of injection of a combination of autologous fascia lata and fat into the vocal fold via the cricothyroid gap for unilateral vocal fold paralysis and to evaluate the therapeutic effect in 12 patients who underwent the procedure. DESIGN: Retrospective analysis of 12 patients. SETTING: Academic research. PATIENTS: A mixture of autologous fascia lata and fat was injected into the thyroarytenoid muscle of the paralyzed vocal fold in 12 patients. MAIN OUTCOME MEASURES: Videolaryngostroboscopy was performed to observe the changes to the vocal fold. The patients' phonatory function before and after surgery was assessed by computerized acoustic analysis and by blinded perceptual evaluation. RESULTS: Videolaryngostroboscopy demonstrated that the paralyzed vocal folds in these patients were pushed medially after the procedure. Statistically significant improvements were found in the perturbation measurements (jitter and shimmer), harmonics to noise ratio, and maximum phonation time. Ratings by a panel of voice experts also showed each voice to be statistically significantly improved after the procedure. No complications were noted. CONCLUSION: A combination of autologous fascia lata and fat injected into the vocal fold for unilateral vocal fold paralysis is a safe and effective therapy.

MPP+ impairs autophagic clearance of alpha-synuclein by impairing the activity of dynein.

Increasing evidence suggests that dynein has an important role in the clearance of misfolded proteins by autophagy. Here we show that treatment of cells with 1-methyl-4-phenylpyridinium (MPP) cause alpha-synuclein overexpression and aggregation, leading to the accumulation of autophagic vacuoles and the recruitment of LC3-II to these vacuoles in the cytoplasm. After MPP treatment, dynein expression decreased and was mainly aggregated at the periphery of cytoplasm and lost its colocalization with alpha-synuclein and lamp1, indicating that dynein lost its function in the aggresome formation and failed to return autophagosome and lysosomes to the center of the cell for degradation. We consider that dynein plays an important role in the autophagic clearance of aggregate-prone proteins.

Role of autophagy and proteasome degradation pathways in apoptosis of PC12 cells overexpressing human alpha-synuclein.

Parkinson's disease is a common neurodegenerative disease in the elderly. Its causes and mechanisms are not clearly understood. To explore the specific role of autophagy and the ubiquitin-proteasome pathway in apoptosis, a specific proteasome inhibitor and macroautophagy inhibitor and stimulator were selected to investigate pheochromocytoma (PC12) cell lines transfected with human mutant (A30P) and wild-type (WT) alpha-synuclein. The apoptosis ratio was assessed by flow cytometry. LC3, heat shock protein 70 (hsp70) and caspase-3 expression in cell culture were determined by Western blot. The hallmarks of apoptosis and autophagy were assessed with transmission electron microscopy. Compared to the control group or the rapamycin (autophagy stimulator) group, the apoptosis ratio in A30P and WT cells was significantly higher after treatment with inhibitors of the proteasome and macroautophagy. The results of Western blots for caspase-3 expression were similar to those of flow cytometry; hsp70 protein was significantly higher in the proteasome inhibitor group than in control, but in the autophagy inhibitor and stimulator groups, hsp70 was similar to control. These findings show that inhibition of the proteasome and autophagy promotes apoptosis, and the macroautophagy stimulator rapamycin reduces the apoptosis ratio. And inhibiting or stimulating autophagy has less impact on hsp70 than the proteasome pathway.

[Apoptosis in nasopharyngeal carcinoma cell line NCE induced by curcumin and its molecular mechanism].

OBJECTIVE: To investigate the mechanism underlying the curcumin-induced apoptosis of nasopharyngeal carcinoma (NPC) cell line NCE cells. METHODS: The characteristics of apoptosis were identified by observation acridine orange and ethidium bromide stains, ultrastructure assay, DNA fragmentation assay and TdT-mediated dUTP nick end labeling method (TUNEL). Mitochondrial membrane potential (delta psi m), activity of caspase-3, cytosol cytochrome C and expression of gene Fas were determined by flow cytometry (FCM), Western Blot and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Several evidences of apoptosis were obtained from curcumin-treated NCE cells by acridine orange and ethidium bromide stains, ultrastructure identification, DNA fragmentation assay and TUNEL staining. And the mean TUNEL-positive rates increased significantly at the 3 different time points (12 h, 24 h and 48 h; 25.6%, 40.3% and 54.5%, respectively). In the curcumin-treated-groups, delta psi m altered significantly and the positive rates increased in a time-dependent manner. At the 3 different time points, the mean positive rates were 26.8%, 42.3% and 68.2%, respectively. When caspase-3 activity was detected, 80.5% cells presented proteases activities after 12 h incubation with curcumin. Western Blot analysis showed that cytoplasmic cytochrome C increased significantly after incubation with curcumin. Flow cytometry and RT-PCR analysis showed that curcumin could up-regulate the Fas expression in time-depended manner , the positive rates of Fas protein increased from 33.6% to 89.9%. CONCLUSIONS: Curcumin induced apoptosis of NCE cells both through mitochondria-dependent pathway and death receptor pathway.

[Repair of the rabbit ear cartilage defects with transforming growth factor-beta1 and allogenic chondrocyte/poly-DL-lactide higher porosity polymer].

OBJECTIVE: To study the repair of the rabbit ear cartilage defects with transforming growth factor-beta1 (TGF-beta1) and allogenic chondrocyte/poly-DL-lactide (PDLLA) higher porosity polymer. METHODS: A total of 18 rabbits were divided into the TGF-beta1 and chondrocytes/PDLLA graft group, the chondrocytes/PDLLA graft group, and the blank control group. Samples were taken out at 4, 12 and 18 weeks after implantation. The histological characteristics were investigated. RESULTS: After 18 weeks of the transplantation, the repaired effects of TGF-beta1 and allogenic chondrocytes/PDLLA graft group was better than the allogenic chondrocytes/PDLLA graft group not only on general sample but also histology, and the blank control group were repaired with fibrous tissue. CONCLUSIONS: The allogenic chondrocytes/PDLLA graft could repair the rabbit ear cartilage defects while TGF-beta1 could improve the quality of the rabbit ear cartilage defects.