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Anti-neurexin-3α antibody-associated encephalitis is rare in clinical practice. It often has a history of pre-infection. It is characterized by abnormal mental behavior, seizures, decreased consciousness, cognitive and sleep disorders, movement disorder, central hypoventilation and autonomic nervous dysfunction. Among them, dyskinesias are mainly involuntary movements of the mouth, face and limbs, dystonia, myoclonic seizures and other manifestations of increased movement. Parkinson′s symptoms manifested as decreased movement are rarely reported. A encephalitis patient with positive anti-neurexin-3α antibody is reported, who is a young female, mainly with parkinsonism such as slow movement, unsteady walking, difficulty in starting and turning around, and inability to hold things in both upper limbs, accompanied by abnormal mental behavior and cognitive dysfunction. After treatment with methylprednisolone and intravenous immunoglobulin, the prognosis is good.
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Objective:To investigate the effects and significance of α-synuclein(α-syn)on the expression level of β-arrestin 2 in Parkinson's disease(PD)in a mouse model.Methods:Twenty-eight C57BL/6J mice with similar motor skills were randomly divided into a model group and a control group, with 14 mice in each group.A PD model was established by injecting preformed fibrils of α-syn into the striatum of the brain, and behavioral changes were monitored after 4 weeks.The expression levels of α-syn, the dopamine receptor(DR), tyrosine hydroxylase(TH), inflammatory factors, β-arrestin 2 and the nuclear transcription factor-κB(NF-κB)signaling pathway-related proteins were determined by Western blotting.The interaction between α-syn and β-arrestin 2 was detected by fluorescence resonance energy transfer(FRET), and the regulation of α-syn on β-arrestin 2 transcriptional activation was detected by the dual luciferase report assay.Results:After 4 weeks of modeling, compared with the control group, the average movement speed of mice in the model group was significantly reduced( t=9.415, P<0.001), the movement track was sparse and concentrated around the open field, and the time needed to climb the pole was significantly prolonged( t=16.412, P<0.001). Compared with the control group, the relative expression of α-synin in astrocytes in the model group increased significantly, the relative expressions of D1DR and TH decreased significantly[(1.14±0.18) vs.(0.53±0.16), (0.67±0.13) vs.(1.15±0.11), (0.46±0.05) vs.(0.81±0.06)]( t=9.810, 10.917 and 17.356, all P<0.001), the relative expression of tumor necrosis factor-α, interleukin-1β, interleukin-6 and NF-κB signaling pathway-related proteins increased significantly( t=3.583, 4.284, 5.396, 11.747, 16.375 and 18.294, all P<0.001), and the relative expression of β-arrestin 2 protein[(0.42±0.11) vs.(1.33±0.14)]in astrocytes decreased significantly( t=19.795, P<0.001). The FRET results suggested a possible direct interaction between α-syn and β-arrestin 2.The results of the dual luciferase report assay showed that the transcription activity of β-arrestin 2 was significantly increased after α-syn gene knockout. Conclusions:The α-syn may induce inflammation in astrocytes by activating the NF-κB signaling pathway and participate in the pathogenesis of PD by reducing dopamine biosynthesis and inhibiting its physiological function through negative regulation of β-arrestin 2.
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Objective@#To investigate the effects of developmental exposure to DEHP on learning and memory of mice.@*Methods@#Male littermates of ICR mice randomly assigned to five experimental groups (n=14 for each condition) on PND4 to receive distilled water, vehicle and 10, 50 and 200 mg/ (kg·d) DEHP from PND5 to PND38 by gavage, weighing and recording body weight of mice. Open field task were conducted on PND 26 and Morris water maze task were begun from PND30 to PND 37 to evaluate spontaneous exploration activity and emotion, spatial learning and memory performance of pubertal mice, respectively. On PND39, all animals were killed and hippocampi were isolated on ice, then total proteins of hippocampus were extracted, followed by determining the expression of PSD95 and synapsin I by western blotting.@*Results@#200 mg/ (kg·d) DEHP significantly reduced the growth of body weight of mice and the time staying in the central area in open field, prolonged the time searching the hidden platform in Morris water maze (P<0.05) . 50 mg/ (kg·d) DEHP didn’t change the growth of body weight and the emotion (P>0.05) , but reduced the percent of time and distance in the target quadrant during the probe trial of mice in Morris water maze (P<0.05) . The results of western blotting showed that DEHP significantly reduced the expression of PSD95 in hippocampus of mice with all dose groups (P<0.01) , but only 200 mg/ (kg·d) DEHP reduced the expression of synapsin I (P<0.05) .@*Conclusion@#Developmental exposure to DEHP can damage the development of synapse in hippocampus, adversely impacting spatial memory performance of mice at a dose that are insufficient to significantly influence the general development and result in anxiety.
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Objective To explore the expression and clinical significance of chromogranin A (CgA) and synaptophysin (Syn) in gastroenteropancreatic neuroendocrine tumors (GEP-NET).MethodsThe data of sixty-six GEP-NET patients treated in the First Affiliated Hospital of Nanjing Medical University were collected between Jan.2003 and May 2009.The expression of CgA and Syn in the tissue of GEP-NET was detected by immunohistochemistry, and its association with clinicopathological characteristics and prognosis of GEP-NET were analyzed.Results In these 66 patients,the positive rate of Syn (87.9％,58/66) was higher than that of CgA (71.3％,47/66,x2 =5.63,P=0.02).CgA and Syn were simultaneously expressed in 64.6％ patients (42/66).In the tissues of GEP-NET,the expression of CgA was related with lymph node metastasis and TNM stages,not related with patients' gender,age,tumor location,function,degree of differentiation,tumor size,infiltration and distant metastasis. Syn was not related with all the above clinicopathological parameters.Three-year survival rate in CgA negative group (47％) was significantly lower than that in positive group (78％,x2 =0.00,P=0.01).ConclusionsSyn was more sensitive than CgA in the diagnosis of GEP-NET.CgA in some extent indicates the prognosis of GEP-NET.
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Objective Precondition is an approach to myocardial protection during ischemia-reper-fusion by inhibiting myocardial cell apoptosis.The purpose of this study was to evaluate the cardioprotective effect using 99Tcm-syuaptotagmin I (Syt I)-C2A to detect myocardial cell apoptosis in the myocardial is-chemia-repedusion rat model.Methods (1) The C2A domain of Syt I was labeled with 99Tcm using 2-iminothiophene hydrochloride (IT) method.Radiochemical purity was determined with thin layer chroma-tography.The binding activity of radiolabeled protein was assessed using eamptothecin-treated Jurket cells.(2) One group of 6 rats was prepared for myocardial ischemia-reperfusion model(A group),and another group of 6 rats was prepared for myocardial ischemia precondition model(B group).99Tcm-Syt I-C2A was injected via the tail vein at a dosage of about 7.4 MBq.At 1h after injection,the rat was sacrificed,and the heart was removed to rinse with saline and dye with triphenyl tetrazolium eoride (TTC).According to the resdt of myocardial dye,theischemic myoeardium was separated from the viable myocardium and weight was measured,and then its radioactivity was determined by gamma counting.The difference of radioactive uptake in the ischemic myocardium between these two group models was compared using percentage activity of injection dose per gram of tissue(%ID/g)±standard deviation(x±s).SPSS 12.0 was used for data analy-sis,and t-test was used to compare data.Results (1) The radiochemical purity of 99Tcm-Syt I-C2A was (98.90±0.43)%,and the radioactivity in the camptothecin-treated group was (10.99±0.55) folds higher than that of non-treated viable control group.(2)In the ischemia-reperfusion model,the radioactive uptake of 99Tcm-Syt,I-C2A was(2.41±0.32)%ID/g in the ischemic myocardium,and(0.16±O.02)%ID/g in the nomud myocardiunm.However,in the myocardial ischemia precondition model,(0.46±0.05)%ID/g in the isehemic myocardium was measured,and(0.20±0.05)%ID/g in the normal myocardium.Uptake of 99Tcm-Syt I-C2A in ischemic myocrdium showed statistically significant difference (t=8.52,P<O.01) between these two groups of models.Conclusion 99Tcm-C2A-glutathione S-transferase (GST) may be used to quantita-tively detect cardioprotective effect of ischemic precondition,which could inhibit myocardium apoptosis on ischemic myocardium in the ischemia-reperfusion rat model.
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Objective To investigate whether intrauterine hypoxia and ischemia can produce long-time effects or NOSI can prevent these damages. Methods Fetal rat intrauterine distress model was constructed. The rats were divided into the normal group, hypoxia and ischemia reperfnsion group and treatment group. Pupa were given to surrogate mothers and the ability of learning and memory at 40 day of age after delivery were examined. Then the water maze test was performed to detect the space learning ability and memory function of rats, and the changing of synaptophysin levels in hippocampns were detected by immunohistochemical staining. Result Behavioral results show that fetal distress produces cognitive impairment demonstrated by Morris water maze performance including a higher escape latency score and a de-creased cross platform time. The COD of Syp positive immunoreactive product in hippocampus were less decreased than that in the normal group or NOSI group. But the behavioral results and the COD of synaptophysin had no difference between normal group and NOSI group. Conclusions Fetal distress produced cognitive impairment and led to the decreasing of synaptophysin in hippocampns. Effective measure can relieve these damages.
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The synapsins are a family of neuron specific phosphoproteins associated with the membranes of synaptic vesicles. The synapsins play important roles in the neurotransmitter release and during the early neuronal development. In this review, we focus on the family members, gene location, distribution, structure and function of the synapsins.
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Objective To study the characteristic of chromogranin A(CgA),synaptophysin(SYN) and neuron-specific enolase(NSE) in cortex and medulla of adrenal.Methods Immunohistochemical method was used to detect the expression of CgA,SYN and NSE in routinely processed tissue specimens from human adrenal neoplasm and hyperplasia.Results The expression of CgA was detected in cortex of adrenocortical adenoma,adrenal neoplasm and chromophile tumor,but not in that of hyperplasia and normal adrenal.The expression of NSE was detected in cortex of adrenal cortical hyperplasia,cortical adenomas and pheochromocyte carcinoma,but not in that of pheochromocytoma and normal adrenal.The expression of SYN was detected in cortex of corticohyperplassia,cortical adenomas,medull neoplasm,chromophile tumor and pheochromocyte carcinoma,but not in that of cortical adenocarcinoma and normal adrenal.The expressions of CgA,NSE and SYN were detected in the medulla of all cases.Conclusion The characteristic of CgA,SYN and NSE in cortex and medulla of adrenal are useful in the differential diagnosis of tumor and hyperplasia in the adrenal.The relationship between the adrenal cortex and medulla is close.Besides the classical hypothalamus-pituitary-adrenal axis(HPAA) and rennin-angiotensin-aldosterone system(RAAS),the adrenal cortex and medulla have the basis of anatomy and endocrinology.
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AIM:To observe the dynamic changes of synapsin I expression and its phosphorylation in hippocampus in vascular dementia(VD)rats.METHODS:Eighty SD rats were randomly divided into sham-operated group(n=40)and VD model group(n=40),and the latter were established by repeatedly clipping the common carotid arteries with an intraperitoneal injection of sodium nitroprusside solution in anesthetized condition.The synaptic ultrastructural changes in hippocampal CA1 region and the expression levels of synapsinⅠ and phosphorylated synapsinⅠin hippocampus were observed by TEM and immunohistochemical staining method respectively in both sham-operated group and VD model group at 15 d,1 month,2 months and 4 months time points.RESULTS:No obviously pathological changes to CA1 area synapse were found in SO group.In model group rats,synaptic circa membrane ambiguity and fusion,synaptic circa membrane structure decreased the postsynaptic density,reduced synaptic vesicles and vesicle cluster.Above pathological changes became gradually severe along with the time prolongation after model-making operation.Compared with sham-operated group,the expression of synapsin I significantly reduced in CA1 region(P0.05)in model group was observed.The number of p-synapsin I positive neurons in DG and hippocampal CA1 region was less in model group than that in sham-operated group(P0.05).CONCLUSION:The damaged synaptic structure and depressed expression of synapsin I and its phosphorylation in presynaptic parts of hippocampus induced by repeatedly cerebral ischemia/reperfusion may contribute to the synaptic transmission disorders,especially the presynaptic disorder which may be one of the important pathogenesis of the initiation and development in vascular dementia rats.
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Objective To investigate the effect of neutral amino acid on preventing Parkinson disease.Methods Mice were injected with L-Valine,L-Pheylalanine,D-Valine or L-Lysine before or after paraquat administration,by which prakinsonian mouse model was constructed.The paraquat immunoreactivity was observed within nigral cell bodies.Then neurodegeneration and ?-synuclein aggregation were observed by immunohistochemistry and Western blot.Results Paraquat immunoreactivity was abolished by the administration of L-Valine,L-Pheylalanine before paraquat exposure.Pre-treatment with these two amino acids also protected the paraquat-induced loss of nigrostriatal dopaminergic cells and formation of thioflavine S-positive aggregates.In contrast, paraquat-induced toxicity was unaffected if animals were injected with these two amino acids after paraquat exposure or pre-treated with D-Valine or L-Lysine.Conclusions L-type neutral amino acids such as L Valine and L-Pheylalanine can prevent paraquat-induced neurodegeneration and a synuclein pathology through a competitive inhibition mechanism with stereospecificity in the central nervous system (CNS).Neutral amino acid could protect the dopaminergic neuron in substantia nigra and may prevent Parkinson disease.
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AIM and METHODS: The immunohistochemical method was used to study the on synapsin ex- press in hippocampal formation during spatial learning and memory in rats. RESULTS: (1 ) In control group there are diffuse brown granules without any obvious granular product in hippocampal fornation and in model group there are synapsin products in the hippocampal formation, especially in the subregion CA3, CA4 and the dentate gyrus after water maze flamed for one week. After two weeks water maze thened the hippocampal formation appear the same dis- tribution of the product edes with darker staining. (2) The light dendity of synapsin products between the model and the control groups showed significant differences, that in the model group was highter than that in the control group (P