Sex Differences in Neuropathology and Cognitive Behavior in APP/PS1/tau Triple-Transgenic Mouse Model of Alzheimer's Disease / 神经科学通报·英文版

Alzheimer's disease (AD) is the most common form of dementia among the elderly, characterized by amyloid plaques, neurofibrillary tangles, and neuroinflammation in the brain, as well as impaired cognitive behaviors. A sex difference in the prevalence of AD has been noted, while sex differences in the cerebral pathology and relevant molecular mechanisms are not well clarified. In the present study, we systematically investigated the sex differences in pathological characteristics and cognitive behavior in 12-month-old male and female APP/PS1/tau triple-transgenic AD mice (3×Tg-AD mice) and examined the molecular mechanisms. We found that female 3×Tg-AD mice displayed more prominent amyloid plaques, neurofibrillary tangles, neuroinflammation, and spatial cognitive deficits than male 3×Tg-AD mice. Furthermore, the expression levels of hippocampal protein kinase A-cAMP response element-binding protein (PKA-CREB) and p38-mitogen-activated protein kinases (MAPK) also showed sex difference in the AD mice, with a significant increase in the levels of p-PKA/p-CREB and a decrease in the p-p38 in female, but not male, 3×Tg-AD mice. We suggest that an estrogen deficiency-induced PKA-CREB-MAPK signaling disorder in 12-month-old female 3×Tg-AD mice might be involved in the serious pathological and cognitive damage in these mice. Therefore, sex differences should be taken into account in investigating AD biomarkers and related target molecules, and estrogen supplementation or PKA-CREB-MAPK stabilization could be beneficial in relieving the pathological damage in AD and improving the cognitive behavior of reproductively-senescent females.

The improvement effect of scFv17 on the gait of triple-transgenic mice / 中国应用生理学杂志

OBJECTIVE@#To observe the gait changes of Alzheimer's disease PS1M146V/APPswe/tauP301L triple-transgenic (3xTg-AD) mice and to investigate the improvement effect of single chain variable domain antibody fragment 17 (scFv17) on the gait.@*METHODS@#In the present study, a selection of 6-month-old 3xTg-AD mice (=18) and C57BL/6 wild-type mice (=24) was performed. First, we observed their gait changes and found that the gait of 12-month-old 3xTg-AD mice was severely damaged. Then, the two groups of mice were randomly divided into four groups:WT+PBS(=12), WT+scFv17(=12), 3xTg-AD+PBS(=9) and 3xTg-AD+scFv17(=9). The gait behavior test and pathological test were performed after 12 weeks'continuous administration of scFv17 (1.5 mg/kg) or an equal volume of PBS (0.01 mol/L) by nasal gavage twice a week.@*RESULTS@#Compared with the same month old wild type mice, the rear track width of 12 month old 3xTg-AD mice was increased(<0.01), swing time percent was decreased (<0.01), stance time percent was increased(<0.01), so the ability of movement coordination and balance was seriously damaged. ScFv17 could improve the coordination and balance ability of 12 month old 3xTg-AD mice(<0.01). The morphological structure of 3xTg-AD mice cerebellar Purkinje cells was improved. The treatment of scFv17 increased the Nissl body number of the cerebellar Purkinje cells of 3xTg-AD mice (<0.01). scFv17 reduced the amyloid β protein (Aβ) plaques in the cerebellar cortex of 3xTg-AD mice (<0.01), and scFv17 reduced the intracellular neurofibrillary tangles (NFT) of the cerebellar Purkinje cells of the 3xTg-AD mice (<0.01).@*CONCLUSIONS@#The coordination and balance ability of 3xTg-AD mice was significantly impaired. ScFv17 can improve gait behaviour in the 3xTg-AD significantly.The mechanism may be related to the improvement of the structure and protein function of cerebellar Purkinje cells, and the eliminating of the Aβ plaques and the neurofibrillary tangles.

Amyloid β protein injection into medial septum impairs hippocampal long-term potentiation and cognitive behaviors in rats / 生理学报

The specific loss of cholinergic neurons and the progressive deficits of cognitive function are the most primary characteristics of Alzheimer's disease (AD). Although the neurotoxicity of amyloid β protein (Aβ) in AD has been investigated extensively, it is still unclear whether the Aβ aggregated in the medial septum (MS), a major cholinergic nucleus projecting to the hippocampus, could affect hippocampal synaptic plasticity and further impair the memory behaviors. The present study investigated the effects of Aβ injection into the MS on hippocampal long-term potentiation (LTP) and cognitive behaviors of rats by using Morris water maze (MWM), Y maze and in vivo hippocampal LTP recording. The effects of kainic acid (KA), an agent with specific neurotoxicity to GABAergic neurons, were also observed. The results showed that: (1) Intra-MS injection of Aβ, not KA, impaired spatial learning and memory of rats in classical and reversal MWM tests; (2) Both Aβ and KA impaired novelty-seeking behavior of rats in Y maze; (3) Intra-MS injection of Aβ, not KA, suppressed in vivo hippocampal LTP in the CA1 region of rats; (4) Both Aβ and KA did not affect the motor ability in behavioral tests and the hippocampal paired-pulse facilitation (PPF) in electrophysiological recording. These results indicate that intra-MS injection of Aβ could impair spatial memory, cognitive flexibility and exploratory motivation, as well as hippocampal LTP in rats, suggesting that the cholinergic neurons in the MS and the septo-hippocampal projection could be important targets of neurotoxic Aβ, and the specific damage of cholinergic neurons in the MS is likely responsible for the impairments of hippocampal synaptic plasticity and cognitive function in AD.

Application of wireless neuronal recording system in fear conditioning of Alzheimer's disease mice - hippocampal Theta oscillation observation / 生理学报

APP/PS1/tau triple transgenic (3xTg) mouse is a classical animal model of Alzheimer's disease (AD), which has abnormalities in recognition and electrophysiological properties at early 6-month-old age. However, few studies were performed by using simultaneously recording cognitive behavior and brain electrical activity in the conscious 3xTg mice. By using a new wireless recording system, we recorded hippocampal Theta oscillations in 3xTg mice during the process of fear conditioning test. The results showed that: (1) in training session, no significant difference in the fear behavior and hippocampal Theta activity was found between 3xTg mice and WT mice; (2) in test session, 3xTg mice showed a significant decrease in freezing ratio compared with WT mice when they were exposed to conditioning stimulus (CS); (3) the 3xTg mice showed lower peak power in Theta oscillation in both Pre-CS and CS duration compared with WT mice; (4) CS effectively induced an increase in the peak frequency of Theta oscillation in WT mice, but not in 3xTg mice. These results indicated that the impairment of cognition behavior in 3xTg mice was accompanied with the decreased peak power and peak frequency of Theta oscillation in the hippocampus, suggesting that a decline in Theta oscillation might be involved in the impairments of the fear conditioning, and the enhanced hippocampal Theta oscillation may be beneficial for improving AD cognitive function.

Surgical treatment for the thoracolumbar spinal tuberculosis with paraplegia / 中国骨伤

<p><b>OBJECTIVES</b>To explore the long-term effects,operating opportunity,indication of anterior debridement and decompression and bone graft in treating thoracolumbar tuberculosis with paraplegia.</p><p><b>METHODS</b>From March 2006 to September 2008, the data of 56 patients with spinal tuberculosis were retrospectively analyzed. They were 36 cases male and 20 cases female, the age in ranging from 19 to 78 years with the mean of 42.5 years; course of disease in ranging from 3 months to 4 years. The lesion level was in T11-L2, including one stage in 6 cases, two stages in 42 cases, three stages in 7 cases, four stages in 1 case. According to the Frankel grade, grade A in 5 cases, B in 25, C in 21, D in 5. Preoperative Cobb angle had 30 cases under 30 degrees, 24 cases in 30 degrees-60 degrees, 2 cases more than 60 degrees [averaged in (35.0 +/- 3.3) degrees]. The mean VAS was 7.3 +/- 2.1 preoperatively. All patients had chemotherapy for 2-3 weeks. The clinical effects were evaluated by Cobb angle, VAS, condition of Frankel grade and fusion segments.</p><p><b>RESULTS</b>All patients were followed up from 12 to 38 months with an average of 24 months. All wound obtained primary healing. The Cobb angle was(19.0 +/- 5.5) degrees immediately after operation, and lost (1.8 +/- 0.7) degrees at the follow up. The mean VAS was 1.4 +/- 0.3 postoperatively and 1.3 +/- 0.4 at final follow up. The Cobb angle and VAS significant improved in postoperatively (P < 0.05), and there was no statically difference between after operation and last follow up(P > 0.05). At 1 year after operation, all patients obstained successful bony fusion. Among 51 cases incomplete paraplegia recovered partially or completely (over Frankel D) through chemotherapy and rehabilitation training for 1-1.5 years; 5 cases of complete paraplegia had partially recovered, 3 cases from Frankel A to C, 2 cases from Frankel A to B.</p><p><b>CONCLUSION</b>Base on the chemotherapeutic effect, paraplegia reason and location, total body condition to select different operative opportunity can effectively relieve spinal compression, stabilize spinal column, correct kyphosis and promote recovery of paraplegia.</p>

Analyisis of Investigation on Psychological Health Conditions of Middle and Primary School Students in Maojian Area of Shiyan City / 实用儿科临床杂志

Objective To understand the psychological health status of the middle and primary school students,and to provide some advice of their mental health care.Methods In 11 611 middle and primary school students in 18 schools in Maojian area of Shiyan city,the students,teachers and parents at 5 schods were investigated a randomely,targets were examined by Achenbach Child Behavior Checklist(CBCL),Pupil Rating Scale Revised Screening for Learning(PRS),Conner's Parent Symptom Questionnaire(PSQ)and Conner's Teacher Rating Scale(TRS)and self-established questionnaires for general information.Results The investigation demonstrated:89.29% of students possessed very promising dreams and sublime pursuits,and had correct outlook on life and values;10.71% of students had comparatively severe psychological problems.The major problems appeared to be indefinite purpose of study,shorted of mental endurance and severe impulsivetrend.Moreover,an-xiety,emotion instability and solitary trend caused indifference,sheepish ness and difficulty in their communication.Conclusion Schools,families and society pay close attention to students,mental health and help the youngsters develop in a healthily psychdogical way.

Survivin expression in midline T-cell lymphoma in relation to Epstin-Barr virus infection / 中国实验血液学杂志

To investigate the expression of survivin gene and its relationship with Epstin-Barr virus (EBV) infection in midline T-cell lymphoma (MTL), immunohistochemistry staining method was used to examine the expression of survivin and EBV-latent membrane protein (LMP-1) in the 41 cases. In situ hybridization (ISH) was used to detect EBV-encoded RNA (EBER1/2). The results showed that the expression of survivin was positive in 26 cases of midline T-cell lymphoma, but no positive was detected in 10 cases of reactive lymphoid tissues. The positive expression ratio of survivin was 12.5% in cases of MTL with low grade of malignancy, and was 75.76% in cases of MTL with middle and high grades of malignancy, the significant difference was found between these two groups (chi(2) = 8.55, P < 0.01). Positive expression ratios of EBER1/2 and LMP-1 were 70.73% and 41.46% respectively. Survivin expression was not significantly different between EBER1/2 positive and negative cases (P > 0.05). It is concluded that survivin expression is up-regulated in MTL, and survivin positive expression rate is associated with the degree of malignancy. Survivin may play a role in the pathogenesis of the MTL by influencing cell apoptosis. EBV infection is not significantly associated with survivin expression in the MTL.

Correlation between Mitochondrial Membrane Potential and Topiramate′s Neuroprotection / 实用儿科临床杂志

Objective To study topiramate′s neuroprotection on primary cultured hippocampal neurons which were injuried by glutamate and its mechanism.Methods The primary cultured hippocampal neurons were made as the research object,and excitotoxicity model was exected with glutamate.Hippocampal neuron survival was assessed by MTT method and hippocampal neuron mitochondrial membrance potential(MMP) was evaluated by fluorescence microscope and flow cytometry.Results Hippocampal neuron survival of normal control was(98.4?0.8)%,and the survival of glutamate model group was(59.6?3.2)%,at the same time,two topiramate′s groups′ cell survivals was(74.1?0.5)% and(79.2?3.4)%,and topiramate with two levels all could obviously increase hippocampal neuron survival((P

Immunophenotypic Features of NK/T Cell Lymphoma in Children and Its Association with Epstein-Barr Virus / 实用儿科临床杂志

Objective To study the immunophenotypic features of NK/T cell lymphoma in children and its association with Epstein-Barr virus (EBV) infection. Methods Five cases of children′s NK/T cell lymphoma were studied. CD45RO, CD3?, CD56, CD20, TIA-1 and granzyme B were detected by immunohistochemistry staining for investigating immunophenotype. The expression of EBV-latent membrane protein (LMP-1) were detected by immunohistochemistry. EBV-encoded RNA (EBER1/2) were detected by in situ hybridization (ISH). Results CD45RO, CD3?, TIA-1 and granzyme B were positive in 5 cases, CD56 was positive in 2 cases, while CD20 negative in 5 cases.EBER1/2 positive in 4 cases and LMP-1 positive in 3 cases.Conclusions NK/T cell lymphoma in children is strong associated with EBV infection,and EBV infection may play an important role in the pathogenesis of children NK/T cell lymphoma.

Early Intervention on Intelligent Development of Premature Infants / 中国心理卫生杂志

Objective:To investigate the effect of early intervention on intelligent development of the premature infants. Method:62 premature infants were randomly assigned to the intervention group and the control group. The early intervention began from the birth of the infants to their 2 years old.Result:At the age of one and two, the mental development index (MDI) and psychomotor development index (PDI) were significantly higher in the intervention group than in the control.Conclusion:Early intervention can improve intelligent development of premature infants.